An Australian Single-Center Cohort of Pediatric Empyema: Incidence, Pathogens and Disease Severity, and the Interaction of the COVID-19 Pandemic.

BACKGROUND: Empyema is the most common complication of pediatric community-acquired pneumonia, posing a significant morbidity to children. Clinicians have observed an increase in empyema rates and acuity in the years following the COVID-19 pandemic. METHODS: This retrospective analysis of children managed for empyema in a tertiary pediatric hospital, aimed to compare the incidence and describe the clinical characteristics prepandemic and postpandemic (2017-2023). RESULTS: There were 222 empyema cases, with a median age of 3 years (0.3-15 years). The majority (87.8%) of cases were managed with a chest drain and fibrinolytics. The remaining underwent minimally invasive video-assisted thoracoscopic surgery. Admissions postpandemic were associated with significantly longer lengths of stays (14 vs 12 days, P ≤ 0.001), higher rates of pediatric intensive care unit admissions (32% vs 26%, P = 0.045), and they required higher level of care (inotropes, noninvasive and invasive ventilation). There were also significantly higher rates of Streptococcus pyogenes (28% vs 7%, P ≤ 0.001), while rates of other organisms were not significantly different. We also noted a significant reduction in immunization rates post-pandemic (95.8% vs 83.1%, P < 0.01); however, there was no significant difference in S. pneumoniae serotypes between epochs. CONCLUSIONS: This study demonstrates an increased rate and severity of pediatric empyemas in the post-pandemic period. We propose that the increase was secondary to the increased rates of S. pyogenes seen in the postpandemic period. This rise in infection rates may be alleviated with nonpharmacologic measures aimed at reducing transmission; however, such measures are not sustainable and should be avoided.

Post COVID-19 conditions in an Australian pediatric cohort, 3 months following a Delta outbreak.

BACKGROUND: Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents. METHODS: The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment. FINDINGS: 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID. INTERPRETATION: During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention. IMPACT: Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity.

Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

Safety and tolerability of bronchoscopic and nebulised administration of bacteriophage.

INTRODUCTION: Pseudomonas aeruginosa is an organism well known for causing significant morbidity and mortality in people living with chronic lung conditions such as cystic fibrosis. We describe the safety, tolerability, and potential efficacy of bronchoscopic and nebulised bacteriophage administration, offering insights into a potential breakthrough for the treatment of chronic infections particularly in children and adolescents. METHOD: A 12-year-old female (F12) and a 17-year-old male (M17), both diagnosed with cystic fibrosis and chronic P. aeruginosa lung infection, underwent bacteriophage treatment (BT). The administration involved bronchoscopic instillation and subsequent nebulisation. This was performed concurrently with intravenous antibiotics and regular physiotherapy delivered in an in-patient setting for 14 days. Microbiological, clinical, and lung function assessments were conducted to assess this treatment modality. RESULTS: No adverse events (fever, localised reaction, wheeze or bronchospasm) occurred during BT. F12 demonstrated a 4% increase, while M17 showed a 5% improvement in FEV1% from their best FEV1% over the past three years following BT. A 12% (F12) and an 8% (M17) improvement from baseline FEV1% was observed. For F12 P. aeruginosa was not isolated from her sputum despite 12 previous hospitalisations for intravenous antibiotics. CONCLUSION: Bronchoscopic and nebulised routes of bacteriophage administration were well-tolerated in these two adolescents. This early report underscores the potential of this treatment modality and encourages clinicians and researchers to actively explore this innovative approach.

The changing epidemiology of pulmonary infection in children and adolescents with cystic fibrosis: an 18-year experience.

