Hepatitis C Virus-HIV Coinfection in the United States Among People Who Inject Drugs: Data Needed for Ending Dual Epidemics.

The overlapping epidemics of hepatitis C virus (HCV) and HIV infection stem from underlying behaviors and health disparities among disproportionately affected populations, especially people who inject drugs (PWID). Characterizing the prevalence of HCV-HIV coinfection offers improved data to address these underlying determinants of health. We performed a literature search for articles that describe US populations, were published during 2005-2021, and summarized evidence of the prevalence of HCV infection in recent HIV clusters and outbreaks among PWID. In population- and community-based studies, HCV antibody prevalence among PWID with HIV ranged from 10.7% to 71.4%, depending on the setting and study design. HCV-HIV coinfection ranged from 70% to 94% among 5 larger HIV clusters or outbreaks among PWID during 2014-2021; where characterized, HCV diagnosis preceded HIV detection by a median of 4 to 5 years. Robust modernized surveillance is needed to support and measure the progress of city, state, and national activities for ending the HIV epidemic and eliminating hepatitis C. Developing and leveraging surveillance systems can identify missed opportunities for prevention, evaluate care, and build capacity for outbreak investigation. In addition, improved data on injection drug use are crucial to inform efforts for improved HCV and HIV testing, prevention, and treatment in settings that serve PWID. By providing data in a wholistic, integrated manner, public health surveillance programs can support efforts to overcome inefficiencies of disease-specific silos, accelerate delivery of preventive and clinical services, and address the excess disease burden and health disparities associated with HCV-HIV coinfection.

Progress and Unfinished Business: Hepatitis B in the United States, 1980-2019.

During 1990-2019, universal infant and childhood vaccination for hepatitis B resulted in a 99% decline in reported cases of acute hepatitis B among children, adolescents, and young adults aged <19 years in the United States; however, during 2010-2019, cases of acute hepatitis B plateaued or increased among adults aged ≥40 years. We conducted a topical review of surveillance strategies that will be critical to support the elimination of hepatitis B as a public health threat in the United States. In 2019, notifiable disease surveillance for acute hepatitis B showed continued transmission, especially among people who inject drugs and people with multiple sexual partners; rates were highest among people who were aged 30-59 years, non-Hispanic White, and living in rural areas. In contrast, newly reported cases of chronic hepatitis B (CHB) were highest among people who were aged 30-49 years, Asian or Pacific Islander, and living in urban areas. The National Health and Nutrition Examination Survey documented the highest CHB prevalence among non-US-born, non-Hispanic Asian people during 2013-2018; only one-third of people with CHB were aware of their infection. In the context of universal adult vaccination (2022) and screening (2023) recommendations for hepatitis B, better data are needed to support programmatic strategies to improve (1) vaccination rates among people with behaviors that put them at risk for transmission and (2) screening and linkage to care among non-US-born people. Surveillance for hepatitis B needs to be strengthened throughout the health care and public health systems.

Characteristics of Emergency Department Patient Visits Referred for Follow-Up Medical Care After Discharge, National Hospital Ambulatory Medicare Care Survey-United States, 2018.

Objective: To describe characteristics of a nationally representative sample of patient visits that ended with a referral for follow-up medical care after discharge from hospital emergency department (ED) visits. Methods: We used 2018 National Hospital Ambulatory Medical Care Survey data to identify patient characteristics associated with higher rates of visits with referrals for follow-up medical care after ED discharge from nonfederal short-stay and general hospitals throughout the United States. Referral included categories of all disposition variables that indicated referral to a source of care consistent with the patient's clinical condition at ED discharge. Results: Approximately 97 million of 130 million visits (29 700/100 000 US resident population) were referred for follow-up medical care during 2018. Visit referral rates were higher among females (33 100) than among males (26 300/100 000 population); higher among Black patients (61 700) than among White patients (25 600/100 000 population); highest in the South (33 200/100 000 population); and similar rates in Nonmetropolitan (29 900/100 000 population) and Metropolitan Statistical Areas (30 200/100 000 population). Visit referral rates were higher for patients with Medicaid/Children's Health Insurance Program (CHIP) (66 900) than those with Medicare (31 500) or private insurance (14 000/100 000 population). Abnormal clinical findings and injuries were the discharge diagnoses most often referred for follow-up medical care. Conclusion: Higher visit referral rates were observed among female sex, non-Hispanic Black race, Medicaid/CHIP, abnormal clinical findings, and injuries. Future studies might reveal reasons that prompted higher referral rates among various patients' characteristics.

