ABSTRACT
Importance: Epigenetic age acceleration is associated with exposure to social and economic adversity and may increase the risk of premature morbidity and mortality. However, no studies have included measures of structural racism, and few have compared estimates within or across the first and second generation of epigenetic clocks. Objective: To determine whether epigenetic age acceleration is positively associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods. Design, Setting, and Participants: This cross-sectional study used data from the My Body My Story (MBMS) study between August 8, 2008, and December 31, 2010, and examination 5 of the Multi-Ethnic Atherosclerosis Study (MESA) from April 1, 2010, to February 29, 2012. In the MBMS, DNA extraction was performed in 2021; linkage of structural measures to the MBMS and MESA, in 2022. US-born individuals were randomly selected from 4 community health centers in Boston, Massachusetts (MBMS), and 4 field sites in Baltimore, Maryland; Forsyth County, North Carolina; New York City, New York; and St Paul, Minnesota (MESA). Data were analyzed from November 13, 2021, to August 31, 2023. Main Outcomes and Measures: Ten epigenetic clocks (6 first-generation and 4 second-generation), computed using DNA methylation data (DNAm) from blood spots (MBMS) and purified monocytes (MESA). Results: The US-born study population included 293 MBMS participants (109 men [37.2%], 184 women [62.8%]; mean [SD] age, 49.0 [8.0] years) with 224 Black non-Hispanic and 69 White non-Hispanic participants and 975 MESA participants (492 men [50.5%], 483 women [49.5%]; mean [SD] age, 70.0 [9.3] years) with 229 Black non-Hispanic, 191 Hispanic, and 555 White non-Hispanic participants. Of these, 140 (11.0%) exhibited accelerated aging for all 5 clocks whose estimates are interpretable on the age (years) scale. Among Black non-Hispanic MBMS participants, epigenetic age acceleration was associated with being born in a Jim Crow state by 0.14 (95% CI, 0.003-0.27) SDs and with birth state conservatism by 0.06 (95% CI, 0.01-0.12) SDs, pooling across all clocks. Low parental educational level was associated with epigenetic age acceleration, pooling across all clocks, for both Black non-Hispanic (0.24 [95% CI, 0.08-0.39] SDs) and White non-Hispanic (0.27 [95% CI, 0.03-0.51] SDs) MBMS participants. Adult impoverishment was positively associated with the pooled second-generation clocks among the MESA participants (Black non-Hispanic, 0.06 [95% CI, 0.01-0.12] SDs; Hispanic, 0.07 [95% CI, 0.01-0.14] SDs; White non-Hispanic, 0.05 [95% CI, 0.01-0.08] SDs). Conclusions and Relevance: The findings of this cross-sectional study of MBMS and MESA participants suggest that epigenetic age acceleration was associated with racialized and economic injustice, potentially contributing to well-documented inequities in premature mortality. Future research should test the hypothesis that epigenetic accelerated aging may be one of the biological mechanisms underlying the well-documented elevated risk of premature morbidity and mortality among social groups subjected to racialized and economic injustice.
Subject(s)
Aging , Epigenesis, Genetic , Epigenomics , Humans , Male , Female , Cross-Sectional Studies , Middle Aged , Epigenomics/methods , Aging/genetics , Aged , Epigenesis, Genetic/genetics , United States , Racism/statistics & numerical data , Adult , Social Justice , Socioeconomic Factors , Aged, 80 and overABSTRACT
Background: Epigenetic Age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional - using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (i) their choice of model; (ii) the primary outcome (EA vs. EAA); and (iii) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA. Results: Our simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered an accelerated EA rate in males and an advanced EA that decelerates over time in children with higher birthweight. Conclusion: Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.