The impact of evolving treatment regimens, airway clearance strategies, and antibiotic combinations on the incidence and prevalence of respiratory infection in cystic fibrosis (CF) in children and adolescents remains unclear. The incidence, prevalence, and prescription trends from 2002 to 2019 with 18,339 airway samples were analysed. Staphylococcus aureus [- 3.86% (95% CI - 5.28-2.43)] showed the largest annual decline in incidence, followed by Haemophilus influenzae [- 3.46% (95% CI - 4.95-1.96)] and Pseudomonas aeruginosa [- 2.80%95% CI (- 4.26-1.34)]. Non-tuberculous mycobacteria and Burkholderia cepacia showed a non-significant increase in incidence. A similar pattern of change in prevalence was observed. No change in trend was observed in infants < 2 years of age. The mean age of the first isolation of S. aureus (p < 0.001), P. aeruginosa (p < 0.001), H. influenza (p < 0.001), Serratia marcescens (p = 0.006) and Aspergillus fumigatus (p = 0.02) have increased. Nebulised amikacin (+ 3.09 ± 2.24 prescription/year, p = 0.003) and colistin (+ 1.95 ± 0.3 prescriptions/year, p = 0.032) were increasingly prescribed, while tobramycin (- 8.46 ± 4.7 prescriptions/year, p < 0.001) showed a decrease in prescription. Dornase alfa and hypertonic saline nebulisation prescription increased by 16.74 ± 4.1 prescriptions/year and 24 ± 4.6 prescriptions/year (p < 0.001). There is a shift in CF among respiratory pathogens and prescriptions which reflects the evolution of cystic fibrosis treatment strategies over time.

Factors influencing treatment response of pulmonary exacerbation in children with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations in cystic fibrosis (CF) significantly impact morbidity and mortality. This study aimed to assess treatment response rates and identify contributing factors towards treatment response. METHODS: In this single-center, retrospective, longitudinal study spanning four years, we analyzed all pulmonary exacerbation admissions. We compared lung function at baseline, admission, end of treatment, and 6-week follow-up. Treatment response was defined as ≥95% recovery of baseline FEV1%. RESULTS: There were 78 children who required a total of 184 admissions. The mean duration of treatment was 14.9±2.9 days. FEV1% returned to 95% of baseline in 59% following treatment. The magnitude of the decline in lung function on admission in children who did not respond to treatment was 21.7±15.2% while the decline in children who responded to treatment was 8.3±9.4%, P<0.001. Children who experienced a decline in FEV1% greater than 40% exhibited an 80% reduced likelihood of returning to their baseline values (OR -0.8, 95% CI -0.988; -0.612). Similarly, those with FEV1% reductions in the ranges of 30-39% (OR -0.63, 95% CI -0.821; -0.439), 20-29% (OR -0.52, 95% CI -0.657; -0.383), and 10-19% (OR -0.239, 95% CI -0.33; -0.148) showed progressively lower odds of returning to baseline. Fourty-eight children required readmission within 7.7±5.4 months, children who responded to treatment had a longer time taken to readmission (8.9±6.4 months) versus children who did not respond to treatment (6.4±3.5 months), (OR: -0.20, 95% CI -0.355; -0.048). CONCLUSIONS: A greater decline in lung function on admission and readmission within 6 months of the initial admission predicts non-response to treatment. This highlights the importance of re-evaluating follow-up strategies following discharge.

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study.

BACKGROUND: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients. METHODS: In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function (from a 24-week parent study; n=399) or F508del-F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit. RESULTS: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in forced expiratory volume in 1 s (FEV1) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV1 % pred was +0.07 (95% CI -0.12-0.26) percentage points among the participants. CONCLUSIONS: ELX/TEZ/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA.

Screening for Cystic Fibrosis Related Complications in the Context of a Pandemic and Altered Models of Care.

Background: Standard of care recommend that patients with cystic fibrosis (CF) require screening investigations to assess for complications. Changing models of care due to the COVID19 pandemic may have impacted completion of recommended screening. Objective: To compare the frequency of screening investigations completed in people with CF before and after the onset of the COVID19 pandemic. Methods: Medical records were reviewed at 4 CF-specialist centers to identify screening investigations completed in the 12-months before and after pandemic onset. Results: Records of 625 patients were reviewed. Prior to pandemic onset, there was between center variability in completion of screening investigations. There was greatest baseline variation between centers in performing oral glucose tolerance test (OGTT); range 38%-69%, exercise tests; 3%-51% and sputum screening for non-tuberculous mycobacteria; 53%-81%. Following pandemic onset, blood tests, and sputum cultures were maintained at the highest rates. Exercise testing, CXR and OGTT exhibited the greatest declines, with reductions at individual centers ranging between 10%-24%, 22%-43%, and 20%-26%, respectively. Return to in-person visits following pandemic onset was variable, ranging from 16% to 74% between centers. Conclusion: Completion of screening investigations varies between CF centers and changes in models of care, such as increased virtual care in response to COVID19 pandemic was associated with reduction in completion of investigations. Centers would benefit from auditing their adherence to standards of care, particularly considering recent changes in care delivery.

