Treatments for Morton's neuroma.

BACKGROUND: Morton's neuroma (MN) is a painful neuropathy resulting from a benign enlargement of the common plantar digital nerve that occurs commonly in the third webspace and, less often, in the second webspace of the foot. Symptoms include burning or shooting pain in the webspace that extends to the toes, or the sensation of walking on a pebble. These impact on weight-bearing activities and quality of life. OBJECTIVES: To assess the benefits and harms of interventions for MN. SEARCH METHODS: On 11 July 2022, we searched CENTRAL, CINAHL Plus EBSCOhost, ClinicalTrials.gov, Cochrane Neuromuscular Specialised Register, Embase Ovid, MEDLINE Ovid, and WHO ICTRP. We checked the bibliographies of identified randomised trials and systematic reviews and contacted trial authors as needed. SELECTION CRITERIA: We included all randomised, parallel-group trials (RCTs) of any intervention compared with placebo, control, or another intervention for MN. We included trials where allocation occurred at the level of the individual or the foot (clustered data). We included trials that confirmed MN through symptoms, a clinical test, and an ultrasound scan (USS) or magnetic resonance imaging (MRI). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed bias using Cochrane's risk of bias 2 tool (RoB 2) and assessed the certainty of the evidence using the GRADE framework. MAIN RESULTS: We included six RCTs involving 373 participants with MN. We judged risk of bias as having 'some concerns' across most outcomes. No studies had a low risk of bias across all domains. Post-intervention time points reported were: three months to less than 12 months from baseline (nonsurgical outcomes), and 12 months or longer from baseline (surgical outcomes). The primary outcome was pain, and secondary outcomes were function, satisfaction or health-related quality of life (HRQoL), and adverse events (AE). Nonsurgical treatments Corticosteroid and local anaesthetic injection (CS+LA) versus local anaesthetic injection (LA) Two RCTs compared CS+LA versus LA. At three to six months: • CS+LA may result in little to no difference in pain (mean difference (MD) -6.31 mm, 95% confidence interval (CI) -14.23 to 1.61; P = 0.12, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Assessed via a pain visual analogue scale (VAS; 0 to 100 mm); a lower score indicated less pain.) • CS+LA may result in little to no difference in function when compared with LA (standardised mean difference (SMD) -0.30, 95% CI -0.61 to 0.02; P = 0.06, I2 = 0%; 2 studies, 157 participants; low-certainty evidence). (Function was measured using: the American Orthopaedic Foot and Ankle Society Lesser Toe Metatarsophalangeal-lnterphalangeal Scale (AOFAS; 0 to 100 points) - we transformed the scale so that a lower score indicated improved function - and the Manchester Foot Pain and Disability Schedule (MFPDS; 0 to 100 points), where a lower score indicated improved function.) • CS+LA probably results in little to no difference in HRQoL when compared to LA (MD 0.07, 95% CI -0.03 to 0.17; P = 0.19; 1 study, 122 participants; moderate-certainty evidence), and CS+LA may not increase satisfaction (risk ratio (RR) 1.08, 95% CI 0.63 to 1.85; P = 0.78; 1 study, 35 participants; low-certainty evidence). (Assessed using the EuroQol five dimension instrument (EQ-5D; 0-1 point); a higher score indicated improved HRQoL.) • The evidence is very uncertain about the effects of CS+LA on AE when compared with LA (RR 9.84, 95% CI 1.28 to 75.56; P = 0.03, I2 = 0%; 2 studies, 157 participants; very low-certainty evidence). Adverse events for CS+LA included mild skin atrophy (3.9%), hypopigmentation of the skin (3.9%) and plantar fat pad atrophy (2.6%); no adverse events were observed with LA. Ultrasound-guided (UG) CS+LA versus non-ultrasound-guided (NUG) CS+LA Two RCTs compared UG CS+LA versus NUG CS+LA. At six months: • UG CS+LA probably reduces pain when compared with NUG CS+LA (MD -15.01 mm, 95% CI -27.88 to -2.14; P = 0.02, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). (Assessed with a pain VAS.) • UG CS+LA probably increases function when compared with NUG CS+LA (SMD -0.47, 95% CI -0.84 to -0.10; P = 0.01, I2 = 0%; 2 studies, 116 feet; moderate-certainty evidence). We do not know of any established minimum clinical important difference (MCID) for the scales that assessed function, specifically, the MFPDS and the Manchester-Oxford Foot Questionnaire (MOXFQ; 0 to 100 points; a lower score indicated improved function.) • UG CS+LA may increase satisfaction compared with NUG CS+LA (risk ratio (RR) 1.71, 95% CI 1.19 to 2.44; P = 0.003, I2 = 15%; 2 studies, 114 feet; low-certainty evidence). • HRQoL was not measured. • UG CS+LA may result in little to no difference in AE when compared with NUG CS+LA (RR 0.42, 95% CI 0.12 to 1.39; P = 0.15, I2 = 0%; 2 studies, 116 feet; low-certainty evidence). AE included depigmentation or fat atrophy for UG CS+LA (4.9%) and NUG CS+LA (12.7%). Surgical treatments Plantar incision neurectomy (PN) versus dorsal incision neurectomy (DN) One study compared PN versus DN. At 34 months (mean; range 28 to 42 months), PN may result in little to no difference for satisfaction (RR 1.06, 95% CI 0.87 to 1.28; P = 0.58; 1 study, 73 participants; low-certainty evidence), or for AE (RR 0.95, 95% CI 0.32 to 2.85; P = 0.93; 1 study, 75 participants; low-certainty evidence) compared with DN. AE for PN included hypertrophic scaring (11.4%), foreign body reaction (2.9%); AE for DN included missed nerve (2.5%), artery resected (2.5%), wound infection (2.5%), postoperative dehiscence (2.5%), deep vein thrombosis (2.5%) and reoperation with plantar incision due to intolerable pain (5%). The data reported for pain and function were not suitable for analysis. HRQoL was not measured. AUTHORS' CONCLUSIONS: Although there are many interventions for MN, few have been assessed in RCTs. There is low-certainty evidence that CS+LA may result in little to no difference in pain or function, and moderate-certainty evidence that UG CS+LA probably reduces pain and increases function for people with MN. Future trials should improve methodology to increase certainty of the evidence, and use optimal sample sizes to decrease imprecision.

