Cervical auscultation in the diagnosis of oropharyngeal aspiration in children: a study protocol for a randomised controlled trial

BackgroundOropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. MethodsWe plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. DiscussionEarly detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children

Singing as an adjunct therapy for children and adults with cystic fibrosis.

Cystic fibrosis is a genetically inherited, life‐threatening condition that affects major organs. The management of cystic fibrosis involves a multi‐faceted daily treatment regimen that includes airway clearance techniques, pancreatic enzymes and other medications. Previous studies have found that compliance with this intensive treatment is poor, especially among adolescents. Because of both the nature and consequences of the illness and the relentless demands of the treatment, many individuals with cystic fibrosis have a poor quality of life. Anecdotal reports suggest that singing may provide both appropriate exercise for the whole respiratory system and a means of emotional expression which may enhance quality of life. This is an update of a previously published review. To evaluate the effects of singing as an adjunct therapy to standard treatment on the quality of life, morbidity, respiratory muscle strength and pulmonary function of children and adults with cystic fibrosis. We searched the Group's Cystic Fibrosis Trials Register and the Cochrane Central Register of Controlled Trials. Date of latest search: 07 January 2019. We also searched major allied complementary data bases, and clinical trial registers. Additionally, we hand searched relevant conference proceedings and journals. Date of latest search: 28 March 2019. Randomised controlled trials in which singing (as an adjunct intervention) is compared with either a control intervention (for example, playing computer games or doing craft activities) or no singing in people with cystic fibrosis. Results of searches were reviewed against pre‐determined criteria for inclusion. Only one eligible trial was available for analysis. Since only one small study (n = 40) was included, no meta‐analysis could be performed. The included randomised controlled study was of parallel design and undertaken at two paediatric hospitals in Australia. The study evaluated the effects of a singing program on the quality of life and respiratory muscle strength of hospitalised children with cystic fibrosis (mean age 11.6 years, 35% male). While the singing group received eight individual singing sessions, the control group participated in preferred recreational activities, such as playing computer games or watching movies. This study was limited by a small sample size (51 participants) and a high drop‐out rate (21%). There were no differences between the groups at either post‐intervention or follow‐up; although by the end of treatment there were some improvements in some of the domains of the quality of life questionnaire Cystic Fibrosis Questionnaire‐Revised (e.g. emotional, social and vitality domains) for both singing and control groups. For the respiratory muscle strength indices, maximal expiratory pressure at follow‐up (six to eight weeks post‐intervention) was higher in the singing group, mean difference 25.80 (95% confidence interval 5.94 to 45.66). There was no difference between groups for any of the other respiratory function parameters (maximal inspiratory pressure, spirometry) at either post‐intervention or follow‐up. No adverse effects were observed in the singing group; adverse events for the control group were not reported in the paper. There is insufficient evidence to determine the effects of singing on quality of life or on the respiratory parameters in people with cystic fibrosis. However, there is growing interest in non‐medical treatments for cystic fibrosis and researchers may wish to investigate the impact of this inexpensive therapy on respiratory function and psychosocial well‐being further in the future.N/

Imaging of brain structural and functional effects in people with human immunodeficiency virus

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting Biotypes of CNS Complications in People Living with HIV, held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH

