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BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.
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BACKGROUND: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. OBJECTIVE: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. STUDY DESIGN: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). RESULTS: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). CONCLUSION: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.
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OBJECTIVE: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. STUDY DESIGN: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. RESULTS: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (ß = - 0.63% 95% CI [-0.8, -0.6] p < 0.001) and remained stable between V2 and PP (ß = - 0.04% [-0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p = 0.0001; V2 rho = - 0.4, p = 0.006), but not PP (rho = - 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. CONCLUSION: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. KEY POINTS: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women..
Subject(s)
Diabetes, Gestational , Serum Albumin , Pregnancy , Humans , Female , Glycated Hemoglobin , Pilot Projects , Postpartum Period , Glucose Tolerance Test , Blood GlucoseABSTRACT
Importance: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment. Objective: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC. Design, Setting, and Participants: Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 89 prolonged symptoms across 9 symptom domains. Results: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents. Conclusions and Relevance: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.
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AIMS/HYPOTHESIS: Clinical trial participation should theoretically reduce barriers to care by ensuring medication and healthcare access. We aimed to evaluate disparities in achieving diabetes treatment targets by race/ethnicity and educational attainment within the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (ClinicalTrials.gov NCT00000620). METHODS: The ACCORD trial included three interventions of varying participant burden: glycaemic (high burden), blood pressure (medium burden) and triglyceride-lowering (low burden). We examined adjusted odds ratios (aORs) for achievement of glycaemic targets, blood pressure targets and a ≥25% reduction in triglyceride levels (a proxy for adherence to fenofibrate therapy) in the first year, and for hypoglycaemia requiring medical assistance at any time, by treatment arm, race/ethnicity and educational attainment using multivariable models adjusted for demographics and clinical characteristics. We explored whether disparities in glycaemic goal achievement were mediated by hypoglycaemia, medication use, change in BMI or number of study visits attended. RESULTS: Compared with White participants, participants who identified as Black, Hispanic and Other race/ethnicity were less likely to achieve glycaemic targets (aOR [95% CI]) 0.63 [0.55,0.71], 0.73 [0.61, 0.88], 0.82 [0.71, 0.96], respectively); Black participants but not Hispanic and Other race/ethnicity participants were less likely to achieve blood pressure targets (aOR [95% CI] 0.77 [0.65, 0.90], 1.01 [0.78, 1.32], 1.01 [0.81, 1.26], respectively); and Black, Hispanic and Other race/ethnicity participants were equally or more likely to achieve triglyceride reduction (aOR [95% CI] 1.77 [1.38, 2.28], 1.34 [0.98, 1.84], 1.43 [1.10, 1.85], respectively). Differences in goal achievement by educational attainment were generally not significant after adjusting for baseline characteristics. Rates of hypoglycaemia requiring medical assistance were highest among Black individuals and those with lower educational attainment. Associations between race/ethnicity and glycaemic control were partially mediated by differences in insulin dosing and oral medication use. CONCLUSIONS/INTERPRETATION: Racially/ethnically minoritised participants in the ACCORD trial were less likely to achieve high-burden (glycaemic) treatment goals but were generally similarly likely to achieve goals of less intensive interventions. Differences in glycaemic treatment goal achievement were partially mediated by differences in medication use but not mediated by hypoglycaemia, change in BMI or study visit attendance.
Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemia , Humans , Goals , Socioeconomic Disparities in Health , Heart Disease Risk Factors , TriglyceridesABSTRACT
BACKGROUND: Hospital-based biobanks are being increasingly considered as a resource for translating polygenic risk scores (PRS) into clinical practice. However, since these biobanks originate from patient populations, there is a possibility of bias in polygenic risk estimation due to overrepresentation of patients with higher frequency of healthcare interactions. METHODS: PRS for schizophrenia, bipolar disorder, and depression were calculated using summary statistics from the largest available genomic studies for a sample of 24 153 European ancestry participants in the Mass General Brigham (MGB) Biobank. To correct for selection bias, we fitted logistic regression models with inverse probability (IP) weights, which were estimated using 1839 sociodemographic, clinical, and healthcare utilization features extracted from electronic health records of 1 546 440 non-Hispanic White patients eligible to participate in the Biobank study at their first visit to the MGB-affiliated hospitals. RESULTS: Case prevalence of bipolar disorder among participants in the top decile of bipolar disorder PRS was 10.0% (95% CI 8.8-11.2%) in the unweighted analysis but only 6.2% (5.0-7.5%) when selection bias was accounted for using IP weights. Similarly, case prevalence of depression among those in the top decile of depression PRS was reduced from 33.5% (31.7-35.4%) to 28.9% (25.8-31.9%) after IP weighting. CONCLUSIONS: Non-random selection of participants into volunteer biobanks may induce clinically relevant selection bias that could impact implementation of PRS in research and clinical settings. As efforts to integrate PRS in medical practice expand, recognition and mitigation of these biases should be considered and may need to be optimized in a context-specific manner.
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Bipolar Disorder , Humans , Genetic Predisposition to Disease , Selection Bias , Genome-Wide Association Study , Bipolar Disorder/epidemiology , Bipolar Disorder/genetics , Multifactorial Inheritance , Risk FactorsABSTRACT
Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
Subject(s)
COVID-19 , SARS-CoV-2 , Female , Adult , Humans , Middle Aged , Male , COVID-19/complications , Prospective Studies , Post-Acute COVID-19 Syndrome , Cohort Studies , Disease Progression , FatigueABSTRACT
BACKGROUND: Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). METHODS: In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. RESULTS: Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. CONCLUSION: Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.
Subject(s)
COVID-19/diagnosis , Dyslipidemias/drug therapy , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Cohort Studies , Dyslipidemias/complications , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , SARS-CoV-2ABSTRACT
AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.
Subject(s)
Diabetes, Gestational , Blood Glucose , Diabetes, Gestational/diagnosis , Female , Glucose , Humans , Parity , Pregnancy , Risk FactorsABSTRACT
BACKGROUND/OBJECTIVE: Obesity is a strong risk factor for adverse outcomes in patients hospitalized with COVID-19, however, the distribution of fat and the amount of muscle mass are more accurate risk factors than BMI. The objective of this study was to assess body composition measures obtained on opportunistic abdominal CTs as predictors of outcome in patients hospitalized with COVID-19. We hypothesized that elevated visceral and intermuscular adipose tissue would be associated with adverse outcome. SUBJECTS/METHODS: Our retrospective study was IRB-approved and HIPAA-compliant. The study group comprised 124 patients (median age: 68 years, IQR: 56, 77; 59 weeks, 65 months) who were admitted with COVID-19 to a single hospital and who had undergone abdominal CT for clinical purposes. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and paraspinal and abdominal muscle cross-sectional areas (CSA) were assessed. Clinical information including prognostic factors, time of admission to the intensive care unit (ICU) and time of death within 28 days were obtained. Multivariate time-to-event competing risk models were fitted to estimate the hazard ratio (HR) for a composite outcome of ICU admission/mortality associated with a one standard deviation increase in each body compositional measure. Each model was adjusted for age, sex, race, BMI, and cardiometabolic comorbidities. RESULTS: There were 50 patients who were admitted to the ICU or deceased over a median time of 1 day [IQR 1, 6] from hospital admission. Higher VAT/SAT ratio (HR of 1.30; 95% CI 1.04-1.62, p = 0.022) and higher IMAT CSA (HR of 1.44; 95% CI 1.10-1.89, p = 0.008) were associated with a reduced time to ICU admission or death in adjusted models. CONCLUSION: VAT/SAT and IMAT are predictors of adverse outcome in patients hospitalized with COVID-19, independent of other established prognostic factors. This suggests that body composition measures may serve as novel biomarkers of outcome in patients with COVID-19.
