Abstract Background Lead is toxic and affects neurodevelopment in children even at low levels. There has been a long-term effort in the United States to reduce exposure to lead in the environment. We ...studied the latest US population blood lead levels and analyzed its trend. Method Blood lead levels in 63,890 participants of the National Health Nutrition and Examination Survey 1999-2014 were analyzed using SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). Results Mean blood lead levels and 95% confidence intervals (CIs) were 1.65 μg/dL (1.62-1.68), 1.44 μg/dL (1.42-1.47), 1.43 μg/dL (1.40-1.45), 1.29 μg/dL (1.27-1.32), 1.27 μg/dL (1.25-1.29), 1.12 μg/dL (1.10-1.14), 0.97 μg/dL (0.95-0.99), and 0.84 μg/dL (0.82-0.86) in 1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012, and 2013-2014, respectively. Blood lead levels decreased significantly ( P <.001), and the trend remained significant when stratified by age, gender, ethnicity, and pregnancy status ( P <.05). Estimated percentages of children with blood lead level ≥5 μg/dL were 9.9% (95% CI, 7.5-12.9), 7.4% (95% CI, 5.9-9.4), 5.3% (95% CI, 4.1-6.9), 2.9% (95% CI, 2.1-3.9), 3.1% (95% CI, 2.0-4.8), 2.1% (95% CI, 1.5-3.1), 2.0% (95% CI, 1.0-3.6), and 0.5% (95% CI, 0.3-1.0) in 1999-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012, and 2013-2014, respectively. The decreasing trend was significant ( P <.05). In children aged 1 to 5 years in the National Health Nutrition and Examination Survey 2011-2014, the estimated 97.5 percentile of blood lead level was 3.48 μg/dL. Conclusions Blood lead levels have been decreasing in the US population. The reference level also should decrease. It is still important to monitor blood lead levels in the population, especially among pregnant women and children aged 1 to 5 years.
Background & Aims
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key to viral persistence in chronic hepatitis B infection. Serum hepatitis B core‐related antigen (HBcrAg) is a ...novel marker for HBV disease. We aimed to determine whether HBcrAg could be a surrogate marker for intrahepatic cccDNA.
Methods
Three hundred and five liver biopsies and the corresponding sera collected from 138 nucleos(t)ide analogues‐treated patients were analysed. 124 patients had paired liver biopsies at baseline and 1‐year post‐treatment, and 43 patients had a third biopsy after 6‐12 years of treatment. Serum HBcrAg, HBV DNA and hepatitis B surface antigen (HBsAg), and intrahepatic HBV DNA and cccDNA were measured.
Results
HBcrAg strongly correlated with cccDNA (r=.70), intrahepatic total HBV DNA (r=.67) and serum HBV DNA (r=.69; all P<.0001). In the 130 samples with undetectable serum HBV DNA, HBcrAg was detectable in 101 (78%) samples, and HBcrAg levels still correlated positively with cccDNA (r=.42, P<.0001). At ≥6 years of therapy, the median logarithmic reduction in HBcrAg was 2.7 log kU/mL, which was comparable to the magnitude of reduction in cccDNA. Twenty‐one patients had undetectable cccDNA after ≥6 years of treatment, in whom 15 (71%) had detectable HBcrAg (range: 1.2‐537 kU/mL).
Conclusions
Serum HBcrAg is a reliable surrogate marker for intrahepatic cccDNA. HBcrAg could be a very sensitive marker to reflect the cccDNA content and persistence of disease even with the cccDNA levels below the detection limit of assays.
