Objective To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.Design 12 week double masked randomised placebo controlled phase III trial.Setting 19 hospitals across England and Wales.Participants 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours’ continuous sleep.Interventions Immediate release melatonin or matching placebo capsules administered 45 minutes before the child’s bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment.Main outcome measures Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy.Results Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (−15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (−37.5 minutes, −55.3 to −19.7 minutes) and actigraphy (−45.3 minutes, −68.8 to −21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups.Conclusions Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required.Trial registration ISRCT No 05534585.

Summary Background COVID‐19 school closures pose a threat to children's wellbeing, but no COVID‐19‐related studies have assessed children's behaviours over multiple years . Objective To examine children's obesogenic behaviours during spring and summer of the COVID‐19 pandemic compared to previous data collected from the same children during the same calendar period in the 2 years prior. Methods Physical activity and sleep data were collected via Fitbit Charge‐2 in 231 children (7–12 years) over 6 weeks during spring and summer over 3 years. Parents reported their child's screen time and dietary intake via a survey on 2–3 random days/week. Results Children's behaviours worsened at a greater rate following the pandemic onset compared to pre‐pandemic trends. During pandemic spring, sedentary behaviour increased (+79 min; 95% CI = 60.6, 97.1) and MVPA decreased (−10 min, 95% CI = −18.2, −1.1) compared to change in previous springs (2018–2019). Sleep timing shifted later (+124 min; 95% CI = 112.9, 135.5). Screen time (+97 min, 95% CI = 79.0, 115.4) and dietary intake increased (healthy: +0.3 foods, 95% CI = 0.2, 0.5; unhealthy: +1.2 foods, 95% CI = 1.0, 1.5). Similar patterns were observed during summer. Conclusions Compared to pre‐pandemic measures, children's PA, sedentary behaviour, sleep, screen time, and diet were adversely altered during the COVID‐19 pandemic. This may ultimately exacerbate childhood obesity.

Porous and nanoscale architectures of inorganic materials have become crucial for a range of energy and catalysis applications, where the ability to control the morphology largely determines the transport characteristics and device performance. Despite the availability of a range of block copolymer self-assembly methods, the conditions for tuning the key architectural features such as the inorganic wall-thickness have remained elusive. Towards this end we have developed solution processing guidelines that enable isomorphic nanostructures with tunable wall-thickness. A new poly(ethylene oxide-b-hexyl acrylate) (PEOb-PHA) structure directing agent (SDA) was used to demonstrate the key solution design criteria. Specifically, the use of a polymer with a high Flory-Huggins effective interaction parameter, χ, and appropriate solution conditions leads to the kinetic entrapment of persistent micelle templates (PMT) for tunable isomorphic architectures. Solubility parameters are used to predict conditions for maintaining persistent micelle sizes despite changing equilibrium conditions. Here the use of different inorganic loadings controls the inorganic wall-thickness with constant pore size. This versatile method enabled a record 55 nm oxide wall-thickness from micelle coassembly as well as the seamless transition from mesoporous materials to macroporous materials by varying the polymer molar mass and solution conditions. The processing guidelines are generalizable and were elaborated with three inorganic systems, including Nb 2 O 5 , WO 3 , and SiO 2 that were thermally stable to 600 o C for access to crystalline materials. access to extensive pore size regimes that seamlessly span from mesopores to macropores. This concept is demonstrated with a new PEO-b-PHA SDA. The use of a polymer with sufficiently high Flory-Huggins interaction parameter is needed to inhibit micelle re-equilibration that would otherwise change the final pore size with different inorganic loadings. Both micelle fusion-fission and unimer expulsion-insertion reactions may be slowed with appropriate solution conditions that inhibit micelle changes. 68-72 The demonstrated broad range of tunable pore sizes fills the gap typically found between block copolymer approaches and colloidal approaches. The resulting materials were stable to high temperatures and enabled the formation of multiple crystalline oxide frameworks. Experimental Methods Reagents: Anhydrous, inhibitor free THF (>99.9%, Aldrich), Niobium (V) ethoxide (99.9%, Fisher) and Tungsten (VI) chloride (99.9%, Acros) were stored inside a glove box and used as received. Concentrated hydrochloric acid (37 wt% ACS grade, VWR) and Tetraethoxysilane (98%, Alfa Aesar) were used as received. Poly(ethylene glycol) methyl ether (M n 20, 000 g mol-1 , Aldrich) was dried by azeotropic distillation with toluene before use.