Subject(s)
Body Composition/physiology , COVID-19 , Obesity , Adipose Tissue/diagnostic imaging , Aged , Biomarkers , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Obesity/complications , Obesity/diagnostic imaging , Obesity/epidemiology , Retrospective Studies , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. STUDY DESIGN: Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. SETTING & PARTICIPANTS: Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. FACTOR: Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. OUTCOMES: Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. RESULTS: Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P=0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P=0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P=0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P=0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P=0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P=0.048). LIMITATIONS: Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. CONCLUSIONS: Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of dying within 30 days.
Subject(s)
Cyclonic Storms , Disaster Planning , Renal Dialysis , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Male , Middle Aged , New Jersey , New York , Renal Dialysis/standards , Time FactorsABSTRACT
OBJECTIVE: To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia. RESEARCH DESIGN AND METHODS: This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%. RESULTS: Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis. CONCLUSIONS: GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health.
Subject(s)
Diabetes, Gestational , Glucose Intolerance , Hypoglycemia , Humans , Female , Hypoglycemia/epidemiology , Hypoglycemia/diagnosis , Hypoglycemia/blood , Infant, Newborn , Diabetes, Gestational/blood , Pregnancy , Adult , Glucose Tolerance Test , Male , Blood Glucose/analysis , Blood Glucose/metabolism , Risk Factors , MothersABSTRACT
IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.
Subject(s)
COVID-19 , Adult , Humans , SARS-CoV-2 , Cross-Sectional Studies , Post-Acute COVID-19 Syndrome , Disease Progression , Risk FactorsABSTRACT
IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/virology , Adolescent , Child , Child, Preschool , Female , Young Adult , Adult , Male , Infant , SARS-CoV-2/isolation & purification , Infant, Newborn , Prospective Studies , Research Design , Cohort Studies , Post-Acute COVID-19 SyndromeABSTRACT
OBJECTIVE: To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Participants underwent oral glucose tolerance tests at ≤15 weeks' gestation (early pregnancy), 24-32 weeks' gestation (mid-late pregnancy), and 6-24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify ß-cell compensation for insulin resistance. RESULTS: Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (ß = -0.20, P < 0.001) and substantially in mid-late pregnancy (ß = -0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (ß = 0.16, P < 0.001) and mid-late pregnancy (ß = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (ß = 215, P = 0.04) but not mid-late pregnancy (ß = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (ß = -0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61-0.79], area under the curve with PIP index 0.87 [95% CI 0.80-0.93]). CONCLUSIONS: ß-Cell function is enhanced in early pregnancy. Deficient first-trimester ß-cell function predicts GDM.
Subject(s)
Diabetes, Gestational , Glucose Intolerance , Insulin Resistance , Female , Pregnancy , Humans , Insulin , Insulin Resistance/physiology , Glucose Tolerance Test , Postpartum Period/physiology , Insulin, Regular, Human , Blood GlucoseABSTRACT
BACKGROUND: Understanding the effect lifestyle intervention (LI) has on important psychological and behavioral variables that are associated with weight loss can help inform LI design, content, and delivery. OBJECTIVE: The aim was to determine the modifiable psychological and behavioral factors that are associated with percent weight loss (%WL) and their relative importance in predicting %WL at 12, 24, and 36 months in the REAL HEALTH-Diabetes randomized controlled trial LI. DESIGN: This is a secondary analysis of LI arms of the REAL HEALTH-Diabetes randomized controlled trial LI cohort over a 24-month intervention period and 12-month follow-up period. Patient-reported outcomes were measured using validated questionnaires that were either self-administered or administered by a research coordinator. PARTICIPANTS/SETTING: Adults with type 2 diabetes