ABSTRACT
Peripheral intravenous cannulation and venipuncture are among the most common invasive procedures in health care and are not without risks or complications. The aim of this study was to evaluate the current training provided to nursing and midwifery undergraduate students. Student knowledge, attitude, practice, and performance regarding these procedural skills were assessed. A knowledge, attitude, and practices survey was disseminated to final year nursing and midwifery students as the first phase of this study. For the second phase of the study, nursing students were video recorded and then observed performing the skill of peripheral intravenous cannulation in a simulated environment. Thirty-eight nursing and midwifery students completed the survey, and 66 nursing students participated in the observation study. Descriptive statistics were performed. The mean knowledge score was 7.2 out of 15.0, (standard deviation [SD] = 2.4), and the mean attitude score was 10.20 out of 18.00 (SD = 4.79). Qualitative data from the survey were categorized to demonstrate specific areas of focus for improving the training. The mean performance score was 16.20 out of 28.00 (SD = 2.98). This study provides valuable input to developing and enhancing evidence-based curricula. It can help educators and supervisors, in both academic and clinical settings, identify areas where clinical performance and education could be enhanced.
Subject(s)
Health Knowledge, Attitudes, Practice , Students, Nursing , Humans , Catheterization , Education, Nursing, Baccalaureate/methods , Phlebotomy , Surveys and QuestionnairesABSTRACT
BACKGROUND: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays. OBJECTIVES: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity. METHODS: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses. RESULTS: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity. CONCLUSIONS: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises.
Subject(s)
Aortic Valve Stenosis , COVID-19 , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Pandemics , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/epidemiology , Treatment Outcome , COVID-19/epidemiology , Registries , Risk FactorsABSTRACT
BACKGROUND: Independent testing of home blood pressure (BP) measurement (HBPM) devices is often lacking, particularly among older and multi-morbid patients. METHODS: We studied the Bpro G2 (using tonometry), Omron HeartGuide (using occlusive oscillometric technology), and Heartisans (using photoplethysmography) wrist watch HBPM devices against a gold standard brachial sphygmomanometer. To test device performance, we used the ISO81060-2 protocol (though this protocol cannot formally validate cuffless devices). We also used linear mixed models to compare adjusted longitudinal BP measurements between devices. Finally, as a surrogate for usability, we recorded instances of device failure where no BP measurement was returned. RESULTS: We enrolled 128 participants (median [Q1-Q3] age 53 [40-65] years, 51% male, 46% on antihypertensive drugs), of whom 100 were suitable for the primary analysis. All three devices had mean BP values within 5 mmHg of sphygmomanometry. However, due to insufficient reliability (e.g., wider than accepted standard deviations of mean BP), none of the three devices passed all criteria required by the ISO81060-2 protocol. In adjusted longitudinal analyses, the Omron device also systematically underestimated systolic and diastolic BP (- 8.46 mmHg; 95% CI 6.07, 10.86; p < 0.001; and - 2.53 mmHg; 95% CI - 4.03, - 1.03; p = 0.001; respectively). Nevertheless, compared to the Omron device, BPro and Heartisans devices had increased odds of failure (BPro: odds ratio [OR] 5.24; p < 0.0001; Heartisans: OR 5.61; p < 0.001). CONCLUSIONS: While we could not formally validate the cuffless devices, our results show that wearable technologies will require improvements to offer reliable BP assessment. This study also highlights the need for validation protocols specifically designed for cuffless BP measurement technologies.
