Search

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies. [ABSTRACT FROM AUTHOR]

Background: Tai Chi Chuan (TTC) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls. Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test. There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test.Methods: In this cross sectional study, 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group. Another 30 sedentary men aged 66.2 were selected to serve as the control group. Measurements included resting heart rate, left and right single leg stance with eyes closed, modified sit and reach test, total body rotation test (left and right), and a three minute step test.Results: Compared with the sedentary group, the TCC group had significantly better scores in resting heart rate, three minute step test heart rate, modified sit and reach, total body rotation test on both right and left side (p < 0.01), and both right and left leg standing with eyes closed (p < 0.05). According to the American Fitness Standards, the TCC group attained the 90th percentile rank for sit and reach and total body rotation test, right and left.Conclusion: Long term regular TCC exercise has favourable effects on the promotion of balance control, flexibility, and cardiovascular fitness in older adults. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described., Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG study. The COG generated a patient list from which patients were randomly selected for chart review by participating sites. A central panel adjudicated CIV prophylaxis received as CPG-consistent or -inconsistent., Results: Twenty-four sites participated. Over half of patients received CPG-inconsistent CIV prophylaxis (HEC: 59/112, 52.6%; MEC: 119/215, 55.3%). The most common reasons for CPG-inconsistency were shortened duration of antiemetic administration or omission of dexamethasone. Site size was not found to be associated with CPG-inconsistent care delivery (HEC: adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.76-1.23; MEC: adjusted OR: 1.07; 95% CI: 0.92-1.24). Additionally, there was no statistically significant association between receipt of CPG-inconsistent care and patient outcomes., Conclusions: Patients receiving MEC or HEC often received CPG-inconsistent CIV prophylaxis. Site size was not associated with receipt of CPG-inconsistent care. Future studies should evaluate strategies to improve CIV control among pediatric oncology patients including those aimed at improving CPG adherence., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Small airway dysfunction (SAD) is increasingly recognized as an important feature of pediatric asthma yet typically relies on spirometry-derived FEF 25-75 to detect its presence. Multiple breath washout (MBW) and oscillometry potentially offer improved sensitivity for SAD detection, but their utility in comparison to FEF 25-75 , and correlations with clinical outcomes remains unclear for school-age asthma. We investigated SAD occurrence using these techniques, between-test correlation and links to clinical outcomes in 57 asthmatic children aged 8-18 years., Methods: MBW and spirometry abnormality were defined as z -scores above/below ± 1.96, generating MBW reference equations from contemporaneous controls ( n  = 69). Abnormal oscillometry was defined as > 97.5 th percentile, also from contemporaneous controls ( n  = 146). Individuals with abnormal FEF 25-75 , MBW, or oscillometry were considered to have SAD., Results: Using these limits of normal, SAD was present on oscillometry in 63% (resistance at 5-20 Hz; R5-R20; >97.5 th percentile), on MBW in 54% (S cond ; z -scores> +1.96) and in spirometry FEF 25-75 in 44% of participants ( z -scores< -1.96). SAD, defined by oscillometry and/or MBW abnormality, occurred in 77%. Among those with abnormal R5-R20, S cond was abnormal in 71%. Correlations indicated both R5-R20 and S cond were linked to asthma medication burden, baseline FEV 1 and reversibility. Additionally, S cond correlated with F E NO and magnitude of bronchial hyper-responsiveness. SAD, detected by oscillometry and/or MBW, occurred in almost 80% of school-aged asthmatic children, surpassing FEF 25-75 detection rates., Conclusions: Discordant oscillometry and MBW abnormality suggests they reflect different aspects of SAD, serving as complementary tools. Key asthma clinical features, like reversibility, had stronger correlation with MBW-derived S cond than oscillometry-derived R5-R20.

Background: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet., Methods: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts., Results: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children., Conclusion: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Background: Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC)., Methods: Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated., Results: Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age., Conclusions: Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

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 (FEV 1 ≥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: S cond 82 %, MBW TG RV 78 %, LCI 74 %, MBW TG IC 68 % and S acin 51 %. CPET VO 2 peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV 1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and S cond 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 S cond 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., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.

