118 results on '"Torzillo PJ"'
Search Results
2. Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic
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McLean, AEB, Webster, SE, Fry, M, Lau, EM, Corte, P, Torzillo, PJ, Troy, LK, Jo, HE, Geis, M, Rhodes, JE, Cleary, S, Spencer, L, and Corte, TJ
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Male ,Patient Education as Topic ,Respiratory System ,Quality of Life ,Humans ,Interdisciplinary Communication ,Female ,respiratory system ,Lung Diseases, Interstitial ,behavioral disciplines and activities ,11 Medical and Health Sciences ,Aged - Abstract
Background and objective The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued. Methods An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions. Results A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity. Conclusion Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.
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- 2020
3. Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in Indigenous infants in Australia
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O’Grady, KF, primary, Carlin, JB, additional, Chang, AB, additional, Torzillo, PJ, additional, Nolan, TM, additional, Ruben, A, additional, and Andrews, RM, additional
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- 2010
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4. Clinical research in Aboriginal health
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Torzillo, PJ, primary
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- 1999
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5. The prevalence of hookworm infection, iron deficiency and anaemia in an Aboriginal community in north‐west Australia
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Torzillo Pj
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business.industry ,Medicine ,General Medicine ,business - Published
- 1997
6. International retrieval of adults on extracorporeal membrane oxygenation support.
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Forrest P, Cheong JY, Vallely MP, Torzillo PJ, Hendel PN, Wilson MK, Bannontt PG, Bayfield MS, Herkes R, Walker SW, Forrest, P, Cheong, J Y, Vallely, M P, Torzillo, P J, Hendel, P N, Wilson, M K, Bannontt, P G, Bayfield, M S, Herkes, R, and Walker, S W
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A retrieval service was established in New South Wales to provide mobile extracorporeal membrane oxygenation support to patients with severe, acute cardiac or respiratory failure. This service has also retrieved four adult patients from Nouméa, New Caledonia to Sydney on extracorporeal membrane oxygenation support, which are the first international retrievals of this type from Australia. We discuss our experience with these patients, three of whom survived to hospital discharge. However, one patient referred from New Caledonia died before extracorporeal membrane oxygenation could be established. [ABSTRACT FROM AUTHOR]
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- 2011
7. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand.
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Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, Kolbe J, Landau LI, Maguire GP, McDonald MI, Reid DW, Thien FC, Torzillo PJ, Chang, Anne B, Bell, Scott C, Byrnes, Cass A, Grimwood, Keith, Holmes, Peter W, King, Paul T, and Kolbe, John
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Consensus recommendations for managing chronic suppurative lung disease (CSLD) and bronchiectasis, based on systematic reviews, were developed for Australian and New Zealand children and adults during a multidisciplinary workshop. The diagnosis of bronchiectasis requires a high-resolution computed tomography scan of the chest. People with symptoms of bronchiectasis, but non-diagnostic scans, have CSLD, which may progress to radiological bronchiectasis. CSLD/bronchiectasis is suspected when chronic wet cough persists beyond 8 weeks. Initial assessment requires specialist expertise. Specialist referral is also required for children who have either two or more episodes of chronic (> 4 weeks) wet cough per year that respond to antibiotics, or chest radiographic abnormalities persisting for at least 6 weeks after appropriate therapy. Intensive treatment seeks to improve symptom control, reduce frequency of acute pulmonary exacerbations, preserve lung function, and maintain a good quality of life. Antibiotic selection for acute infective episodes is based on results of lower airway culture, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients whose condition does not respond promptly or adequately to oral antibiotics are hospitalised for more intensive treatments, including intravenous antibiotics. Ongoing treatment requires regular and coordinated primary health care and specialist review, including monitoring for complications and comorbidities. Chest physiotherapy and regular exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and vaccines administered according to national immunisation schedules. Individualised long-term use of oral or nebulised antibiotics, corticosteroids, bronchodilators and mucoactive agents may provide a benefit, but are not recommended routinely. [ABSTRACT FROM AUTHOR]
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- 2010
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8. Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-risk Settings: A Randomized Controlled Trial.
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Kok HC, McCallum GB, Yerkovich ST, Grimwood K, Fong SM, Nathan AM, Byrnes CA, Ware RS, Nachiappan N, Saari N, Morris PS, Yeo TW, Oguoma VM, Masters IB, de Bruyne JA, Eg KP, Lee B, Ooi MH, Upham JW, Torzillo PJ, and Chang AB
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- Humans, Child, Preschool, Infant, Male, Female, Double-Blind Method, Treatment Outcome, New Zealand, Australia, Malaysia, Amoxicillin-Potassium Clavulanate Combination therapeutic use, Amoxicillin-Potassium Clavulanate Combination administration & dosage, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Community-Acquired Infections drug therapy, Hospitalization, Pneumonia drug therapy
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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., Competing Interests: A.B.C., K.G., S.T.Y., R.S.W., G.B.M., P.S.M., J.W.U., and P.J.T. report grants from NHMRC and NHMRC-managed grants (Medical Research Futures Fund), during the conduct of the study. ABC is also an independent data management committee member for clinical trials for Moderna (COVID-19 and EBV vaccines) and of an unlicensed vaccine (GlaxoSmithKline) and monoclonal antibody (AstraZeneca), received fees from the institution for consulting on the study designs for Zambon and Boehringer Ingelheim, airfares for travel from the European Respiratory Society and Boehringer Ingelheim, and personal fees for being an author of two UpToDate chapters that are outside the submitted work. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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9. Chronic respiratory disease in Indigenous peoples: a framework to address inequity and strengthen respiratory health and health care globally.
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Chang AB, Kovesi T, Redding GJ, Wong C, Alvarez GG, Nantanda R, Beltetón E, Bravo-López M, Toombs M, Torzillo PJ, and Gray DM
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- Humans, Chronic Disease therapy, Chronic Disease ethnology, Global Health, Healthcare Disparities ethnology, Respiratory Tract Diseases therapy, Respiratory Tract Diseases ethnology, Respiratory Tract Diseases epidemiology, Health Services, Indigenous organization & administration, Health Status Disparities, Risk Factors, Health Inequities, Indigenous Peoples
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Indigenous peoples around the world bear a disproportionate burden of chronic respiratory diseases, which are associated with increased risks of morbidity and mortality. Despite the imperative to address global inequity, research focused on strengthening respiratory health in Indigenous peoples is lacking, particularly in low-income and middle-income countries. Drivers of the increased rates and severity of chronic respiratory diseases in Indigenous peoples include a high prevalence of risk factors (eg, prematurity, low birthweight, poor nutrition, air pollution, high burden of infections, and poverty) and poor access to appropriate diagnosis and care, which might be linked to colonisation and historical and current systemic racism. Efforts to tackle this disproportionate burden of chronic respiratory diseases must include both global approaches to address contributing factors, including decolonisation of health care and research, and local approaches, co-designed with Indigenous people, to ensure the provision of culturally strengthened care with more equitable prioritisation of resources. Here, we review evidence on the burden of chronic respiratory diseases in Indigenous peoples globally, summarise factors that underlie health disparities between Indigenous and non-Indigenous people, propose a framework of approaches to improve the respiratory health of Indigenous peoples, and outline future directions for clinical care and research., Competing Interests: Declaration of interests ABC reports multiple grants related to studies on Indigenous children's lung health to her institution from the Australian National Health and Medical Research Council (NHMRC); she is also the lead author of several point-of-care manuals and educational resources related to Indigenous children's lung health, for which no payments have been received. TK reports personal fees for advisory board membership from Covis Pharma Canada. GJR reports payment of a training grant to his institution from the US Maternal and Child Health Bureau of the Health Resources & Services Administration; he is also an editor of the paediatric pulmonology section of UpToDate. GGA reports a grant for a study on Indigenous lung health to his institution from the Canadian Institute of Health Research. MT reports multiple grants related to studies on Indigenous health to her institution from the NHMRC; she also established two Aboriginal-controlled primary health-care services. PJT reports multiple grants related to studies on Indigenous lung health to his institution from the NHMRC; he is also the medical director of an Aboriginal-controlled primary health-care service and has co-authored point-of-care manuals and educational resources related to Indigenous lung health, for which no payments have been received. DMG reports grant funding and consulting fees from the Wellcome Trust, unrelated to this manuscript, and support for attending conferences from the Pan African Thoracic Society; she is also Treasurer of the Pan African Thoracic Society Executive Committee. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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10. 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.