The 5q31 variants associated with psoriasis and Crohn's disease are distinct

Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B and IL23R, but other genetic risk factors also exist. We recently reported three psoriasis-associated single nucleotide polymorphisms (SNPs) in the 5q31 locus, a region of high linkage disequilibrium laden with inflammatory pathway genes. The aim of this study was to assess whether other variants in the 5q31 region are causal to these SNPs or make independent contributions to psoriasis risk by genotyping a comprehensive set of tagging SNPs in a 725 kb region bounded by IL3 and IL4 and testing for disease association. Ninety SNPs, capturing 86.4% of the genetic diversity, were tested in one case–control sample set (467 cases/460 controls) and significant markers (Pallelic < 0.05) (n = 9) were then tested in two other sample sets (981 cases/925 controls). All nine SNPs were significant in a meta-analysis of the combined sample sets. Pair-wise conditional association tests showed rs1800925, an intergenic SNP located just upstream of IL13 (Mantel–Haenszel Pcombined = 1.5 × 10−4, OR = 0.77 [0.67–0.88]), could account for observed significant association of all but one other SNP, rs11568506 in SLC22A4 [Mantel–Haenszel Pcombined = 0.043, OR = 0.68 (0.47–0.99)]. Haplotype analysis of these two SNPs showed increased significance for the two common haplotypes (rs11568506–rs1800925: GC, Pcombined = 5.67 × 10−6, OR = 1.37; GT, Pcombined = 6.01 × 10−5, OR = 0.75; global haplotype P = 8.93 × 10−5). Several 5q31-region SNPs strongly associated with Crohn's disease (CD) in the recent WTCCC study were not significant in the psoriasis sample sets tested here. These results identify the most significant 5q31 risk variants for psoriasis and suggest that distinct 5q31 variants contribute to CD and psoriasis risk

Three-weekly doses of azithromycin for Indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial

Background: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis.Methods: Infants aged &le;24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h.Results: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: &minus;6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: &minus;8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p &lt; 0.001), but had no significant effect upon virus detection rates.Conclusion: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis.Clinical trial registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099

The Cost of Acute Respiratory Infections With Cough Among Urban Aboriginal and Torres Strait Islander Children

Introduction: Acute respiratory infections with cough (ARIwC) contribute considerably to childhood morbidity, yet few studies have examined the cost of these illnesses among Australian children. Moreover, of the few studies that have, none are inclusive of Aboriginal and/or Torres Strait Islander children, despite this population experiencing a greater burden of respiratory illnesses. This study aimed to determine the costs of ARIwC among urban Aboriginal and/or Torres Strait Islander children from the perspective of caretakers, the public healthcare system, and employers.Methods: This cost of illness study used data collected from Aboriginal and/or Torres Strait Islander children aged &lt;5 years enrolled in a 12 month prospective cohort study conducted through an urban primary healthcare clinic in Queensland, Australia. Illness-related resource use was collected for each episode of ARIwC reported, and costed at market rates. Linear regression was used to (a) examine cost per episode by season of illness onset and cough duration and (b) examine cost per month of observation by baseline child and family characteristics.Results: During the study period, a total of 264 episodes of ARIwC were reported among 138 children. The total mean cost was estimated to be $AU252 per non-hospitalized episode (95$991 (95%CI 514–1468). Winter episodes and episodes resulting in chronic cough were associated with significantly higher costs per episode. A prior history of wheezing, connections to traditional lands and parent/guardian belief that antibiotics should be given until symptoms resolved were associated with significantly higher cost per child month of observation.Conclusion: The cost of ARIwC in this predominantly disadvantaged population is substantial, particularly for caretakers and this needs to be considered in both clinical management and public health initiatives. The importance of cultural factors on health and burden of illness should not be overlooked. Further research into the prevention of chronic cough may play an important role in reducing the economic burden of pediatric respiratory infections

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised c

BackgroundRecurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. MethodsA multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (&lt;6 years and &ge;6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged &ge;6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged &ge;6 years; and vaccine safety. DiscussionAs H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis

Weak-signal extraction enabled by deep-neural-network denoising of diffraction data

Removal or cancellation of noise has wide-spread applications for imaging and acoustics. In every-day-life applications, denoising may even include generative aspects which are unfaithful to the ground truth. For scientific applications, however, denoising must reproduce the ground truth accurately. Here, we show how data can be denoised via a deep convolutional neural network such that weak signals appear with quantitative accuracy. In particular, we study X-ray diffraction on crystalline materials. We demonstrate that weak signals stemming from charge ordering, insignificant in the noisy data, become visible and accurate in the denoised data. This success is enabled by supervised training of a deep neural network with pairs of measured low- and high-noise data. This way, the neural network learns about the statistical properties of the noise. We demonstrate that using artificial noise (such as Poisson and Gaussian) does not yield such quantitatively accurate results. Our approach thus illustrates a practical strategy for noise filtering that can be applied to challenging acquisition problems.Comment: 8 pages, 4 figure