Characteristics of Persons Treated for Hepatitis C Using National Pharmacy Claims Data, United States, 2014-2020.

Using national pharmacy claims data for 2014-2020, 843 329 persons were treated for hepatitis C at least once. The proportion treated increased annually among persons aged <40 years, insured by Medicaid, and treated by primary care providers. Monitoring hepatitis C treatment is essential to identify barriers to treatment access.

Prevalence of HBV Infection, Vaccine-Induced Immunity, and Susceptibility Among At-Risk Populations: US Households, 2013-2018.

BACKGROUND AND AIMS: In the USA, HBV is one of the leading causes of chronic liver disease and cirrhosis and is a major cause of liver cancer. We aimed to estimate the prevalence of past and present HBV infection, susceptibility to HBV infection, and vaccine-induced immunity to hepatitis B among the US population during 2013-2018. APPROACH AND RESULTS: Prevalence estimates and 95% CIs were analyzed using 2013-2018 data from the National Health and Nutrition Examination Survey. Serologic testing among noninstitutionalized persons aged ≥ 6 years was used for classifying persons as total hepatitis B core antibody (anti-HBc), indicative of current or previous (ever having had) HBV infection; HBsAg, indicative of current HBV infection; and antibody to ABsAg (anti-HBs), indicative of immunity attributable to hepatitis B vaccination. Persons who tested negative for anti-HBc, HBsAg, and anti-HBs were considered susceptible to HBV infection. Non-US-born residents accounted for 69.1% of the population with chronic HBV infection and were 9.1 times more likely to be living with chronic hepatitis B, compared with US-born persons. Among adults aged ≥ 25 years who resided in US households, an estimated 155.8 million persons (or 73.4%) were susceptible to HBV infection, and an estimated 45.4 million had vaccine-induced immunity to hepatitis B. Men who have sex with men (MSM) were 3.6 times more likely to have ever been infected with HBV; however, MSM were just as likely to have vaccine-induced immunity to hepatitis B as non-MSM. CONCLUSION: Despite increasing immune protection among young persons vaccinated after birth, the estimated prevalence of persons living with chronic hepatitis B in the USA has remained unchanged at 0.3% since 1999.

Sexually Transmitted Infections Among US Women and Men: Prevalence and Incidence Estimates, 2018.

BACKGROUND: The most recent estimates of the number of prevalent and incident sexually transmitted infections (STIs) in the United States were for 2008. We provide updated estimates for 2018 using new methods. METHODS: We estimated the total number of prevalent and incident infections in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus, sexually transmitted hepatitis B, and sexually transmitted HIV. Updated per-capita prevalence and incidence estimates for each STI were multiplied by the 2018 full resident population estimates to calculate the number of prevalent and incident infections. STI-specific estimates were combined to generate estimates of the total number of prevalent and incident STIs overall, and by sex and age group. Primary estimates are represented by medians, and uncertainty intervals are represented by the 25th (Q1) and 75th (Q3) percentiles of the empirical frequency distributions of prevalence and incidence for each STI. RESULTS: In 2018, there were an estimated 67.6 (Q1, 66.6; Q3, 68.7) million prevalent and 26.2 (Q1, 24.0; Q3, 28.7) million incident STIs in the United States. Chlamydia, trichomoniasis, genital herpes, and human papillomavirus comprised 97.6% of all prevalent and 93.1% of all incident STIs. Persons aged 15 to 24 years comprised 18.6% (12.6 million) of all prevalent infections; however, they comprised 45.5% (11.9 million) of all incident infections. CONCLUSIONS: The burden of STIs in the United States is high. Almost half of incident STIs occurred in persons aged 15 to 24 years in 2018. Focusing on this population should be considered essential for national STI prevention efforts.