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Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland K, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Skull SA, Oguoma VM, Chatfield MD, Lehmann D, Brennan-Jones CG, Binks MJ, Licciardi PV, Andrews RM, Snelling T, Krause V, Carapetis J, Chang AB, and Morris PS
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- Humans, Infant, Australia epidemiology, Child, Preschool, Female, Male, Prevalence, Vaccines, Conjugate administration & dosage, Pneumococcal Infections prevention & control, Pneumococcal Infections epidemiology, Immunization Schedule, Pneumococcal Vaccines administration & dosage, Pneumococcal Vaccines therapeutic use, Hearing Loss epidemiology, Otitis Media epidemiology, Otitis Media prevention & control
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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., Competing Interests: AJL received funds from NHMRC paid to the institution, and GSK provided materials for immunogenicity assays. AJL received funds from Merck Sharp and Dohme for analysis of pneumococcal carriage, payment to institution. ABC served as advisor on a Data Safety Monitoring Board for an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has multiple project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. ABC received Royalties or licences as an author of cough and bronchiectasis topics, and Partial reimbursement for airfares as a speaker for European Respiratory Society. All payments were to the institution. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to Merck Sharp and Dohme Australia. All other authors (DL, CGB-J, HS-V, MJB, MDC, PVL, PSM, PJT) declare no competing interests., (Copyright: © 2024 Leach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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11. Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.
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Chang AB, Yerkovich ST, Baines KJ, Burr L, Champion A, Chatfield MD, Eg KP, Goyal V, Marsh RL, McCallum GB, McElrea M, McPhail S, Morgan LC, Morris PS, Nathan AM, O'Farrell H, Sanchez MO, Parsons M, Schultz A, Torzillo PJ, West NP, Versteegh L, Marchant JM, and Grimwood K
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Young Adult, Disease Progression, Double-Blind Method, Randomized Controlled Trials as Topic, Treatment Outcome, Bronchiectasis drug therapy, Expectorants therapeutic use, Multicenter Studies as Topic, Quality of Life, Thioglycolates therapeutic use, Thiophenes therapeutic use
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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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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12. Chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand: TSANZ position statement summary.
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Grimwood K, Kennedy E, Toombs M, Torzillo PJ, and Chang AB
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- Child, Adult, Adolescent, Humans, New Zealand epidemiology, Suppuration, Australia epidemiology, Chronic Disease, Lung Diseases, Bronchiectasis epidemiology, Bronchiectasis therapy
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- 2023
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13. Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.
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Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Skull SA, Oguoma VM, Chatfield M, Lehmann D, Binks MJ, Licciardi PV, Andrews R, Snelling T, Krause V, Carapetis J, Chang AB, and Morris PS
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- Infant, Child, Humans, Child, Preschool, Infant, Newborn, Australia epidemiology, Vaccines, Conjugate therapeutic use, Pneumococcal Vaccines, Streptococcus pneumoniae, Randomized Controlled Trials as Topic, Otitis Media epidemiology, Otitis Media prevention & control, Otitis Media drug therapy, Pneumococcal Infections epidemiology, Pneumococcal Infections prevention & control, Pneumococcal Infections drug therapy, Deafness
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Objectives: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage., Methods: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose., Results: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%., Conclusion: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs., Competing Interests: Declaration of competing interest AJL received funds from NHMRC paid to the institution, and GSK provided materials for immunogenicity assays. AJL received funds from Merck Sharp and Dohme for analysis of pneumococcal carriage, payment to institution. ABC served as advisor on a Data Safety Monitoring Board for an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has multiple project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. ABC received Royalties or licences as an author of cough and bronchiectasis topics, and Partial reimbursement for airfares as a speaker for European Respiratory Society. All payments were to the institution. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to MSD Australia. All other authors (DL, HS-V, MB, MC, PL, PSM, PT) declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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14. Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.
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Chang AB, Bell SC, Byrnes CA, Dawkins P, Holland AE, Kennedy E, King PT, Laird P, Mooney S, Morgan L, Parsons M, Poot B, Toombs M, Torzillo PJ, and Grimwood K
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- Child, Humans, Adult, Adolescent, New Zealand, Australia, Anti-Bacterial Agents therapeutic use, Bronchiectasis therapy, Bronchiectasis drug therapy, Lung Diseases drug therapy
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This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)
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- 2023
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15. 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.
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Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Chatfield MD, Lehmann D, Binks M, Chang AB, Carapetis J, Krause V, Andrews R, Snelling T, Skull SA, Licciardi PV, Oguoma VM, and Morris PS
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- Antibodies, Bacterial immunology, Australia, Haemophilus influenzae immunology, Humans, Immunoglobulin G immunology, Infant, Infant, Newborn, Pneumococcal Infections immunology, Pneumococcal Infections prevention & control, Respiratory Tract Infections, Streptococcus pneumoniae immunology, Time Factors, Hearing Loss immunology, Immunization, Secondary, Indigenous Peoples, Nasopharynx immunology, Nasopharynx microbiology, Otitis Media immunology, Pneumococcal Vaccines administration & dosage, Pneumococcal Vaccines immunology, Vaccines, Conjugate administration & dosage, Vaccines, Conjugate immunology
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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)., Competing Interests: Declaration of interests ABC served as advisor on an unlicensed vaccine (GlaxoSmithKline) and an unlicensed monoclonal antibody (AstraZeneca), was an adviser on an unlicensed molecule for chronic cough (Merck); and has various project grants and a Centre of Research Excellence relating to various aspects of bronchiectasis in children from the National Health and Medical Research Council. PM served on a data safety and monitoring board for the Novavax COVID-19 vaccine. JB provided a report to MSD Australia. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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16. 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.
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McCallum GB, Fong SM, Grimwood K, Nathan AM, Byrnes CA, Ooi MH, Nachiappan N, Saari N, Morris PS, Yeo TW, Ware RS, Elogius BW, Oguoma VM, Yerkovich ST, de Bruyne J, Lawrence KA, Lee B, Upham JW, Torzillo PJ, and Chang AB
- Subjects
- Amoxicillin therapeutic use, Amoxicillin-Potassium Clavulanate Combination adverse effects, Anti-Bacterial Agents, Child, Double-Blind Method, Humans, Infant, Community-Acquired Infections drug therapy, Community-Acquired Infections microbiology, Pneumonia drug therapy
- Abstract
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., Competing Interests: A.B.C. is supported by a National Health and Medical Research Council practitioner fellowship (number 1154302) and Children’s Hospital Foundation Queensland (Grant 50286). The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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17. Study Protocol for Preventing Early-Onset Pneumonia in Young Children Through Maternal Immunisation: A Multi-Centre Randomised Controlled Trial (PneuMatters).
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Chang AB, Toombs M, Chatfield MD, Mitchell R, Fong SM, Binks MJ, Smith-Vaughan H, Pizzutto SJ, Lust K, Morris PS, Marchant JM, Yerkovich ST, O'Farrell H, Torzillo PJ, Maclennan C, Simon D, Unger HW, Ellepola H, Odendahl J, Marshall HS, Swamy GK, and Grimwood K
- Abstract
Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal- Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae , and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27
+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size ( n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246., Competing Interests: KG participated in a rotavirus strain outbreak advisory board for GlaxoSmithKline, Rixensart, Belgium. ABC has received fees to the institution from work relating to IDMC membership of an unlicensed vaccine (GSK), and a COVID-19 vaccine (Moderna) outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Toombs, Chatfield, Mitchell, Fong, Binks, Smith-Vaughan, Pizzutto, Lust, Morris, Marchant, Yerkovich, O'Farrell, Torzillo, Maclennan, Simon, Unger, Ellepola, Odendahl, Marshall, Swamy and Grimwood.)- Published
- 2022
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18. Long-term outcomes of adults with acute respiratory failure treated with veno-venous extracorporeal membrane oxygenation.
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Gray EL, Forrest P, Southwood TJ, Totaro RJ, Plunkett BT, and Torzillo PJ
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- Adult, Australia, Humans, Male, Retrospective Studies, Extracorporeal Membrane Oxygenation, Respiratory Distress Syndrome therapy, Respiratory Insufficiency therapy
- Abstract
Veno-venous extracorporeal membrane oxygenation is increasingly used for severe but potentially reversible acute respiratory failure in adults; however, there are limited data regarding long-term morbidity. At our institution, most patients requiring veno-venous extracorporeal membrane oxygenation have been followed up by a single physician. Our primary aim was to describe the serial long-term morbidity for respiratory, musculoskeletal and psychological functioning., A retrospective audit of inpatient and outpatient medical records was conducted. A total of 125 patients treated with veno-venous extracorporeal membrane oxygenation for primary respiratory failure were included. The patients were young (mean (standard deviation) age 43.7 (4.1) years), obese (mean (standard deviation) body mass index 30.8 (10.4) kg/m
2 ), and mostly were male (59%). Most patients (60%) had no comorbidities., The survival rate to discharge was 70%, with body mass index and the number of comorbidities being independent predictors of survival on multiple logistic regression analysis. Over half (57%) of the Australian survivors had regular outpatient follow-up. They had a median of three reviews (range 1-9) over a median of 11.8 months (range 1.5-79) months. Breathlessness and weakness resolved in most within six months, with lung function abnormalities taking longer to resolve. Over half (60%) returned to employment within six months of discharge. Over a quarter (29%) displayed symptoms of anxiety, depression or post-traumatic stress disorder.- Published
- 2021
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19. Absence of human papillomavirus in nasopharyngeal swabs from infants in a population at high risk of human papillomavirus infection.