ABSTRACT
Importance: DNA methylation (DNAm) provides a plausible mechanism by which adverse exposures become embodied and contribute to health inequities, due to its role in genome regulation and responsiveness to social and biophysical exposures tied to societal context. However, scant epigenome-wide association studies (EWAS) have included structural and lifecourse measures of exposure, especially in relation to structural discrimination. Objective: Our study tests the hypothesis that DNAm is a mechanism by which racial discrimination, economic adversity, and air pollution become biologically embodied. Design: A series of cross-sectional EWAS, conducted in My Body My Story (MBMS, biological specimens collected 2008-2010, DNAm assayed in 2021); and the Multi Ethnic Study of Atherosclerosis (MESA; biological specimens collected 2010-2012, DNAm assayed in 2012-2013); using new georeferenced social exposure data for both studies (generated in 2022). Setting: MBMS was recruited from four community health centers in Boston; MESA was recruited from four field sites in: Baltimore, MD; Forsyth County, NC; New York City, NY; and St. Paul, MN. Participants: Two population-based samples of US-born Black non-Hispanic (Black NH), white non-Hispanic (white NH), and Hispanic individuals (MBMS; n=224 Black NH and 69 white NH) and (MESA; n=229 Black NH, n=555 white NH and n=191 Hispanic). Exposures: Eight social exposures encompassing racial discrimination, economic adversity, and air pollution. Main outcome: Genome-wide changes in DNAm, as measured using the Illumina EPIC BeadChip (MBMS; using frozen blood spots) and Illumina 450k BeadChip (MESA; using purified monocytes). Our hypothesis was formulated after data collection. Results: We observed the strongest associations with traffic-related air pollution (measured via black carbon and nitrogen oxides exposure), with evidence from both studies suggesting that air pollution exposure may induce epigenetic changes related to inflammatory processes. We also found suggestive associations of DNAm variation with measures of structural racial discrimination (e.g., for Black NH participants, born in a Jim Crow state; adult exposure to racialized economic residential segregation) situated in genes with plausible links to effects on health. Conclusions and Relevance: Overall, this work suggests that DNAm is a biological mechanism through which structural racism and air pollution become embodied and may lead to health inequities.
ABSTRACT
Epigenetic clocks are increasingly being used as a tool to assess the impact of a wide variety of phenotypes and exposures on healthy ageing, with a recent focus on social determinants of health. However, little attention has been paid to the sociodemographic characteristics of participants on whom these clocks have been based. Participant characteristics are important because sociodemographic and socioeconomic factors are known to be associated with both DNA methylation variation and healthy ageing. It is also well known that machine learning algorithms have the potential to exacerbate health inequities through the use of unrepresentative samples - prediction models may underperform in social groups that were poorly represented in the training data used to construct the model. To address this gap in the literature, we conducted a review of the sociodemographic characteristics of the participants whose data were used to construct 13 commonly used epigenetic clocks. We found that although some of the epigenetic clocks were created utilizing data provided by individuals from different ages, sexes/genders, and racialized groups, sociodemographic characteristics are generally poorly reported. Reported information is limited by inadequate conceptualization of the social dimensions and exposure implications of gender and racialized inequality, and socioeconomic data are infrequently reported. It is important for future work to ensure clear reporting of tangible data on the sociodemographic and socioeconomic characteristics of all the participants in the study to ensure that other researchers can make informed judgements about the appropriateness of the model for their study population.
ABSTRACT
The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its effects via soft robotic actuations. Occlusion of the FSDSR porous membrane was monitored over 7 days in a rodent model using electrochemical impedance spectroscopy. The electrical resistance of the fibrotic capsule correlated to its increase in thickness and volume. Our FibroSensing membrane showed great sensitivity in detecting changes at the abiotic/biotic interface, such as collagen deposition and myofibroblast proliferation. The potential of the FSDSR to overcome fibrotic capsule formation and maintain constant drug dosing over time was demonstrated in silico and in vitro. Controlled closed loop release of methylene blue into agarose gels (with a comparable fold change in permeability relating to 7 and 28 days in vivo) was achieved by adjusting the magnitude and frequency of pneumatic actuations after impedance measurements by the FibroSensing membrane. By sensing fibrotic capsule formation in vivo, the FSDSR will be capable of probing and adapting to the foreign body response through dynamic actuation changes. Informed by real-time sensor signals, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrotic capsule formation.