The Estimated Direct Lifetime Medical Costs of Sexually Transmitted Infections Acquired in the United States in 2018.

BACKGROUND: We estimated the lifetime medical costs attributable to sexually transmitted infections (STIs) acquired in 2018, including sexually acquired human immunodeficiency virus (HIV). METHODS: We estimated the lifetime medical costs of infections acquired in 2018 in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs, such as STI prevention. For each STI, except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually. RESULTS: Incident STIs in 2018 imposed an estimated $15.9 billion (25th-75th percentile: $14.9-16.9 billion) in discounted, lifetime direct medical costs (2019 US dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one fourth of the cost of incident STIs when including HIV, but about three fourths when excluding HIV. STIs among 15- to 24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs. CONCLUSIONS: Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.

Incidence and Prevalence of Sexually Transmitted Hepatitis B, United States, 2013-2018.

BACKGROUND: Sexual transmission of hepatitis B virus (HBV) is common in the United States. In 2008, an estimated 50% of HBV infections were attributed to sexual transmission. Among 21,600 acute infections that occurred in 2018, the proportion attributable to sexual transmissions is unknown. METHODS: Objectives of this study were to estimate incidence and prevalence of hepatitis B attributable to sexual transmission among the US population 15 years and older for 2013 to 2018. Incidence estimates were calculated for confirmed cases submitted to Centers for Disease Control and Prevention from 14 states. A hierarchical algorithm defining sexually transmitted acute HBV infections as the absence of injection drug use among persons reporting sexual risk factors was applied to determine proportion of hepatitis B infections attributable to sexual transmission nationally. National Health and Nutrition Examination Survey public use data files were analyzed to calculate prevalence estimates of hepatitis B among US households and proportion attributed to sexual transmission was conservatively determined for HBV-infected non-US-born Americans who migrated from HBV endemic countries. RESULTS: During 2013 to 2018, an estimated 47,000 (95% confidence interval [CI], 27,000-116,000) or 38.2% of acute HBV infections in the United States were attributable to sexual transmission. During 2013 to 2018, among the US noninstitutionalized population, an estimated 817,000 (95% CI, 613,000-1,100,000) persons 15 years and older were living with hepatitis B, with an estimated 103,000 (95% CI, 89,000-118,000) infections or 12.6% attributable to sexual transmission. CONCLUSIONS: These findings provide evidence sexually transmitted HBV infections remain a public health problem and underscore the importance of interventions to improve vaccination among at-risk populations.

Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed. AIMS: To assess the incidence of PG and identify factors associated with PG in IBD patients. METHODS: A search of electronic databases (Ovid and PubMed) was conducted between 1966 and 2019. Studies that calculated the incidence of PG in IBD patient cohorts were included. Patient demographics, IBD subtype, and EIM presence were recorded. A review of our institutional database of 1057 IBD patients was conducted. A multivariate regression model and meta-analysis were conducted to identify risk factors for PG. A random effects model was used to combine the data of included studies. RESULTS: Fourteen studies were included in addition to 1057 IBD patients and 26 PG cases from the Louisville cohort. In total, there were 379 cases of PG in the cumulative cohort of 61,695 IBD patients. The PG incidence in individual studies ranged from 0.4 to 2.6%. In the institutional cohort, ocular EIMs and a permanent stoma were significant risk factors for PG. In the meta-analysis, PG was associated with female gender (RR = 1.328, 95% CI 1.161-1.520), Crohn's disease (RR = 1.193, 95% CI 1.001-1.422), erythema nodosum (RR = 9.281, 95% CI 6.081-14.164), and ocular EIM (RR = 4.55, 95% CI 3.04-6.81). There was study heterogeneity when assessing IBD subtype, ocular, and joint EIMs. CONCLUSIONS: There are conflicting data on the incidence and risk factors for PG. This meta-analysis confirms an association between PG and female gender, Crohn's disease, erythema nodosum, and ocular EIM that have been described in smaller studies.

Deaths Associated With Hepatitis C Virus Infection Among Residents in 50 States and the District of Columbia, 2016-2017.

