Medicine (Austin & Northern Health) - Research Publications

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    Prior sleep-wake behavior predicts mental health resilience among adults in the United States during the COVID-19 pandemic
    Czeisler, M ; Capodilupo, E ; Weaver, M ; Czeisler, C ; Howard, M ; Rajaratnam, SMW ( 2021-06-22)
    Rigorous nonpharmaceutical interventions (e.g., stay-at-home orders, remote-work directives) were implemented in early 2020 for coronavirus disease 2019 (COVID-19) pandemic containment in the U.S. During this time, increased sleep duration and delayed sleep timing were reported through surveys (Leone et al., 2021) and wearable data (Rezaei and Grandner, 2021), as were elevated adverse mental health symptom (Czeisler et al., 2020). Inter-relationships between sleep and mental health have not been examined using longitudinal objective sleep-wake data, during these abruptly imposed lifestyle changes. We examined objective sleep-wake data and surveyed mental health data collected among 4,912 U.S. adult users of a validated sleep wearable (WHOOP, Boston, Massachusetts) before and during the COVID-19 pandemic. Comparing the pre-pandemic (January 1 to March 12, 2020) and acute pandemic-onset intervals (March 13 to April 12, 2020), participants exhibited increased mean sleep duration (0.25h [95% CI = 0.237-0.270]), later sleep onset (18m [17.378-20.045]) and offset (36m [35.111-38.106]), and increased consistency of sleep timing (3.51 [3.295-3.728] out of 100); all P < 0.0001. Generally, participants with persistent sleep deficiency and low sleep consistency had higher odds of symptoms of anxiety or depression, burnout, and new or increased substance use during the pandemic. Decreases in sleep duration (adjusted odds ratio [aOR] = 1.30, 95% CI = 1.03-1.65, P = 0.025) and sleep consistency (2.05 [1.17-3.67], P = 0.009) were associated with increased anxiety and depression symptoms during the pandemic. We suggest that sleep duration and consistency may be important predictors of risk of adverse mental health outcomes during a pandemic. M.J. Leone, M. Sigman, D.A. Golombek. Effects of lockdown on human sleep and chronotype during the COVID-19 pandemic. Curr Biol 30 (16), R930–R931 (2020). N. Rezaei N, M.A. Grandner. Changes in sleep duration, timing, and variability during the COVID-19 pandemic: Large-scale Fitbit data from 6 major US cities. Sleep Health 10.1016/j.sleh.2021.02.008. (2021). M.É. Czeisler, R.I. Lane, E. Petrosky, et al., Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic - United States, June 24-30, 2020. MMWR Morb Mortal Wkly Rep 69 (32), 1049–1057 (2020).

    Significance Statement

    The coronavirus disease 2019 (COVID-19) pandemic has had profound effects on health, including increased sleep duration and worsened mental health. We examined associations between (1) objective sleep-wake data before and during the COVID-19 pandemic and (2) adverse mental health symptoms and substance use among users of a validated sleep wearable. We found that, in general, participants with persistent sleep deficiency and low sleep consistency had higher odds of symptoms of anxiety or depression, new or increased substance use, and burnout. Our findings suggest that sleep of sufficient duration and consistent timing are associated with mental health resilience, exemplified in this case by the impact of the pandemic and related abrupt lifestyle changes on adverse mental health symptoms.
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    COVID-19 Vaccine Intentions in the United States—December 2020 to March 2021
    Czeisler, M ; Rajaratnam, SMW ; Howard, M ; Czeisler, C ( 2021-05-17)


    SARS-CoV-2 containment is estimated to require attainment of high (>80%) post-infection and post-vaccination population immunity.


    To assess COVID-19 vaccine intentions among US adults and their children, and reasons for vaccine hesitancy among potential refusers.


    Internet-based surveys were administered cross-sectionally to US adults during December 2020 and February to March 2021 (March-2021).


    Surveys were administered through Qualtrics using demographic quota sampling.


    A large, demographically diverse sample of 10,444 US adults (response rate, 63.9%).

    Main Outcomes and Measures

    COVID-19 vaccine uptake, intentions, and reasons for potential refusal. Adults living with or caring for children aged 2 to 18 years were asked about their intent to have their children vaccinated. Multivariable weighted logistic regression models were used to estimate adjusted odds ratios for vaccine refusal.


    Of 5256 March-2021 respondents, 3467 (66.0%) reported they would definitely or most likely obtain a COVID-19 vaccine as soon as possible (ASAP Obtainers), and an additional 478 (9.1%) reported they were waiting for more safety and efficacy data before obtaining the vaccine. Intentions for children and willingness to receive a booster shot largely matched personal COVID-19 vaccination intentions. Vaccine refusal (ie, neither ASAP Obtainers nor waiting for more safety and efficacy data) was most strongly associated with not having obtained an influenza vaccine in 2020 (adjusted odds ratio, 4.11 [95% CI, 3.05-5.54]), less frequent mask usage (eg, rarely or never versus always or often, 3.92 [2.52-6.10]) or social gathering avoidance (eg, rarely or never versus always or often, 2.65 [1.95-3.60]), younger age (eg, aged 18-24 versus over 65 years, 3.88 [2.02-7.46]), and more conservative political ideology (eg, very conservative versus very liberal, 3.58 [2.16-5.94]); all P <.001.

    Conclusions and Relevance

    Three-quarters of March-2021 respondents in our large, demographically diverse sample of US adults reported they would likely obtain a COVID-19 vaccine, and 60% of adults living with or caring for children plan to have them vaccinated as soon as possible. With an estimated 27% of the US population having been infected with SARS-CoV-2, once vaccines are available to children and they have been vaccinated, combined post-infection and post-vaccination immunity will approach 80% of the US population in 2021, even without further infections.