Detection of bile acids in bronchoalveolar lavage fluid defines the inflammatory and microbial landscape of the lower airways in infants with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is a genetic condition characterized by neutrophilic inflammation and recurrent infection of the airways. How these processes are initiated and perpetuated in CF remains largely unknown. We have demonstrated a link between the intestinal microbiota-related metabolites bile acids (BA) and inflammation in the bronchoalveolar lavage fluid (BALF) from children with stable CF lung disease. To establish if BA indicate early pathological processes in CF lung disease, we combined targeted mass spectrometry and amplicon sequencing-based microbial characterization of 121 BALF specimens collected from 12-month old infants with CF enrolled in the COMBAT-CF study, a multicentre randomized placebo-controlled clinical trial comparing azithromycin versus placebo. We evaluated whether detection of BA in BALF is associated with the establishment of the inflammatory and microbial landscape of early CF lung disease, and whether azithromycin, a motilin agonist that has been demonstrated to reduce aspiration of gastric contents, alters the odds of detecting BA in BALF. We also explored how different prophylactic antibiotics regimens impact the early life BALF microbiota. RESULTS: Detection of BA in BALF was strongly associated with biomarkers of airway inflammation, more exacerbation episodes during the first year of life, increased use of oral antibiotics with prolonged treatment periods, a higher degree of structural lung damage, and distinct microbial profiles. Treatment with azithromycin, a motilin agonist, which has been reported to reduce aspiration of gastric contents, did not reduce the odds of detecting BA in BALF. Culture and molecular methods showed that azithromycin does not alter bacterial load or diversity in BALF. Conversely, penicillin-type prophylaxis reduced the odds of detecting BAs in BALF, which was associated with elevated levels of circulating biomarkers of cholestasis. We also observed that environmental factors such as penicillin-type prophylaxis or BAs detection were linked to distinct early microbial communities of the CF airways, which were associated with different inflammatory landscapes but not with structural lung damage. CONCLUSIONS: Detection of BA in BALF portend early pathological events in CF lung disease. Benefits early in life associated with azithromycin are not linked to its antimicrobial properties. Video Abstract.

Protocol for a feasibility, acceptability and safety study of the PICO device (negative pressure wound therapy) in acute paediatric burns.

INTRODUCTION: Negative pressure wound therapy (NPWT) in acute burn care may decrease the time to re-epithelialisation by more than 20%. Despite this, the perceived burden of use; including therapeutic, physical and financial, have limited the use of NPWT in acute burn care. This might be minimised by using the small, ultraportable, single-use NPWT device PICO as opposed to larger devices, which to date has never been studied in acute burn care. This research will; therefore, primarily assess the feasibility, acceptability and safety of PICO in paediatric burns. Secondary outcomes include time to re-epithelialisation, pain, itch, cost and scar formation. METHODS AND ANALYSIS: This protocol details a clinical trial methodology and is pre-results. This single site, prospective, pilot randomised controlled trial will be conducted in an Australian quaternary paediatric burns centre. Participants must be aged ≤16 years, otherwise well and managed within 24 hours of sustaining a burn that fits beneath a PICO dressing. Thirty participants will be randomised to one of three groups: group A: Mepitel and ACTICOAT, group B: Mepitel, ACTICOAT and PICO and group C: Mepitel, ACTICOAT Flex and PICO. Patient outcomes will be recorded at each dressing change to assess efficacy and safety outcomes until 3 months postburn wound re-epithelialisation. Surveys, randomisation and data storage will be undertaken via online platforms and physical data storage collated at the Centre for Children's Health Research, Brisbane, Australia. Analysis will be done by using StataSE 17.0 statistical software. ETHICS AND DISSEMINATION: Ethics has been obtained from Queensland Health and Griffith Human Research Ethics committees including a site-specific approval. These data will be disseminated via clinical meetings, conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000009718.