Hematopoietic stem cell transplantation (HSCT) is undertaken in children with the aim of curing a range of malignant and nonmalignant conditions. Unfortunately, pulmonary complications, especially bronchiolitis obliterans syndrome (BOS), are significant sources of morbidity and mortality post-HSCT. Currently, criteria developed by a National Institutes of Health (NIH) working group are used to diagnose BOS in children post-HSCT. Unfortunately, during the development of a recent American Thoracic Society (ATS) Clinical Practice Guideline on this topic, it became apparent that the NIH criteria have significant limitations in the pediatric population, leading to late diagnosis of BOS. Specific limitations include use of an outdated pulmonary function testing reference equation, a reliance on spirometry, use of a fixed forced expiratory volume in 1 second (FEV 1 ) threshold, focus on obstructive defects defined by FEV 1 /vital capacity, and failure to acknowledge that BOS and infection can coexist. In this review, we summarize the evidence regarding the limitations of the current criteria. We also suggest potential evidence-based ideas for improving these criteria. Finally, we highlight a new proposed criteria for post-HSCT BOS in children that were developed by the authors of the recently published ATS clinical practice guideline, along with a pathway forward for improving timely diagnosis of BOS in children post-HSCT., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis., Methods: We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving., Results: We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement., Conclusions: This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation., Methods: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts., Results: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised., Conclusions: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Fetal exposure to tobacco smoking throughout pregnancy is associated with wheezing in infancy. We investigated the influence of in utero smoking exposure on lung ventilation homogeneity and the relationship between lung ventilation inhomogeneity at 7 weeks of age and wheezing in the first year of life., Methods: Maternal smoking was defined as self-reported smoking of tobacco or validated by exhaled (e)CO > 6 ppm. Lung function data from healthy infants (age 5-9 weeks) born to asthmatic mothers and parent-reported respiratory questionnaire data aged 12 months were collected in the Breathing for Life Trial (BLT) birth cohort. Tidal breathing analysis and SF 6 -based Multiple Breath Washout testing were performed in quiet sleep. Descriptive statistics and regression analysis were used to assess associations., Results: Data were collected on 423 participants. Infants born to women who self-reported smoking during pregnancy (n = 42) had higher lung clearance index (LCI) than those born to nonsmoking mothers (7.90 vs. 7.64; p = .030). Adjusted regression analyzes revealed interactions between self-reported smoking and LCI (RR: 1.98, 95% CI: 1.07-3.63, 0.028, for each unit increase in LCI) and between eCO > 6 ppm and LCI (RR: 2.25, 95% CI: 1.13-4.50, 0.022) for the risk of wheeze in the first year of life., Conclusion: In utero tobacco smoke exposure induces lung ventilation inhomogeneities. Furthermore, an interaction between smoke exposure and lung ventilation inhomogeneities increases the risk of having a wheeze in the first year of life., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI., Competing Interests: BTF has served on a data safety monitoring board for Astellas and BTF's institution has received grant support from Allovir and Pfizer as well as CDC, FDA and NIH for research performed. CD has received support from Abramson Cancer Center K12 and a CIHR Fellowship Award. TL's institution has received an unrestricted research grant by Gilead Sciences and TL has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from: Astra Zeneca, EUSA Pharma, Gilead Sciences, MSD/Merck and Pfizer. TL has received support for attending meetings and/or travel from EUSA Pharma and has served on a data safety monitoring board or advisory board for: EUSA Pharma, Gilead Sciences, Merck/MSD, Mundipharma, Pfizer and Pharming. TL has had a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid at: Working Party Infection German Society of Pediatric Oncology and Hematology and Working Party Infection German Society of Pediatric Infectious Diseases. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2024 The Author(s).)

