Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Patterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19). METHODS: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using viral culture and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical and epidemiologic metadata were reviewed. RESULTS: We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset and in 1 of 67 (1.5%) immunocompetent patients 10 days after symptom onset (P = .001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients. CONCLUSIONS: Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.

Blood utilization in five Chinese hospitals shows low hemoglobin thresholds in medical patients.

BACKGROUND: The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown. STUDY DESIGN AND METHODS: We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals. RESULTS: In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4). CONCLUSION: Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown.

Use of External Quality Control Material for HIV-1 RNA Testing To Assess the Comparability of Data Generated in Separate Laboratories and the Stability of HIV-1 RNA in Samples after Prolonged Storage.

The National Institute of Allergy and Infectious Diseases (NIAID) AIDS Clinical Trials Group (ACTG) stores specimens from its clinical trials in a biorepository and permits the use of these specimens for nonprotocol exploratory studies, once the studies for the original protocol are concluded. We sought to assess the comparability of the data generated from real-time HIV-1 RNA testing during two clinical trials with the data generated from the retesting of different aliquots of the same samples after years of storage at -80°C. Overall, there was 92% agreement in the data generated for 1,570 paired samples (kappa statistic = 0.757; 95% confidence interval [CI], 0.716 to 0.797), where samples were tested in one laboratory using the microwell plate (MWP) version of the Roche HIV-1 Monitor test within 1 to 37 days of collection and retested in another laboratory using the Cobas version of the assay after a median of 6.7 years of storage (range, 5.7 to 8.6 years). Historical external quality control data submitted to the NIAID Virology Quality Assurance program (VQA) by client laboratories using the same two versions of the Monitor assay were used to differentiate between systematic differences in the assays to evaluate the stability of HIV-1 RNA in the stored samples. No significant loss of RNA was noted in samples containing either a low concentration (<50 copies/ml) or a high concentration (≥50 copies/ml) of HIV-1 RNA (P = 0.10 and P = 0.90, respectively) regardless of the time in storage. These data confirm the quality of the plasma samples in the ACTG biorepository following long-term storage.

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with increased susceptibility to recurrent skin infections. OBJECTIVE: We sought to determine why a subset of patients with AD have an increased risk of disseminated viral skin infections. METHODS: Human subjects with AD with a history of eczema herpeticum (EH) and various control groups were enrolled. Vaccinia virus (VV) expression was measured by means of PCR and immunofluorescent staining in skin biopsy specimens from each study group after incubation with VV. Transgenic mice with a constitutively active signal transducer and activator of transcription 6 gene (STAT6) were characterized for response to VV skin inoculation. Genotyping for 10 STAT6 single nucleotide polymorphisms (SNPs) was performed in a white patient sample (n = 444). RESULTS: VV gene and protein expression were significantly increased in the skin of patients with EH compared with other subject groups after incubation with VV in vitro. Antibody neutralization of IL-4 and IL-13 resulted in lower VV replication in patients with a history of EH. Mice that expressed a constitutively active STAT6 gene compared with wild-type mice had increased mortality and satellite lesion formation after VV skin inoculation. Significant associations were observed between STAT6 SNPs and EH (rs3024975, rs841718, rs167769, and rs703817) and IFN-γ production. The strongest association was observed for a 2-SNP haplotype (patients with AD with a history of EH vs patients with AD without a history of EH, 24.9% vs 9.2%; P = 5.17 × 10(-6)). CONCLUSION: The STAT6 gene increases viral replication in the skin of patients with AD with a history of EH. Further genetic association studies and functional investigations are warranted.

Human atopic dermatitis complicated by eczema herpeticum is associated with abnormalities in IFN-γ response.