    Key Points


    What are COVID-19 vaccines intentions, for adults and for children under their care?


    Two-thirds of 5256 US adults surveyed in early 2021 indicated they would obtain a COVID-19 vaccine as soon as possible. Intentions for children and booster vaccines largely matched personal vaccine intentions. Refusal was more common among adults who were younger, female, Black, very politically conservative, less educated, less adherent with COVID-19 prevention behaviors (eg, wearing masks), had more medical mistrust, or had not received influenza vaccines in 2020.


    Tailored vaccine promotion efforts and vaccine programs may improve vaccine uptake and contribute to US immunity against COVID-19.
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    Mental Health, Substance Use, and Suicidal Ideation Among Unpaid Caregivers in the United States During the COVID-19 Pandemic: Relationships to Age, Race/Ethnicity, Employment, and Caregiver Intensity
    Czeisler, M ; Drane, A ; Winnay, S ; Capodilupo, E ; Czeisler, C ; Rajaratnam, SMW ; Howard, M ( 2021-02-05)


    To estimate the prevalence of unpaid caregiving during the coronavirus disease 2019 (COVID-19) pandemic, and to identify factors associated with adverse mental health symptoms, substance use, and suicidal ideation in this population, which provides critical support in health care systems by providing care to older adults and those with chronic conditions.


    In June 2020, Internet-based surveys with questions about demographics, caregiving responsibilities, and mental health were administered to US adults aged ≥18 years. Demographic quota sampling and survey weighting to improve cross-sectional sample representativeness of age, gender, and race/ethnicity. Prevalence ratios for adverse mental health symptoms were estimated using multivariable Poisson regressions.


    Of 9,896 eligible invited adults, 5,412 (54.7%) completed surveys; 5,011 (92.6%) respondents met screening criteria and were analysed, including 1,362 (27.2%) caregivers. Caregivers had higher prevalences of adverse mental health symptoms than non-caregivers, including anxiety or depressive disorder symptoms (57.6% vs 21.5%, respectively, p<0.0001) having recently seriously considered suicide (33.4% vs 3.7%, p<0.0001). Symptoms were more common among caregivers who were young vs older adults (e.g., aged 18–24 vs ≥65 years, aPR 2.75, 95% CI 1.95–3.88, p<0.0001), Hispanic or Latino vs non-Hispanic White (1.14, 1.04–1.25, p=0.0044), living with vs without disabilities (1.18, 1.10–1.26, p<0.0001), and with moderate and high vs low Caregiver Intensity Index scores (2.31, 1.65–3.23; 2.81, 2.00–3.94; both p<0.0001). Suicidal ideation was more prevalent among non-Hispanic Black vs non-Hispanic White caregivers (1.48, 1.15–1.90, p=0.0022).


    Caregivers, who accounted for one in four US adult respondents in this nationally representative sample, more commonly reported adverse mental health symptoms than non-caregivers. Increased visibility of and access to mental health care resources are urgently needed to address mental health challenges of caregiving.
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    Systematic analysis of key parameters for genomics-based real-time detection and tracking of multidrug-resistant bacteria
    Gorrie, C ; Da Silva, AG ; Ingle, D ; Higgs, C ; Seemann, T ; Stinear, T ; Williamson, D ; Kwong, J ; Grayson, L ; Sherry, N ; Howden, B ( 2020-09-25)
    Background: Pairwise single nucleotide polymorphisms (SNPs) are a cornerstone for genomic approaches to multidrug-resistant organisms (MDROs) transmission inference in hospitals. However, the impact of key analysis parameters on these inferences has not been systematically analysed. Methods: We conducted a multi-hospital 15-month prospective study, sequencing 1537 MDRO genomes for comparison; methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus faecium , and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae . We systematically assessed the impact of sample and reference genome diversity, masking of prophage and regions of recombination, cumulative genome analysis compared to a three-month sliding-window, and the comparative effects each of these had when applying a SNP threshold for inferring likely transmission (≤15 SNPs for S. aureus , ≤25 for other species). Findings: Across the species, using a reference genome of the same sequence type provided a greater degree of pairwise SNP resolution, compared to species and outgroup-reference alignments that typically resulted in inflated SNP distances and the possibility of missed transmission events. Omitting prophage regions had minimal impacts, however, omitting recombination regions a highly variable effect, often inflating the number of closely related pairs. Estimating pairwise SNP distances was more consistent using a sliding-window than a cumulative approach. Interpretation: The use of a closely-related reference genome, without masking of prophage or recombination regions, and a sliding-window for isolate inclusion is best for accurate and consistent MDRO transmission inference. The increased stability and resolution provided by these approaches means SNP thresholds for putative transmission inference can be more reliably applied among diverse MDROs. Funding: This work was supported by the Melbourne Genomics Health Alliance (funded by the State Government of Victoria, Department of Health and Human Services, and the ten member organizations); an National Health and Medical Research Council (Australia) Partnership grant (GNT1149991) and individual grants from National Health and Medical Research Council (Australia) to NLS (GNT1093468), JCK (GNT1008549) and BPH (GNT1105905).
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    Guidelines on the Diagnosis, Clinical Assessments, Treatment and Management for CLN2 Disease Patients
    Mole, S ; Schulz, A ; Badoe, E ; Berkovic, S ; Reyes, EDL ; Dulz, S ; Gissen, P ; Gilbert, N ; Lourenco, C ; Mink, J ; Murphy, N ; Nickel, M ; Olaya, J ; Scarpa, M ; Scheffer, I ; Simonati, A ; Specchio, N ; Von Lobbecke, I ; Wang, R ; Williams, R ( 2020-10-28)


    CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2), or Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL), is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition.


    An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.


    : Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality).


    This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease. This addresses the clinical need to complement other information available.