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Smith-Vaughan HC, Cheng AC, Tabrizi SN, Wurzel DF, Beissbarth J, Leach AJ, Morris PS, Binks MJ, Torzillo PJ, Chang AB, and Marsh RL
- Abstract
Maternal urogenital human papillomavirus (HPV) infection may place neonates at risk of HPV acquisition and subsequently lower respiratory infections as HPV can influence development of immunity. The respiratory HPV prevalence is not known in remote-dwelling Aboriginal infants, who are at high risk of respiratory infection and where the population prevalence of urogenital HPV in women is high. These data are necessary to inform HPV vaccination regimens. A retrospective analysis using PCR specific for HPV was performed on 64 stored nasopharyngeal swabs from remote-dwelling Aboriginal infants < 6 months of age, with and without hospitalised pneumonia. HPV DNA was not detected in any specimen. Despite the negative result, we cannot exclude a role for HPV in respiratory infections affecting infants in this population; however, our data do not support HPV as an important contributor to acute respiratory infection in remote-dwelling Aboriginal children., Competing Interests: None., (© 2021 Chinese Medical Association. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development.)
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- 2021
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20. Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.
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Cooper WA, Mahar A, Myers JL, Grainge C, Corte TJ, Williamson JP, Vallely MP, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Lau EMT, Raghu G, and Troy LK
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- Aged, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Biopsy, Bronchoscopy, Cryosurgery, Idiopathic Pulmonary Fibrosis pathology
- Abstract
Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; Dl
CO , 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).- Published
- 2021
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21. 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.
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Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Wilson N, Arrowsmith B, Beissbarth J, Chatfield MD, Oguoma VM, and Morris PS
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- Australia, Child, Haemophilus influenzae, Humans, Infant, Pneumococcal Vaccines, Vaccines, Conjugate, Otitis Media prevention & control, Pneumococcal Infections prevention & control
- Abstract
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.
- Published
- 2021
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22. Otitis media guidelines for Australian Aboriginal and Torres Strait Islander children: summary of recommendations.
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Leach AJ, Morris PS, Coates HL, Nelson S, O'Leary SJ, Richmond PC, Gunasekera H, Harkus S, Kong K, Brennan-Jones CG, Brophy-Williams S, Currie K, Das SK, Isaacs D, Jarosz K, Lehmann D, Pak J, Patel H, Perry C, Reath JS, Sommer J, and Torzillo PJ
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- Australia, Child, Child Health, Evidence-Based Medicine, Humans, Practice Guidelines as Topic, Native Hawaiian or Other Pacific Islander, Otitis Media diagnosis, Otitis Media prevention & control, Otitis Media therapy
- Abstract
Introduction: The 2001 Recommendations for clinical care guidelines on the management of otitis media in Aboriginal and Torres Islander populations were revised in 2010. This 2020 update by the Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander Children used for the first time the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Main Recommendations: We performed systematic reviews of evidence across prevention, diagnosis, prognosis and management. We report ten algorithms to guide diagnosis and clinical management of all forms of otitis media. The guidelines include 14 prevention and 37 treatment strategies addressing 191 questions., Changes in Management as a Result of the Guidelines: A GRADE approach is used. Targeted recommendations for both high and low risk children. New tympanostomy tube otorrhoea section. New Priority 5 for health services: annual and catch-up ear health checks for at-risk children. Antibiotics are strongly recommended for persistent otitis media with effusion in high risk children. Azithromycin is strongly recommended for acute otitis media where adherence is difficult or there is no access to refrigeration. Concurrent audiology and surgical referrals are recommended where delays are likely. Surgical referral is recommended for chronic suppurative otitis media at the time of diagnosis. The use of autoinflation devices is recommended for some children with persistent otitis media with effusion. Definitions for mild (21-30 dB) and moderate (> 30 dB) hearing impairment have been updated. New "OMapp" enables free fast access to the guidelines, plus images, animations, and multiple Aboriginal and Torres Strait Islander language audio translations to aid communication with families., (© 2021 Commonwealth of Australia and The Menzies School of Health Research. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)
- Published
- 2021
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23. Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial.
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Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Wilson N, Arrowsmith B, Beissbarth J, Chatfield MD, Oguoma VM, Licciardi P, Skull S, Andrews R, Carapetis J, McDonnell J, Krause V, and Morris PS
- Abstract
Background: Aboriginal children living in remote communities are at high risk of early and persistent otitis media. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are primary pathogens. Vaccines with potential to prevent early OM have not been evaluated in this population. We compared immunogenicity (ELISA and opsonophagocytic activity) of a combination of Synflorix™ (PHiD-CV10, 10 serotypes and protein D of NTHi) and Prevenar13™ (PCV13, 10 serotypes plus 3, 6A, and 19A), with recommended schedules., Methods: This open-label superiority trial randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to PCV13 (P) at 2-4-6 months (_PPP), PHiD-CV10 (S) at 2-4-6 months (_SSS), or PHiD-CV10 at 1-2-4 plus PCV13 at -6 months (SSSP). Primary outcomes (blinded) were immunogenicity against PCV13-only serotypes 3, 6A, 19A, and PHiD-CV10-only protein D at 7 months. Secondary outcomes include immunogenicity against all serotypes at 2, 4 and 7 months., Findings: Between 2011 and 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(1 4 1). An intention to treat approach including all available data was used. The SSSP group had superior immunogenicity against serotypes 3, 6A, and 19A compared to _SSS (OPA GMT ratios 8.1 to 59.5, p < 0.001), and against protein D compared to _PPP (GMC ratio 11.9 (95%CI 9.7 to 14.6)). Immune responses to protein D and 3, 6A, and 19A in SSSP were not significantly lower (i.e. no harm) than either _SSS or _PPP. For ten common serotypes responses at 2, 4 and 7 months were superior for SSSP (following 1-, 2-, and 4- doses) than _SSS and _PPP (following 0-, 1-, and 3- doses). At 4 months, _SSS was superior to _PPP. Reactogenicity and hospitalisations were rare and unrelated to the intervention., Interpretation: From two months, the 1-2-4-6-month combined schedule (SSSP) was safe and significantly more immunogenic than 2-4-6-month schedules. The earlier responses may be beneficial in high-risk populations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)
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- 2021
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24. Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.
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McLean AEB, Webster SE, Fry M, Lau EM, Corte P, Torzillo PJ, Troy LK, Jo HE, Geis M, Rhodes JE, Cleary S, Spencer L, and Corte TJ
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- Aged, Female, Humans, Male, Patient Education as Topic, Quality of Life, Interdisciplinary Communication, Lung Diseases, Interstitial epidemiology
- Abstract
Background and Objective: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued., Methods: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions., Results: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity., Conclusion: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD., (© 2020 Asian Pacific Society of Respirology.)
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- 2021
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25. Methodologies of COLDICE and Cryo-PID studies: details make the difference.
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Lau EMT, Grainge C, Williamson JP, Corte TJ, Cooper WA, Phillips MJ, Torzillo PJ, Vallely MP, Raghu G, and Troy LK
- Abstract
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3769). EMTL, CG, TJC, JPW, MJP, PJT, MPV and LKT report grants from Erbe Elektromedizin, non-financial support from Elektromedizin, grants from Medtronic, non-financial support from Cook Medical, grants from Rymed, non-financial support from Karl-Storz, non-financial support from Zeiss, non-financial support from Olympus, during the conduct of the study. WAC reports non-financial support from Zeiss and Olympus. In addition, MPV reports personal fees for consultancy and advisory board work for Medtronic, and TJC reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from Roche, personal fees from BMS, personal fees from Promedior, grants from Gilead, personal fees from Ad Alta, grants from Bayer, grants from Biogen, outside the submitted work. The other authors have no conflicts of interest to declare.
- Published
- 2020
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26. Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.
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Troy LK, Grainge C, Corte TJ, Williamson JP, Vallely MP, Cooper WA, Mahar A, Myers JL, Lai S, Mulyadi E, Torzillo PJ, Phillips MJ, Jo HE, Webster SE, Lin QT, Rhodes JE, Salamonsen M, Wrobel JP, Harris B, Don G, Wu PJC, Ng BJ, Oldmeadow C, Raghu G, and Lau EMT
- Subjects
- Australia, Biopsy methods, Female, Humans, Lung pathology, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Vital Capacity, Biopsy statistics & numerical data, Bronchoscopy methods, Cryobiology methods, Idiopathic Pulmonary Fibrosis diagnosis, Lung Diseases, Interstitial diagnosis
- Abstract
Background: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique., Methods: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549., Findings: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis., Interpretation: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed., Funding: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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27. Effectiveness of a chronic cough management algorithm at the transitional stage from acute to chronic cough in children: a multicenter, nested, single-blind, randomised controlled trial.