Background: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described., Methods: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations., Results: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed., Conclusions: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Rhinovirus (RV) positive bronchiolitis episodes in infancy confer a higher risk to develop asthma in later childhood with associated lung function impairments. We aimed to investigate the association between the type of virus causing a bronchiolitis hospitalization episode and lung ventilation inhomogeneities at preschool age., Methods: Infants hospitalized with a clinical diagnosis of moderate (ward admission) or severe (pediatric intensive care ward admission) bronchiolitis were prospectively followed-up at preschool age to assess nitrogen (N 2 ) multiple breath washout (MBW). Lung clearance index (LCI), functional residual capacity (FRC), and concentration normalized phase III slope analysis (Sn III ) indices were reported from ≥2 technically acceptable trials. Differences between groups were calculated using logistic and linear regression and adjusted for confounders (sex, age at bronchiolitis admission, height at visit, maternal asthma, and doctor-diagnosed asthma, including interaction terms between the latter three). An interaction term was included in a regression model to test for an interaction between RV bronchiolitis severity and MBW parameters at preschool age., Results: One hundred and thirty-nine subjects attended preschool follow-up, of which 84 out of 103 (82%) performing MBW had technically acceptable data. Children with a history of RV positive bronchiolitis (n = 39) had increased LCI (adjusted β-coefficient [aβ] = 0.33, 95% confidence interval [CI] 0.02-0.65, p = 0.040) and conductive airways ventilation inhomogeneity [S cond ] (aβ = 0.016, CI 0.004-0.028, p = 0.011) when compared with those with a RV negative bronchiolitis history (n = 45). In addition, we found a statistical interaction between RV bronchiolitis and bronchiolitis severity strengthening the association with LCI (aβ = 0.93, CI 0.20-1.58, p = 0.006)., Conclusion: Children with a history of hospital admission for RV positive bronchiolitis in infancy might be at a higher risk of lung ventilation inhomogeneities at preschool age, arising from the peripheral conducting airways., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Landscape fires are increasing in frequency and severity globally. In Australia, extreme bushfires cause a large and increasing health and socioeconomic burden for communities and governments. People with asthma are particularly vulnerable to the effects of landscape fire smoke (LFS) exposure. Here, we present a position statement from the Thoracic Society of Australia and New Zealand. Within this statement we provide a review of the impact of LFS on adults and children with asthma, highlighting the greater impact of LFS on vulnerable groups, particularly older people, pregnant women and Aboriginal and Torres Strait Islander peoples. We also highlight the development of asthma on the background of risk factors (smoking, occupation and atopy). Within this document we present advice for asthma management, smoke mitigation strategies and access to air quality information, that should be implemented during periods of LFS. We promote clinician awareness, and the implementation of public health messaging and preparation, especially for people with asthma., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor., Methods: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study., Results: 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment., Conclusions: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory., Competing Interests: Conflict of interest: None of the authors have personal financial relationships with any organisations that might have an interest in the submitted work., (Copyright ©The authors 2023.)

Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic fibrosis management has emerged-one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation. Understanding the effects of modulators in populations excluded from clinical trials is also crucial. Furthermore, establishing appropriate disease measures to assess efficacy in the youngest potential trial participants and in those whose post-modulator lung function is in the typical range for people without chronic lung disease is essential for continued drug development. Finally, recognising that a health outcome gap has been created for some people and widened for others who are not eligible for, cannot tolerate, or do not have access to modulators is important., Competing Interests: Declaration of interests In the last 36 months, unrelated to this work, JLT-C has received grants to her institution from the Cystic Fibrosis Foundation (CFF), the National Institutes of Health, Vertex Pharmaceuticals, Eloxx, and 4DMT; she has received fees from Vertex Pharmaceuticals related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. JLT-C has served as chair of a data monitoring committee for AbbVie. She serves as the adult patient care representative to the CFF board of trustees, and on the CFF's clinical research executive committee, clinical research advisory board, as immediate past chair of the Cystic Fibrosis Therapeutics Development Network's Sexual Health, Reproduction and Gender Research working group, and as co-chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily's Entourage, on the American Thoracis Society Respiratory Health Awards Working Group, and as chair-elect of the International Conference Committee. She is an associate editor for the Journal of Cystic Fibrosis and a member of the international advisory board for The Lancet Respiratory Medicine. She serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health National Heart, Lung, and Blood Institute. PDR reports that his previous institution, The Children's Hospital at Westmead, Sydney, has received remuneration for services provided by the Australian Central Over-Reading Centre he established for pharmaceutical-sponsored and investigator-led studies in cystic fibrosis. This renumeration will also be the case for his current institution (the University of Queensland) moving forward. MS has received grants and research support from: GSK, Insmed, Novartis, Trudell Pharma, Tel Aviv League for Lung Diseases; consultation fees from AstraZeneca, Boehringer Ingelheim, Dexcel, GSK, Kamada, Syncrony Medical, Trumed, Zambon; and speaker's fees from AstraZeneca, Boeringer Ingelheim, GSK, Kamada, Novartis, PhysioAssist, Sanofi, and Teva. MS serves as a data and safety monitoring board member for Bonus Biotherapeutics. MS is a member of management board of EMBARC, a member of the executive committee of the Israel Society for TB and Mycobacterial Diseases, an associate editor for the American Journal of Respiratory and Critical Care Medicine, and an editorial board member for the European Respiratory Journal and Chest. DGD reports grants from Chiesi Farmaceutici, the CF Trust, and the CFF to his institution. He reports consulting fees from Vertex and Insmed; and payments from Chiesi and Gilead for presentations. DGD receives support from the European Cystic Fibrosis Society and CFF for travel to meetings. He participates on a data and safety monitoring board for the Nomab trial and CSL Behring. He serves on the research oversight scientific board for the UK Clinical Trials Accelerator Platform and is the Director of the European Cystic Fibrosis Society Clinical Trials Network., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale., Competing Interests: PSH received grants or research support from NIH; royalties or licenses from Lippincott; consulting fees from MSKCC and participated on the REACH Board at Nemours, Delaware. SNCR received grants from CIHR, CCS and Kids Cancer Care-IMPACT. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2023 The Author(s).)

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4 + T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 + T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus . This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4 + T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Pulmonary chronic graft- versus -host disease (cGVHD) is a substantial cause of pulmonary morbidity and mortality post-haematopoietic stem cell transplantation (HSCT). Current spirometry-based monitoring strategies have significant limitations. Understanding the utility of novel peripheral airway function tests - multiple breath washout (MBW) and oscillometry - is critical in efforts to improve detection, facilitate earlier intervention and improve outcomes. In this scoping review, we identified 17 studies investigating MBW or oscillometry, or both, after allogenic HSCT. Despite small study numbers limiting the ability to draw firm conclusions, several themes were evident. Detectable peripheral airway abnormality in MBW occurred in a substantial proportion prior to HSCT. MBW indices post-HSCT were more frequently abnormal than spirometry when reporting group data and among those with extrapulmonary cGVHD and pulmonary cGVHD. Changes in MBW indices over time may be more indicative of pulmonary complications than absolute values at any given time point. Oscillometry indices were often normal at baseline, but more frequently abnormal in those who developed pulmonary cGVHD. Pooling currently available individual participant data across these studies may improve our ability to formally compare their respective sensitivity and specificity at specific time points and assess the trajectory of MBW and oscillometry indices over time., Competing Interests: Conflict of interest: N. Sonneveld has nothing to disclose. Conflict of interest: J.H. Rayment has nothing to disclose. Conflict of interest: J. Usemann has nothing to disclose. Conflict of interest: K.G. Nielsen has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose., (Copyright ©The authors 2023.)

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., Competing Interests: Conflict of Interest The authors have no conflict of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Sensor errors resulting in elevated values of N 2 concentration [N 2 ] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity ( S cond and S acin ) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices. Using a two-compartment model with differing specific ventilation (SV) such that the lower SV unit empties late, noise-free MBW were simulated both corrected and uncorrected for the recent sensor error. S cond was calculated using regression of normalized phase III slope (Sn III ) against lung turnover (TO) from a TO range starting at 1.5 and ending at an upper turnover (TO upper ) between 4 and 8 (default 6) over a range of simulated values. The principal effect of the sensor error was that as the MBW proceeded the phase III slope of successive breaths was normalized by an increasingly overestimated [N 2 ], resulting in Sn III values that fell precipitously at high TO, greatly reducing S cond . Reanalysis of previously published data and of simulated data showed a large proportional bias in S cond , whereas S acin was only minimally affected. In adult subject data, reducing TO upper below 5.5 was associated with a large drop of up to ∼60% in S cond calculated from data corrected for sensor error. Raising the upper TO limit elevated S cond by ∼20% but with a large concomitant increase in variability. In contrast to S cond , S acin was relatively unaffected by changes in TO upper with changes of <3%. This work serves to emphasize that the upper limit of TO of 6 represents an appropriate upper limit for the calculation of S cond . NEW & NOTEWORTHY Sensor errors that elevated values of N 2 concentration in commercial multiple-breath washout (MBW) devices resulted in errors in calculated parameters including S cond and S acin . We examined the mechanism of the change in values produced by these errors and explored the appropriateness of the calculation of S cond and S acin . This work serves to emphasize that the current algorithm in use is appropriate for the calculation of S cond and S acin .