BACKGROUND: The basis for increased susceptibility of patients with atopic dermatitis (AD) to develop disseminated viral skin infections such as eczema herpeticum (AD with a history of eczema herpeticum, ADEH(+)) is poorly understood. OBJECTIVE: We sought to determine whether subjects with AD prone to disseminated viral skin infections have defects in their IFN responses. METHODS: GeneChip profiling was used to identify differences in gene expression of PBMCs from patients with ADEH(+) compared with patients with AD without a history of eczema herpeticum (ADEH(-)) and nonatopic controls. Key differences in protein expression were verified by enzyme-linked immunosorbent spot assay and/or ELISA. Clinical relevance was further demonstrated by a mouse model of disseminated viral skin infection and genetic association analysis for genetic variants in IFNG and IFNGR1 and ADEH among 435 cases and controls. RESULTS: We demonstrate by global gene expression analysis selective transcriptomic changes within the IFN superfamily of PBMCs from subjects with ADEH(+) reflecting low IFN-γ and IFN-γ receptor gene expression. IFN-γ protein production was also significantly lower in patients with ADEH(+) (n = 24) compared with patients with ADEH(-) (n = 20) and nonatopic controls (n = 20). IFN-γ receptor knockout mice developed disseminated viral skin infection after epicutaneous challenge with vaccinia virus. Genetic variants in IFNG and IFNGR1 single nucleotide polymorphisms (SNPs) were significantly associated with ADEH (112 cases, 166 controls) and IFN-γ production: a 2-SNP (A-G) IFNGR1 haplotype (rs10457655 and rs7749390) showed the strongest association with a reduced risk of ADEH+ (13.2% ADEH(+) vs 25.5% ADEH(-); P = .00057). CONCLUSION: Patients with ADEH(+) have reduced IFN-γ production, and IFNG and IFNGR1 SNPs are significantly associated with ADEH(+) and may contribute to an impaired immune response to herpes simplex virus.

Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine.

BACKGROUND: Asthma was the most common comorbidity of patients hospitalized with 2009 H1N1 influenza. OBJECTIVE: We sought to assess the immunogenicity and safety of an unadjuvanted, inactivated 2009 H1N1 vaccine in patients with severe versus mild-to-moderate asthma. METHODS: We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in October-November 2009. Severe asthma was defined as need for 880 µg/d or more of inhaled fluticasone equivalent, systemic corticosteroids, or both. Within each severity group, participants were randomized to receive intramuscularly 15 or 30 µg of 2009 H1N1 vaccine twice 21 days apart. Immunogenicity end points were seroprotection (hemagglutination inhibition assay titer ≥40) and seroconversion (4-fold or greater titer increase). Safety was assessed through local and systemic reactogenicity, asthma exacerbations, and pulmonary function. RESULTS: In patients with mild-to-moderate asthma (n = 217), the 2009 H1N1 vaccine provided equal seroprotection 21 days after the first immunization at the 15-µg (90.6%; 95% CI, 83.5% to 95.4%) and 30-µg (95.3%; 95% CI, 89.4% to 98.5%) doses. In patients with severe asthma (n = 173), seroprotection 21 days after the first immunization was 77.9% (95% CI, 67.7% to 86.1%) and 94.1% (95% CI, 86.8% to 98.1%) at the 15- and 30-µg doses, respectively (P = .004). The second vaccination did not provide further increases in seroprotection. Participants with severe asthma who are older than 60 years showed the lowest seroprotection (44.4% at day 21) with the 15-µg dose but had adequate seroprotection with 30 µg. The 2 dose groups did not differ in seroconversion rates. There were no safety concerns. CONCLUSION: Monovalent inactivated 2009 H1N1 pandemic influenza vaccine was safe and provided overall seroprotection as a surrogate of efficacy. In patients older than 60 years with severe asthma, a 30-µg dose might be more appropriate.

Blood myo-inositol concentrations in preterm and term infants.

OBJECTIVE: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age. DESIGN/METHODS: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values. RESULTS: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 µmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants). CONCLUSIONS: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.

Application of a Sanger-Based External Quality Assurance Strategy for the Transition of HIV-1 Drug Resistance Assays to Next Generation Sequencing.

The National Institute of Allergy and Infectious Diseases (NIAID) Virology Quality Assurance (VQA) established a robust proficiency testing program for Sanger sequencing (SS)-based HIV-1 drug resistance (HIVDR) testing in 2001. While many of the lessons learned during the development of such programs may also apply to next generation sequencing (NGS)-based HIVDR assays, challenges remain for the ongoing evaluation of NGS-based testing. These challenges include a proper assessment of assay accuracy and the reproducibility of low abundance variant detection, intra- and inter-assay performance comparisons among laboratories using lab-defined tests, and different data analysis pipelines designed for NGS. In collaboration with the World Health Organization (WHO) Global HIVDR Laboratory Network and the Public Health Agency of Canada, the Rush VQA program distributed archived proficiency testing panels to ten laboratories to evaluate internally developed NGS assays. Consensus FASTA files were submitted using 5%, 10%, and 20% variant detection thresholds, and scored based on the same criteria used for SS. This small study showed that the SS External Quality Assurance (EQA) approach can be used as a transitional strategy for using NGS to generate SS-like data and for ongoing performance while using NGS data from the same quality control materials to further evaluate NGS assay performance.

