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BACKGROUND. We investigated residual [beta] cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM). METHODS. Serum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among nonresponders (all C-peptide values after meal 0.2), intermediate (>0.03 to RESULTS. Of the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C- peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and nonresponders demonstrated similar rates of advanced microvascular complications. CONCLUSION. [beta] Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of >0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia. TRIAL REGISTRATION. ClinicalTrials.gov NCT00360815 and NCT00360893. FUNDING. Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157)., Introduction Insulin secretion declines in most individuals with type 1 diabetes mellitus (T1DM) as duration of diabetes increases, yet residual insulin secretion, as detected by circulating C-peptide after a meal [...]

Context: Obesity and diabetes are established risk factors for severe SARS-CoV-2 outcomes, but less is known about their impact on susceptibility to COVID-19 infection and general symptom severity. Objective: We hypothesized that those with obesity or diabetes would be more likely to self-report a positive SARS-CoV-2 test, and, among those with a positive test, have greater symptom severity and duration. Methods: Among 44 430 COVID-19 Community Research Partnership participants, we evaluated the association of self-reported and electronic health record obesity and diabetes with a self-reported positive COVID-19 test at any time. Among the 2663 participants with a self-reported positive COVID-19 test during the study, we evaluated the association of obesity and diabetes with self-report of symptom severity, duration, and hospitalization. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and health care worker status. Results: We found a positive graded association between body mass index (BMI) category and positive COVID-19 test (overweight odds ratio [OR] 1.14 [1.05-1.25]; obesity I OR 1.29 [1.17-2.42]; obesity II OR 1.34 [1.19-1.50]; obesity III OR 1.53 [1.35-1.73]), and a similar but weaker association with COVID-19 symptoms and severity among those with a positive test. Diabetes was associated with COVID-19 infection but not symptoms after adjustment, with some evidence of an interaction between obesity and diabetes. Conclusion: While the limitations of this health system convenience sample include generalizability and selection around test seeking, the strong graded association of BMI and diabetes with self-reported COVID-19 infection suggests that obesity and diabetes may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic factors. [ABSTRACT FROM AUTHOR]

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2–17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0–22.0) in May 2021 to 54.1% (95% CrI 46.7–61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12–17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies of SARS-CoV-2 vaccine effectiveness depend on accurate ascertainment of vaccination receipt, date, and product type. Self-reported vaccine data may be more readily available to and less expensive for researchers than assessing medical records. Methods: We surveyed adult participants in the COVID-19 Community Research Partnership who had an authenticated Electronic Health Record (EHR) (N = 41,484) concerning receipt of SARS-CoV-2 vaccination using a daily survey beginning in December 2020 and a supplemental survey in September–October 2021. We compared self-reported information to that available in the EHR for the following data points: vaccine brand, date of first dose, and number of doses using rates of agreement and Bland–Altman plots for visual assessment. Self-reported data was available immediately following vaccination (in the daily survey) and at a delayed interval (in a secondary supplemental survey). Results: For the date of first vaccine dose, self-reported "immediate" recall was within ±7 days of the date reported in the "delayed" survey for 87.9% of participants. Among the 19.6% of participants with evidence of vaccination in their EHR, 95% self-reported vaccination in one of the two surveys. Self-reported dates were within ±7 days of documented EHR vaccination for 97.6% of the "immediate" surveys and 92.0% of the "delayed" surveys. Self-reported vaccine product details matched those in the EHR for over 98% of participants for both "immediate" and "delayed" surveys. Conclusions: Self-reported dates and product details for COVID-19 vaccination can be a good surrogate when medical records are unavailable in large observational studies. A secondary confirmation of dates for a subset of participants with EHR data will provide internal validity. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination. Methods: Adult community residents were invited to participate in the study between April 2020 and February 2021. Demographic information was collected and daily symptom screen was completed using a secure, HIPAA-compliant, online portal. A portion of participants were mailed kits containing a lateral flow assay to be used in-home to test for presence of anti-SARS-CoV-2 IgM or IgG antibodies. The cumulative proportion of participants who tested positive at least once during the study was estimated. A standard Cox proportional hazards model was constructed to illustrate the probability of seroconversion over time up to December 20, 2020 (before vaccines available). A separate analysis was performed to describe the influence of vaccines through February 15, 2021. Results: 17,688 participants contributed at least one serology result. 68.7% of the population were female, and 72.2% were between 18 and 59 years of age. The average number of serology results submitted per participant was 3.0 (±1.9). By December 20, 2020, the overall probability of seropositivity in the CCRP population was 32.6%. By February 15, 2021 the probability among healthcare workers and non-healthcare workers was 83% and 49%, respectively. An inflection upward in the probability of seropositivity was demonstrated around the end of December, suggesting an influence of vaccinations, especially for healthcare workers. Among healthcare workers, those in the oldest age category (60+ years) were 38% less likely to have seroconverted by February 15, 2021. Conclusions: Results of this study suggest more North Carolina residents may have been infected with SARS-CoV-2 than the number of documented cases as determined by positive RNA or antigen tests. The influence of vaccinations on seropositivity among North Carolina residents is also demonstrated. Additional research is needed to fully characterize the impact of seropositivity on immunity and the ultimate course of the pandemic. [ABSTRACT FROM AUTHOR]

