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Background: Titration of oxygen therapy to target safe oxygen saturation (SpO 2 ) values is a vital part of care for preterm infants, but is difficult to achieve, particularly in settings in which oxygen, monitoring technology, and human resources are scarce. We aimed to evaluate the safety and efficacy of automated titration of oxygen therapy partnered with a low-cost continuous positive airway pressure (CPAP) device versus manual oxygen control in preterm infants requiring CPAP in a high-mortality, low-resource setting., Methods: In this open-label, randomised, crossover trial, preterm infants with a gestational age younger than 34 weeks (or a birthweight <2 kg if gestation was unknown) who were aged 12 h or older and required CPAP and oxygen were recruited at two hospitals in southwest Nigeria. Participants were randomly assigned (1:1) to one of two intervention sequences (ie, to commence the study on automated oxygen control or manual oxygen control) with block randomisation (blocks of 4 and 6) and stratification by health facility. The study statistician was masked to treatment group assignment, but the participants' parents or caregivers and clinical staff were not. Participants received automated or manual oxygen control for two 24-h periods in random sequence. Automated oxygen titration was done with a control algorithm with proven efficacy in high-resource settings. During periods of manual control, oxygen therapy was adjusted by clinicians. The primary outcome was the adjusted mean difference in the proportion of time participants spent in the SpO 2 target range (ie, SpO 2 91-95% when receiving oxygen or SpO 2 91-100% when not receiving oxygen) between automated and manual oxygen control, analysed by intention to treat with weighted repeated measures mixed model linear regression. This trial is registered with ClinicalTrials.gov, NCT05508308, and is completed., Findings: Between Sept 13, 2022, and Sept 11, 2023, 72 infants were screened, and 49 (22 female, 27 male; median gestation 29 weeks [IQR 28-31]; median birthweight 1·2 kg [1·1-1·5]) were enrolled in the study and randomly assigned. A total of 80 study periods for 46 infants contributed data to the analysis of the primary outcome as three (6%) of the 49 participants had no oxygenation data from either study period. The mean proportion of time spent in the SpO 2 target range was higher during automated control periods than during periods of manual control (adjusted mean 88·1% [95% CI 84·0-92·2] vs 30·1% [20·9-39·3]; adjusted mean difference 58·0% [95% CI 48·0-67·9]; p<0·0001). There were no device-related adverse patient outcomes and short-term safety outcomes favoured automated control., Interpretation: Automated titration of oxygen partnered with a low-cost CPAP device improved time spent in the safe SpO 2 range compared with manual control. There is high potential for this technology to mitigate the risk of oxygen-mediated complications in preterm infants in low-resource settings., Funding: National Health and Medical Research Council Australia and University of Tasmania., Competing Interests: Declaration of interests The University of Tasmania (UTAS) holds a patent concerning automated control of inspired oxygen concentration in the newborn infant and has entered into a licensing agreement with SLE allowing use of the VDL1.1 algorithm (as OxyGenie) in SLE respiratory support devices. No licensing agreement exists pertaining to the low-resource setting. RS, ACG, and SB receive salary support from the Melbourne Children's Research Institute, and RS receives salary support from the Royal Australian College of Physicians. LM was supported by a UTAS Graduate Research Scholarship. AAB has received salary support from University College Hospital, Ibadan, and serves as a trustee of the Oxygen for Life Initiative. GFD was supported by the Crafoord Institute scholarship. PAD has received personal royalties in relation to commercialisation of the VDL1.1 oxygen control algorithm (OxyGenie), which were donated in full to support neonatal research; has received support for travel to scientific meetings from Chiesi Farmaceutici and SLE; and holds National Health and Medical Research Council (NHMRC) grants (grant IDs 2015140, 1158555, and 1182515). HRG has received general salary and grant support for child health research from the Royal Children's Hospital Foundation, NHMRC (grant ID 2009026), the Bill & Melinda Gates Foundation (INV 043011), and the Swedish Research Council; and has served as a trustee and advisor on oxygen-related projects with OLI and as an unpaid advisor for Lifebox Foundation. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Hypoxaemia (low oxygen saturation in blood) is a key predictor of in-hospital mortality, affecting people of all ages with many different conditions. Early detection and treatment of hypoxaemia are critical, but there are few data to quantify hypoxaemia burden outside the child pneumonia population. We aimed to estimate hypoxaemia prevalence for adults and children with acute illness attending health facilities in low-income and middle-income countries (LMICs)., Methods: We conducted a systematic review and meta-analysis, searching MEDLINE, PubMed, Embase, Cumulated Index in Nursing and Allied Health Literature, Index Medicus, and Google Scholar for studies reporting hypoxaemia prevalence among patients attending health facilities. We included articles with original data on peripheral blood oxygen saturation (SpO 2 ), from an LMIC, published between Jan 1, 1998, and Jan 10, 2023. We included studies in acutely unwell people of any age and with any condition, but excluded those admitted to intensive care units, receiving perioperative care, or attending hospital for preventive or chronic care. We assessed study quality using Joanna Briggs Institute's Checklist for Prevalence Studies. Two reviewers independently conducted title and abstract screening, full-text review, data extraction, and quality assessment, requesting summary data from authors. We reported pooled prevalence of hypoxaemia (typically defined as SpO 2 <90%) overall and by condition, using a random-effects meta-analysis model. This study is registered with PROSPERO, CRD42019136622., Findings: We identified 9173 unique records from searches and included 213 in meta-analyses involving 601 757 participants. The majority of studies were from the World Bank regions of sub-Saharan Africa (108 [51%] of 213) or south Asia (58 [27%]). The pooled prevalence of hypoxaemia among admitted patients was 24·5% (95% CI 19·9-29·4) for neonates (aged 0-28 days), 12·1% (10·0-14·4) for children (aged 1 month-17 years), and 10·8% (4·9-18·7) for adults (aged ≥18 years). Hypoxaemia prevalence was highest in neonatal and primary respiratory conditions but still common in many other conditions. Hypoxaemia was associated with 4·84 (95% CI 4·11-5·69) times higher odds of death than no hypoxaemia., Interpretation: Hypoxaemia is common across all age groups and a range of primary respiratory and other critical illnesses and is strongly associated with death. These estimates will inform oxygen-related strategies and programmes, and integration of pulse oximetry and oxygen into clinical guidelines, service structures, and strategies for maternal, neonatal, child, adolescent, and adult health., Funding: Bill & Melinda Gates Foundation, the ELMA Foundation, and Unitaid., Competing Interests: Declaration of interests HRG received general salary and grant support for child health research from the Royal Children's Hospital Foundation (Melbourne, VIC, Australia), the Australian National Health and Medical Research Council (ID 2009026), the Bill & Melinda Gates Foundation (INV 043011), and the Swedish Research Council, and has served as a trustee and adviser on oxygen-related projects with the Oxygen for Life Foundation, Lifebox Foundation, Unitaid, and Asian Development Bank. RS received general salary and grant support for child health research from the Murdoch Children's Research Institute and the Royal Australasian College of Physicians scholarship. AER received general salary and grant support for child health research from icddr,b, Global Affairs Canada, the US Agency for International Development (USAID), the UK Foreign, Commonwealth and Development Office, the Government of Bangladesh, WHO, UN Population Fund, the University of Edinburgh (Edinburgh, UK), the University of North Carolina (Chapel Hill, NC, USA), the University of Sheffield (Sheffield, UK), and Unitaid. FL and JLM worked for the Clinton Health Access Initiative, which has received grants related to oxygen service delivery from the Gates Foundation (INV 043011), ELMA Foundation (22-F0021), Unitaid, USAID, FHI 360, and GiveWell. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: HRG declares general research salary support; grants for research related to pneumonia, oxygen, and continuous positive airway pressure (CPAP); travel support to attend meetings; and leadership roles with non-profit organisations working on pulse oximetry and oxygen. JO declares grant support for research related to CPAP and travel support to attend a symposium related to oxygen.