Multi-Laboratory Comparison of Next-Generation to Sanger-Based Sequencing for HIV-1 Drug Resistance Genotyping.

Next-generation sequencing (NGS) is increasingly used for HIV-1 drug resistance genotyping. NGS methods have the potential for a more sensitive detection of low-abundance variants (LAV) compared to standard Sanger sequencing (SS) methods. A standardized threshold for reporting LAV that generates data comparable to those derived from SS is needed to allow for the comparability of data from laboratories using NGS and SS. Ten HIV-1 specimens were tested in ten laboratories using Illumina MiSeq-based methods. The consensus sequences for each specimen using LAV thresholds of 5%, 10%, 15%, and 20% were compared to each other and to the consensus of the SS sequences (protease 4-99; reverse transcriptase 38-247). The concordance among laboratories' sequences at different thresholds was evaluated by pairwise sequence comparisons. NGS sequences generated using the 20% threshold were the most similar to the SS consensus (average 99.6% identity, range 96.1-100%), compared to 15% (99.4%, 88.5-100%), 10% (99.2%, 87.4-100%), or 5% (98.5%, 86.4-100%). The average sequence identity between laboratories using thresholds of 20%, 15%, 10%, and 5% was 99.1%, 98.7%, 98.3%, and 97.3%, respectively. Using the 20% threshold, we observed an excellent agreement between NGS and SS, but significant differences at lower thresholds. Understanding how variation in NGS methods influences sequence quality is essential for NGS-based HIV-1 drug resistance genotyping.

Assessment of carotid intima-media thickness in subjects with ischemic cerebrovascular events undergoing endarterectomy.

BACKGROUND AND AIM: In clinical settings, the degree of lumen stenosis is the parameter used to select patients for carotid surgery. The present study was designed to measure carotid intima-media thickness (IMT), an indicator of atherosclerotic burden, in a sample of consecutive patients with ischemic cerebrovascular events referred for endarterectomy. METHODS AND RESULTS: Carotid endarterectomy specimens from 55 consecutive patients (age 66+/-10 years) admitted to hospital with recent documented atherothrombotic ischemic cerebrovascular events were compared with 24 carotid arteries from people (age 68+/-11 years) who had died from documented causes unrelated to cerebrovascular disease. Measurement of extracranial carotid atherosclerosis was made from three anatomically defined segments, using image-processing software. A total of 426 cross sections was analyzed. Increasing IMT measures were clearly associated with increased risk of an ischemic event. Single maximum IMT values of 2.33 mm (95% CI, 1.69-2.96) for the common carotid, 2.45 mm (95% CI, 1.97-2.93) for the bifurcation, and 2.23 (95% CI, 1.83-2.64) for the internal carotid were associated with a 75% probability of a cerebrovascular ischemic accident. Receiver operator characteristic curve analyses demonstrated that the diagnostic ability of IMT measurements performed at the level of internal carotid artery to separate cases from controls was greater than common carotid artery or bifurcation measurements. CONCLUSIONS: The present pathology study provides data on IMT in patients admitted to hospital for cerebrovascular accidents and referred for carotid endarterectomy.

Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin.

Insulin resistance is an important risk factor for development of type 2 diabetes as well as other chronic conditions, including hypertension, cardiovascular disease, and colon cancer. To find genes for insulin resistance it is necessary to assess insulin action in large populations. We have previously measured insulin action in a large cohort of subjects (Insulin Resistance and Atherosclerosis Study [IRAS] Family Study) using the minimal model approach. In this study, we compare sensitivity from the minimal model (insulin sensitivity index [S(I)]) with the measure of insulin resistance emanating from the homeostasis model assessment (HOMA) approach. The former measure emerges from the glycemic response to endogenous and exogenous insulin; the latter is based solely on fasting measures of glucose and insulin. A total of 112 pedigrees were represented, including 1,362 individuals with full phenotypic assessment. Heritability of S(I) was significantly greater than that for HOMA (0.310 vs. 0.163) and for fasting insulin (0.171), adjusted for age, sex, ethnicity, and BMI. In addition, correlation between S(I) and either HOMA or fasting insulin was only approximately 50% accounted for by genetic factors, with the remainder accounted for by environment. Thus S(I), a direct measure of insulin sensitivity, is determined more by genetic factors rather than measures such as HOMA, which reflect fasting insulin.

Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS).

