Retrospective review of treatment outcomes and costs in children with sleep disordered breathing assessed with multi-channel studies.

Current UK guidance on OSA management recommends only selective use of sleep studies - when there is diagnostic uncertainty, in children with comorbidities or to evaluate perioperative risk in those with suspected severe OSA. Routine use of sleep studies to confirm a diagnosis of obstructive sleep apnoea (OSA) in children before adenotonsillectomy is not currently recommended. We report the findings of a novel paediatric sleep service based on routine use of multi-channel sleep studies (MCSS) before adenotonsillectomy and present the results of a service evaluation assessing the impact of our practise on treatment outcomes and cost. We conducted a retrospective study of 264 children with sleep disordered breathing seen in our centre between July 2018-June 2019, using medical records and a sleep study database to determine treatment outcomes and costs. Using responses from a questionnaire completed by otolaryngologists for a separate prospective study, we compare our costs with estimates of those associated with a standard UK model of care i.e. with selective use of sleep studies. We estimate that our routine use of MCSS reduced the number of adenotonsillectomies by 44 % but at higher monetary costs than those estimated for the standard model of care. We note however, that reconfiguring our service to arrange a sleep study before the initial appointment, rather than after, would result in the service being cost neutral compared with the standard model. We also estimate that use of home multi-channel studies in our service would bring a significant cost saving (∼£50,000 - £80,000 per annum) compared to standard care.

Prospective evaluation of the impact of multi-channel studies on treatment outcomes in children with sleep disordered breathing.

There are significant variations in practice regarding the use of sleep studies in children with symptoms of sleep disordered breathing (SDB) prior to adenotonsillectomy. Current UK guidance recommends the selective use of sleep studies to confirm a diagnosis of obstructive sleep apnoea (OSA) when there is diagnostic uncertainty, in children with comorbidities, or to assess perioperative risk when severe OSA is suspected. We have developed a novel paediatric sleep service over the past decade based on the routine use of multi-channel sleep studies (MCSS) before adenotonsillectomy. We present the results of a prospective evaluation assessing the impact of our service on treatment outcomes. We conducted a prospective service evaluation of 49 children with SDB seen between July 2021 and August 2022. We used medical records and a sleep study database to determine treatment outcomes. Otolaryngologists completed a questionnaire before each multi-channel sleep study to help evaluate the impact of sleep study findings on surgical decision making. Questionnaire responses before MCSS showed that clinicians thought 66 % of children were 'likely', 'very likely' or 'definitely' would require surgery but only 54 % of children underwent surgery following their sleep study. We estimate that the use of MCSS was associated with a 21 % reduction in children undergoing surgery in this small sample. We conclude that our use of MCSS facilitates conservative management, allowing a significant reduction in the number of children with SDB undergoing surgery, but further validation of MCSS against polysomnography is required.

Observational Study of Pulse Transit Time in Children With Sleep Disordered Breathing.

Background: Pulse transit time (PTT) is a non-invasive measure of arousals and respiratory effort for which we aim to identify threshold values that detect sleep disordered breathing (SDB) in children. We also compare the sensitivity and specificity of oximetry with the findings of a multi-channel study. Methods: We performed a cross-sectional observational study of 521 children with SDB admitted for multi-channel sleep studies (pulse oximetry, ECG, video, sound, movement, PTT) in a secondary care centre. PTT data was available in 368 children. Studies were categorised as normal; primary snoring; upper airway resistance syndrome (UARS); obstructive sleep apnoea (OSA), and "abnormal other." Receiver operator characteristic curves were constructed for different PTT (Respiratory swing; Arousal index) thresholds using a random sample of 50% of children studied (training set); calculated thresholds of interest were validated against the other 50% (test set). Study findings were compared with oximetry categories (normal, inconclusive, abnormal) using data (mean and minimum oxygen saturations; oxygen desaturations > 4%) obtained during the study. Results: Respiratory swing of 17.92 ms identified SDB (OSA/UARS) with sensitivity: 0.80 (C.I. 0.62-0.90) and specificity 0.79 (C.I. 0.49-0.87). PTT arousal index of 16.06/ hour identified SDB (OSA/UARS) with sensitivity: 0.85 (95% C.I. 0.67-0.92) and specificity 0.37 (95% C.I. 0.17-0.48). Oximetry identified SDB (OSA) with sensitivity: 0.38 (C.I. 0.31-0.46) and specificity 0.98 (C.I. 0.97-1.00). Conclusions: PTT is more sensitive but less specific than oximetry at detecting SDB in children. The additional use of video and sound enabled detection of SDB in twice as many children as oximetry alone.