BACKGROUND: Mortality associated with hepatitis C virus (HCV) has been well-documented nationally, but an examination across regions and jurisdictions may inform health-care planning. METHODS: To document HCV-associated deaths sub-nationally, we calculated age-adjusted, HCV-associated death rates and compared death rate ratios (DRRs) for 10 US regions, 50 states, and Washington, D.C., using the national rate and described rate changes between 2016 and 2017 to determine variability. We examined the mean age at HCV-associated death, and rates and proportions by sex, race/ethnicity, and birth year. RESULTS: In 2017, there were 17 253 HCV-associated deaths, representing 4.13 (95% confidence interval [CI], 4.07-4.20) deaths/100 000 standard population, in a significant, 6.56% rate decline from 4.42 in 2016. Age-adjusted death rates significantly surpassed the US rate for the following jurisdictions: Oklahoma; Washington, D.C.; Oregon; New Mexico; Louisiana; Texas; Colorado; California; Kentucky; Tennessee; Arizona; and Washington (DRRs, 2.87, 2.77, 2.24, 1.62, 1.57, 1.46, 1.36, 1.35, 1.35, 1.35, 1.32, and 1.32, respectively; P < .05). Death rates ranged from a low of 1.60 (95% CI, 1.07-2.29) in Maine to a high of 11.84 (95% CI, 10.82-12.85) in Oklahoma. Death rates were highest among non-Hispanic (non-H) American Indians/Alaska Natives and non-H Blacks, both nationally and regionally. The mean age at death was 61.4 years (range, 56.6 years in West Virginia to 64.1 years in Washington, D.C.), and 78.6% of those who died were born during 1945-1965. CONCLUSIONS: In 2016-2017, the national HCV-associated mortality declined but rates remained high in the Western and Southern regions and Washington, D.C., and among non-H American Indians/Alaska Natives, non-H Blacks, and Baby Boomers. These data can inform local prevention and control programs to reduce the HCV mortality burden.

Underreporting of Hepatitis B and C virus infections - Pennsylvania, 2001-2015.

CONTEXT: In Pennsylvania, reporting of viral hepatitis B (HBV) and viral hepatitis C (HCV) infections to CDC has been mandated since 2002. Underreporting of HBV and HCV infections has long been identified as a problem. Few reports have described the accuracy of state surveillance case registries for recording clinically-confirmed cases of HBV and HCV infections, or the characteristics of populations associated with lower rates of reporting. OBJECTIVE: The primary objective of the current study is to estimate the proportion of HBV and HCV infections that went unreported to the Pennsylvania Department of Health (PDoH), among patients in the Geisinger Health System of Pennsylvania. As a secondary objective, we study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest: sex, age group, race/ethnicity, rural status, and year of initial diagnosis. DESIGN: Per medical record review, the study population was limited to Geisinger Health System patients, residing in Pennsylvania, who were diagnosed with a chronic HBV and/or HCV infection, between 2001 and 2015. Geisinger Health System patient medical records were matched to surveillance records of confirmed cases reported to the Pennsylvania Department of Health (PDoH). To quantify the extent that underreporting occurred among the Geisinger Health System study participants, we calculated the proportion of study participants that were not reported to PDoH as confirmed cases of HBV or HCV infections. An analysis of adjusted prevalence ratio estimates was conducted to study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest. RESULTS: Geisinger Health System patients living with HBV were reported to PDoH 88.4% (152 of 172) of the time; patients living with HCV were reported to PDoH 94.6% (2,257 of 2,386) of the time; and patients who were co-infected with both viruses were reported to PDoH 72.0% (18 of 25) of the time. Patients living with HCV had an increased likelihood of being reported if they were: less than or equal to age 30 vs ages 65+ {PR = 1.2, [95%CI, (1.1, 1.3)]}, and if they received their initial diagnosis of HCV during the 2010-2015 time period vs the 1990-1999 time period {PR = 1.08, [95%CI, (1.05, 1.12)]}. CONCLUSION: The findings in this study are promising, and suggests that PDoH has largely been successful with tracking and monitoring viral hepatitis B and C infections, among persons that were tested for HBV and/or HCV. Additional efforts should be placed on decreasing underreporting rates of HCV infections among seniors (ages 65 and over), and persons who are co-infected with HBV and HCV.