Asthma and Susceptibility to COVID-19 in Australian Children During Alpha, Delta and Omicron Waves of the COVID-19 Pandemic.

Purpose: Earlier coronavirus-19 (COVID-19) pandemic reports did not implicate increased disease burden in asthmatics while subsequent findings have been inconsistent. To date, the impact of COVID-19 on childhood asthma remains undetermined and is further complicated with ongoing emergence of new variants. This study aimed to investigate association between asthma and COVID-19 for children in New South Wales (NSW), Australia and compare its differences across four major outbreaks from alpha, delta and omicron variants/subvariants. Methods: This is a retrospective cross-sectional study of all children aged ≤17 years old who sought care for COVID-19 at Sydney Children's Hospitals Network (SCHN) between 1 January 2020 and 31 May 2022. Results: Of the 18,932 children with polymerase chain reaction (PCR) confirmed COVID-19 who attended SCHN, 60% received their care during delta wave, and 5.41% (n = 913) had prior diagnosis of asthma. Among children with COVID-19, the odds of having asthma were lower during alpha (aOR = 0.43; 95% CI, 0.19-0.83) and delta wave (aOR = 0.84; 95% CI, 0.73-0.96), but were higher during omicron wave (aOR = 1.56; 95% CI, 1.23-1.95). Length of hospital stay (LOS) for asthmatic children were increased by 0.55 days and 1.17 days during delta and the second omicron wave, respectively. Intensive care and mechanical ventilation requirements were not significantly different between asthmatic and non-asthmatic children. Eleven deaths were reported but none had asthma. Conclusion: Although children with asthma were more susceptible to COVID-19 infections during omicron waves compared to that of alpha or delta waves, they were not at greater risk of COVID-19 severity at any stage of the outbreak regardless of the predominant SARS-CoV-2 variants/subvariants.

A systematic review on the use of bacteriophage in treating Staphylococcus aureus and Pseudomonas aeruginosa infections in cystic fibrosis.

BACKGROUND: Respiratory infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are a major concern for cystic fibrosis (CF) patients due to increasing antibiotic resistance. Bacteriophages, which are viruses that selectively target and kill bacteria, are being studied as an alternative treatment for these infections. This systematic review evaluates the safety and effectiveness of bacteriophages for the treatment of CF-related infections caused by S. aureus and/or P. aeruginosa. We conducted a search for original, published articles in the English language up to March 2023. Studies that administered bacteriophages via intravenous, nebulised, inhaled, or intranasal routes were included, with no comparators required. In vitro and in vivo studies were eligible for inclusion, and only animal in vivo studies that utilised a CF transmembrane conductance regulator (CFTR) animal model were included. Bacteriophage treatment resulted in a decrease in bacterial load in both humans and animals infected with P. aeruginosa. Complete eradication of P. aeruginosa was only observed in one human subject. Additionally, there was a reduction in biofilm, improvement in resistance profile, and reduced pulmonary exacerbations in individual case reports. Evidence suggests that bacteriophage therapy may be a promising treatment option for CF-related infections caused by P. aeruginosa and S. aureus. However, larger and more robust trials are needed to establish its safety and efficacy and create necessary evidence for global legislative frameworks.

Single-arm, open-labelled, safety and tolerability of intrabronchial and nebulised bacteriophage treatment in children with cystic fibrosis and Pseudomonas aeruginosa.