ß2-agonists do not work in children under 2†years of age: myth or maxim?

Wheezy infants do not respond to bronchodilators despite evidence of functioning ß-adrenoceptors. This is because the predominant aetiology, bronchiolitis, is characterised by small airway oedema and increased mucus, for which ß2-agonists are ineffective. http://bit.ly/2Ws9ffh.

A 2:1 receptor/C60 complex as a nanosized universal joint.

Buckycatcher II, a C51 H24 hydrocarbon with two corannulene pincers on a dibenzonorbornadiene tether, exhibits an affinity toward C60 in organic solvents that is dramatically higher than the original buckycatcher C60 H28 and other corannulene-based molecular receptors for fullerenes. In addition to the formation of an usual 1:1 C60 @catcher inclusion complex, a trimeric C60 @(catcher)2 assembly is detected in solutions and in the solid state. X-ray structure determination reveals a remarkable "universal joint" solvent-free crystal arrangement of the trimer, with a single fullerene cage wrapped by four corannulene subunits of two cooperating catcher receptors.

Thermodynamics of host-guest interactions between fullerenes and a buckycatcher.

(1)H NMR and isothermal titration calorimetry (ITC) experiments were employed to obtain reliable thermodynamic data for the formation of the 1:1 inclusion complexes of fullerenes C(60) and C(70) with the buckycatcher (C(60)H(28)). NMR measurements were done in toluene-d8 and chlorobenzene-d5 at 288, 298, and 308 K, while the ITC titrations were performed in toluene, chlorobenzene, o-dichlorobenzene, anisole, and 1,1,2,2-tetrachloroethane at temperatures from 278 to 323 K. The association constants, K(a), obtained with both techniques are in very good agreement. The thermodynamic data obtained by ITC indicate that generally the host-guest association is enthalpy-driven. Interestingly, the entropy contributions are, with rare exceptions, slightly stabilizing or close to zero. Neither ΔH nor ΔS is constant over the temperature range studied, and these thermodynamic functions exhibit classical enthalpy/entropy compensation. The ΔCp values calculated from the temperature dependence of the calorimetric ΔH values are negative for the association of both fullerenes with the buckycatcher in toluene. The negative ΔCp values are consistent with some desolvation of the host-cavity and the guest in the inclusion complexes, C(60)@C(60)H(28) and C(70)@C(60)H(28).

Corannulene subunit acts as a diene in a cycloaddition reaction: synthesis of C80H32 corannulyne tetramer.

Distortion of six-membered rings in corannulene subunits of corannulyne (1,2-didehydrocorannulene) cyclotrimer activates the system for a cycloaddition reaction with another corannulyne unit. This unprecedented cycloaddition in which a corannulene fragment acts as a diene produces the largest oligomer of corannulyne reported to date. X-ray crystallography reveals the highly nonplanar structure of the tetramer which exhibits conformational and optical absorption properties very different from those of the cyclotrimer.

Acid cleavable surface enhanced raman tagging for protein detection.

