Does Sleep Position Influence Sleep-Disordered Breathing in Infants With Cleft Palate: A Feasibility Study?

OBJECTIVE: Cleft palate (CP) can affect breathing, leading to sleep-disordered breathing (SDB). Sleep position can affect SDB, but the optimum sleep position for infants with CP is unknown. We aimed to determine the design of a pragmatic study to investigate the effect of the 2 routinely advised sleep positions in infants with CP on oxygen saturations. DESIGN: A multicentered observational cohort. SETTING: Four UK-based cleft centers, 2 advising supine- and 2 side-lying sleep positions for infants with CP. PARTICIPANTS: Infants with isolated CP born July 1, 2015, and December 31, 2016. Of 48 eligible infants, 30 consented (17 side-lying; 13 supine). INTERVENTIONS: Oxygen saturation (SpO2) and end-tidal carbon dioxide (ETCO2) home monitoring at age 1 and 3 months. Qualitative interviews of parents. OUTCOME MEASURES: Willingness to participate, recruitment, retention, and acceptability/success (>90 minutes recording) of SpO2 and ETCO2 monitoring. RESULTS: SpO2 recordings were obtained during 50 sleep sessions on 24 babies (13 side-lying) at 1 month (34 sessions >90 minutes) and 50 sessions on 19 babies (10 side-lying) at 3 months (27 sessions >90 minutes). The ETCO2 monitoring was only achieved in 12 sessions at 1 month and 6 at 3 months; only 1 was >90 minutes long. The ETCO2 monitoring was reported by the majority as unacceptable. Parents consistently reported the topic of sleep position in CP to be of importance. CONCLUSIONS: This study has demonstrated that it is feasible to perform domiciliary oxygen saturation studies in a research setting and has suggested that there may be a difference in the effects of sleep position that requires further investigation. We propose a study with randomization is indicated, comparing side-lying with supine-lying sleep position, representing an important step toward better understanding of SDB in infants with CP.

How are trial outcomes prioritised by stakeholders from different regions? Analysis of an international Delphi survey to develop a core outcome set in gastric cancer surgery.

BACKGROUND: International stakeholder participation is important in the development of core outcome sets (COS). Stakeholders from varying regions may value health outcomes differently. Here, we explore how region, health income and participant characteristics influence prioritisation of outcomes during development of a COS for gastric cancer surgery trials (the GASTROS study). METHODS: 952 participants from 55 countries participating in a Delphi survey during COS development were eligible for inclusion. Recruits were grouped according to region (East or West), country income classification (high and low-to-middle income) and other characteristics (e.g. patients; age, sex, time since surgery, mode of treatment, surgical approach and healthcare professionals; clinical experience). Groups were compared with respect to how they categorised 56 outcomes identified as potentially important to include in the final COS ('consensus in', 'consensus out', 'no consensus'). Outcomes categorised as 'consensus in' or 'consensus out' by all 3 stakeholder groups would be automatically included in or excluded from the COS respectively. RESULTS: In total, 13 outcomes were categorised 'consensus in' (disease-free survival, disease-specific survival, surgery-related death, recurrence of cancer, completeness of tumour removal, overall quality of life, nutritional effects, all-cause complications, intraoperative complications, anaesthetic complications, anastomotic complications, multiple organ failure, and bleeding), 13 'consensus out' and 31 'no consensus'. There was little variation in prioritisation of outcomes by stakeholders from Eastern or Western countries and high or low-to-middle income countries. There was little variation in outcome prioritisation within either health professional or patient groups. CONCLUSION: Our study suggests that there is little variation in opinion within stakeholder groups when participant region and other characteristics are considered. This finding may help COS developers when designing their Delphi surveys and recruitment strategies. Further work across other clinical fields is needed before broad recommendations can be made.

Methods for conducting international Delphi surveys to optimise global participation in core outcome set development: a case study in gastric cancer informed by a comprehensive literature review.