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O'Grady KF, Grimwood K, Torzillo PJ, Rablin S, Lovie-Toon Y, Kaus M, Arnold D, Roberts J, Buntain H, Adsett D, King A, Scott M, Anderson J, Toombs M, and Chang AB
- Subjects
- Acute Disease, Algorithms, Australia epidemiology, Case-Control Studies, Child, Preschool, Chronic Disease, Cough diagnosis, Evidence-Based Practice methods, Female, Humans, Infant, Male, Patient Care Management trends, Prospective Studies, Respiratory Tract Diseases complications, Respiratory Tract Diseases epidemiology, Single-Blind Method, Time Factors, Cough classification, Cough therapy, Patient Care Management methods, Respiratory Tract Diseases diagnosis
- Abstract
Background: Chronic (lasting at least 4 weeks) cough in children is an important cause of morbidity. An algorithmic approach to the management of coughs in children evaluated in observational studies and a randomised controlled trial (RCT) enrolled children referred with median cough duration of 16 weeks to specialist centres. We investigated whether applying an evidence-based cough management algorithm in non-specialist settings earlier, once cough persisted for more than 4 weeks, improved cough resolution compared with usual care., Methods: We undertook a multicentre, single-blind RCT nested within a prospective cohort study of children (<15 years) in Australia presenting to three primary care or three hospital emergency departments with an acute respiratory illness with cough. Children were excluded if they had a known diagnosis of an underlying chronic medical condition (excluding asthma) or had an immunosuppressive illness or were taking immunomodulating drugs for more than 2 weeks in the preceding 30 days, or had severe symptoms requiring inpatient hospitalisation. Children were followed up for 8 weeks; those with a persistent cough at day 28 were randomly assigned to the cough management algorithm or to usual care. Randomisation was stratified by reason for presentation, study site, and cough duration (4 weeks to <6 weeks vs ≥6 weeks) using computer-generated permuted blocks (block size of four) with a 1:1 allocation. The primary outcome was the proportion of children with cough resolution at day 56 (defined as resolved if the child did not cough for at least 3 days and nights since day 28 or a more than 75% reduction in their average day and night cough score). Absolute risk differences (RD
absolute ) were calculated by modified intention-to-treat analysis (ITT). This trial is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12615000132549., Findings: Between July 7, 2015, and Oct 31, 2018, 1018 children were screened, 509 were enrolled in the cohort study, and of 115 children in the ITT analysis, 57 were randomly assigned to the intervention group and 58 to the control group. Children had a median age of 1·6 years (IQR 1·0-4·5); 45 (39%) of 115 were Indigenous, and 59 (51%) were boys. By day 56, 33 (58%) of 57 children in the intervention group achieved cough resolution compared with 23 (40%) 58 in the control group; cough resolution was unknown in 12 (21%) of 57 children receiving the intervention and in 13 (22%) of 58 receiving the control. The RDabsolute assuming children with an unknown cough outcome were still coughing at day 56 was 18·3% (95% CI 0·3-36·2); the number needed-to-treat for benefit was five (95% CI 3-364); the adjusted odds ratio was 1·5 (95% CI 1·3-1·6), favouring the intervention group., Interpretation: This study suggests an evidence-based cough management algorithm improves cough resolution in community-based children in the early phases of chronic cough. However, larger studies to confirm these findings in primary care are required., Funding: National Health and Medical Research Council., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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28. Nocturnal hypoxaemia is associated with adverse outcomes in interstitial lung disease.
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Troy LK, Young IH, Lau EMT, Wong KKH, Yee BJ, Torzillo PJ, and Corte TJ
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- Aged, Female, Humans, Hypertension, Pulmonary etiology, Hypoxia complications, Idiopathic Pulmonary Fibrosis complications, Lung Diseases, Interstitial complications, Male, Middle Aged, Polysomnography, Predictive Value of Tests, Progression-Free Survival, Proportional Hazards Models, Respiratory Function Tests, Severity of Illness Index, Sleep, Sleep Apnea, Obstructive complications, Sleep, REM, Survival Rate, Time Factors, Hypertension, Pulmonary physiopathology, Hypoxia physiopathology, Idiopathic Pulmonary Fibrosis physiopathology, Lung Diseases, Interstitial physiopathology, Sleep Apnea, Obstructive physiopathology
- Abstract
Background and Objective: Sleep-disordered breathing (SDB) has been reported as highly prevalent in idiopathic pulmonary fibrosis (IPF) and other interstitial lung disease (ILD) populations. Nocturnal oxygen desaturation (NOD), or the total sleep time spent with SpoO
2 < 90% (TST < 90), can occur both with and without associated apnoeas, and is common in ILD. This study aimed to characterize abnormal SDB and extent of TST < 90 in ILD patients and evaluate relationships between TST < 90 and markers of disease severity, development of pulmonary hypertension (PH) and mortality., Methods: Consecutive, newly referred ILD patients attending a specialist clinic underwent polysomnography (PSG). Serial lung function tests, echocardiography and other clinical variables were recorded. Predictors of PH and mortality were evaluated using logistic regression and Cox proportional hazards regression analyses., Results: A total of 92 ILD patients (including 44 with IPF) underwent PSG. At least mild obstructive sleep apnoea (OSA) was observed in 65.2%, with rapid eye movement (REM)-related events occurring frequently. At least 10% TST < 90 (designated 'significant NOD') was present in 35.9% of patients, and was associated with PH at baseline echocardiography. Multiple indices of hypoxaemia during sleep, including significant NOD, predicted the development of new or worsening PH. TST < 90 predicted overall and progression-free survival., Conclusion: Nocturnal oxygen saturation is associated with poorer prognosis in ILD patients and may contribute towards the pathogenesis of pulmonary vascular disease., (© 2019 Asian Pacific Society of Respirology.)- Published
- 2019
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29. Efficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial.
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Goyal V, Grimwood K, Ware RS, Byrnes CA, Morris PS, Masters IB, McCallum GB, Binks MJ, Smith-Vaughan H, O'Grady KF, Champion A, Buntain HM, Schultz A, Chatfield M, Torzillo PJ, and Chang AB
- Subjects
- Administration, Oral, Amoxicillin administration & dosage, Anti-Bacterial Agents administration & dosage, Australia, Azithromycin administration & dosage, Child, Child, Preschool, Clavulanic Acid administration & dosage, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Lung drug effects, Lung physiopathology, Male, New Zealand, Treatment Outcome, Amoxicillin therapeutic use, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Bronchiectasis drug therapy, Bronchiectasis physiopathology, Clavulanic Acid therapeutic use
- Abstract
Background: Bronchiectasis guidelines recommend antibiotics for the treatment of acute respiratory exacerbations, but randomised placebo-controlled trials in children are lacking. We hypothesised that oral amoxicillin-clavulanate and azithromycin would each be superior to placebo in achieving symptom resolution of non-severe exacerbations in children by day 14 of treatment., Methods: In this multicentre, three-arm, parallel, double-dummy, double-blind, randomised placebo-controlled trial at four paediatric centres in Australia and New Zealand, we enrolled children aged 1-18 years with CT-confirmed bronchiectasis unrelated to cystic fibrosis, who were under the care of a respiratory physician and who had had at least two respiratory exacerbations in the 18 months before study entry. Participants were allocated (1:1:1) at exacerbation onset to receive oral suspensions of amoxicillin-clavulanate (45 mg/kg per day) plus placebo azithromycin, azithromycin (5 mg/kg per day) plus placebo amoxicillin-clavulanate, or both placebos for 14 days. An independent statistician prepared a computer-generated, permuted-block (size 2-8) randomisation sequence, stratified by centre, age, and cause. Participants, caregivers, study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was the proportion of children with exacerbation resolution by day 14 in the intention-to-treat population. Treatment groups were compared using generalised linear models. Statistical significance was set at p<0·0245 to account for multiple comparisons. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000011886) and is completed., Findings: Between April 17, 2012, and March 1, 2017, 604 children were screened and 252 were enrolled. Between July 31, 2012, and June 26, 2017, 197 children were allocated at the start of an exacerbation (63 to the amoxicillin-clavulanate group, 67 to the azithromycin group, and 67 to the placebo group). Respiratory viruses were identified in 82 (53%) of 154 children with available nasal swabs on day 1 of treatment. Primary outcome data were available for 196 (99%) children (one child with missing data [placebo group] was recorded as non-resolved according to criteria defined a priori). By day 14, exacerbations had resolved in 41 (65%) children in the amoxicillin-clavulanate group, 41 (61%) in the azithromycin group, and 29 (43%) in the placebo group. Compared with placebo, relative risk for resolution by day 14 was 1·50 (95% CI 1·08-2·09, p=0·015; number-needed-to-treat [NNT] 5 [95% CI 3-20]) in the amoxicillin-clavulanate group and 1·41 (1·01-1·97, p=0·042; NNT 6 [3-79]) in the azithromycin group. Adverse events were recorded in 19 (30%) children in the amoxicillin-clavulanate group, 20 (30%) in the azithromycin group, and 14 (21%) in the placebo group, but no events were severe or life-threatening., Interpretation: Amoxicillin-clavulanate treatment is beneficial in terms of resolution of non-severe exacerbations of bronchiectasis in children, and should remain the first-line oral antibiotic in this setting., Funding: National Health and Medical Research Council (Australia), Cure Kids (New Zealand)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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30. Cryobiopsy versus open lung biopsy in the diagnosis of interstitial lung disease (COLDICE): protocol of a multicentre study.