INTRODUCTION: Cystic fibrosis (CF) is a multisystem condition that is complicated by recurrent pulmonary infections requiring aggressive antibiotic treatment. This predisposes the patient to complications such as sensorineural hearing loss, renal impairment, hypersensitivity and the development of antibiotic resistance. Pseudomonas aeruginosa is one of the more common organisms which cause recurrent infections and result in greater morbidity and mortality in people living with CF. Bacteriophages have been identified as a potential alternative or adjunct to antibiotics. We hypothesise that bacteriophage therapy is a safe and well-tolerated treatment in children with CF infected with P. aeruginosa infection in their airways. METHODS: This single-arm, open-labelled, non-randomised trial will run for a maximum period of 36 months with up to 10 participants. Adolescents (≥12 years and <18 years of age) who continue to shed P.aeruginosa (within 3 months of enrolment) despite undergoing eradication therapy previously, will be considered for this trial. Non-genetically modified bacteriophages that have demonstrated obligate lytic activity against each of the study participants' P. aeruginosa strains will be selected and prepared according to a combination of established protocols (isolation, purification, sterility testing and packaging) to achieve close to good manufacturing practice recommendations. The selected bacteriophage will be administered endo-bronchially first under direct vision, followed by two times a day nebulisation for 7 days in addition to standard CF treatment (intravenous antibiotics, physiotherapy to be completed as inpatient for 10-14 days). Safety and tolerability will be defined as the absence of (1) fever above 38.5°C occurring within 1 hour of the administration of the nebulised bacteriophage, (2) a 10% decline in spirometry (forced expiratory volume in 1 s %) measured preadministration and postadministration of the first dose of nebulised bacteriophage. Clinical reviews including repeat sputum cultures and spirometry will be performed at 3, 6, 9 and 12 months following bacteriophage treatment. ETHICS AND DISSEMINATION: Our clinical trial is conducted in accordance with (1) good clinical practice, (2) Australian legislation, (3) National Health and Medical Research Council guidelines for the ethical conduct of research. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trial Registry (ACTRN12622000767707).

Real world impact of 13vPCV in preventing invasive pneumococcal pneumonia in Australian children: A national study.

BACKGROUND: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. METHODS: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. RESULTS: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls. CONCLUSION: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.

Clinical outcomes of adults and children with cystic fibrosis during the COVID-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic was associated with restricted community movement and limited access to healthcare facilities, resulting in changed clinical service delivery to people with cystic fibrosis (CF). This study aimed to determine clinical outcomes of Australian adults and children with CF in the 12-months following the onset of the COVID-19 pandemic. METHODS: This longitudinal cohort study used national registry data. Primary outcomes were 12-month change in percent predicted forced expiratory volume in one second (FEV1 %pred), body mass index (BMI) in adults and BMI z-scores in children. A piecewise linear mixed-effects model was used to determine trends in outcomes before and after pandemic onset. RESULTS: Data were available for 3662 individuals (median age 19.6 years, range 0-82). When trends in outcomes before and after pandemic onset were compared; FEV1 %pred went from a mean annual decline of -0.13% (95%CI -0.36 to 0.11) to a mean improvement of 1.76% (95%CI 1.46-2.05). Annual trend in BMI improved from 0.03 kg/m2 (95%CI -0.02-0.08) to 0.30 kg/m2 (95%CI 0.25-0.45) and BMI z-scores improved from 0.05 (95%CI 0.03-0.07) to 0.12 (95%CI 0.09-0.14). Number of hospitalisations decreased from a total of 2656 to 1957 (p < 0.01). Virtual consultations increased from 8% to 47% and average number of consultations per patient increased from median (IQR) of 4(2-5) to 5(3-6) (p < 0.01). CONCLUSION: In the 12-months following the onset of the COVID-19 pandemic, there was an improvement in the clinical outcomes of people with CF when compared to the pre-pandemic period.

Approaches to the management of haemoptysis in young people with cystic fibrosis.