BACKGROUND: Core outcome sets (COS) should be relevant to key stakeholders and widely applicable and usable. Ideally, they are developed for international use to allow optimal data synthesis from trials. Electronic Delphi surveys are commonly used to facilitate global participation; however, this has limitations. It is common for these surveys to be conducted in a single language potentially excluding those not fluent in that tongue. The aim of this study is to summarise current approaches for optimising international participation in Delphi studies and make recommendations for future practice. METHODS: A comprehensive literature review of current approaches to translating Delphi surveys for COS development was undertaken. A standardised methodology adapted from international guidance derived from 12 major sets of translation guidelines in the field of outcome reporting was developed. As a case study, this was applied to a COS project for surgical trials in gastric cancer to translate a Delphi survey into 7 target languages from regions active in gastric cancer research. RESULTS: Three hundred thirty-two abstracts were screened and four studies addressing COS development in rheumatoid and osteoarthritis, vascular malformations and polypharmacy were eligible for inclusion. There was wide variation in methodological approaches to translation, including the number of forward translations, the inclusion of back translation, the employment of cognitive debriefing and how discrepancies and disagreements were handled. Important considerations were identified during the development of the gastric cancer survey including establishing translation groups, timelines, understanding financial implications, strategies to maximise recruitment and regulatory approvals. The methodological approach to translating the Delphi surveys was easily reproducible by local collaborators and resulted in an additional 637 participants to the 315 recruited to complete the source language survey. Ninety-nine per cent of patients and 97% of healthcare professionals from non-English-speaking regions used translated surveys. CONCLUSION: Consideration of the issues described will improve planning by other COS developers and can be used to widen international participation from both patients and healthcare professionals.

Study protocol for randomised clinical trial comparing the effectiveness of side-lying sleep positioning to back-lying at reducing oxygen desaturation resulting from obstructive sleep apnoea in infants with cleft palate (SLUMBRS2).

INTRODUCTION: The craniofacial abnormalities found in infants with cleft palate (CP) decrease their airway patency and increase their risk of obstructive sleep apnoea (OSA). We hypothesise that optimising sleep position in infants with CP may improve airway patency and offer a 'low-cost, high-impact' intervention to prevent the negative impacts of OSA. Because cleft centres give inconsistent advice about sleep position: some recommend back-lying and others side-lying, we will compare these in a randomised controlled trial. METHODS AND ANALYSIS: The aim is to determine the clinical effectiveness of side-lying as compared with back-lying sleep positioning in terms of reducing oxygen desaturation resulting from OSA in 244 infants aged 3-5 weeks of age, diagnosed with an isolated CP in/by UK cleft centres. Primary outcome is the 4% Oxygen Desaturation Index measured using pulse oximetry during sleep. RESEARCH PLAN: 1. Multicentre randomised controlled trial of side-lying compared with back-lying sleep positioning in reducing oxygen desaturation resulting from OSA in infants with CP at one month of age. 2. Internal pilot questionnaire-based study to support parents and clinicians regarding study participation, seeking to identify and address any barriers to recruitment. Monitoring data from the internal pilot will be used in the final analysis. 3. Co-development of new UK recommendations with Cleft Lip and Palate Association (CLAPA) regarding sleep position for infants with CP. ETHICS AND DISSEMINATION: The study protocol has received the favourable opinion of the West Midlands-South Birmingham Research Ethics Committee. Study results will be published on affiliated webpages and in peer-reviewed publications and conference contributions. TRIAL REGISTRATION NUMBER: NCT04478201.

The benefits of preserving residual hearing following cochlear implantation: a systematic review.

