Post-PICU sleep efficiency and quality of life in infants and toddlers with acquired brain injury.

STUDY OBJECTIVES: We aimed to investigate the use of sleep efficiency (SE) as a measure of sleep disturbance in infants and toddlers with acquired brain injury (ABI) and evaluate associations between SE and child health-related quality of life and family outcomes. METHODS: Retrospective cohort study of 101 children ages 3-36 months who survived critical care for ABI. SE was quantified from the Brief Infant Sleep Questionnaire as a ratio of nighttime sleep to total time in bed; poor SE was defined as < 80%. Outcome measures included the Pediatric Quality of Life Inventory Core Total Score (health-related quality of life) and Family Impact Module Total Score. Spearman's correlation quantified associations between SE and outcomes. Multivariable linear regression tested association between poor SE and health-related quality of life controlling for significant covariates (age, diagnosis, comorbidities, worsening Functional Status Scale). RESULTS: Following ABI, median SE was 91.7 (interquartile range = 83.3, 95.5). Nineteen (19%) children had poor SE (< 80%). SE correlated significantly with quality of life (Spearman's correlation = .307) and Family Impact Module (Spearman's correlation = .309; both P < .01). When controlling for covariates, poor SE significantly increased risk for lower health-related quality of life (ß-coefficient = -7.0; 95% confidence interval= -13.4, -0.6). CONCLUSIONS: One in five infants and young children with ABI have poor SE that is associated with poorer child and family health outcomes. Our study underscores the potential importance of sleep following ABI to optimize recovery and the need for additional investigation of SE in infants and young children. CITATION: Klapp JM, Hall TA, Riley AR, Janzen D, Williams CN. Post-PICU sleep efficiency and quality of life in infants and toddlers with acquired brain injury. J Clin Sleep Med. 2024;20(1):75-83.

Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria.

Pegvaliase is approved to reduce phenylalanine (Phe) levels for people with phenylketonuria (PKU). PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862) data were analyzed to evaluate the relationship between Phe and inattention in adult participants with PKU. In the modified-intent-to-treat population (N = 156), baseline mean (SE) plasma Phe was 1263 (29) µmol/L and the Attention Deficit Hyperactivity Disorder Rating Scale-IV Inattentive (IA) symptoms score was 9.8 (0.5). Mean (SE) IA scores fell 9.0 (1.1) in Quartile 1 (Phe reduction between 1166 and 2229 µmol/L) versus 4.3 (0.7) in Quartile 4 (Phe reduction of 139 µmol/L to increase of 934 µmol/L), p = 0.004. Least squares mean (SE) change from baseline IA score was -7.9 (0.7) for participants with final Phe ≤ 360 µmol/L and -4.5 (0.7) for final Phe > 360 µmol/L, p < 0.001. In the inattention subgroup, IA scores fell 13.3 (1.5) in Quartile 1 (Phe reduction between 1288 and 2229 µmol/L) versus 6.2 (1.3) in Quartile 4 (Phe reduction of 247 to increase of 934 µmol/L), p = 0.009. Inattention symptoms improved among those whose Phe levels decreased, particularly those with high baseline IA scores. IA improvements were larger among participants with the greatest plasma Phe reductions, supporting this value as a therapeutic goal.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes.

Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure.

The design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here.

Identification and treatment of obesity as a standard of care for all patients in children's hospitals.

Obese children and adolescents have unique needs for specialized medical equipment while hospitalized and might require special diets and physical activity options as part of their medical treatment. It is important that patients with a diagnosis of obesity be identified on admission so that appropriate equipment and resources can be provided. We examined what components a healthy hospital environment should include and sought to determine if children's hospitals provide a healthy hospital environment that offers these components. In addition, we sought to determine if children's hospitals have policies in place to identify children with obesity so that appropriate resources and services can be offered to treat that diagnosis. We surveyed National Association of Children's Hospitals and Related Institutions member hospitals via a Web-based questionnaire and found that the majority of them do not have policies in place to identify patients with obesity. We did find that the majority of hospitals reported innovative programs or services to provide a healthy hospital environment for their patients, visitors, and staff but acknowledged limitations in providing some services. Specifically, children's hospitals can and should improve on their identification and management of obese pediatric patients.

Beyond executive function: non-executive cognitive abilities in individuals with PKU.

Individuals with early-treated phenylketonuria (ETPKU) most often present with impairment in executive function (EF) and average intelligence compared to the general population. The topic of this review, which is less often discussed, is non-EF impairments that may be associated with ETPKU. Studies that have included assessment of non-EF cognitive functions such as information processing speed, fine motor skills, and perception and visual-spatial abilities suggest that individuals with ETPKU are compromised in these areas. Those assessing non-EF cognitive functions of language skills, long-term memory, and learning skills have yielded mixed results, with some suggesting impairment and others suggesting intact abilities. Although more studies are required, research to date suggests that mechanisms for non-EF deficits may include prefrontal cortex dopamine deficiency and/or white matter abnormalities related to elevated blood phenylalanine levels. For individuals with ETPKU to reach their full potential in life, it is vital to address the challenges associated with EF and non-EF deficits by identifying impairments and appropriate treatment strategies.