OBJECTIVE: To evaluate the association of vitamin E with incidence of type 2 diabetes and to do so separately among individuals who did and those who did not report regular use of vitamin supplementation. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) included 895 nondiabetic adults at baseline (including 303 with impaired glucose tolerance [IGT]), 148 of whom developed type 2 diabetes according to World Health Organization (WHO) criteria during the 5-year follow-up. At baseline, dietary vitamin E was estimated by a validated food frequency interview, usual supplement use was confirmed by supplement label, and plasma alpha-tocopherol was measured. Analyses were conducted separately for individuals who did (n = 318) and did not (n = 577) use vitamin E supplements. RESULTS: Among supplement nonusers, reported mean intake of vitamin E (mg alpha-tocopherol equivalents [alpha-TE]) did not differ between those who remained nondiabetic (n = 490) and those who developed diabetes (n = 87) (10.5 +/- 5.5 vs. 9.5 +/- 4.8 [means +/- SD], respectively, NS). After adjustment for demographic variables, obesity, physical activity, and other nutrients, the association remained nonsignificant (odds ratio [OR] 0.80, 95% CI 0.13-5.06) for the highest level of intake (> or =20 mg alpha-TE) compared with the lowest level (1-4 alpha-TE). However, results for plasma concentration of alpha-tocopherol showed a significant protective effect both before and after adjustment for potential confounders (adjusted OR 0.12, 95% CI 0.02-0.68, for the highest quintile vs. the lowest quintile; overall test for trend, P < 0.01). Among individuals who reported habitual use of vitamin E supplements (at least once per month in the year before baseline; 259 remained nondiabetic and 59 developed diabetes), no protective effect was observed for either reported intake of vitamin E or plasma concentration of alpha-tocopherol CONCLUSIONS: A protective effect of vitamin E may exist within the range of intake available from food. This effect may go undetected within studies of high-dose supplement use, which appears to hold no additional protective benefit.

Insulin sensitivity and the risk of incident hypertension: insights from the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: The insulin resistance syndrome has been described as including hypertension. Previous studies have documented cross-sectional associations between insulin sensitivity (S(I)) and blood pressure or prevalent hypertension. Prospective data have been sparse. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) is a prospective study of the associations of S(I) with atherosclerosis and other risk factors for cardiovascular disease. We examined the association between S(I), measured using the frequently sampled intravenous glucose tolerance test with minimal model analysis, and incident hypertension (defined as per the Joint National Committee), at the 5-year examination in 840 IRAS participants who were free of hypertension at the baseline examination. RESULTS: Adjusted for age, sex, ethnicity, and smoking status, for each unit greater S(I), the risk of hypertension was 10% lower (95% CI 2-19, P < 0.05). CONCLUSIONS: These findings, from a prospective study, support the presence of a modest protective association between greater S(I) and lower risk of hypertension. These findings support the contention that interventions that improve S(I) may be beneficial with respect to the development of hypertension and cardiovascular disease. This contention should be tested in randomized clinical trials.

Ethnic and racial differences in diabetes care: The Insulin Resistance Atherosclerosis Study.

OBJECTIVE: Diabetes and its complications disproportionately affect African Americans and Hispanics. Complications could be prevented with appropriate medical care. We compared five processes of care and three outcomes of care among African Americans, Hispanics, and non-Hispanic whites. RESEARCH DESIGN AND METHODS: We used data from the Insulin Resistance Atherosclerosis Study (1993-1998) of participants with known diabetes. African Americans and Hispanics were compared with non-Hispanic whites from the same region. Five process measures (treatment of diabetes, hypertension, hyperlipidemia, albuminuria, and coronary artery disease) and three outcome measures (control of diabetes, hypertension, and hyperlipidemia) were evaluated. RESULTS: Comparison groups were similar in baseline characteristics. African Americans and Hispanics were equally likely as their non-Hispanic white comparison group to receive treatment for diabetes, hypertension, hyperlipidemia, albuminuria, and coronary artery disease, although treatment rates for hyperlipidemia and albuminuria were poor for all groups. African Americans were more likely to have poorly controlled diabetes (HbA(1c) >8.0%: OR 2.23, 95% CI 1.26-3.94). Both African American and Hispanics were significantly more likely to have borderline or poorly controlled hypertension than non-Hispanic whites (blood pressure >130-140/85-90 or >140/90 mmHg: African American/non-Hispanic white OR 3.22, 95% CI 1.57-6.59; Hispanic/non-Hispanic white 3.14, 1.35-7.3). CONCLUSIONS: The rates of treatment for diabetes and associated comorbidities are similar across all three ethnic groups. Few individuals in any ethnic group received treatment for hyperlipidemia and albuminuria. Ethnic disparities exist in control of diabetes and hypertension. Programs should be tested to improve overall quality of care and eliminate these disparities.