OBJECTIVE: Systematically review the current literature for evidence on the "real-life" benefits of hearing preservation cochlear implantation (HPCI) for children and adults. DESIGN: Systematic search of Pubmed, MEDLINE, EMBASE, CINHAL and Cochrane Library for MesH terms hearing¸ preservation and cochlear implantation. Inclusion criteria were the "real-life" benefit of HPCI i.e. other than pre- and post-operative pure tone thresholds. Exclusion criteria were non-English language, conference abstracts, reviews and animal and cadaveric studies. Risk of bias was assessed using the Evidence Project Tool. STUDY SAMPLE: 37 studies that matched criteria for review with 8/37 including children and 29/37 including adults. RESULTS: HPCI was associated with better speech perception in noise in 18/26 papers and better music perception in 4/5 papers. There was no significant benefit reported in speech perception in quiet (14/20 papers) or binaural cues (3/4 papers), nor was there convincing evidence of HPCI outperforming bimodal users (5/7 papers). QoL scores were high amongst HPCI patients (2/2 papers). Interpretation of findings was hindered by small study groups and significant heterogeneity in various parameters. CONCLUSION: Current literature on the "real-life" benefit of HPCI, although limited, supports the existence of meaningful benefit, especially in speech perception in noise and music perception.

Toward a Core Outcome Set for Head, Neck, and Respiratory Disease in Mucopolysaccharidosis Type II: Systematic Literature Review and Assessment of Heterogeneity in Outcome Reporting

Abstract The mucopolysaccharidoses (MPS) are a relatively uncommon group of inherited metabolic disorders, with significant negative implications for life span and aspects of quality of life. Their rarity means that producing evidence to guide best practice has often entailed assimilating findings from multiple studies. Core outcome sets (COS) are being increasingly used across medicine as a potential solution to the problems arising from heterogeneous reporting of outcomes in effectiveness studies. A COS is a recommended minimum set of outcomes that should be measured for a given condition in an effectiveness study, with the ultimate aim of increasing the value of clinical information by enabling meaningful comparison and combination of data from various sources. A systematic review identified 41 outcomes measured in published studies and ongoing and completed clinical trials, with individual outcomes being measured using a variety of measurement instruments/tools. This work represents the important initial steps in the development of COS for head, neck, and respiratory disorders in MPS type II, raising awareness of the extent of heterogeneity in outcome reporting and determining the scope of outcomes and corresponding instruments currently used. The next step will be to use the generated "longlist" of outcomes to develop an electronic Delphi prioritization exercise with the intention of reaching a consensus regarding the most important outcomes to measure in effectiveness studies for head, neck, and respiratory disease in MPS type II.

Skin sensitization induced Langerhans' cell mobilization: variable requirements for tumour necrosis factor-α.

Upon antigen/allergen recognition, epidermal Langerhans' cells (LC) are mobilized and migrate to the local lymph node where they play a major role in initiating or regulating immune responses. It had been proposed that all chemical allergens induce LC migration via common cytokine signals delivered by TNF-α and IL-1ß. Here the dependence of LC migration on TNF-α following treatment of mice with various chemical allergens has been investigated. It was found that under standard conditions the allergens oxazolone, paraphenylene diamine, and trimellitic anhydride, in addition to the skin irritant sodium lauryl sulfate, were unable to trigger LC mobilization in the absence of TNF-α signalling. In contrast, two members of the dinitrohalobenezene family (2,4-dinitrochlorobenzene [DNCB] and 2,4-dinitrofluorobenzene [DNFB]) promoted LC migration independently of TNF-R2 (the sole TNF-α receptor expressed by LC) and TNF-α although the presence of IL-1ß was still required. However, increasing doses of oxazolone overcame the requirement of TNF-α for LC mobilization, whereas lower doses of DNCB were still able to induce LC migration in a TNF-α-independent manner. These novel findings demonstrate unexpected heterogeneity among chemical allergens and furthermore that LC can be induced to migrate from the epidermis via different mechanisms that are either dependent or independent of TNF-α. Although the exact mechanisms with regard to the signals that activate LC have yet to be elucidated, these differences may translate into functional speciation that will likely impact on the extent and quality of allergic sensitization.