Activity and outcomes of autologous stem cell transplantation in the private sector in Australia.

BACKGROUND: Few Australasian autologous stem cell transplantation (ASCT) programmes perform ASCT in the private sector. Relatively little is known about ASCT outcomes in the private sector, which varies in care delivery models to the public system. AIMS: To investigate transplantation activity and survival outcomes at Icon Cancer Centre's Brisbane-based private clinical and laboratory ASCT programme over a 23-year period. METHODS: Retrospective, observational study of all adults who underwent ASCT at Icon between 1996 and 2018. Main outcome measures were transplant activity, overall survival (OS) and 100-day and 1-year transplant-related mortality (TRM). Outcomes were benchmarked against the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). RESULTS: Between 1996 and 2018, 1676 ASCT were performed in 1454 patients. From 2010 to 2018, ASCT performed at Icon contributed 40% of all South East Queensland ASCT. In the past 5 years, 21% of Icon's patients were aged ≥70 years, compared with 5% across Australasia. For the entire cohort, 100-day and 1-year TRM was 1.1% and 1.7%, respectively, while for those aged ≥70 years, it was 2.0% and 3.1%. For ASCT performed between 2014 and 2018, 100-day and 1-year TRM was 0.8% and 1.4%, which was half the TRM rates reported by the ABMTRR. The 10-year post-transplant OS at Icon was higher than the ABMTRR data, across all disease subtypes. CONCLUSION: We report excellent OS and low TRM, demonstrating the critical role of the private sector in the administration of this highly complex therapy. The Icon ASCT programme is the largest ASCT contributor in Queensland. It is inclusive of patients aged ≥70 years, demonstrating low and acceptable TRM.

Single versus double hamstring tendon graft in anterior cruciate ligament reconstruction in the paediatric patient: a single-blind randomised controlled trial study protocol.

INTRODUCTION: There is currently no clear indication in the literature regarding a single or double hamstring tendon (single bundle) autograft for anterior cruciate ligament (ACL) reconstruction in the paediatric patient. The primary aim of this single blind randomised controlled trial is to determine whether a single or double hamstring tendon graft ACLR leads to superior clinical outcomes postsurgery in paediatric patients with ACL injury. METHODS AND ANALYSIS: Single site, prospective, single blind, randomised controlled trial with two parallel treatment arms. 100 patients aged 10-18 years who present with an isolated ACL tear±meniscal injury, verified on MRI, will be randomly allocated to one of the two surgical groups. The primary outcomes will be side-to-side difference in anterior tibial translation and graft failure incidence 12 months postsurgery. Primary and secondary outcomes will also be assessed at 2-year and 5-year postsurgery. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and at international conferences and disseminated to participants and healthcare professionals via newsletters and hospital presentations. This study is approved by the Children's Health Queensland Hospital and Health Service Human Research Ethics committee. TRIAL REGISTRATION NUMBER: ACTRN12620001170910p; Australian New Zealand Clinical Trials Registry.

The effect of azithromycin on structural lung disease in infants with cystic fibrosis (COMBAT CF): a phase 3, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Structural lung disease and neutrophil-dominated airway inflammation is present from 3 months of age in children diagnosed with cystic fibrosis after newborn screening. We hypothesised that azithromycin, given three times weekly to infants with cystic fibrosis from diagnosis until age 36 months, would reduce the extent of structural lung disease as captured on chest CT scans. METHODS: A phase three, randomised, double-blind, placebo-controlled trial was done at eight paediatric cystic fibrosis centres in Australia and New Zealand. Infants (aged 3-6 months) diagnosed with cystic fibrosis following newborn screening were eligible. Exclusion criteria included prolonged mechanical ventilation in the first 3 months of life, clinically significant medical disease or comorbidities other than cystic fibrosis, or macrolide hypersensitivity. Participants were randomly assigned (1:1) to receive either azithromycin (10 mg/kg bodyweight orally three times per week) or matched placebo until age 36 months. Randomisation was done with a permuted block strategy and an interactive web-based response system, stratified by study site. Unblinding was done once all participants completed the trial. The two primary outcomes were the proportion of children with radiologically defined bronchiectasis, and the percentage of total lung volume affected by disease. Secondary outcomes included clinical outcomes and exploratory outcomes were inflammatory markers. Analyses were done with the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT01270074). FINDINGS: Between June 15, 2012, and July 10, 2017, 281 patients were screened, of whom 130 were enrolled, randomly assigned, and received first study dose. 68 participants received azithromycin and 62 received placebo. At 36 months, 88% (n=50) of the azithromycin group and 94% (n=44) of the placebo group had bronchiectasis (odds ratio 0·49, 95% CI 0·12 to 2·00; p=0·32), and total airways disease did not differ between groups (median difference -0·02%, 95% CI -0·59 to 0·56; p=0·96). Secondary outcome results included fewer days in hospital for pulmonary exacerbations (mean difference -6·3, 95% CI -10·5 to -2·1; p=0·0037) and fewer courses of inhaled or oral antibiotics (incidence rate ratio 0·88, 95% CI 0·81 to 0·97; p=0·0088) for those in the azithromycin group. For the preplanned, exploratory analysis, concentrations of airway inflammation were lower for participants receiving azithromycin, including interleukin-8 (median difference -1·2 pg/mL, 95% CI -1·9 to -0·5; p=0·0012) and neutrophil elastase activity (-0·6 µg/mL, -1·1 to -0·2; p=0·0087) at age 36 months, although no difference was noted between the groups for interleukin-8 or neutrophil elastase activity at 12 months. There was no effect of azithromycin on body-mass index at age 36 months (mean difference 0·4, 95% CI -0·1 to 0·9; p=0·12), nor any evidence of pathogen emergence with the use of azithromycin. There were few adverse outcomes with no differences between the treatment groups. INTERPRETATION: Azithromycin treatment from diagnosis of cystic fibrosis did not reduce the extent of structural lung disease at 36 months of age; however, it did reduce airway inflammation, morbidity including pulmonary exacerbations in the first year of life and hospitalisations, and improved some clinical outcomes associated with cystic fibrosis lung disease. Therefore we suggest thrice-weekly azithromycin is a strategy that could be considered for the routine early management of paediatric patients with cystic fibrosis. FUNDING: Cystic Fibrosis Foundation.