Severe COVID‐19 has a poor prognosis, while the genetic mechanism underlying severe COVID‐19 remains largely unknown. We aimed to identify genes that are potentially causally associated with severe ...COVID‐19. We conducted a summary data‐based Mendelian randomization (SMR) analysis using expression quantitative trait loci (eQTL) data from 49 different tissues as the exposure and three COVID‐19‐phenotypes (very severe respiratory confirmed COVID‐19 severe COVID‐19, hospitalized COVID‐19, and SARS‐CoV‐2 infection) as the outcomes. SMR using multiple SNPs was used as a sensitivity analysis to reduce false positive rate. Multiple testing was corrected using the false discovery rate (FDR) q‐value. We identified 309 significant gene‐trait associations (FDR q value < 0.05) across 46 tissues for severe COVID‐19, which mapped to 64 genes, of which 38 are novel. The top five most associated protein‐coding genes were Interferon Alpha and Beta Receptor Subunit 2 (IFNAR2), 2′‐5′‐Oligoadenylate Synthetase 3 (OAS3), mucin 1 (MUC1), Interleukin 10 Receptor Subunit Beta (IL10RB), and Napsin A Aspartic Peptidase (NAPSA). The potential causal genes were enriched in biological processes related to type I interferons, interferon‐gamma inducible protein 10 production, and chemokine (C‐X‐C motif) ligand 2 production. In addition, we further identified 23 genes and 5 biological processes which are unique to hospitalized COVID‐19, as well as 13 genes that are unique to SARS‐CoV‐2 infection. We identified several genes that are potentially causally associated with severe COVID‐19. These findings improve our limited understanding of the mechanism of COVID‐19 and shed light on the development of therapeutic agents for treating severe COVID‐19.
The significance of hepatitis B e‐antigen (HBeAg) seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive ...scores for hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3‐ to 6‐monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC‐ESC) and HBsAg seroclearance (HBsAg‐ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow‐up of 36.0 and 18.3 years, respectively. Only 3.5% and 3.0% had persistently normal alanine aminotransferase (ALT) and HBV DNA <2logs IU/mL, respectively, after ESC. For patients with 100%, 100%‐90%, 90%‐50%, 50%‐10%, 10%‐0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC, respectively (P < 0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5%, respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The area under receiver operating characteristics for HCC‐ESC and HBsAg‐ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74, respectively. Conclusion: Male sex, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC‐ESC and HBsAg‐ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. (Hepatology 2018)
Introduction: Obesity is a public health crisis in the USA. This study aimed to estimate the prevalence of obesity and severe obesity in US children and adolescents and identify novel targetable risk ...factors associated with childhood obesity. Methods: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35,907 children aged 2–19 with body mass index (BMI) data were included. Obesity and severe obesity were defined as BMI ≥95th percentile and ≥120% of 95th percentile of US Centers for Disease Control and Prevention growth charts, respectively. Trends in the prevalence of obesity and subgroup analyses according to socioeconomic factors and language used in the interview were analyzed. Results: The prevalence of obesity and severe obesity increased from 14.7 95% confidence interval: 12.9–17.0% to 19.2 17.2–21.0% and 3.9 2.9–5.0% to 6.1 4.8–8.0% in 1999–2018, respectively (p = 0.001 and p = 0.014, respectively). In 2017–2018, the prevalence of obesity among children from Spanish-speaking households was 24.4 22.4–27.0%, higher than children from English-speaking households (p = 0.027). Conclusion: The prevalence of childhood obesity kept increasing in 1999–2018. The problem is worse in children from Spanish-speaking households. Novel and targeted public health intervention strategies are urgently warranted to effectively halt the rising epidemic of childhood obesity.
Several studies reported hematological abnormalities after vaccination against the coronavirus disease 2019 (COVID‐19). We evaluated the association between COVID‐19 vaccines (CoronaVac and BNT162b2) ...and hematological abnormalities. We conducted nested case–control and self‐controlled case series analyses using the data from the Hong Kong Hospital Authority and the Department of Health, HKSAR. Outcomes of interest were thrombocytopenia, leukopenia, and neutropenia. Adjusted odds ratios (aORs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In total, 1 643 419 people received COVID‐19 vaccination (738 609 CoronaVac; 904 810 BNT162b2). We identified 457 and 422 cases after CoronaVac and BNT162b2 vaccination, respectively. For CoronaVac, the incidence of thrombocytopenia, leukopenia, and neutropenia was 2.51, 1.08, and 0.15 per 10 000 doses. For BNT162b2, the corresponding incidence was 1.39, 1.17, and 0.26 per 10 000 doses. The incidence per 10 000 COVID‐19 cases were 1254, 2341, and 884, respectively. We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24–2.02; day 0–14, IRR 2.21; 95% CI 1.59–3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID‐19 still outweigh the risk of hematological abnormalities.
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