Site-specific progression of carotid artery intimal-medial thickness.

PURPOSE: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among carotid artery sites and examine the influence of diabetes and sex on these correlations. METHODS: Ultrasonographic IMT measurements from the near and far walls of common and internal segments in the arteries of 1207 participants of the Insulin Resistance Atherosclerosis Study (IRAS) were analyzed to estimate the underlying correlations of IMT changes (average of 5.2 years) among artery sites after correction for measurement error. RESULTS: Differences in IMT progression associated with diabetes and sex were evident at all sites. IMT changes were strongly correlated between left and right arteries (r=0.32-0.73) and near and far walls (r=0.42-0.87). Correlations of IMT changes at corresponding sites of internal versus common segments were reduced from r=0.32 among normal individuals to r=0.09 among those with diabetes, but were similar for women and men. CONCLUSIONS: IMT progression is a diffuse process involving all carotid artery sites. Diabetes does not influence the bilateral and radial nature of progression, but reduces the correlation between distal sites within an artery. Pooling measurements across arteries and walls often yields the most efficient analyses.

Evaluation of vaccine-induced antibody responses: impact of new technologies.

Host response to vaccination has historically been evaluated based on a change in antibody titer that compares the post-vaccination titer to the pre-vaccination titer. A four-fold or greater increase in antigen-specific antibody has been interpreted to indicate an increase in antibody production in response to vaccination. New technologies, such as the bead-based assays, provide investigators and clinicians with precise antibody levels (reported as concentration per mL) in ranges below and above those previously available through standard assays such as ELISA. Evaluations of bead assay data to determine host response to vaccination using fold change and absolute change, with a general linear model used to calculate adjusted statistics, present very different pictures of the antibody response when pre-vaccination antibody levels are low. Absolute changes in bead assay values, although not a standard computation, appears to more accurately reflect the host response to vaccination for those individuals with extremely low pre-vaccination antibody levels. Conversely, for these same individuals, fold change may be very high while post-vaccination antibodies do not achieve seroprotective levels. Absolute change provides an alternate method to characterize host response to vaccination, especially when pre-vaccination levels are very low, and may be useful in studies designed to determine associations between host genotypes and response to vaccination.

Increased risk of acute hepatitis B among adults with diagnosed diabetes mellitus.

INTRODUCTION: The risk of acute hepatitis B among adults with diabetes mellitus is unknown. We investigated the association between diagnosed diabetes and acute hepatitis B. METHODS: Confirmed acute hepatitis B cases were reported in 2009-2010 to eight Emerging Infections Program (EIP) sites; diagnosed diabetes status was determined. Behavioral Risk Factor Surveillance System respondents residing in EIP sites comprised the comparison group. Odds ratios (ORs) comparing acute hepatitis B among adults with diagnosed diabetes versus without diagnosed diabetes were determined by multivariate logistic regression, adjusting for age, sex, and race/ethnicity, and stratified by the presence or absence of risk behaviors for hepatitis B virus (HBV) infection. RESULTS: During 2009-2010, EIP sites reported 865 eligible acute hepatitis B cases among persons aged ≥23 years; 95 (11.0%) had diagnosed diabetes. Comparison group diabetes prevalence was 9.1%. Among adults without hepatitis B risk behaviors and with reported diabetes status, the OR for acute hepatitis B comparing adults with and without diabetes was 1.9 (95% confidence interval [CI] = 1.4, 2.6); ORs for adults ages 23-59 and ≥60 years were 2.1 (95% CI = 1.6, 2.8) and 1.5 (95% = CI 0.9, 2.5), respectively. CONCLUSIONS: Diabetes was independently associated with an increased risk for acute hepatitis B among adults without HBV risk behaviors.

Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting.