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Troy LK, Grainge C, Corte T, Williamson JP, Vallely MP, Cooper W, Mahar AM, Lai S, Mulyadi E, Torzillo PJ, Salamonsen M, Don G, Myers J, Raghu G, and Lau EMT
- Subjects
- Cryosurgery, Humans, Biopsy methods, Lung pathology, Lung Diseases, Interstitial pathology, Multicenter Studies as Topic methods, Research Design
- Abstract
Introduction: Transbronchial lung cryobiopsy (TBLC) is a novel, minimally invasive technique for obtaining lung tissue for histopathological assessment in interstitial lung disease (ILD). Despite its increasing popularity, the diagnostic accuracy of TBLC is not yet known. The COLDICE Study (Cryobiopsy versus Open Lung biopsy in the Diagnosis of Interstitial lung disease allianCE) aims to evaluate the agreement between TBLC and surgical lung biopsy sampled concurrently from the same patients, for both histopathological and multidisciplinary discussion (MDD) diagnoses., Methods and Analysis: This comparative, multicentre, prospective trial is enrolling patients with ILD requiring surgical lung biopsy to aid with their diagnosis. Participants are consented for both video-assisted thoracoscopic surgical (VATS) biopsy and TBLC within the same anaesthetic episode. Specimens will be blindly assessed by three expert pathologists both individually and by consensus. Each tissue sample will then be considered in conjunction with clinical and radiological data, within a centralised MDD. Each patient will be presented twice in random order, once with TBLC data and once with VATS data. Meeting participants will be blinded to the method of tissue sampling. The accuracy of TBLC will be assessed by agreement with VATS at (1) histopathological analysis and (2) MDD diagnosis. Data will be collected on interobserver agreement between pathologists, interobserver agreement between MDD participants, and detailed clinical and procedural characteristics., Ethics and Dissemination: The study is being conducted in accordance with the International Conference on Harmonisation Guideline for Good Clinical Practice and Australian legislation for the ethical conduct of research., Trial Registration Number: ACTRN12615000718549., Competing Interests: Competing interests: LKT received study-related unrestricted educational grants or inkind support from the aforementioned commercial entities, on behalf of the COLDICE Investigator Team. MPV sits on the advisory boards of Medtronic and Edwards Lifesciences, and consults for Edwards Lifesciences and Abbott. GR provides consultation for Bellerophon, Biogen, BMS, FibroGen, Gilead, Nitto, Revistan, Promedior, Sanofi, Veracyte, Roche-Genentech, Avalyn and Boehringer Ingelheim. JM is an unpaid collaborator in the Veracyte BRAVE Trial.
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- 2019
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31. Impact of the 23-valent pneumococcal polysaccharide vaccination in pregnancy against infant acute lower respiratory infections in the Northern Territory of Australia.
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Binks MJ, Moberley SA, Balloch A, Leach AJ, Nelson S, Hare KM, Wilson C, Nelson J, Morris PS, Ware RS, Tang MLK, Torzillo PJ, Carapetis JR, Mulholland K, and Andrews RM
- Abstract
Background: Indigenous children in Australia's Northern Territory are densely colonised with the pneumococcus within weeks of birth antecedent to a high prevalence of acute lower respiratory infection (ALRI). We assessed the impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in pregnancy against infant ALRI in this setting., Methods: In an open label, allocation concealed, outcome-assessor blinded, randomised controlled trial conducted in the Northern Territory of Australia, healthy Indigenous women aged 17-39 years were randomised to receive the 23vPPV during pregnancy ( n = 75; 30-36 weeks gestation), at birth ( n = 75), or at 7 months post-partum ( n = 77). Randomisation was stratified by community of residence. In a secondary analysis, we compared the incidence of ALRI hospitalisations and ALRI clinic presentations (ascertained from electronic medical records) among infants of pregnancy vaccinees versus infants of mothers not vaccinated in pregnancy (controls) in the first year of life., Results: ALRI hospitalisation incidence was 12.3 per 100 child-years among infants of pregnancy vaccinees compared with 15.8 per 100 child-years among controls (hazard ratio (HR) 0.77, 95%CI 0.29-2.03). ALRI hospitalisations were more common among remote compared to urban infants (27.7 versus 8.6 per 100 child-years). Stratification by dwelling highlighted a differential antenatal vaccine effect against ALRI hospitalisations ( urban HR 2.45, 95%CI 0.60-9.99; remote HR 0.21, 95%CI 0.04-1.08). ALRI clinic presentation incidence was similar among infants of pregnancy vaccinees and controls., Conclusions: In this small study, antenatal 23vPPV vaccination was not associated with a reduced incidence of infant ALRI hospitalisations or ALRI clinic presentations during the first year of life. A potential differential effect between urban and remote settings warrants further investigation., Trial Registration: PneuMum; ClinicalTrials.gov NCT00714064., Competing Interests: The study was approved by the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC 05/52). Written consent was obtained for access to each child’s medical records to complete all of the described outcomes of the study including publication of non-identifiable data.No individually identifiable data were included in this publication.AJL has received research and conference support from GlaxoSmithKline (GSK) and Pfizer. PSM and EKM have received research funding from GSK. EKM has served on Advisory Boards for GSK and Pfizer. Other authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2018
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32. Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial.
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Goyal V, Grimwood K, Byrnes CA, Morris PS, Masters IB, Ware RS, McCallum GB, Binks MJ, Marchant JM, van Asperen P, O'Grady KF, Champion A, Buntain HM, Petsky H, Torzillo PJ, and Chang AB
- Subjects
- Administration, Oral, Adolescent, Amoxicillin-Potassium Clavulanate Combination adverse effects, Anti-Bacterial Agents adverse effects, Azithromycin adverse effects, Child, Child, Preschool, Disease Progression, Double-Blind Method, Equivalence Trials as Topic, Female, Humans, Infant, Male, Time Factors, Treatment Outcome, Young Adult, beta-Lactamase Inhibitors adverse effects, Amoxicillin-Potassium Clavulanate Combination therapeutic use, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Bronchiectasis drug therapy, beta-Lactamase Inhibitors therapeutic use
- Abstract
Background: Although amoxicillin-clavulanate is the recommended first-line empirical oral antibiotic treatment for non-severe exacerbations in children with bronchiectasis, azithromycin is also often prescribed for its convenient once-daily dosing. No randomised controlled trials involving acute exacerbations in children with bronchiectasis have been published to our knowledge. We hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with bronchiectasis., Methods: We did this parallel-group, double-dummy, double-blind, non-inferiority randomised controlled trial in three Australian and one New Zealand hospital between April, 2012, and August, 2016. We enrolled children aged 1-19 years with radiographically proven bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation, children were randomly assigned to oral suspensions of either amoxicillin-clavulanate (22·5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per day) and placebo for 21 days. We used permuted block randomisation (stratified by age, site, and cause) with concealed allocation. The primary outcome was resolution of exacerbation (defined as a return to baseline) by 21 days in the per-protocol population, with a non-inferiority margin of -20%. We assessed several secondary outcomes including duration of exacerbation, time to next exacerbation, laboratory, respiratory, and quality-of-life measurements, and microbiology. This trial was registered with the Australian/New Zealand Registry (ACTRN12612000010897)., Findings: We screened 604 children and enrolled 236. 179 children had an exacerbation and were assigned to treatment: 97 to amoxicillin-clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin-clavulanate group. The risk difference showed non-inferiority (-0·3%, 95% CI -11·8 to 11·1). Exacerbations were significantly shorter in the amoxicillin-clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14 days [8-16]; p=0·014). Adverse events were attributed to the trial medication in 17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the amoxicillin-clavulanate group (relative risk 0·9, 95% CI 0·5 to 1·5)., Interpretation: By 21 days of treatment, azithromycin is non-inferior to amoxicillin-clavulanate for resolving exacerbations in children with non-severe bronchiectasis. In some patients, such as those with penicillin hypersensitivity or those likely to have poor adherence, azithromycin provides another option for treating exacerbations, but must be balanced with risk of treatment failure (within a 20% margin), longer exacerbation duration, and the risk of inducing macrolide resistance., Funding: Australian National Health and Medical Research Council., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
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- 2018
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33. Bacteria and viruses in the nasopharynx immediately prior to onset of acute lower respiratory infections in Indigenous Australian children.