and overweight/obesity (N = 142) from community health centers, primary care, and local endocrinology practices affiliated with Massachusetts General Hospital in Boston, MA, between 2015 and 2020, were randomized to LI and were included in the analysis. INTERVENTION: The LI was a lower intensity adaptation of Look Action for Health in Diabetes's (HEALTH) evidence-based LI delivered either in-person or via telephone. Registered dietitians delivered 19 group sessions during the first 6 months followed by 18 monthly sessions. MAIN OUTCOME MEASURES: The association of psychological (diabetes-related distress, depression, autonomous motivation, diet and exercise self-efficacy, and social support for healthy behaviors) and behavioral (fat-related diet and dietary self-regulation) variables with %WL. STATISTICAL ANALYSIS: Baseline and 6-month change scores in psychological and behavioral variables were modeled as predictors of %WL at 12, 24, and 36 months using linear regression. Random forests were used to compare the relative importance of changes in the variables in predicting %WL. RESULTS: Six-month improvement in autonomous motivation, exercise self-efficacy, diet self-efficacy, and dietary self-regulation were associated with %WL at 12 and 24 months, but not at 36 months. Improvement in fat-related diet behavior and depressive symptoms were the only variables associated with %WL at all three timepoints. Autonomous motivation, dietary self-regulation, and low-fat diet behaviors were the three most important predictors of %WL during the 2-year LI. CONCLUSIONS: The REAL HEALTH-Diabetes randomized controlled trial LI resulted in 6-month improvements in modifiable psychological and behavioral factors that were associated with %WL. LI programs for weight loss should focus on skills and strategies to promote autonomous motivation, flexible dietary self-regulation, and habituation of low-fat eating habits during the intervention period.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Diabetes Mellitus, Type 2/complications , Obesity , Weight Loss/physiology , Life Style , Diet, Fat-RestrictedABSTRACT
OBJECTIVE: Pregnant individuals are universally screened for gestational diabetes mellitus (GDM). Gestational glucose intolerance (GGI) (an abnormal initial GDM screening test without a GDM diagnosis) is not a recognized diabetes risk factor. We tested for an association between GGI and diabetes after pregnancy. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of individuals followed for prenatal and primary care. We defined GGI as an abnormal screening glucose-loading test result at ≥24 weeks' gestation with an oral glucose tolerance test (OGTT) that did not meet GDM criteria. The primary outcome was incident diabetes. We used Cox proportional hazards models with time-varying exposures and covariates to compare incident diabetes risk in individuals with GGI and normal glucose tolerance. RESULTS: Among 16,836 individuals, there were 20,359 pregnancies with normal glucose tolerance, 2,943 with GGI, and 909 with GDM. Over a median of 8.4 years of follow-up, 428 individuals developed diabetes. Individuals with GGI had increased diabetes risk compared to those with normal glucose tolerance in pregnancy (adjusted hazard ratio [aHR] 2.01 [95% CI 1.54-2.62], P < 0.001). Diabetes risk increased with the number of abnormal OGTT values (zero, aHR 1.54 [1.09-2.16], P = 0.01; one, aHR 2.97 [2.07-4.27], P < 0.001; GDM, aHR 8.26 [6.49-10.51], P < 0.001 for each compared with normal glucose tolerance). The fraction of cases of diabetes 10 years after delivery attributable to GGI and GDM was 8.5% and 28.1%, respectively. CONCLUSIONS: GGI confers an increased risk of future diabetes. Routinely available clinical data identify an unrecognized group who may benefit from enhanced diabetes screening and prevention.
Subject(s)
Diabetes, Gestational , Glucose Intolerance , Pregnancy , Female , Humans , Glucose Intolerance/epidemiology , Retrospective Studies , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Glucose Tolerance Test , Glucose , Risk Factors , Blood GlucoseABSTRACT
OBJECTIVE: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.
Subject(s)
Diabetes, Gestational , Glucose Intolerance , Pregnancy , Female , Humans , Glucose Intolerance/epidemiology , Birth Weight , Retrospective Studies , Diabetes, Gestational/epidemiology , Diabetes, Gestational/diagnosis , Pregnancy Outcome , Glucose , Blood GlucoseABSTRACT
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.