We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters S cond , S acin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRC M ), dead space volume (V D ), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of S acin (S acin-M ). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRC M  < 5.2%, V D  < 5.4%, [Formula: see text] < 9.0%, and S acin-M  < 45.6% for controlled breathing, and FRC M  < 4.6%, V D  < 5.3%, [Formula: see text] < 13.2%, and S acin-M  < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with S cond  < 73.6% and S acin  < 49.2% for controlled breathing and S cond  < 35.0% and S acin  < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter S cond ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients., Methods: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered., Results: We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients., Conclusion: The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

Previous studies suggest that infants with Robin sequence show a pattern of steady improvement in the severity of airway obstruction, and of their treatment requirements, during infancy., Methods: Three infants with Robin sequence and severe obstructive sleep apnea were managed with nasal continuous positive airways pressure (CPAP). Multiple measures of airway obstruction were made during infancy, including CPAP pressure evaluations and sleep studies (screening and polysomnography studies). Parameters reported include obstructive apnea-hypopnea index, oxygen desaturation parameters, and CPAP pressures required for effective airway management., Results: CPAP pressure requirements increased in all three infants during their first weeks of life. Apnea indices on polysomnography did not track with the CPAP pressure requirements. Peak pressure requirements were at 5 and 7 weeks for two patients, with subsequent gradual decline and cessation of therapy CPAP at 39 and 74 weeks, respectively. The third patient had a complicated course, jaw distraction at 17 weeks, and biphasic CPAP pressure requirement (first peak at 3 weeks, but maximum pressure at 74 weeks), with cessation of CPAP at 75 weeks., Conclusions: The observed pattern of early increases in CPAP pressure requirements for infants with Robin sequence adds to the complexities of managing this disorder. Factors that may lead to this pattern of change in airway obstruction are discussed., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals., Methods: We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal., Results: During seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable., Conclusions: A summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santesso 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.)

Pneumonia is the number one cause of disease and deaths in children under five years old, outside the neonatal period, with the greatest number of cases reported from resource-limited settings. The etiology is variable, with not much information on the local etiology drug resistance profile in many countries. Recent studies suggest an increasing contribution from respiratory viruses, also in children with severe pneumonia, with an increased relative contribution in settings that have good vaccine coverage against common bacterial pathogens. Respiratory virus circulation was greatly reduced during highly restrictive measures to contain the spread of COVID-19 but rebounded once COVID-19 restrictions were relaxed. We conducted a comprehensive literature review of the disease burden, pathogens, case management and current available prevention of community acquired childhood pneumonia, with a focus on rational antibiotic use, since the treatment of respiratory infections is the leading cause of antibiotic use in children. Consistent application of revised World Health Organisation (WHO) guidance that children presenting with coryzal symptoms or wheeze can be managed without antibiotics in the absence of fever, will help to reduce unnecessary antibiotic use, as will increased availability and use of bedside inflammatory marker tests, such as C-reactive protein (CRP) in children with respiratory symptoms and fever., Competing Interests: The 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., (© 2023 Nguyen, Robinson, Fitzgerald and Marais.)

Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple-breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulfur hexafluoride (SF 6 ) MBW outcomes, to data collected using updated commercial SF 6 MBW equipment, and to produce device-specific equations if necessary. SF 6 MBW was performed in 327 healthy children aged 0.1-18.4 yr [151 (46%) girls], 191 (58.4%) <3 yr. z-Scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression was performed to produce device-specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF ( n = 138 test occasions), and 49 adults with lung disease. Historical SF 6 MBW reference equations were unsuitable for EXHALYZER D data. In contrast to LCI and log 10 (LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log 10 (FRC). Significant predictors for VDE and log 10 (FRC), respectively, were log 10 (age) and sex, and log 10 (height), sex, and posture. VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted. NEW & NOTEWORTHY Lung clearance index (LCI) is the most used outcome from the multiple-breath washout test. As known for decades, the LCI is not linearly related to dead space ventilation, giving difficulties interpreting changes over time and in clinical trials. We present a new and improved outcome based on LCI, the ventilation distribution efficiency (VDE), which solves this problem by being linearly related to dead space ventilation. A pediatric age range reference equation for VDE is presented.

Background: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification., Methods: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid., Results: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these., Conclusions: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections., Competing Interests: Potential conflicts of interest. G. F. H. is a consultant for and receives grant support not directly related to this work from Janssen Pharmaceuticals (Collaborative Research Agreement); reports consulting fees from Janssen Inc and Tessera Inc; and reports presentation honoraria from the Pittsburgh Foundation and a leadership or fiduciary role with the Charles E. Kaufman Foundation scientific advisory board. R. M. De. and G. F. H. are co-inventors on patent applications related to the use of phages for treating nontuberculous mycobacterial (NTM) infections filed by the University of Pittsburgh of the Commonwealth System of Higher Education. D. v. D. is a consultant for Actavis, Tetraphase, Sanofi Pasteur, MedImmune, Astellas, Merck, Allergan, T2Biosystems, Roche, Achaogen, Neumedicine, Shionogi, Pfizer, Entasis, QPex, Wellspring, Karius, Melinta, and Utility; receives an editor’s stipend from British Society for Antimicrobial Chemotherapy; has received funding for unrelated projects from NIH, Merck, and Shionogi; reports payments for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Pfizer and Entasis; reports paid participation on a data and safety monitoring board (DSMB) or advisory board for Utility, Union, Entasis, and Merck; and reports a paid leadership or fiduciary role with the British Society for Antimicrobial Chemotherapy. K. A. C. has received consulting fees from Insmed (clinical trial site), Hillrom (clinical trial site), Paratek, Microbion, and AN2, and reports honoraria for a presentation from Insmed. G. H. receives grant support unrelated to this study from Karius, Allovir, and AstraZeneca, and reports participation on a DSMB or advisory board with Karius. R. T. S. is a paid consultant to Vir Biotechnology and to LysNtech; holds stock options in Antiva Biosciences and CytoDyn and stock or stock options with NoniGenex and Arcturus; previously served as an uncompensated member of the AmpliPhi scientific advisory board; reports grants or contracts paid to institution from the National Institute of Allergy and Infectious Diseases; reports consulting fees from Pfizer, Sempra Energy, and Nurix; has patents planned, issued, or pending for orally bioavailable anti-coronavirus compounds; reports paid participation on DSMBs or advisory boards for Merck, VIr Biosciences, SNIPR Biome, and Pardes Biosciences; and holds leadership or fiduciary roles with the International Antiviral Society (IAS)–USA and Specialists in Global Health. C. A. B. reports contracts to institution for clinical trials from Gilead and DNAe; payment to author for educational lectures from IAS-USA, Practice Point Communications (Optimal Management of HIV Disease and Hepatitis Clinical Conference [OPMAN] conference), and University of Arizona; has received payment for travel to the OPMAN conference from Practice Point Communications; served on a DSMB for ViiV/GlaxoSmith Kline; has held unpaid volunteer roles with IAS-USA and the Conference on Retroviruses and Opportunistic Infections Foundation Board; and has served as Deputy Editor/Associate Editor for the Infectious Diseases Society of America. A. K. reports the following grants or contracts unrelated to this work: National Health and Medical Research Council (NHMRC, Australia) Investigator Grant at Emerging Leadership 1 level, Conquer CF, Innovation Grant from Cystic Fibrosis Australia, Research Establishment Fellowship