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Smith-Vaughan HC, Binks MJ, Beissbarth J, Chang AB, McCallum GB, Mackay IM, Morris PS, Marsh RL, Torzillo PJ, Wurzel DF, Grimwood K, Nosworthy E, Gaydon JE, Leach AJ, MacHunter B, Chatfield MD, Sloots TP, and Cheng AC
- Subjects
- Acute Disease epidemiology, Australia epidemiology, Bacteria classification, Bacteria genetics, Case-Control Studies, Child, Preschool, Cross-Over Studies, Female, Hospitalization, Humans, Infant, Male, Moraxella catarrhalis genetics, Moraxella catarrhalis isolation & purification, Native Hawaiian or Other Pacific Islander, Polymerase Chain Reaction, Prevalence, Respiratory Tract Infections epidemiology, Retrospective Studies, Streptococcus pneumoniae genetics, Streptococcus pneumoniae isolation & purification, Viruses genetics, Bacteria isolation & purification, Nasopharynx microbiology, Nasopharynx virology, Respiratory Tract Infections microbiology, Respiratory Tract Infections virology, Viruses isolation & purification
- Abstract
Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0-21 days before ALRI onset (case); (2) 90-180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22-7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97-3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls.
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- 2018
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34. The clinical, immunological and microbiological impact of the 10-valent pneumococcal-Protein D conjugate vaccine in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: A multi-centre, double-blind, randomised controlled trial.
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O'Grady KF, Chang AB, Cripps A, Mulholland EK, Smith-Vaughan H, Wood N, Danchin M, Thornton R, Wilson A, Torzillo PJ, Morris PM, Richmond P, Rablin S, Arnold D, Connor A, Goyal V, Stoney T, Perrett K, and Grimwood K
- Abstract
We aimed to determine the efficacy of the 10-valent pneumococcal- Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to <18-years with recurrent protracted bacterial bronchitis (rPBB), chronic suppurative lung disease (CSLD) or bronchiectasis. In a multi-centre, double-blind randomised controlled trial, children received two doses, 2-months apart of the 10vPHiD-CV or quadrivalent meningococcal-ACYW
135 conjugate vaccine. Active surveillance for acute exacerbations, respiratory symptoms and antibiotic use was undertaken through to 12-months after the second vaccine dose (clinical cohort only). Serum, saliva and nasopharyngeal swabs were collected to measure immunological and microbiological effects (immunology cohort). Between December 2012 and August 2015, 62 children were enrolled onto the clinical protocol (1 excluded from clinical analyses due to unblinding), while 74 contributed to the immunology cohort (overall mean age = 6.8-years (standard deviation = 3.7), 42 (56.8%) male). The absolute risk difference comparing the 10vPHiD-CV group (n = 31 children) to the MenACYW135 group (n = 30 children) for acute exacerbations was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0, 0.9). Compared to the MenACYW135 group, children who received the 10vPHiD-CV were less likely to have respiratory symptoms in each fortnight of surveillance (incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and required fewer short-course (<14-days duration) antibiotics (IDR 0.81, 95% CI 0.61, 1.09). The vaccine was immunogenic and no serious adverse events related to the vaccine were reported. In conclusion, 10vPHiD-CV might have a future role in managing children with rPBB, CSLD and bronchiectasis, but larger multicentre trials are needed to confirm or refute findings from this preliminary study.- Published
- 2018
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35. The Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Cardiac Sarcoidosis.
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Stanton KM, Ganigara M, Corte P, Celermajer DS, McGuire MA, Torzillo PJ, Corte TJ, and Puranik R
- Subjects
- Adult, Aged, Biopsy, Cardiomyopathies pathology, Humans, Male, Middle Aged, Retrospective Studies, Sarcoidosis pathology, Algorithms, Cardiomyopathies diagnosis, Gadolinium administration & dosage, Magnetic Resonance Imaging, Sarcoidosis diagnostic imaging
- Abstract
Background: Autopsy reports suggest that cardiac sarcoidosis occurs in 20 to 25% of patients with pulmonary sarcoidosis, yet the clinical ante-mortem diagnosis is made in only 5% of cases. Current diagnostic algorithms are complex and lack sensitivity. Cardiac Magnetic Resonance imaging (CMR) provides an opportunity to detect myocardial involvement in sarcoidosis. The aim of this study is to determine the prevalence and clinical significance of late gadolinium enhancement (LGE) on CMR in patients with sarcoidosis., Methods: Consecutive patients with biopsy-proven sarcoidosis undergoing CMR were retrospectively evaluated for cardiac sarcoidosis. Medical records were correlated with CMR., Results: Forty-six patients were evaluated. Late gadolinium enhancement was present in 22%, indicating myocardial involvement, and 70% had corresponding hyper-intense T2 signal indicating active inflammation. Late gadolinium enhancement was 18%+/-9.7% of overall left ventricular (LV) mass and most commonly located in the basal to mid septum. There was no association between LGE and cardiovascular symptoms or pulmonary stage. Eighty per cent of patients with LGE did not fulfill conventional diagnostic criteria for cardiac sarcoidosis. However, LGE was associated with clinically significant arrhythmia (p<0.01) and a lower LVEF (p=0.04)., Conclusions: Using CMR, we identified a higher prevalence of cardiac sarcoidosis than previously reported clinical studies, a prevalence which is more consistent with autopsy data. The presence of LGE was highly correlated with clinically significant arrhythmias and lower LVEF., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)
- Published
- 2017
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36. Effectiveness of a cough management algorithm at the transitional phase from acute to chronic cough in Australian children aged <15 years: protocol for a randomised controlled trial.
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O'Grady KF, Grimwood K, Toombs M, Sloots TP, Otim M, Whiley D, Anderson J, Rablin S, Torzillo PJ, Buntain H, Connor A, Adsett D, Meng Kar O, and Chang AB
- Subjects
- Acute Disease, Adolescent, Child, Chronic Disease, Cohort Studies, Female, Humans, Male, Prospective Studies, Queensland, Algorithms, Cough physiopathology, Cough therapy, Research Design
- Abstract
Introduction: Acute respiratory infections (ARIs) are leading causes of hospitalisation in Australian children and, if recurrent, are associated with increased risk of chronic pulmonary disorders later in life. Chronic (>4 weeks) cough in children following ARI is associated with decreased quality-of-life scores and increased health and societal economic costs. We will determine whether a validated evidence-based cough algorithm, initiated when chronic cough is first diagnosed after presentation with ARI, improves clinical outcomes in children compared with usual care., Methods and Analysis: A multicentre, parallel group, open-label, randomised controlled trial, nested within a prospective cohort study in Southeast Queensland, Australia, is underway. 750 children aged <15 years will be enrolled and followed weekly for 8 weeks after presenting with an ARI with cough. 214 children from this cohort with persistent cough at day 28 will be randomised to either early initiation of a cough management algorithm or usual care (107 per group). Randomisation is stratified by reason for presentation, site and total cough duration at day 28 (<6 and ≥6 weeks). Demographic details, risk factors, clinical histories, examination findings, cost-of-illness data, an anterior nasal swab and parent and child exhaled carbon monoxide levels (when age appropriate) are collected at enrolment. Weekly contacts will collect cough status and cost-of-illness data. Additional nasal swabs are collected at days 28 and 56. The primary outcome is time-to-cough resolution. Secondary outcomes include direct and indirect costs of illness and the predictors of chronic cough postpresentation., Ethics and Dissemination: The Children's Health Queensland (HREC/15/QRCH/15) and the Queensland University of Technology University (1500000132) Research Ethics Committees have approved the study. The study will inform best-practice management of cough in children., Trial Registration Number: ACTRN12615000132549., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
- Published
- 2017
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37. Bronchiectasis: shaking off its orphan status.
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Torzillo PJ
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- Humans, Bronchiectasis
- Published
- 2016
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38. Clinical impact of the interstitial lung disease multidisciplinary service.