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Background Excessive screen time ($$\ge$$ ≥ 2 h per day) is associated with childhood overweight and obesity, physical inactivity, increased sedentary time, unfavorable dietary behaviors, and disrupted sleep. Previous reviews suggest intervening on screen time is associated with reductions in screen time and improvements in other obesogenic behaviors. However, it is unclear what study characteristics and behavior change techniques are potential mechanisms underlying the effectiveness of behavioral interventions. The purpose of this meta-analysis was to identify the behavior change techniques and study characteristics associated with effectiveness in behavioral interventions to reduce children’s (0–18 years) screen time. Methods A literature search of four databases (Ebscohost, Web of Science, EMBASE, and PubMed) was executed between January and February 2020 and updated during July 2021. Behavioral interventions targeting reductions in children’s (0–18 years) screen time were included. Information on study characteristics (e.g., sample size, duration) and behavior change techniques (e.g., information, goal-setting) were extracted. Data on randomization, allocation concealment, and blinding was extracted and used to assess risk of bias. Meta-regressions were used to explore whether intervention effectiveness was associated with the presence of behavior change techniques and study characteristics. Results The search identified 15,529 articles, of which 10,714 were screened for relevancy and 680 were retained for full-text screening. Of these, 204 studies provided quantitative data in the meta-analysis. The overall summary of random effects showed a small, beneficial impact of screen time interventions compared to controls (SDM = 0.116, 95CI 0.08 to 0.15). Inclusion of the Goals, Feedback, and Planning behavioral techniques were associated with a positive impact on intervention effectiveness (SDM = 0.145, 95CI 0.11 to 0.18). Interventions with smaller sample sizes (n < 95) delivered over short durations (< 52 weeks) were associated with larger effects compared to studies with larger sample sizes delivered over longer durations. In the presence of the Goals, Feedback, and Planning behavioral techniques, intervention effectiveness diminished as sample size increased. Conclusions Both intervention content and context are important to consider when designing interventions to reduce children’s screen time. As interventions are scaled, determining the active ingredients to optimize interventions along the translational continuum will be crucial to maximize reductions in children’s screen time.

Biases introduced in early-stage studies can lead to inflated early discoveries. The risk of generalizability biases (RGBs) identifies key features of feasibility studies that, when present, lead to reduced impact in a larger trial. This meta-study examined the influence of RGBs in adult obesity interventions. Behavioral interventions with a published feasibility study and a larger scale trial of the same intervention (e.g., pairs) were identified. Each pair was coded for the presence of RGBs. Quantitative outcomes were extracted. Multilevel meta-regression models were used to examine the impact of RGBs on the difference in the effect size (ES, standardized mean difference) from pilot to larger scale trial. A total of 114 pairs, representing 230 studies, were identified. Overall, 75% of the pairs had at least one RGB present. The four most prevalent RGBs were duration (33%), delivery agent (30%), implementation support (23%), and target audience (22%) bias. The largest reductions in the ES were observed in pairs where an RGB was present in the pilot and removed in the larger scale trial (average reduction ES À0.41, range À1.06 to 0.01), compared with pairs without an RGB (average reduction ES À0.15, range À0.18 to À0.14). Eliminating RGBs during early-stage testing may result in improved evidence.

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Acquired tracheomegaly is a rare condition associated with pulmonary fibrosis, connective tissue disease and the use of cuffed tracheal tubes. We describe the urgent tracheal re-intubation and subsequent tracheal repair of a previously well 58-year-old man who developed tracheostomy-related tracheomegaly during prolonged mechanical ventilation for coronavirus disease 2019 pneumonitis. Urgent tracheal re-intubation was required due to a persistent cuff leak, pneumomediastinum and malposition of the tracheostomy tube. We describe the additional challenges and risks associated with airway management in patients with tracheomegaly, and discuss how even in urgent cases these can be mitigated through planning and teamwork. We present a stepwise approach to tracheal re-intubation past a large tracheal dilatation, including the use of an Aintree catheter inserted via the existing tracheal stoma for oxygenation or tracheal re-intubation if required. Computed tomography imaging was valuable in characterising the defect and developing a safe airway management strategy before starting the procedure. This report emphasises the role of planning, teamwork and the development of an appropriate airway strategy in the safe management of complex cases.