Background: Estimating population prevalence and incidence of prior SARS-CoV-2 infection is essential to formulate public health recommendations concerning the COVID-19 pandemic. However, interpreting estimates based on sero-surveillance requires an understanding of the duration of elevated antibodies following SARS-CoV-2 infection, especially in the large number of people with pauci-symptomatic or asymptomatic disease.Methods: We examined > 30,000 serology assays for SARS-CoV-2 specific IgG and IgM assays acquired longitudinally in 11,468 adults between April and November 2020 in the COVID-19 Community Research Partnership.Results: Among participants with serologic evidence for infection but few or no symptoms or clinical disease, roughly 50% sero-reverted in 30 days of their initial positive test. Sero-reversion occurred more quickly for IgM than IgG and for antibodies targeting nucleocapsid protein compared with spike proteins, but was not associated with age, sex, race/ethnicity, or healthcare worker status.Conclusions: The short duration of antibody response suggests that the true population prevalence of prior SARS-CoV-2 infection may be significantly higher than presumed based on earlier sero-surveillance studies. The impact of the large number of minimally symptomatic COVID-19 cases with only a brief antibody response on population immunity remains to be determined. [ABSTRACT FROM AUTHOR]

Background: Randomization is the foundation of any clinical trial involving treatment comparison. It helps mitigate selection bias, promotes similarity of treatment groups with respect to important known and unknown confounders, and contributes to the validity of statistical tests. Various restricted randomization procedures with different probabilistic structures and different statistical properties are available. The goal of this paper is to present a systematic roadmap for the choice and application of a restricted randomization procedure in a clinical trial.Methods: We survey available restricted randomization procedures for sequential allocation of subjects in a randomized, comparative, parallel group clinical trial with equal (1:1) allocation. We explore statistical properties of these procedures, including balance/randomness tradeoff, type I error rate and power. We perform head-to-head comparisons of different procedures through simulation under various experimental scenarios, including cases when common model assumptions are violated. We also provide some real-life clinical trial examples to illustrate the thinking process for selecting a randomization procedure for implementation in practice.Results: Restricted randomization procedures targeting 1:1 allocation vary in the degree of balance/randomness they induce, and more importantly, they vary in terms of validity and efficiency of statistical inference when common model assumptions are violated (e.g. when outcomes are affected by a linear time trend; measurement error distribution is misspecified; or selection bias is introduced in the experiment). Some procedures are more robust than others. Covariate-adjusted analysis may be essential to ensure validity of the results. Special considerations are required when selecting a randomization procedure for a clinical trial with very small sample size.Conclusions: The choice of randomization design, data analytic technique (parametric or nonparametric), and analysis strategy (randomization-based or population model-based) are all very important considerations. Randomization-based tests are robust and valid alternatives to likelihood-based tests and should be considered more frequently by clinical investigators. [ABSTRACT FROM AUTHOR]

Health informatics applications reduce time intervals in acute coronary syndromes, but their impact on guideline adherence is unknown. This pre–post intervention study compared guideline adherence between telemedically supported (n = 101, April 2014–July 2015) and conventional on-scene care (n = 120, January 2014–March 2014) in acute coronary syndrome. A multivariate logistic regression was performed for dependent variables: adverse events 0 versus 0, p = NA; electrocardiogram 101 versus 120, p = NA; acetylic salicylic acid 91 versus 102, p = 0.21; heparin 92 versus 112, p = 0.99; morphine 96 versus 107, p = 0.33; oxygen 83 versus 102, p = 0.92; glyceroltrinitrate 55 versus 90, p = 0.038; correct destination: 100 versus 119, p = 1.0. The time from ambulance arrival to hospital arrival was prolonged with telemedicine: 48.7 ± 11 min versus 35.5 ± 8.1 min, p < 0.001. Guideline adherence showed no differences except for glyceroltrinitrate. Prolonged time requirements are critical, though explainable. However, this approach enables a timely and high-quality backup strategy if only paramedics are on-scene. [ABSTRACT FROM AUTHOR]

Objective: Obesity and diabetes are established risk factors for severe SARS-CoV-2 outcomes, but less is known about their impact on susceptibility to COVID-19 infection and general symptom severity. We hypothesized that those with obesity or diabetes would be more likely to self-report a positive SARS-CoV-2 test, and among those with a positive test, have greater symptom severity and duration., Methods: Among 44,430 COVID-19 Community Research Partnership participants, we evaluated the association of self-reported and electronic health record obesity and diabetes with a self-reported positive COVID-19 test at any time. Among the 2,663 participants with a self-reported positive COVID-19 test during the study, we evaluated the association of obesity and diabetes with self-report of symptom severity, duration, and hospitalization. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and healthcare worker status., Results: We found a positive graded association between Body Mass Index (BMI) category and positive COVID-19 test (Overweight OR = 1.14 [1.05-1.25]; Obesity I OR = 1.29 [1.17-2.42]; Obesity II OR = 1.34 [1.19-1.50]; Obesity III OR = 1.53 [1.35-1.73]), and a similar but weaker association with COVID-19 symptoms and severity among those with a positive test. Diabetes was associated with COVID-19 infection but not symptoms after adjustment, with some evidence of an interaction between obesity and diabetes., Conclusions: While the limitations of this health system convenience sample include generalizability and selection around test-seeking, the strong graded association of BMI and diabetes with self-reported COVID-19 infection suggests that obesity and diabetes may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We characterize the overall incidence and risk factors for breakthrough infection among fully vaccinated participants in the North Carolina COVID-19 Community Research Partnership cohort. Among 15,808 eligible participants, 638 reported a positive SARS-CoV-2 test after vaccination. Factors associated with a lower risk of breakthrough in the time-to-event analysis included older age, prior SARS-CovV-2 infection, higher rates of face mask use, and receipt of a booster vaccination. Higher rates of breakthrough were reported by participants vaccinated with BNT162b2 or Ad26.COV2.S compared to mRNA-1273, in suburban or rural counties compared to urban counties, and during circulation of the Delta and Omicron variants.