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis.

BACKGROUND: Despite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life. METHODS: We examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017. RESULTS: Lung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0-5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4-13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV1) Z-score (p<0.001), -1.277 (0.221) for FEV1/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV1/FVC p = 0.001, FEF25-75p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV1/FVC% p = 0.001, FEV1p = 0.05, FEF25-75p = 0.02). No examined factor predicted a decline in the FVC Z-score. CONCLUSIONS: Action in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.

Potentially Pathogenic Organisms in Stools and Their Association With Acute Diarrheal Illness in Children Aged <2 Years.

BACKGROUND: Acute diarrheal illness (ADI) causes a substantial disease burden in high-income countries. We investigated associations between potentially pathogenic organisms in stools and ADI by polymerase chain reaction (PCR) in Australian children aged <2 years. METHODS: Children in a community-based birth cohort had gastrointestinal symptoms recorded daily and stool samples collected weekly until their second birthday. Diarrhea was defined as ≥3 liquid or looser than normal stools within a 24-hour period. PCR assays tested for 11 viruses, 5 bacteria, and 4 protozoa. Detections of a new organism or of the same following at least 2 negative tests were linked to ADIs, and incidence rates and estimates of association with ADI were calculated. RESULTS: One hundred fifty-four children provided 11 111 stool samples during 240 child-years of observation, and 228 ADIs were linked to samples. Overall, 6105 (55%) samples tested positive for a target organism. The incidence rate of 2967 new detections was 11.9 (95% confidence interval 11.4-12.3) per child-year, with 2561 (92%) new detections unrelated to an ADI. The relative risk of an ADI was 1.5-6.4 times greater for new detections of adenovirus, enterovirus, norovirus GII, parechovirus A, wild-type rotavirus, sapovirus GI/II/IV/V, Salmonella, Blastocystis, and Cryptosporidium, compared to when these were absent. CONCLUSIONS: Wild-type rotavirus, norovirus GII, sapovirus GI/II/IV/V, adenovirus 40/41, and Salmonella were associated with ADI in this age group and setting. However, high levels of asymptomatic shedding of potential pathogens in stools from children may contribute to diagnostic confusion when children present with an episode of ADI.

Respiratory virus detection during the COVID-19 pandemic in Queensland, Australia.

OBJECTIVE: To determine if non-pharmaceutical interventions (NPIs) impacted on respiratory virus detections in Queensland, Australia, during the COVID-19 pandemic year of 2020. METHODS: We analysed weekly counts of influenza, human metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and adenovirus available from a Queensland laboratory network for the year 2020. These were compared with averaged counts from 2015 to 2019. RESULTS: Overall, 686,199 tests were performed. The timing of NPI implementation was associated with a sharp and sustained decline in influenza, where during the typical annual influenza season (weeks 23-40) no cases were detected from 163,296 tests compared with an average of 26.1% (11,844/45,396) of tests positive in 2015-2019. Similar results were observed for human metapneumovirus and parainfluenza. Respiratory syncytial virus detections also declined but increased in weeks 48-52 (5.6%; 562/10,078) to exceed the 2015-2019 average (2.9%; 150/5,018). Rhinovirus detections increased after schools reopened, peaking in weeks 23-27 (57.4%; 36,228/63,115), exceeding the 2017-2019 detections during that period (21.9%; 8,365/38,072). CONCLUSIONS: NPIs implemented to control COVID-19 were associated with altered frequency and proportions of respiratory virus detections. Implications for public health: NPIs derived from influenza pandemic plans were associated with profound decreases in influenza detections during 2020.

Effect of a Remotely Delivered Weight Loss Intervention in Early-Stage Breast Cancer: Randomized Controlled Trial.