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Jo HE, Glaspole IN, Levin KC, McCormack SR, Mahar AM, Cooper WA, Cameron R, Ellis SJ, Cottee AM, Webster SE, Troy LK, Torzillo PJ, Corte P, Symons KM, Taylor N, and Corte TJ
- Subjects
- Aged, Australia, Disease Management, Female, Humans, Male, Middle Aged, Quality Improvement, Referral and Consultation standards, Treatment Outcome, Idiopathic Pulmonary Fibrosis diagnosis, Idiopathic Pulmonary Fibrosis therapy, Interdisciplinary Communication, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial therapy, Patient Care Team organization & administration
- Abstract
Background and Objective: Multidisciplinary discussions (MDDs) have been shown to improve diagnostic accuracy in interstitial lung disease (ILD) diagnosis. However, their clinical impact on patient care has never been clearly demonstrated. We describe the effect that an ILD multidisciplinary service has upon the diagnosis and management of patients with suspected ILD., Methods: Patients at two specialized centres with suspected ILD underwent ILD multidisciplinary team review (ILD-MDT) (standard ILD clinic visit and diagnostic review at ILD-MDD). We compared changes in ILD diagnosis and management at referral to those following the ILD-MDT., Results: Ninety patients, 60% males (54/90), aged 67.3 years (SD = 11.4) were reviewed for suspected ILD. Overall, the ILD-MDT resulted in a change in specific ILD diagnosis in 48/90 (53%) patients. Of the 27 patients referred with a diagnosis of idiopathic pulmonary fibrosis (IPF), the diagnosis was changed at MDD in 10 patients. In contrast, seven patients had their diagnosis changed to IPF. There was also a significant reduction in 'unclassifiable' diseases and disease behaviour classifications provided additional information beyond ILD diagnosis., Conclusion: Dedicated tertiary ILD-MDT service has an important clinical impact on the care of the ILD patient, with frequent changes in ILD diagnosis and subsequent management. Further research to investigate long-term clinical outcomes of ILD-MDT is required., (© 2016 Asian Pacific Society of Respirology.)
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- 2016
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39. Upper airway viruses and bacteria detection in clinical pneumonia in a population with high nasal colonisation do not relate to clinical signs.
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Chang AB, Smith-Vaughan H, Sloots TP, Valery PC, Whiley D, Beissbarth J, and Torzillo PJ
- Abstract
Indigenous Australian children have high (up to 90%) rates of nasopharyngeal microbial colonisation and of hospitalisation for pneumonia. In Indigenous children hospitalised with pneumonia in Central Australia, we describe the nasopharyngeal detection of viruses and bacteria and assessed whether their presence related to signs of pneumonia (tachypnoea and/or chest in-drawing) on hospital admission and during subsequent days. Nasopharyngeal swabs (NPS) and data were prospectively collected from 145 children (median age = 23.5 months, interquartile range [IQR] 8.7-50) hospitalised with pneumonia at Alice Springs Hospital, Australia, between April 2001 and July 2002. The cohort was enrolled in a randomised controlled study using zinc and/or vitamin A supplementation. NPS were taken within 24 hours of hospitalisation and kept frozen at-80°C until analysed in 2014. Polymerase chain reaction (PCR) was used to detect Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Chlamydophila pneumoniae, Mycoplasma pneumoniae , and 16 respiratory viruses. Uni- and multi-variate analyses were used to examine the relationships. One or more organisms were present in 137 (94.5%) NPS; 133 (91.7%) detected ≥ 1 bacterium, 34 (37.2%) for ≥ 1 virus and 50 (34.5%) were positive for both viruses and bacteria. C. pneumoniae (n = 3) and M. pneumoniae (n = 2) were rare. In multi-variate analyses, age < 12 months (odds ratio [OR] 6.6 [95% confidence interval {CI} 1.7-25.4]) and fever (OR 4.1 [95% CI 1.7-10.4]) were associated with tachypnoea and chest in-drawing. However the presence of bacteria and/or virus type was not associated with tachypnoea and/or chest in-drawing on admission or during recovery. In children with high nasopharyngeal microbial colonisation rates, the utility of NPS in determining the diagnosis of clinical pneumonia or duration of tachypnoea or in-drawing is likely limited. Larger cohort and case-control studies are required to confirm our findings., (© The Author(s) 2015.)
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- 2015
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40. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.
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Hare KM, Grimwood K, Chang AB, Chatfield MD, Valery PC, Leach AJ, Smith-Vaughan HC, Morris PS, Byrnes CA, Torzillo PJ, and Cheng AC
- Subjects
- Anti-Bacterial Agents therapeutic use, Australia, Bacteria isolation & purification, Bacterial Infections drug therapy, Bronchiectasis complications, Carrier State microbiology, Child, Child, Preschool, Female, Humans, Infant, Macrolides therapeutic use, Male, New Zealand, Pacific Islands, Placebos administration & dosage, Population Groups, Anti-Bacterial Agents pharmacology, Azithromycin therapeutic use, Bacteria drug effects, Bacterial Infections microbiology, Drug Resistance, Bacterial, Macrolides pharmacology, Nasopharynx microbiology
- Abstract
Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.
- Published
- 2015
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41. Dobutamine stress for evaluation of right ventricular reserve in pulmonary arterial hypertension.
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Sharma T, Lau EM, Choudhary P, Torzillo PJ, Munoz PA, Simmons LR, Naeije R, and Celermajer DS
- Subjects
- Adult, Aged, Asymptomatic Diseases, Cardiotonic Agents pharmacology, Echocardiography, Stress methods, Exercise Test methods, Female, Humans, Male, Middle Aged, Reproducibility of Results, Dobutamine pharmacology, Hypertension, Pulmonary complications, Ventricular Dysfunction, Right diagnosis, Ventricular Dysfunction, Right etiology, Ventricular Dysfunction, Right physiopathology, Ventricular Function, Right drug effects
- Abstract
Right ventricular contractile response to pharmacological stress in pulmonary arterial hypertension (PAH) has not been characterised. We evaluated right ventricular contractile reserve in adults with PAH using dobutamine stress echocardiography. 16 PAH patients and 18 age-matched controls underwent low-dose dobutamine stress echocardiography. Contractile reserve was assessed by the change (Δ; peak stress minus rest value) in tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (S'). A subgroup of 13 PAH patients underwent treadmill cardiopulmonary exercise testing for peak oxygen uptake (V'O2peak). At rest, TAPSE and S' were reduced in the PAH group compared with controls (1.7 ± 0.4 versus 2.4 ± 0.2 cm and 9.7 ± 2.6 versus 12.5 ± 1.2 cm · s(-1), respectively; p<0.05). Contractile reserve was markedly attenuated in PAH compared to controls (ΔTAPSE 0.1 ± 0.2 versus 0.6 ± 0.3 cm and ΔS' 4.6 ± 2.8 versus 11.2 ± 3.6 cm · s(-1); p<0.0001). In the sub-group of PAH patients with preserved right ventricular systolic function at rest, contractile reserve remained depressed compared to controls. V'O2peak was significantly correlated with ΔS' (r=0.87, p=0.0003) and change in stroke volume (r=0.59, p=0.03). Dobutamine stress can reveal sub-clinical reduction in right ventricular contractile reserve in patients with PAH. A correlation with exercise capacity suggests potential clinical value beyond resting measurements., (Copyright ©ERS 2015.)
- Published
- 2015
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42. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand Thoracic Society of Australia and New Zealand guidelines.
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Chang AB, Bell SC, Torzillo PJ, King PT, Maguire GP, Byrnes CA, Holland AE, O'Mara P, and Grimwood K
- Published
- 2015
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43. Toward making inroads in reducing the disparity of lung health in Australian indigenous and new zealand māori children.
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Chang AB, Marsh RL, Upham JW, Hoffman LR, Smith-Vaughan H, Holt D, Toombs M, Byrnes C, Yerkovich ST, Torzillo PJ, O'Grady KA, and Grimwood K
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- 2015
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44. Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.
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Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, Brown NJ, McIntyre P, Smith-Vaughan H, Skull S, Balloch A, Andrews R, Carapetis J, McDonnell J, Krause V, and Morris PS
- Subjects
- Australia, Clinical Protocols, Female, Haemophilus Infections immunology, Haemophilus Infections microbiology, Haemophilus influenzae, Humans, Infant, Infant, Newborn, Male, Nasopharynx immunology, Pneumococcal Infections immunology, Pneumococcal Infections microbiology, Research Design, Risk, Streptococcus pneumoniae immunology, Vaccines, Conjugate immunology, Haemophilus Infections prevention & control, Immunization Schedule, Native Hawaiian or Other Pacific Islander, Pneumococcal Infections prevention & control, Pneumococcal Vaccines immunology
- Abstract
Introduction: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection., Methods and Analyses: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM., Ethics and Dissemination: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals., Trial Registration Numbers: ACTRN12610000544077 and NCT01174849., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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45. The radiological diagnosis of pneumonia in children.
