Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. Findings: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. Funding: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. Translations: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section

Laser induced periodic surface structures on polymer nanocomposites with carbon nanoadditives

Laser induced periodic surface structures (LIPSS) are formed on poly(trimethylene terephthalate) and its composites with single-walled carbon nanotubes (SWCNT) and with both SWCNT and expanded graphite (EG) upon irradiation with a Q-Switched Nd:YAG laser (266 nm, 8 ns). The morphology of the polymer films was characterized by atomic force microscopy. A cantilever with a colloidal probe was used to obtain information about surface adhesion. Surface energies were estimated by contact angle measurements using different liquids. Chemical modification in the materials upon irradiation was assessed by Raman spectroscopy. Results show a dependence of the number of pulses required for LIPSS formation as a consequence of the presence of the carbon nanoadditive and an increase of the hydrophilic character of surfaces after irradiation. Moreover, the polar component of the surface free energy changes significantly and surface adhesion increases by the addition of the additive to the polymer matrix. Additionally, the adhesion force decreases after laser nanostructuring as a consequence of a lower contact area in the nanostructured material.The authors gratefully acknowledge financial support from the MINECO (FIS2013-44174-P, MAT2014-59187-R, MAT2015-66443-C02-1-R, FIS2015-71933-REDT, CTQ2016-75880-P) and Junta de Castilla y León (Project SA046U16). RIR is grateful for the International Scholarship number 314197 provided by Consejo Nacional de Ciencia y Tecnología (CONACyT-México) and E.R. thanks MINECO for a Ramón y Cajal contract (RYC-2011-08069). The authors thank J. V. Garcı́a Ramos for the Raman measurements