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Background and aimWith the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times.MethodsWe searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.ResultsOf 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06–0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38–1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07–1.30, p < 0.00001). There was “very low” certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain.InterpretationThe COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain.Systematic review registration[https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256].

ContextChildren with Down syndrome are at risk for obstructive sleep apnea, which may not be resolved by adenotonsillecotmy, as well as other respiratory disorders that may impact breathing during sleep. Long-term non-invasive ventilation, including continuous and bilevel positive airway pressure delivery, is an alternate treatment strategy.ObjectiveTo assess the use and outcomes of long-term non-invasive ventilation in children with Down syndrome including comparison to other children using long-term non-invasive ventilation.Data SourcesThe search strategy for the scoping review used Medical Subject Headings (MeSH) and free-text terms for “child” and “non-invasive ventilation.” MEDLINE (Ovid), Embase (Ovid), CINAHL (Ebsco), Cochrane Library (Wiley), and PubMed databases were searched (1990-2021).Study SelectionThe scoping review results were searched to identify studies including data on at least three children with Down Syndrome using long-term non-invasive ventilation.Data ExtractionStudy characteristics, subject characteristics, technology type, and outcome measurements were extracted.ResultsA total of 28 articles included 543 children with Down syndrome using long-term non-invasive ventilation. Children with Down syndrome accounted for 18% of children using long-term non-invasive ventilation. Data on efficacy, feasibility, and adherence in children with Down syndrome are comparable to other children. Children with Down syndrome may have greater difficulty initiating long-term non-invasive ventilation, longer time to establish use, and a higher rate of inability to establish use. Outcome data is limited but suggest favorable impact on cardiac function and attention.LimitationsArticles related to long-term non-invasive ventilation use in adolescents and young adults may have been excluded.ConclusionsChildren with Down syndrome make up a significant portion of the population of children using long-term non-invasive ventilation. While there is more limited data available with respect to the use and outcomes for children with Down syndrome compared to the other children, long-term non-invasive ventilation is an effective and well-tolerated therapy with no clear differences in the use or outcomes for children with Down syndrome. Additional work is needed to understand potential challenges around establishing long-term non-invasive ventilation use in children with Down syndrome.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=206533, identifier: CRD206533.