Background: In 2019, Nigeria reported the highest mortality rate in children younger than 5 years globally. We aimed to assess a whole-systems approach to improving child mortality in northern Nigeria., Methods: We conducted a community-based, parallel-arm, pragmatic, cluster randomised controlled trial in Kiyawa local government area, Jigawa state, Nigeria, and a concurrent mixed-methods process evaluation using ethnography and quantitative implementation monitoring. Trial clusters were population catchment areas of 32 government primary health-care facilities. Compounds were randomly sampled, proportional to cluster size, and all women aged 16-49 years and children younger than 5 years who were permanent residents were eligible for inclusion and recruited as the evaluation population. Children younger than 7 days were recruited but excluded from analysis. Evaluation clusters were allocated to intervention or control via simple randomisation with a 1:1 ratio. Cluster names were written on paper, folded, and placed in a container by community representatives. Different community representatives took out names one by one, with the first half assigned to receive the intervention. The intervention consisted of three components: participatory learning and action (PLA) groups for men and women (including compound heads [ie, the member of the compound that residents deemed most senior]), partnership defined quality scorecard (PDQS), and health-care worker capacity building; it was delivered from March 1, 2021, to Dec 31, 2022. We could not mask participants, field staff, or intervention-delivery staff to cluster allocation but baseline, endline, and follow-up data excluded information on cluster allocation. PLA groups involved separate groups of up to 25 men or women from all villages in the intervention clusters. The primary outcome was all-cause mortality in children aged 7 days to 59 months between Oct 1, 2021, and Sept 20, 2022, referred to as the evaluation period. The trial was prospectively registered (ISRCTN 39213655) and the protocol has been published., Findings: We recruited 3800 compounds at baseline, with 12 893 children contributing to analysis of the primary outcome (7316 [56·8%] of 12 893 in the intervention group and 5577 [43·3%] in the control group). 6617 (51·3%) of 12 893 children were male, 6275 (48·7%) were female, and one (<0·1%) child had missing sex data. Sampled compounds randomly came from 388 (91·3%) of 425 villages in the 32 clusters. We conducted verbal autopsies for 1182 deaths, of which 369 (31·2%) were children aged 7 days to 59 months during the evaluation period. Of these 369, 91 (24·7%) were classified as pneumonia deaths. Children contributed a median 361 days (IQR 236-365) to the analysis, with 369 (2·9%) of 12 893 children censored on their date of death, 1545 (12·0%) on their 5th birthday, and 3392 (26·3%) on the date of the most recent follow-up in which their residence or survival status was known. We found no significant decrease in all-cause mortality (hazard ratio 0·95, 95% CI 0·68-1·33; p=0·79) or suspected pneumonia mortality (0·79, 0·43-1·46; p=0·46) in the intervention group. The process evaluation showed low coverage and issues in reach of the intervention, but qualitative data highlighted mechanisms for positive effects on health and relationships., Interpretation: Our intervention did not affect mortality. However, due to the high child mortality in this region, further efforts should be made to adapt our participatory whole-systems approach to use communities of action within compounds., Funding: GSK and Save the Children UK., Translation: For the Hausa translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests HRG, EDM, and CK are advisors to Lifebox Foundation. AAB, AGF, and HRG are board members for the Oxygen for Life Initiative, which has provided oxygen-training services to the INSPIRING project. SA, TA, and PV are employees of Save the Children UK, part of the partnership funding for this trial and evaluation. TFO and MM are employees of and stockholders in GSK, part of the partnership funding for this trial and evaluation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Medical oxygen services are essential for the care of acutely unwell patients. We aimed to assess the effects of a multilevel, multicomponent health-system intervention on hypoxaemia detection, oxygen therapy, and mortality among neonates and children attending level IV health centres and hospitals in Uganda., Methods: For this before-after intervention study, we included children who attended paediatric or neonatal wards of 24 level IV health centres and seven general or regional referral hospitals in the Busoga and North Buganda regions of Uganda between June 1, 2020, and June 30, 2022. All neonates younger than 1 month and children aged 1 month to 14 years were eligible for inclusion. We excluded neonates who were not sick but stayed in the maternity ward for routine postnatal care. The intervention involved clinical training, mentorship, and supportive supervision; provision of pulse oximeters and cylinder-based oxygen sources; biomedical-capacity support; and support to develop and disseminate oxygen supply strategies, oxygen therapy guidelines, and lists of essential oxygen supplies. Trained research assistants extracted individual patient data