Limited evidence exists on the effects of weight loss on chronic disease risk and patient-reported outcomes in breast cancer survivors. Breast cancer survivors (stage I-III; body mass index 25-45 kg/m2) were randomized to a 12-month, remotely delivered (22 telephone calls, mailed material, optional text messages) weight loss (diet and physical activity) intervention (n = 79) or usual care (n = 80). Weight loss (primary outcome), body composition, metabolic syndrome risk score and components, quality of life, fatigue, musculoskeletal pain, menopausal symptoms, fear of recurrence, and body image were assessed at baseline, 6 months, 12 months (primary endpoint), and 18 months. Participants were 55 ± 9 years and 10.7 ± 5.0 months post-diagnosis; retention was 81.8% (12 months) and 80.5% (18 months). At 12-months, intervention participants had significantly greater improvements in weight (-4.5% [95%CI: -6.5, -2.5]; p < 0.001), fat mass (-3.3 kg [-4.8, -1.9]; p < 0.001), metabolic syndrome risk score (-0.19 [-0.32, -0.05]; p = 0.006), waist circumference (-3.2 cm [-5.5, -0.9]; p = 0.007), fasting plasma glucose (-0.23 mmol/L [-0.44, -0.02]; p = 0.032), physical quality of life (2.7 [0.7, 4.6]; p = 0.007; Cohen's effect size (d) = 0.40), musculoskeletal pain (-0.5 [-0.8, -0.2]; p = 0.003; d = 0.49), and body image (-0.2 [-0.4, -0.0]; p = 0.030; d = 0.31) than usual care. At 18 months, effects on weight, adiposity, and metabolic syndrome risk scores were sustained; however, significant reductions in lean mass were observed (-1.1 kg [-1.7, -0.4]; p < 0.001). This intervention led to sustained improvements in adiposity and metabolic syndrome risk.

Effectiveness of topical silicone gel and pressure garment therapy for burn scar prevention and management in children 12-months postburn: A parallel group randomised controlled trial.

OBJECTIVE: The longer-term effectiveness of silicone and pressure burn scar interventions was evaluated at 12-months postburn. DESIGN: Parallel group, randomised trial. SETTING: Hospital outpatient clinics, research centre. PARTICIPANTS: Children referred for burn scar management following grafted or spontaneously healed acute burn injuries or scar reconstruction surgery. INTERVENTIONS: Participants were randomised to: (1) topical silicone gel only, (2) pressure garment only, or (3) combined topical silicone gel and pressure garment. MAIN MEASURES: Primary outcomes were scar thickness (blinded ultrasound measurement) and itch intensity (caregiver proxy-report, numeric rating scale). RESULTS: Of 153 participants randomised who received the interventions (silicone n = 51, pressure garment n = 49, combined n = 53), 86 were followed-up at 12-months postburn (n = 34, n = 28, n = 24). No differences were identified for the primary outcomes using intention-to-treat analysis. Scar thickness mean difference (95% confidence interval) = 0.00 cm (-0.04, 0.05); -0.03 cm (-0.07, 0.02); 0.03 cm (-0.02, 0.08) and scar itch = 0.09 (-0.88, 1.06); -0.21 (-1.21, 0.79); 0.30 (-0.73, 1.32) for silicone vs pressure; silicone vs combined and combined vs pressure respectively. No serious adverse effects occurred. CONCLUSION: Similar to short-term results, the combined intervention offered no statistically or clinically significant benefit for improving the primary outcomes compared to each intervention alone. No differences in the primary outcomes were identified between the silicone and pressure alone groups.

Normal saline and lung recruitment with paediatric endotracheal suction (NARES): A pilot, factorial, randomised controlled trial.

BACKGROUND/OBJECTIVE: Endotracheal suction is one of the most common and harmful procuedres performed on mechanically ventilated children. The aim of the study was to establish the feasibility of a randomised controlled trial (RCT) examining the effectiveness of normal saline instillation (NSI) and a positive end-expiratory pressure recruitment manoeuvre (RM) with endotracheal suction in the paediatric intensive care unit. METHODS: Pilot 2 × 2 factorial RCT. The study was conducted at a 36-bed tertiary paediatric intensive care unit in Australia. Fifty-eight children aged less than 16 years undergoing tracheal intubation and invasive mechanical ventilation. (i) NSI or no NSI and (ii) RM or no RM with endotracheal suction . The primary outcome was feasibility; secondary outcomes were ventilator-associated pneumonia (VAP), change in end-expiratory lung volume assessed by electrical impedance tomography, dynamic compliance, and oxygen saturation-to-fraction of inspired oxygen (SpO2/FiO2) ratio. RESULTS/FINDINGS: Recruitment, retention, and missing data feasibility criteria were achieved. Eligibility and protocol adherence criteria were not achieved, with 818 patients eligible and 58 enrolled; cardiac surgery was the primary reason for exclusion. Approximately 30% of patients had at least one episode of nonadherence. Children who received NSI had a reduced incidence of VAP; however, this did not reach statistical significance (incidence rate ratio = 0.12, 95% confidence interval = 0.01-1.10; p = 0.06). NSI was associated with a significantly reduced SpO2/FiO2 ratio up to 10 min after suction. RMs were not associated with a reduced VAP incidence (incidence rate ratio = 0.31, 95% confidence interval = 0.05-1.88), but did significantly improve end-expiratory lung volume at 2 and 5 min after suction, dynamic compliance, and SpO2/FiO2 ratio. CONCLUSION: RMs provided short-term improvements in end-expiratory lung volume and oxygenation. NSI with suction led to a reduced incidence of VAP; however, a definitive RCT is needed to test statistical differences. A RCT of study interventions is worthwhile and may be feasible with protocol modifications including the widening of participant eligibility.

