sleep

Importance
The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.

Objective
To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.

Design, Setting, and Participants
Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.

Interventions
Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).

Main Outcomes and Measures
The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.

Results
Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction = .73).

Conclusions and Relevance
Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Trial Registration
ISRCTN Identifier: ISRCTN76888927

Disorders of Arousal  (DOA) are mental and motor behaviors arising from NREM sleep. They comprise a spectrum of manifestations of increasing intensity from confusional arousals to sleep terrors to sleepwalking.

Although DOA in childhood are usually harmless, in adulthood they are often associated with injurious or violent behaviors to the patient or others. Driving motor vehicles, suspected suicide, and even homicide or attempted homicide have been described during sleepwalking in adults. Furthermore, adult DOA need to be differentiated from other sleep disorders such as Sleep-related Hypermotor Epilepsy or REM Sleep Behavior Disorder.

Although many aspects of DOA have been clarified in the last two decades there is still a lack of objective and quantitative diagnostic criteria for DOA.

Recent advances in EEG analysis and in the semiological characterization of DOA motor patterns have provided a better definition of DOA diagnosis.

Our article focuses on the DOA diagnostic process describing accurately the newest DOA clinical, EEG and video-polysomnographic tools in order to aid clinicians in DOA assessment.