from case notes using a standardised electronic data collection form. Data were collected on health-facility details, age, sex, clinical signs and symptoms, admission diagnoses, pulse oximetry readings, oxygen therapy details, and final patient outcome. The primary outcome was the proportion of admitted neonates and children with a pulse oximetry oxygen saturation reading documented in their patient case notes on day 1 of health-facility admission (ie, pulse oximetry coverage). We used mixed-effects logistic regression to evaluate the effect of the intervention., Findings: We obtained data on 71 997 eligible neonates and children admitted to 31 participating health facilities; the primary analysis included 10 001 patients in the pre-intervention period (ie, June 1 to Oct 30, 2020) and 51 329 patients in the post-intervention period (ie, March 1, 2021, to June 30, 2022). Because 1356 patients had missing data for sex, 4365 (46·7%) of 9347 in the pre-intervention group and 22 831 (46·2%) of 49 410 in the post-intervention group were female; 4982 (53·3%) in the pre-intervention group and 26 579 (53·8%) in the post-intervention group were male. The proportion of neonates and children with pulse oximetry at admission increased from 2365 (23·7%) of 10 001 in the pre-intervention period to 45 029 (87·7%) of 51 328 in the post-intervention period. Adjusted analysis indicated greater likelihood of a patient receiving pulse oximetry during the post-intervention period compared with the pre-intervention period (adjusted odds ratio 40·10, 95% CI 37·38-42·93; p<0·0001)., Interpretation: Large-scale improvements in hospital oxygen services are achievable and have the potential to improve clinical outcomes. Governments should be encouraged to develop national oxygen plans and focus investment on interventions that have been shown to be effective, including the introduction of pulse oximetry into routine hospital care and clinical and biomedical mentoring and support., Funding: Bill & Melinda Gates Foundation and ELMA Philanthropies., Translations: For the Luganda and Lusoga translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests HRG is an adviser to the Lifebox Foundation and Unitaid and receives a salary from the University of Melbourne. YK, JM, BK, SE, DK, AZ, LNK, and FL were employed by Clinton Health Access Initiative during implementation of the oxygen programme in Uganda. YK, BK, SE, AZ, DK, and LNK received a salary from Clinton Health Access Initiative Uganda. CO is employed by the Ugandan Ministry of Health. FEK and FS receive a salary from Makerere University. HA declares no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO 2 ] 90-93%) and severe hypoxaemia (ie, SpO 2 <90%). We suggest that moderate hypoxaemia in the primary care setting should prompt careful clinical re-assessment, consideration of referral, and close follow-up. We provide practical guidance to better support front-line health-care workers to use pulse oximetry, including rethinking traditional binary SpO 2 thresholds and promoting a more nuanced approach to identification and emergency treatment of the severely ill child., Competing Interests: Declaration of interests All authors have received institutional fellowship or grant funding related to pulse oximetry and oxygen research, including funding to conduct the original studies reanalysed in this Viewpoint: Save the Children UK (AGF, TC, CK, and HRG); Bill & Melinda Gates Foundation (AGF, TD, HRG, YK, EDM, AHB, SA, and TC); ELMA Philantrophies (YK); Swedish Research Council (HH, CK, and EDM); Einhorn Family Foundation (HH); Wellcome Trust (TC, CK, and EDM); National Institutes of Health (EDM and SH); WHO (TC, EDM, AHB, SA, and TC); United States Agency for International Development (EDM); US Centers for Disease Control and Prevention (EDM); Thrasher Research Fund (EDM); Moderna (EDM); National Health and Medical Research Council (HRG); and Royal Children's Hospital Foundation (HRG). YK is employed by Clinton Health Access Initiative, which contributes to global pulse oximetry and oxygen strategy. TC has received consulting fees from the UN and chairs a steering committee for an adolescent mental health trial in Nepal. HRG and EDM have served as advisers to the Tools for Integrated Management of Childhood Illness–Améliorer l'Identification des détresses Respiratoires chez l'Enfant (AIRE) pulse oximetry trial. EDM co-chairs the Union Child Pneumonia Working Group; HRG and CK co-chair the Lancet Global Health Commission on Medical Oxygen. AGF and HRG are board members for Oxygen for Life Initiative, a non-profit research and implementation group for pulse oximetry and oxygen. HRG, CK, and EDM have served as advisers to Lifebox Foundation, a non-governmental organisation that aims to increases access to pulse oximetry., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)