Phoebe Ivain

INTRODUCTION: The Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG‐DS) is a sensitive cognitive test for Alzheimer's disease (AD)–related decline in people with DS, but needs updates for sensitivity, cultural adaptability, and additional memory/executive function items. This study aimed to develop and validate the CAMCOG‐DS‐II.METHODS: In this multi‐language, multi‐site study, the psychometric properties of the CAMCOG‐DS‐II were evaluated against previously validated measures in 223 participants (mean age: 40.18 years) with DS across seven countries.RESULTS: The CAMCOG‐DS‐II had a high completion rate, minimal floor/ceiling effects (compared to the modified Cued Recall Test, the CANTAB Paired Associates Learning, and the Purdue Pegboard), strong validity and reliability, and performance was unaffected by language across sites. It differentiated between those with/without AD and distinguished clinically rated cognitively stable and prodromal individuals.CONCLUSION: The CAMCOG‐DS‐II is a sensitive measure of cognitive performance in people with DS at risk of AD. Its cross‐language and site reliability support its potential use in AD–DS clinical trials.Highlights: Developed and validated the Cambridge Cognitive Examination modified for use in people with Down syndrome (CAMCOG‐DS‐II) for Alzheimer's disease in Down syndrome. CAMCOG‐DS‐II shows increased sensitivity to Alzheimer's disease–related decline in Down syndrome. Improved applicability across an international and culturally diverse population. Differentiates Alzheimer's disease status: cognitively stable, prodromal, and clinical.

Importance: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown.Objective: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn).Design, Setting, and Participants: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks’ gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020.Exposure: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging.Main Outcomes and Measures: ThalamicN-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months.Results: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg;P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%;P = .01), and more likely to be intubated at birth (78.9% vs 29.1%;P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%;P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], −0.28; 95% CI, −1.62 to 1.07;P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, −0.62 to 0.71;P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08;P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09;P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41).Conclusions and Relevance: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs.Trial Registration: ClinicalTrials.gov Identifier:NCT02387385

Although none of the major cooling trials mandated routine pre-emptive sedation, anecdotal evidence suggests that opioids are widely used during neonatal cooling therapy. We examined the current practice of pre-emptive opioid sedation during cooling therapy in the UK neonatal units and to compare this with major USA and Canadian neonatal units. We designed an electronic survey (Qualtrics LLC, Provo, Utah, USA) with 10 questions covering sedation practices during cooling including the drugs used, dose, duration and the reason for sedation for ventilated and non-ventilated babies. The survey was emailed to the lead clinicians of all 52 UK cooling centres directly. In the USA/Canada, the survey was distributed through the Neurocritical Care Special Interest Group, which is a virtual worldwide network of brain researchers. Responses were then screened for duplications and data completeness prior to analysis. All 52 (100% response rate) UK and 34 of the USA/Canadian cooling centres completed …