'How many audits do you really need?': Learnings from 5-years of peripheral intravenous catheter audits.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are medical devices used to administer intravenous therapy but can be complicated by soft tissue or bloodstream infection. Monitoring PIVC safety and quality through clinical auditing supports quality infection prevention however is labour intensive. We sought to determine the optimal patient 'number' for clinical audits to inform evidence-based surveillance. METHODS: We studied a dataset of cross-sectional PIVC clinical audits collected over five years (2015-2019) in a large Australian metropolitan hospital. Audits included adult medical, surgical, women's, cancer, emergency and critical care patients, with audit sizes of 69-220 PIVCs. The primary outcome was PIVC complications for one or more patient reported symptom/auditor observed sign of infection or other complications. Complication prevalence and 95% confidence interval (CI) were calculated. We modelled scenarios of low (10%), medium (20%) and high (50%) prevalence estimates against audit sizes of 20, 50, 100, 150, 200, 250, and 300. This was used to develop a decision-making tool to guide audit size. RESULTS: Of 2274 PIVCs evaluated, 475 (21%) had a complication. Complication prevalence per round varied from 7.8% (95% CI, 4.2-12.9) to 39% (95% CI, 32.0-46.4). Precision improved with larger audit size and lower complication rates. However, precision was not meaningfully improved by auditing >150 patients at a complication rate of 20% (95% CI 13.9%-27.3%), nor >200 patients at a complication rate of 50% (95% CI 42.9%-57.1%). CONCLUSION: Audit sizes should be 100 to 250 PIVCs per audit round depending on complication prevalence.

Lifestyle-related behaviors and health-related quality of life among children and adolescents in China.

PURPOSE: To investigate associations of five typical lifestyle-related behavioral risk factors (insufficient physical activity, prolonged screen viewing, deprived sleeping, consumption of fast food and sugar-sweetened beverage) with health-related quality of life (HRQoL) among school students in China. METHODS: Students aged 9-17 years (grades 4-12) were randomly selected from primary and high schools in Nanjing, China, to participate in this cross-sectional study in 2018. The outcome variable, HRQoL, was assessed using the Child Health Utility 9D (CHU9D) instrument and scored from 0 (worst) to 1 (best). Physical activity (including screen viewing and sleeping) and dietary intake were measured using a validated Physical Activity Scale and Food Frequency Questionnaire, respectively. Lifestyle-related behaviors were categorized as sufficient/insufficient or no/yes, and their associations with HRQoL were assessed using mixed-effects linear regression models. RESULTS: Overall, 4388 participants completed the questionnaire (response rate = 97.6%). Students with insufficient physical activity [mean difference (MD) = - 0.03; 95% confidence interval (CI) = - 0.04, - 0.01], prolonged screen time (MD = - 0.06; 95% CI = - 0.07, - 0.04), insufficient sleeping time (MD = - 0.04; 95% CI = - 0.07, - 0.02), consumption of sugar-sweetened beverage (MD = - 0.02; 95% CI = - 0.03, - 0.01) or fast food intake (MD = - 0.03; 95% CI = - 0.04, - 0.02) reported significantly lower HRQoL scores. When considered additively, each additional lifestyle-related risk factor was associated with an average decrease of 0.03 units (95% CI: - 0.03, - 0.02) CHU9D score. CONCLUSIONS: For Chinese students, HRQoL was positively associated with physical activity and sleep duration, but negatively with screen time and consumption of sugar-sweetened beverage and fast food. Moreover, lifestyle-related behaviors may have an additive effect on HRQoL.

Volatile organic compound breath testing detects in-situ squamous cell carcinoma of bronchial and laryngeal regions and shows distinct profiles of each tumour.

Volatile organic compound (VOC) breath testing of lung and head and neck squamous cell carcinoma (SCC) has been widely studied, however little is known regarding VOC profiles of in-situ SCC. A prospective study of VOC in patients with histologically proven SCC, either in-situ or advanced, and controls. Breath samples were analysed using the E-nose Cyranose ®320 and by gas chromatography/mass spectroscopy. Predictive models were developed using bootstrap forest using all 32 sensors. Data from 55 participants was analysed: 42 SCC cases comprising 20 bronchial (10 in-situ, 10 advanced) and 22 laryngeal (12 in-situ, 10 advanced), and 13 controls. There were 32 (76%) male SCC cases with mean age 63.6 (SD = 9.5) compared with 11 (85%) male controls with mean age 61.9 (SD = 10.1). Predictive models for in situ cases had good sensitivity and specificity compared to controls (overall, 95% and 69%; laryngeal, 100% and 85%; bronchial, 77% and 80%). When distinguishing in-situ and advanced tumours, sensitivity and specificity 82% and 75% respectively. For different tumour types (bronchial versus advanced laryngeal) sensitivity and specificity were 100% and 80% respectively. VOCs isolated from in-situ cancers included some previously demonstrated in advanced cancers and some novel VOCs. In-situ bronchial and laryngeal cancer can be detected by VOC analysis. Distinction from normal controls and between the two tumour types could allow screening in high risk groups for these curable lesions.

Efficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial.

BACKGROUND: Bronchiectasis guidelines recommend antibiotics for the treatment of acute respiratory exacerbations, but randomised placebo-controlled trials in children are lacking. We hypothesised that oral amoxicillin-clavulanate and azithromycin would each be superior to placebo in achieving symptom resolution of non-severe exacerbations in children by day 14 of treatment. METHODS: In this multicentre, three-arm, parallel, double-dummy, double-blind, randomised placebo-controlled trial at four paediatric centres in Australia and New Zealand, we enrolled children aged 1-18 years with CT-confirmed bronchiectasis unrelated to cystic fibrosis, who were under the care of a respiratory physician and who had had at least two respiratory exacerbations in the 18 months before study entry. Participants were allocated (1:1:1) at exacerbation onset to receive oral suspensions of amoxicillin-clavulanate (45 mg/kg per day) plus placebo azithromycin, azithromycin (5 mg/kg per day) plus placebo amoxicillin-clavulanate, or both placebos for 14 days. An independent statistician prepared a computer-generated, permuted-block (size 2-8) randomisation sequence, stratified by centre, age, and cause. Participants, caregivers, study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was the proportion of children with exacerbation resolution by day 14 in the intention-to-treat population. Treatment groups were compared using generalised linear models. Statistical significance was set at p<0·0245 to account for multiple comparisons. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000011886) and is completed. FINDINGS: Between April 17, 2012, and March 1, 2017, 604 children were screened and 252 were enrolled. Between July 31, 2012, and June 26, 2017, 197 children were allocated at the start of an exacerbation (63 to the amoxicillin-clavulanate group, 67 to the azithromycin group, and 67 to the placebo group). Respiratory viruses were identified in 82 (53%) of 154 children with available nasal swabs on day 1 of treatment. Primary outcome data were available for 196 (99%) children (one child with missing data [placebo group] was recorded as non-resolved according to criteria defined a priori). By day 14, exacerbations had resolved in 41 (65%) children in the amoxicillin-clavulanate group, 41 (61%) in the azithromycin group, and 29 (43%) in the placebo group. Compared with placebo, relative risk for resolution by day 14 was 1·50 (95% CI 1·08-2·09, p=0·015; number-needed-to-treat [NNT] 5 [95% CI 3-20]) in the amoxicillin-clavulanate group and 1·41 (1·01-1·97, p=0·042; NNT 6 [3-79]) in the azithromycin group. Adverse events were recorded in 19 (30%) children in the amoxicillin-clavulanate group, 20 (30%) in the azithromycin group, and 14 (21%) in the placebo group, but no events were severe or life-threatening. INTERPRETATION: Amoxicillin-clavulanate treatment is beneficial in terms of resolution of non-severe exacerbations of bronchiectasis in children, and should remain the first-line oral antibiotic in this setting. FUNDING: National Health and Medical Research Council (Australia), Cure Kids (New Zealand).

Full blood counts are not predictive of the risk of medication-related osteonecrosis of the jaws: a case-control study.

OBJECTIVES: The role of immune function in susceptibility to medication-related osteonecrosis of the jaws (MRONJ) remains unclear. This study investigated whether full blood counts, as a measure of systemic health and immune function, predict the development of MRONJ. STUDY DESIGN: A case-control study was conducted in Brisbane, Australia. A total of 57 cases diagnosed with MRONJ from January 2010 to March 2017 were identified from hospital records and individually matched with up to 4 controls using primary disease, sex, age, and antiresorptive therapy (total sample = 249). Demographic and clinical data were extracted and associations were investigated using conditional logistic regression. RESULTS: A total of 67% of cases and 65% of controls reported at least 1 result outside of the laboratory reference range (odds ratio = 0.7; 95% confidence interval: 0.3, 1.5; P = .29). The most commonly reported abnormal results were low hemoglobin (53% of cases, 48% of controls) and low hematocrit (33% of cases, 25% of controls). There were no significant differences between groups in any of the reported parameters. CONCLUSIONS: Patients taking antiresorptive medications often return blood test results outside the standard laboratory reference range. Altered blood counts were not limited to patients who developed MRONJ and do not appear to be clinically useful in identifying patients at high risk for this condition.

The effectiveness of non-surgical interventions for common plantar digital compressive neuropathy (Morton's neuroma): a systematic review and meta-analysis.