Dye conjugation is a common strategy improving the surface enhanced Raman detection sensitivity of biomolecules. Reported is a proof-of-concept study of a novel surface enhanced Raman spectroscopic tagging strategy termed as acid-cleavable SERS tag (ACST) method. Using Rhodamine B as the starting material, we prepared the first ACST prototype that consisted of, from the distal end, a SERS tag moiety (STM), an acid-cleavable linker, and a protein reactive moiety. Complete acid cleavage of the ACST tags was achieved at a very mild condition that is 1.5% trifluoroacetic acid (TFA) aqueous solution at room temperature. SERS detection of this ACST tagged protein was demonstrated using bovine serum albumin (BSA) as the model protein. While the SERS spectrum of intact ACST-BSA was entirely dominated by the fluorescent signal of STM, quality SERS spectra can be readily obtained with the acid cleaved ACST-BSA conjugates. Separation of the acid cleaved STM from protein further enhances the SERS sensitivity. Current SERS detection sensitivity, achieved with the acid cleaved ACST-BSA conjugate is ∼5 nM in terms of the BSA concentration and ∼1.5 nM in ACST content. The dynamic range of the cleaved ACST-BSA conjugate spans four orders of magnitudes from ∼10 nM to ∼100 µM in protein concentrations. Further improvement in the SERS sensitivity can be achieved with resonance Raman acquisition. This cleavable tagging strategy may also be used for elimination of protein interference in fluorescence based biomolecule detection.

Sensitive carbohydrate detection using surface enhanced Raman tagging.

Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were ∼1 nM in concentration for all the RT-carbohydrate conjugates and ∼10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 µM. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is ∼3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques.

Ratiometric Raman spectroscopy for quantification of protein oxidative damage.

A novel ratiometric Raman spectroscopic (RMRS) method has been developed for quantitative determination of protein carbonyl levels. Oxidized bovine serum albumin (BSA) and oxidized lysozyme were used as model proteins to demonstrate this method. The technique involves conjugation of protein carbonyls with dinitrophenyl hydrazine (DNPH), followed by drop coating deposition Raman spectral acquisition (DCDR). The RMRS method is easy to implement because it requires only one conjugation reaction, uses a single spectral acquisition, and does not require sample calibration. Characteristic peaks from both protein and DNPH moieties are obtained in a single spectral acquisition, allowing the protein carbonyl level to be calculated from the peak intensity ratio. Detection sensitivity for the RMRS method is approximately 0.33 pmol carbonyl per measurement. Fluorescence and/or immunoassay-based techniques only detect a signal from the labeling molecule and, thus, yield no structural or quantitative information for the modified protein, whereas the RMRS technique allows protein identification and protein carbonyl quantification in a single experiment.

Effective treatment strategies for paediatric community-acquired pneumonia.

Pneumonia is the leading cause of death in children under 5 years of age worldwide and a cause of morbidity in a considerable number of children. A number of studies have sought to identify the ideal choice of antibiotics, route of administration and optimum duration of treatment based on the most likely aetiological agents. Emerging bacterial resistance to antibiotics is also an important consideration in treatment. However, inconsistent clinical and radiological definitions of pneumonia make comparison between studies difficult. There is also a lack of well designed adequately powered randomised controlled trials. This review describes the difficulties encountered in diagnosing community-acquired pneumonia, aetiology, treatment strategies with recommendations and highlights areas for further research.

Paediatric consequences of fetal growth restriction.

The evidence for outcome following fetal growth restriction (FGR) has previously been inferred from studies, based on babies who were born small for gestational age (SGA). Great care is required when evaluating studies in this area due to a number of potential confounders. It does appear, however, that FGR is associated with an increased risk of poor neurological outcome. This includes an increased risk of cerebral palsy in babies greater than 32 weeks' gestation. Below 32 weeks, the effects of prematurity appear to negate the effects of FGR. FGR is also associated with cognitive deficit and behaviour problems. Babies with poor prenatal head growth appear to have a worse cognitive outcome. However, the role of 'fetal brain sparing' remains unclear, as impaired cognitive outcome is still evident in babies with appropriate head growth. Recent studies, which have identified FGR more accurately using fetal growth standards, have found an increased incidence of major intracranial injury and other adverse neonatal outcomes, which had previously been thought to occur less frequently in FGR babies. FGR is also associated with poor postnatal growth. The majority of children with FGR demonstrate catch-up growth in the first 2 years of life. Children who fail to demonstrate catch-up growth have a high risk of long-term growth problems. There is evidence of impaired growth hormone activity in some children with FGR who have persistent poor growth in the postnatal period.