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O'Grady KF, Torzillo PJ, Frawley K, and Chang AB
- Abstract
Despite the importance of paediatric pneumonia as a cause of short and long-term morbidity and mortality worldwide, a reliable gold standard for its diagnosis remains elusive. The utility of clinical, microbiological and radiological diagnostic approaches varies widely within and between populations and is heavily dependent on the expertise and resources available in various settings. Here we review the role of radiology in the diagnosis of paediatric pneumonia. Chest radiographs (CXRs) are the most widely employed test, however, they are not indicated in ambulatory settings, cannot distinguish between viral and bacterial infections and have a limited role in the ongoing management of disease. A standardised definition of alveolar pneumonia on a CXR exists for epidemiological studies targeting bacterial pneumonias but it should not be extrapolated to clinical settings. Radiography, computed tomography and to a lesser extent ultrasonography and magnetic resonance imaging play an important role in complicated pneumonias but there are limitations that preclude their use as routine diagnostic tools. Large population-based studies are needed in different populations to address many of the knowledge gaps in the radiological diagnosis of pneumonia in children, however, the feasibility of such studies is an important barrier., (© The Author(s) 2014.)
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- 2014
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46. Respiratory exacerbations in indigenous children from two countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.
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Redding GJ, Singleton RJ, Valery PC, Williams H, Grimwood K, Morris PS, Torzillo PJ, McCallum GB, Chikoyak L, Holman RC, and Chang AB
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- Alaska epidemiology, Australia epidemiology, Bronchiectasis drug therapy, Bronchodilator Agents therapeutic use, Child, Child, Preschool, Chronic Disease, Cohort Studies, Female, Humans, Infant, Longitudinal Studies, Lung Diseases drug therapy, Male, Population Groups, Prospective Studies, Risk Factors, Suppuration, Bronchiectasis epidemiology, Bronchiectasis ethnology, Cough epidemiology, Cough ethnology, Lung Diseases epidemiology, Lung Diseases ethnology
- Abstract
Background: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis., Methods: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter., Results: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators., Conclusions: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.
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- 2014
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47. Acute respiratory infections among Indigenous children.
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Torzillo PJ and Chang AB
- Subjects
- Female, Humans, Male, Hospitalization statistics & numerical data, Respiratory Tract Infections epidemiology
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- 2014
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48. Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis.
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Singleton RJ, Valery PC, Morris P, Byrnes CA, Grimwood K, Redding G, Torzillo PJ, McCallum G, Chikoyak L, Mobberly C, Holman RC, and Chang AB
- Subjects
- Australia epidemiology, Bronchiectasis diagnosis, Bronchiectasis economics, Bronchiectasis etiology, Child, Child, Preschool, Chronic Disease, Developed Countries, Female, Follow-Up Studies, Humans, Infant, Lung Diseases diagnosis, Lung Diseases economics, Lung Diseases etiology, Male, Medical History Taking, New Zealand epidemiology, Risk Factors, Socioeconomic Factors, Suppuration economics, Suppuration ethnology, Suppuration etiology, United States epidemiology, Bronchiectasis ethnology, Health Status Disparities, Indians, North American statistics & numerical data, Lung Diseases ethnology, Native Hawaiian or Other Pacific Islander statistics & numerical data
- Abstract
Objective: Indigenous children in developed countries are at increased risk of chronic suppurative lung disease (CSLD), including bronchiectasis. We evaluated sociodemographic and medical factors in indigenous children with CSLD/bronchiectasis from Australia, United States (US), and New Zealand (NZ)., Methods: Indigenous children aged 0.5-8 years with CSLD/bronchiectasis were enrolled from specialist clinics in Australia (n = 97), Alaska (n = 41), and NZ (n = 42) during 2004-2009, and followed for 1-5 years. Research staff administered standardized parent interviews, reviewed medical histories and performed physical examinations at enrollment., Results: Study children in all three countries had poor housing and sociodemographic circumstances at enrollment. Except for increased household crowding, most poverty indices in study participants were similar to those reported for their respective local indigenous populations. However, compared to their local indigenous populations, study children were more often born prematurely and had both an increased frequency and earlier onset of acute lower respiratory infections (ALRIs). Most (95%) study participants had prior ALRI hospitalizations and 77% reported a chronic cough in the past year. Significant differences (wheeze, ear disease and plumbed water) between countries were present., Discussion: Indigenous children with CSLD/bronchiectasis from three developed countries experience significant disparities in poverty indices in common with their respective indigenous population; however, household crowding, prematurity and early ALRIs were more common in study children than their local indigenous population. Addressing equity, especially by preventing prematurity and ALRIs, should reduce risk of CSLD/bronchiectasis in indigenous children., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2014
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49. Pulmonary hypertension leads to a loss of gravity dependent redistribution of regional lung perfusion: a SPECT/CT study.
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Lau EM, Bailey DL, Bailey EA, Torzillo PJ, Roach PJ, Schembri GP, Corte TJ, and Celermajer DS
- Subjects
- Female, Humans, Hypertension, Pulmonary physiopathology, Male, Middle Aged, ROC Curve, Severity of Illness Index, Gravitation, Hypertension, Pulmonary diagnosis, Posture physiology, Pulmonary Circulation physiology, Tomography, Emission-Computed, Single-Photon methods, Tomography, X-Ray Computed methods
- Abstract
Objective: Pre-capillary pulmonary hypertension (PHT) is characterised by progressive pulmonary vascular obliteration and loss of vascular reserves. In health, regional lung perfusion redistributes under the influence of gravity due to the presence of recruitable vessels. We investigated a combined single photon emission computed tomography/CT (SPECT/CT) method for assessing the pulmonary circulation by quantifying the gravity dependent redistribution of lung perfusion., Design: Characterisation of patients versus healthy controls., Patients: 15 patients with pre-capillary PHT and 11 healthy controls., Setting: University hospital clinic., Intervention: Regional lung perfusion was measured using SPECT/CT in two different postures (supine vs upright). A perfusion redistribution index (PRI) was used to quantify the cranial-caudal shift in regional lung perfusion resulting from gravitational (postural) change., Main Outcome Measure: PRI was compared between cases and controls, and correlated with markers of disease severity in cases., Results: Patients with pre-capillary PHT had notably reduced PRI compared to controls (0.02±0.06 vs. 0.28±0.15 normalised perfusion/cm, p<0.0001). PRI was significantly associated with prognostic parameters such as 6 min walk distance (r=0.60, p=0.018), functional class (p=0.008), and tricuspid annular plane systolic excursion (r=0.58, p=0.022). The receiver operating characteristic curve showed that PRI differentiated patients with pre-capillary PHT from controls with AUC=0.94 (p<0.001)., Conclusions: With SPECT/CT, gravity dependent redistribution of lung perfusion can be quantified using the PRI derived from supine and upright perfusion analysis. The potential utility of PRI for the non-invasive detection of PHT and assessment of disease severity warrants further study.
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- 2014
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50. Mailed versus frozen transport of nasal swabs for surveillance of respiratory bacteria in remote Indigenous communities in Australia.
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O'Grady KA, Whiley DM, Torzillo PJ, Sloots TP, and Lambert SB
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- Adolescent, Adult, Australia epidemiology, Child, Child, Preschool, Female, Humans, Male, Real-Time Polymerase Chain Reaction, Respiratory Tract Infections epidemiology, Sensitivity and Specificity, Young Adult, Nasal Cavity microbiology, Native Hawaiian or Other Pacific Islander, Public Health Surveillance methods, Respiratory Tract Infections ethnology, Respiratory Tract Infections microbiology, Specimen Handling methods
- Abstract
Background: Surveillance programs and research for acute respiratory infections in remote Australian communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting nasal swabs from a remote setting for bacterial polymerase chain reaction (PCR) testing., Methods: We sampled every individual who presented to a remote community clinic over a three week period in August at a time of low influenza and no respiratory syncytial virus activity. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for six bacterial species was undertaken using real-time PCR., Results: One hundred and forty participants were enrolled who contributed 150 study visits and paired specimens for testing. Respiratory illnesses accounted for 10% of the reasons for presentation. Bacteria were identified in 117 (78%) presentations for 110 (79.4%) individuals; Streptococcus pneumoniae and Haemophilus influenzae were the most common (each identified in 58% of episodes). The overall sensitivity for any bacterium detected in mailed specimens was 82.2% (95% CI 73.6, 88.1) compared to 94.8% (95% CI 89.4, 98.1) for frozen specimens. The sensitivity of the two methods varied by species identified., Conclusion: The mailing of unfrozen nasal specimens from remote communities appears to influence the utility of the specimen for bacterial studies, with a loss in sensitivity for the detection of any species overall. Further studies are needed to confirm our finding and to investigate the possible mechanisms of effect., Clinical Trial Registration: Australia and New Zealand Clinical Trials Registry Number: ACTRN12609001006235.
- Published
- 2013
- Full Text
- View/download PDF
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