Subject(s)
Foreign Bodies , Robotics , Humans , Drug Delivery Systems , Electric Impedance , Methylene BlueABSTRACT
BACKGROUND: Time-sensitive emergencies in areas of low population density have statistically poorer outcomes. This includes incidents of major trauma. This study assesses the effect that population density at a receiving hospital of a major trauma patient has on survival. METHODS: Patients meeting Trauma Audit Research Network criteria for major trauma from 2016 to 2020 in Ireland were included in this retrospective observational study. Incident data were retrieved from the Major Trauma Audit, while data on population density were calculated from Irish state sources. The primary outcome measure of survival to discharge was compared to population density using logistic regression, adjusted for demographic and incident variables. Records were divided into population density tertiles to assess for between-group differences in potential predictor variables. RESULTS: Population density at a receiving hospital had no impact on mortality in Irish major trauma patients from our logistic regression model (OR = 1.01, 95% CI 0.98-1.05, p = 0.53). Factors that did have an impact were age, Charlson Comorbidity Index, Injury Severity Score, and the presence of an Orthopaedic Surgery service at the receiving hospital (all p < 0.001). Age and Charlson Comorbidity Index differed slightly by population density tertile; both were higher in areas of high population density (all p < 0.001). CONCLUSIONS: Survival to discharge in Irish major trauma patients does not differ substantially based on population density. This is an important finding as Ireland moves to a new trauma system, with features based on population distribution. An Orthopaedic Surgery service is an important feature of a major trauma receiving hospital and its presence improves outcomes.
Subject(s)
Patient Discharge , Wounds and Injuries , Humans , Ireland/epidemiology , Population Density , Logistic Models , Injury Severity Score , Retrospective Studies , Wounds and Injuries/epidemiology , Wounds and Injuries/therapyABSTRACT
BACKGROUND: Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study. METHODS: We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. FINDINGS: Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. INTERPRETATION: These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity. FUNDING: Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.
Subject(s)
Adverse Childhood Experiences , Male , Adult , Female , Child , Humans , Adolescent , Infant, Newborn , Infant , Child, Preschool , Longitudinal Studies , Prospective Studies , Canada , Parents , Epigenesis, GeneticABSTRACT
OBJECTIVES: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.
Subject(s)
Heart Failure , Heart-Assist Devices , Adult , Humans , Heart-Assist Devices/adverse effects , Simendan , Propensity Score , Retrospective Studies , Heart Failure/drug therapy , Heart Failure/surgery , Registries , Treatment OutcomeABSTRACT
Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity different from the same isotype in whole serum, probably due to competition from the other isotypes present. Using purified antibody isotypes from naïve Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with binding to the S region S1 expressed in insect cells (S1 Sf21) significant for IgG, IgA, and IgM. Assessing longitudinal response for constant concentrations of purified antibody isotypes for a patient subset demonstrated that the relative proportion of antigen-specific IgGs decreased over time for severe disease, but the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen-specific serum IgA and IgM playing a role in maintaining longer-term protection, important for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Immunoglobulin M , Antibodies, Viral , Immunoglobulin G , Nucleocapsid Proteins , Immunoglobulin A , Patient Acuity , Spike Glycoprotein, CoronavirusABSTRACT
Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation (DNAm) patterns), we report on 3 different approaches in the epidemiologic literature-1 incorrect and 2 correct-on the treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%) or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introduced by use of the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias towards the null, and we discuss implications for extant research and recommendations for best practices.
