Coronavirus disease 2019 has caused a marked increase in all-cause deaths in the US, mostly among older adults. 1 Although the burden of COVID-19 among hospitalized younger adults has been described, fewer data focus on mortality in this demographic, owing to lower case-fatality rates. 2 Excess mortality reflects the full burden of the pandemic that may go uncaptured due to uncoded COVID-19 and other pandemic-related deaths. Accordingly, we examined allcause excess mortality and COVID-19-related mortality during the early pandemic period among adults aged 25 to 44 years. Because unintentional drug overdoses are the usual leading cause of death in this demographic, COVID-19 deaths were compared with unintentional opioid deaths.Methods | To determine excess mortality (the gap between observed and expected deaths), projected monthly expected deaths for 2020 were calculated by applying autoregressive integrated moving averages to US population and mortality counts (2015)(2016)(2017)(2018)(2019). 3 We examined 2020 population and seasonal autoregressive integrated moving averages for each of the 10 US Department of Health and Human Services (HHS) regions, which comprise the entire US and are the smallest subdivisions for which 2020 age-stratified COVID-19 mortality data are currently available from the National Center for Health Statistics. Population covariates were used to calculate 95% CIs for expected deaths.Observed all-cause mortality and COVID-19 mortality (coded as either "underlying cause" or "multiple cause" of death) for March 1, 2020, to July 31, 2020, were obtained from provisional National Center for Health Statistics data (released October 28, 2020). 4 Unintentional opioid overdose death counts (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes X41-X44, Y11-Y15, and T40.0-6) for the corresponding period of 2018 (the most recently available data) were assembled for each HHS region. 3 Incident rates per 100 000 person-months with 95% CIs were calculated for COVID-19 and unintentional opioid deaths using SAS, version 9.4. Statistical significance was defined as a 95% CI that excluded the null value.This study used publicly available data and was not subject to institutional review approval.

The initial COVID-19 outbreak in the US caused disruptions in usual behavioral patterns. [1][2][3] To assess associated changes in external causes of death, we analyzed monthly trends from 2015 to 2020 in deaths resulting from drug overdoses, homicide, unintentional injuries, motor vehicle crashes, and suicide in the first 6 months of the pandemic. 4074 3576 (3263-3889) 1.14 (1.05-1.25) August 4182 3624 (3304-3943) 1.15 (1.06-1.27) Total 21 050 20 325 (18 510-22 140) 1.04 (0.95-1.14) Suicide March 3933 4196 (3996-4396) 0.94 (0.89-0.98) April 3447 4118 (3893-4344) 0.84 (0.79-0.89) May 3742 4289 (4057-4521) 0.87 (0.83-0.92) June 3951 4246 (4012-4480) 0.93 (0.88-0.98) July 4126 4377 (4143-4611) 0.94 (0.89-1) August 3973 4377 (4143-4612) 0.91 (0.86-0.96) Total 23 172 25 604 (24 243-26 964) 0.91 (0.86-0.96) Abbreviation: OER, observed-to-expected ratios.

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Background: All-cause excess mortality (the number of deaths that exceed projections in any period) has been widely reported during the Covid-19 pandemic. Whether excess mortality has occurred during the Delta wave is less well understood. Methods: We performed an observational study using data from the Massachusetts Department of Health. Five years of US Census population data and CDC mortality statistics were applied to a seasonal autoregressive integrated moving average (sARIMA) model to project the number of expected deaths for each week of the pandemic period, including the Delta period (starting in June 2021, extending through August 28th 2021, for which mortality data are >99% complete). Weekly Covid-19 cases, Covid-19-attributed deaths, and all-cause deaths are reported. County-level excess mortality during the vaccine campaign are also reported, with weekly rates of vaccination in each county that reported 100 or more all-cause deaths during any week included in the study period. Results: All-cause mortality was not observed after March 2021, by which time over 75% of persons over 65 years of age in Massachusetts had received a vaccination. Fewer deaths than expected (which we term 'deficit mortality') occurred both during the summer of 2020, the spring of 2021 and during the Delta wave (beginning June 13, 2021 when Delta isolates represented >10% of sequenced cases). After the initial wave in the spring of 2020, more Covid-19-attributed deaths were recorded that all-cause excess deaths, implying that Covid-19 was misattributed as the underlying cause, rather than a contributing cause of death in some cases. Conclusion: In a state with high vaccination rates, excess mortality has not been recorded during the Delta period. Deficit mortality has been recorded during this period.

BackgroundDespite approximately 55.9 million annual mild traumatic brain injuries (mTBIs) worldwide, the accurate diagnosis of mTBI continues to challenge clinicians due to symptom ambiguity, reliance on subjective report and presentation variability. Non-invasive fluid biomarkers of mTBI offer a biological measure to diagnose and monitor mTBI without the need for blood draws or neuroimaging. The objective of this study is to systematically review the utility of such biomarkers to diagnose mTBI and predict disease progression.MethodsA systematic review performed in PubMed, Scopus, Cochrane and Web of Science followed by a manual search of references without a specified timeframe. Search strings were generated and run (27 June 2022) by a research librarian. Studies were included if they: (1) included human mTBI subjects, (2) assessed utility of a non-invasive biomarker and (3) published in English. Exclusion criteria were (1) non-mTBI subjects, (2) mTBI not assessed separately from moderate/severe TBI, (3) required intracranial haemorrhage or (4) solely assesses genetic susceptibility to mTBI.ResultsA total of 29 studies from 27 subject populations (1268 mTBI subjects) passed the inclusion and exclusion criteria. Twelve biomarkers were studied. Salivary RNAs, including microRNA, were assessed in 11 studies. Cortisol and melatonin were assessed in four and three studies, respectively. Eight salivary and two urinary biomarkers contained diagnostic or disease monitoring capability.DiscussionThis systematic review identified several salivary and urinary biomarkers that demonstrate the potential to be used as a diagnostic, prognostic and monitoring tool for mTBI. Further research should examine miRNA-based models for diagnostic and predictive utility in patients with mTBI.PROSPERO registration numberCRD42022329293.