Haemoptysis occurs in up to 25 % of young people with Cystic fibrosis (CF) [1]. We undertook a literature review and described the management approach to haemoptysis in CF between 2010 and 2020 at an Australian tertiary paediatric centre, The Children's Hospital Westmead, Sydney, New South Wales, using a retrospective review of the medical records which identified 67 episodes. Sixty episodes met inclusion criteria, including 31 patients. Using the US CF Foundation guidelines, episodes were classified as scant (53.3 %), moderate (38.3 %) or massive (8.3 %). Fifty-two percent of patients were female, mean age at presentation was 15.4 years (SD+/- 2.4) and 58 % were homozygous for the Fdel508 genotype. Twelve episodes (9 patients) required bronchial artery embolization (BAE). BAE was used in all cases of massive haemoptysis 5/5 (100 %), 6/23 (22 %) episodes of moderate and 1/32 (3 %) episode of scant haemoptysis as an elective procedure for recurrent haemoptysis. Our literature review and institutional experience highlights the need for up-to-date management guidelines in the management of haemoptysis in Cystic Fibrosis. Based on our experience, we provide a proposed algorithm to help guide the management of haemoptysis in CF.

The role of exome sequencing in childhood interstitial or diffuse lung disease.

BACKGROUND: Children's interstitial and diffuse lung disease (chILD) is a complex heterogeneous group of lung disorders. Gene panel approaches have a reported diagnostic yield of ~ 12%. No data currently exist using trio exome sequencing as the standard diagnostic modality. We assessed the diagnostic utility of using trio exome sequencing in chILD. We prospectively enrolled children meeting specified clinical criteria between 2016 and 2020 from 16 Australian hospitals. Exome sequencing was performed with analysis of an initial gene panel followed by trio exome analysis. A subset of critically ill infants underwent ultra-rapid trio exome sequencing as first-line test. RESULTS: 36 patients [median (range) age 0.34 years (0.02-11.46); 11F] were recruited from multiple States and Territories. Five patients had clinically significant likely pathogenic/pathogenic variants (RARB, RPL15, CTCF, RFXANK, TBX4) and one patient had a variant of uncertain significance (VIP) suspected to contribute to their clinical phenotype, with VIP being a novel gene candidate. CONCLUSIONS: Trio exomes (6/36; 16.7%) had a better diagnostic rate than gene panel (1/36; 2.8%), due to the ability to consider a broader range of underlying conditions. However, the aetiology of chILD in most cases remained undetermined, likely reflecting the interplay between low penetrant genetic and environmental factors.

Personalized tobramycin dosing in children with cystic fibrosis: a comparative clinical evaluation of log-linear and Bayesian methods.

BACKGROUND: Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF). OBJECTIVES: To compare clinical and performance outcomes for LLR and BF. PATIENTS AND METHODS: A quasi-experimental intervention study was conducted at a tertiary children's hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible. RESULTS: A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood samples collected during a single hospital admission. The timeframe for blood sampling was more flexible with BF, with TDM samples collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0-24 target of ≥100 mg/L·h was more frequently attained using BF (72%; 92/128) compared with LLR (50%; 124/248) (P < 0.001). Incidence of acute kidney injury was rare in both groups. CONCLUSIONS: LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children.

Pulmonary function testing during SARS-CoV-2: An ANZSRS/TSANZ position statement.

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a joint position paper on pulmonary function testing during coronavirus disease 2019 (COVID-19) in July 2021. A working group was formed via an expression of interest to members of both organizations and commenced work in September 2021. A rapid review of the literature was undertaken, with a 'best evidence synthesis' approach taken to answer the research questions formed. This allowed the working group to accept findings of prior relevant reviews or societal document where appropriate. The advice provided is for providers of pulmonary function tests across all settings. The advice is intended to supplement local infection prevention and state, territory or national directives. The working group's key messages reflect a precautionary approach to protect the safety of both healthcare workers (HCWs) and patients in a rapidly changing environment. The decision on strategies employed may vary depending on local transmission and practice environment. The advice is likely to require review as evidence grows and the COVID-19 pandemic evolves. While this position statement was contextualized specifically to the COVID-19 pandemic, the working group strongly advocates that any changes to clinical/laboratory practice, made in the interest of optimizing the safety and well-being of HCWs and patients involved in pulmonary function testing, are carefully considered in light of their potential for ongoing use to reduce transmission of other droplet and/or aerosol borne diseases.