BACKGROUND: Morton's neuroma (MN) is a compressive neuropathy of the common plantar digital nerve. It is a common compressive neuropathy often causing significant pain which limits footwear choices and weight bearing activities. This paper aims to review non-surgical interventions for MN, to evaluate the evidence base for the clinical management of MN. METHODS: Electronic biomedical databases (CINAHL, EMBASE, MEDLINE and Cochrane) were searched to January 2018 for studies evaluating the effectiveness of non-surgical interventions for Morton's neuroma. Outcome measures of interest were treatment success rate (SR) (binary) and pain as measured using 100-point visual analogue scale (VAS) (continuous). Studies with and without control groups were included and were evaluated for methodological quality using the Downs and Black Quality Index. Results from randomised controlled trials (RCT) were compared between-groups, and case series were compared pre- versus post-treatment. Effect estimates are presented as odds ratios (OR) for binary data or mean differences (MD) for continuous data. Random effects models were used to pool effect estimates across studies where similar treatments were used. Heterogeneity was assessed using the I 2 statistic. RESULTS: A total of 25 studies met the inclusion criteria, seven RCTs and 18 pre/post case series. Eight different interventions were identified, with corticosteroid or sclerosing injections being the most often reported (seven studies each). Results from a meta-analysis of two RCTs found corticosteroid injection decreased pain more than control on VAS (WMD: -5.3, 95%CI: -7.5 to - 3.2). Other RCTs reported efficacy of: manipulation/mobilisation versus control (MD: -15.3, 95%CI: -29.6 to - 1.0); extracorporeal shockwave therapy versus control (MD: -5.9, 95%CI: -21.9 to 10.1). Treatment success was assessed for extracorporeal shockwave therapy versus control (OR: 0.3, 95%CI: 0.0 to 7.1); and corticosteroid injection vs footwear/padding (OR: 6.0, 95%CI: 1.9 to 19.2). Sclerosing and Botox injections, radiofrequency ablation and cryoneurolysis have been investigated by case series studies, however these were of limited methodological quality. CONCLUSIONS: Corticosteroid injections and manipulation/mobilisation are the two interventions with the strongest evidence for pain reduction, however high-quality evidence for a gold standard intervention was not found. Although the evidence base is expanding, further high quality RCTs are needed.

Both non-surgical dental treatment and extractions increase the risk of medication-related osteonecrosis of the jaw: case-control study.

OBJECTIVES: Medication-related osteonecrosis of the jaws (MRONJ) is a serious condition whose risk factors remain unclear. The aim of this study is to investigate the role of oral health and of dental treatment in the development of MRONJ. MATERIALS AND METHODS: A case-control study was conducted in Brisbane, Australia. Hospital records were used to identify incident cases of MRONJ between January 2010 and March 2017. Cases were individually matched to up to 3 controls according to age, sex, primary disease, and type of antiresorptive therapy. Demographic data, medical histories and public dental records were collected. Associations between oral health, dental treatment, and MRONJ were investigated using conditional logistic regression. RESULTS: Overall, 44 cases were identified and matched to 115 controls (total sample = 159). Only one-third of patients received a dental examination in the year prior to commencing antiresorptive therapy (27% of cases and 34% of controls). After adjusting for potentially confounding variables, non-surgical dental treatment (OR = 6.3; 95% CI = 2.1, 19.1; p < 0.001) and dental extractions (OR = 8.0; 95% CI = 3.0, 21.0, p < 0.001) were significantly associated with development of MRONJ. CONCLUSIONS: Current levels of preventative dental care are insufficient to eliminate the need for dental treatment and extractions during antiresorptive therapy, and the consequent increase in risk of MRONJ. CLINICAL RELEVANCE: Optimizing the health of the oral cavity and ongoing preventative dental care must be a priority for patients prior to the initiation of antiresorptive medications.

A review of children with severe trauma admitted to pediatric intensive care in Queensland, Australia.

BACKGROUND: The aim of this study is to review patient characteristics, injury patterns, and outcomes of trauma cases admitted to pediatric intensive care in Children's Health Queensland, Brisbane, Queensland, Australia. METHODS: Routinely recorded data collected prospectively from the Children's Health Queensland Trauma Service registry from November 2008 to October 2015 were reviewed. Demographic and clinical characteristics of trauma cases in children under 16 years of age are described, and their association with age and mortality analyzed. RESULTS: There were 542 cases of pediatric trauma identified and 66.4% were male. The overall mortality since January 2012 was 11.1%. The median injury severity score (ISS) was 11 (IQR = 9-22), 48.2% (n = 261) had an ISS > 12 and 41.7% (n = 226) patients had an ISS > 15. The most common injury patterns were isolated head injury (29.7%; n = 161) and multiple trauma (31.2%; n = 169). In 28.4% of cases (n = 154) surgery was required. The home was reported to be the most common place of injury (37.6%; n = 204). Children aged 0-4 years were least likely to survive their injury (15.3% mortality) compared with the 5-9 (5.6% mortality) and 10-15 (9.0% mortality) age groups. Higher mortality was associated with more severe injuries, abdomen/spine/thorax injuries, inflicted injuries, drowning and hanging. CONCLUSION: This description of major pediatric trauma cases admitted to pediatric intensive care in Children's Health Queensland, Australia, will inform future pediatric major trauma service requirements as it identifies injury patterns and profiles, injury severity, management and mortality across different age groups.