Subject(s)
Aging , Epigenesis, Genetic , Humans , Aging/genetics , DNA Methylation , Epigenomics , Body Mass IndexABSTRACT
OBJECTIVES: There has been a steady increase in the number of studies of the complex relationship between glucose and electrical cardiac activity which use simultaneous continuous glucose monitors (CGM) and continuous electrocardiogram (ECG). However, data collected on the same individual tend to be similar (yielding correlated or dependent data) and require analyses that take into account that correlation. Many opt for simplified techniques such as calculating one measure from the data collected and analyse one observation per subject. These simplified methods may yield inconsistent and biased results in some instances. In this systematic review, we aim to examine the adequacy of the statistical analyses performed in such studies and make recommendations for future studies. RESEARCH QUESTIONS: What are the objectives of studies collecting simultaneous CGM and ECG data? Do methods used in analysing CGM and continuous ECG data fully optimise the data collected? DESIGN: Systematic review. DATA SOURCES: PubMed and Web of Science. METHODS: A comprehensive search of the PubMed and Web of Science databases to June 2022 was performed. Studies utilising CGM and continuous ECG simultaneously in people with diabetes were included. We extracted information about study objectives, technologies used to collect data and statistical analysis methods used for analysis. Reporting was done following PRISMA guidelines. RESULTS: Out of 118 publications screened, a total of 31 studies met the inclusion criteria. There was a diverse array of study objectives, with only two studies exploring the same exposure-outcome relationship, allowing only qualitative analysis. Only seven studies (23%) incorporated methods which fully utilised the study data using methods that yield the correct power and minimize type I error rate. The rest (77%) used analyses that summarise the data first before analysis and/or totally ignored data dependency. Of those who applied more advanced methods, one study performed both simple and correct analyses and found that ignoring data structure resulted in no association whilst controlling for repeated measures yielded a significant relationship. CONCLUSION: Most studies underutilised statistical methods suitable for analysis of dynamic continuous data, potentially attenuating their statistical power and overall conclusions. We recommend that aggregated data be used only as exploratory analysis, while primary analysis should use methods applied to the raw data such as mixed models or functional data analyses. These methods are widely available in many free, open source software applications.
Subject(s)
Blood Glucose , Diabetes Mellitus , Humans , Blood Glucose/analysis , Electrocardiography, Ambulatory , Blood Glucose Self-Monitoring/methodsABSTRACT
In the face of the global pandemic caused by the disease COVID-19, researchers have increasingly turned to simple measures to detect and monitor the presence of the disease in individuals at home. We sought to determine if measures of neuromotor coordination, derived from acoustic time series, as well as phoneme-based and standard acoustic features extracted from recordings of simple speech tasks could aid in detecting the presence of COVID-19. We further hypothesized that these features would aid in characterizing the effect of COVID-19 on speech production systems. A protocol, consisting of a variety of speech tasks, was administered to 12 individuals with COVID-19 and 15 individuals with other viral infections at University Hospital Galway. From these recordings, we extracted a set of acoustic time series representative of speech production subsystems, as well as their univariate statistics. The time series were further utilized to derive correlation-based features, a proxy for speech production motor coordination. We additionally extracted phoneme-based features. These features were used to create machine learning models to distinguish between the COVID-19 positive and other viral infection groups, with respiratory- and laryngeal-based features resulting in the highest performance. Coordination-based features derived from harmonic-to-noise ratio time series from read speech discriminated between the two groups with an area under the ROC curve (AUC) of 0.94. A longitudinal case study of two subjects, one from each group, revealed differences in laryngeal based acoustic features, consistent with observed physiological differences between the two groups. The results from this analysis highlight the promise of using nonintrusive sensing through simple speech recordings for early warning and tracking of COVID-19.
Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , Speech/physiology , Acoustics , Noise , Speech Production Measurement/methodsABSTRACT
BACKGROUND: Acute kidney injury (AKI) is a frequent and severe complication of both COVID-19-related acute respiratory distress syndrome (ARDS) and non-COVID-19-related ARDS. The COVID-19 Critical Care Consortium (CCCC) has generated a global data set on the demographics, management and outcomes of critically ill COVID-19 patients. The LUNG-SAFE study was an international prospective cohort study of patients with severe respiratory failure, including ARDS, which pre-dated the pandemic. METHODS: The incidence, demographic profile, management and outcomes of early AKI in patients undergoing invasive mechanical ventilation for COVID-19-related ARDS were described and compared with AKI in a non-COVID-19-related ARDS cohort. RESULTS: Of 18,964 patients in the CCCC data set, 1699 patients with COVID-19-related ARDS required invasive ventilation and had relevant outcome data. Of these, 110 (6.5%) had stage 1, 94 (5.5%) had stage 2, 151 (8.9%) had stage 3 AKI, while 1214 (79.1%) had no AKI within 48 h of initiating invasive mechanical ventilation. Patients developing AKI were older and more likely to have hypertension or chronic cardiac disease. There were geo-economic differences in the incidence of AKI, with lower incidence of stage 3 AKI in European high-income countries and a higher incidence in patients from middle-income countries. Both 28-day and 90-day mortality risk was increased for patients with stage 2 (HR 2.00, p < 0.001) and stage 3 AKI (HR 1.95, p < 0.001). Compared to non-COVID-19 ARDS, the incidence of shock was reduced with lower cardiovascular SOFA score across all patient groups, while hospital mortality was worse in all groups [no AKI (30 vs 50%), Stage 1 (38 vs 58%), Stage 2 (56 vs 74%), and Stage 3 (52 vs 72%), p < 0.001]. The time profile of onset of AKI also differed, with 56% of all AKI occurring in the first 48 h in patients with COVID-19 ARDS compared to 89% in the non-COVID-19 ARDS population. CONCLUSION: AKI is a common and serious complication of COVID-19, with a high mortality rate, which differs by geo-economic location. Important differences exist in the profile of AKI in COVID-19 versus non-COVID-19 ARDS in terms of their haemodynamic profile, time of onset and clinical outcomes.
Subject(s)
Acute Kidney Injury , COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Prospective Studies , Risk Factors , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Retrospective Studies , Intensive Care Units , Hospital MortalityABSTRACT
OBJECTIVE: Jewish suicides increased heavily under Nazi-rule. This research investigated risk factors for dying from suicide according to sociodemographic characteristics, local context, and time periods. METHODS: Nazi-registration of Amsterdam residents of Jewish origin in 1941 linked to death and suicide lists. The added suicides after the Nazi-invasion (1940, n = 115) and the suicides when deportation trains ran (1942/1943, n = 182) were each matched to 25 controls using sex and age. Suicide was compared across migrant, occupational, marital, and religious status and neighborhood religiosity. Conditional logistic regression was applied, stratified by time period. RESULTS: In 1940, immigrant (cf. native born, odds ratio (OR) 1.89, 95%CI 1.21-2.96, p = .005) and married Jews (cf. previously married) showed higher suicide risk; members of Israelite Congregations (cf. nonmembers, OR 0.35, 95%CI 0.22-0.56, p < .001) showed reduced risk. Jews living in low synagogue rate neighborhoods showed higher risk compared to those living in neighborhoods without any synagogues (OR 2.48, 95%CI 1.65-3.72, p < .001) while those living in high synagogue rate neighborhoods showed no increased risk (OR 0.58, 95%CI 0.30-1.11, p = .10). In 1942/1943, the association between religious status (OR 1.07, 95%CI 0.67, 1.72, p = .77), synagogue rate (OR 1.27, 95%CI 0.91-1.77, p = .16), immigrant status (OR 1.30, 95%CI 0.92-1.84, p = .14) and suicide attenuated; Jews in managerial/professional occupations (cf. workers) or unmarried (cf. married) showed higher risk. CONCLUSIONS: In 1940, immigrants' higher suicide risk likely indicates greater fear of Nazis while religious affiliation's lower risk might indicate a protective effect of religious belief. In 1942/1943, risk differences markedly attenuated likely indicating increased fear of Nazis among all Jews.HighlightsReligiously affiliated Jews showed reduced risk of dying from suicide after the Nazi-invasionJewish immigrants showed higher risk of dying from suicide after the Nazi-invasionBy 1942/1943, these risks attenuated indicating fear of the Nazis spread and nullified religion's protection.