OBJECTIVE: Hyperglycemia worsens outcomes in critical illness. This randomized, double-blind, placebo-controlled clinical trial tested whether insulin treatment of hyperglycemia during cardiopulmonary bypass would reduce neurologic, neuro-ophthalmologic, and neurobehavioral outcomes after coronary artery bypass grafting. METHODS: Three hundred eighty-one nondiabetic patients undergoing isolated coronary artery bypass grafting were given infusions of insulin or placebo when their blood glucose concentration exceeded 100 mg/dL during cardiopulmonary bypass. The primary outcome measure was the combined incidence of new neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death observed at 4 to 8 days postoperatively. This same measure was assessed secondarily at 6 weeks and 6 months. Length of hospital stay was also compared as a secondary assessment. RESULTS: The 2 groups were well matched at baseline. The insulin-treated group had significantly lower blood glucose concentrations during bypass. Sixty-six percent of subjects in the insulin-treated group and 67% of subjects in the control group demonstrated a new or worsening neurologic, neuro-ophthalmologic, or neurobehavioral deficit or neurologic death at the 4- to 8-day assessment. Outcomes were also similar in the 2 groups at 6 weeks (37% and 39% incidence, respectively) and 6 months (30% and 25%, respectively). Median lengths of stay were 7 and 6 days, respectively, in the treatment and control groups. None of these outcome differences was statistically significant. CONCLUSION: Attempted control of hyperglycemia during cardiopulmonary bypass had no significant effect on the combined incidence of neurologic, neuro-ophthalmologic, or neurobehavioral deficits or neurologic death and failed to shorten the length of hospital stay. These results do not contradict those of other studies showing that aggressive control of hyperglycemia in the postoperative period will improve outcome.

The impact of pedigree structure on heritability estimates for pulse pressure in three studies.

OBJECTIVES: Pulse pressure (PP) is a measure of large artery stiffness and has been shown to be an important predictor of cardiovascular morbidity and mortality. The aims of the present study were to investigate the heritability of PP in three studies, the Diabetes Heart Study (DHS), the Insulin Resistance Atherosclerosis Family Study (IRAS FS), and the NHLBI Family Heart Study (FHS), to estimate the residual heritability after inclusion of a common set of covariates, and to investigate the impact of pedigree structure on estimating heritability. METHODS AND RESULTS: DHS is primarily a sibling pair nuclear family study design, while both IRAS FS and FHS have large pedigrees. Heritability estimates of log-transformed PP were obtained using variance component models. After adjusting for age, gender, ethnicity/center, height, diabetes status, and mean arterial pressure (MAP), heritability estimates of PP were 0.40 +/- 0.08 , 0.22 +/- 0.05, and 0.19 +/- 0.03 in DHS, IRAS FS, and FHS, respectively. The heritability estimate from DHS was significantly different from both IRAS FS and FHS (both p values <0.05). A random re-sampling technique (modified bootstrap) was used to explore the heritability in the IRAS FS and FHS data when these pedigrees were trimmed to mimic the DHS pedigree structure. The re-sampling method (mimicking a sibling pair nuclear family design in all studies) yielded PP heritability estimates of 0.37, 0.34, and 0.27 in DHS, IRAS FS, and FHS, respectively. There was no significant difference among the heritability estimates from the three studies based on the re-sampling method. CONCLUSION: We have shown that PP has a moderately heritable component in three different studies. These data illustrate the influence of pedigree structure can have on estimating heritability. Thoughtful comparisons of heritability estimates must consider study design factors such as pedigree structure.

Metabolic predictors of 5-year change in weight and waist circumference in a triethnic population: the insulin resistance atherosclerosis study.

Insulin resistance, insulin secretion, and glucose tolerance may predict weight change. A total of 1,194 adults aged 39-69 years at baseline (46% with normal glucose tolerance according to World Health Organization criteria, 23% with impaired glucose tolerance, and 31% with type 2 diabetes mellitus who were not taking insulin) were evaluated at baseline (1992-1994) and after 5 years. Baseline insulin sensitivity (S(I)) was measured by means of a 12-sample, insulin-enhanced, frequently sampled intravenous glucose tolerance test. Insulin secretion was assessed in terms of acute insulin response and disposition index, both obtained from the frequently sampled intravenous glucose tolerance test. At follow-up, 25% of subjects had lost more than 2.27 kg (>5 pounds), 38% weighed within 2.27 kg of their baseline weight, and 37% had gained more than 2.27 kg. In separate models, greater weight loss occurred among those with type 2 diabetes than among those with either impaired glucose tolerance or normal glucose tolerance (p < 0.001); baseline acute insulin response and disposition index were positively associated and baseline fasting insulin level was inversely associated with 5-year weight change (p < 0.05 for each; data were adjusted for baseline body mass index and demographic and behavior change variables). Upon simultaneous inclusion of metabolic variables within glucose tolerance status groups, none was a significant predictor of weight loss. Apart from glucose tolerance status itself, measures of insulin metabolism appear to have little effect on weight change over 5 years.