from the Royal Australasian College of Physicians and Research Award from the Australasian Society for Infectious Diseases (all paid to institution); payment to institution for grant application review for the Italian Cystic Fibrosis Research Foundation; unpaid role as member of DSMB for FluBubs (Safety and Immunogenicity of Early Quadrivalent Influenza Vaccine); unpaid leadership or fiduciary roles as Deputy Director (Clinical) of Phage Australia, pediatric infectious diseases research representative on the Australian Society for Infectious Diseases Clinical Research Network Steering Committee and the Australia and New Zealand Paediatric Infectious Diseases Group Executive Committee, member of the Sydney Children’s Hospitals Network Human Research Ethics Committee Scientific Advisory Committee, and member of the Sydney Children’s Hospitals Network Advanced Therapeutics Steering Committee. A. W. B. reports a role as a part-time employee of the Cystic Fibrosis Foundation, which provides some grant support to G. F. H.’s laboratory and, for the purposes of this manuscript, is the treating physician of one of the NTM patients in the cystic fibrosis clinic at Inova Fairfax Hospital. C. B. G. reports consulting fees from Advisory Janssen. B. J. M. reports an NHMRC Investigator Grant and philanthropic grant from the Curing Homesickness Foundation, both paid to institution and unrelated to this work; unpaid participation as member of the DSMB for the PATRIC trial; and unpaid position as board director of the Australasian Society for Infectious Diseases. M. G. T. O. reports a Cystic Fibrosis Foundation Adult Center Award and Cystic Fibrosis Foundation Therapeutic Development Center Award, unrelated to this work; support for attending meetings and/or travel, paid to University of Miami, from the Cystic Fibrosis Foundation Adult Center Award for attending North American Cystic Fibrosis Conference and a Cystic Fibrosis Foundation Therapeutic Development Center Award for attending the Therapeutics Development Network spring meeting; and an unpaid position as Cystic Fibrosis Lifestyle Foundation board member. J. I. reports an Investigator Grant (personal support) unrelated to this work from NHMRC. A. M. reports consulting fees paid to author as a member of the Air Liquide Advisory Board. J. A. N. reports contracts or grants unrelated to this work from the Cystic Fibrosis Foundation. M. S. reports funding on a project to set up a phage therapy laboratory in Finland, unrelated to this work, from the Jane and Aatos Erkko Foundation. P. W. reports consulting fees from AstraZeneca, GlaxoSmithKline, Pfizer, Sanofi Regeneron, and Vertex; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, and Vertex; and a leadership or fiduciary role with the Cystic Fibrosis Australia National Asthma Council of Australia. D. E. M. reports stock or stock options (no payments) with Moderna (1 share) and Pfizer (5 shares). R. M. Da. reports grants from the NIH unrelated to this work (grant number K01-AI125726 [principal investigator]). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Gallstone disease is becoming increasingly common in the UK, with one in six people developing gallstones and over 100 000 cholecystectomies being performed annually. The gallbladder stores bile produced by the liver and, in the presence of fat in the stomach, releases bile into the duodenum to promote the emulsification and absorption of fats and fat-soluble vitamins from the small bowel. Although most people with gallstones remain asymptomatic throughout their lifetime, approximately 20% go on to develop complications of varying severity, ranging from biliary colic to ascending cholangitis, which can be fatal if left untreated. Ultrasound is the most reliable investigation for confirming gallstone disease. Cholecystectomy provides definitive treatment of symptomatic disease and is usually offered as a laparoscopic, day-case procedure. This article explores the pathogenesis and management of gallstone disease.

This clinical practice guideline provides recommendations for preventing acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. The recommendations are based on two systematic reviews of randomized controlled trials evaluating interventions to prevent (1) acute phase CINV and (2) delayed phase CINV. Recommendations for acute phase and delayed phase CINV prophylaxis are made for patients receiving chemotherapy of varying emetogenicity, as well as for patients not able to receive dexamethasone or a neurokinin-1 receptor antagonist. Evidence gaps, including antiemetic safety and optimal dosing, were identified., (© 2022 Wiley Periodicals LLC.)

Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation ( F /MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA ( n  = 60) or placebo ( n  = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index 2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index 2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P  < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV 1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F /MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)