Estimating Annual Births to Hepatitis B Surface Antigen-Positive Women in the United States by Using Data on Maternal Country of Birth.

OBJECTIVE: A national estimate of births to hepatitis B surface antigen (HBsAg)-positive women can help public health programs plan surveillance, educational, and outreach activities to improve identification and management of at-risk women and infants. Stratifying mothers by country of birth allows for the application of region-specific HBsAg prevalence estimates, which can more precisely estimate the number of at-risk infants. The objective of our study was to estimate the number of births to HBsAg-positive women in the United States with more granularity than previous models. METHODS: We developed a model that incorporated maternal country of birth (MCOB) and updated HBsAg prevalence estimates. We assessed birth certificate data by MCOB, and we stratified US-born mothers by race/ethnicity, US territory-born mothers by territory, and non-US-born mothers by region. We multiplied and summed data in each subcategory by using HBsAg prevalence estimates calculated from the 2009-2014 National Health and Nutrition Examination Surveys or Perinatal Hepatitis B Prevention Program. We compared the findings of our MCOB model with a race/ethnicity model. RESULTS: In 2015, an estimated 20 678 infants were born to HBsAg-positive women in the United States, representing 0.5% of all births. Births to US-born and non-US-born women comprised 77.2% and 21.5% of all births, respectively, and 40.1% and 57.9% of estimated births to HBsAg-positive women, respectively. The estimated contribution of births to HBsAg-positive women varied by MCOB region, from 4 (0.03%) infants born to women from Australia/Oceania to 5795 (28.0%) infants born to women from East Asia. Our MCOB model estimated 5666 fewer births to HBsAg-positive women than did the race/ethnicity model. CONCLUSIONS: As global vaccine programs reduce HBsAg prevalence, the MCOB model can incorporate evolving HBsAg prevalence estimates for women from various regions of the world.

Development of a human cadaver model for training in laparoscopic donor nephrectomy.

BACKGROUND: The organ procurement network recommends a surgeon record 15 cases as surgeon or assistant for laparoscopic donor nephrectomies (LDN) prior to independent practice. The literature suggests that the learning curve for improved perioperative and patient outcomes is closer to 35 cases. In this article, we describe our development of a model utilizing fresh tissue and objective, quantifiable endpoints to document surgical progress, and efficiency in each of the major steps involved in LDN. MATERIALS AND METHODS: Phase I of model development focused on the modifications necessary to maintain visualization for laparoscopic surgery in a human cadaver. Phase II tested proposed learner-based metrics of procedural competency for multiport LDN by timing procedural steps of LDN in a novice learner. RESULTS: Phases I and II required 12 and nine cadavers, with a total of 35 kidneys utilized. The following metrics improved with trial number for multiport LDN: time taken for dissection of the gonadal vein, ureter, renal hilum, adrenal and lumbrical veins, simulated warm ischemic time (WIT), and operative time. CONCLUSION: Human cadavers can be used for training in LDN as evidenced by improvements in timed learner-based metrics. This simulation-based model fills a gap in available training options for surgeons.

A Highly Predictive Model for Diagnosis of Colorectal Neoplasms Using Plasma MicroRNA: Improving Specificity and Sensitivity.

OBJECTIVE: To develop a plasma-based microRNA (miRNA) diagnostic assay specific for colorectal neoplasms, building upon our prior work. BACKGROUND: Colorectal neoplasms [colorectal cancer (CRC) and colorectal advanced adenoma (CAA)] frequently develop in individuals at ages when other common cancers also occur. Current screening methods lack sensitivity, specificity, and have poor patient compliance. METHODS: Plasma was screened for 380 miRNAs using microfluidic array technology from a "Training" cohort of 60 patients, (10 each) control, CRC, CAA, breast cancer, pancreatic cancer, and lung cancer. We identified uniquely dysregulated miRNAs specific for colorectal neoplasia (P < 0.05, false discovery rate: 5%, adjusted α = 0.0038). These miRNAs were evaluated using single assays in a "Test" cohort of 120 patients. A mathematical model was developed to predict blinded sample identity in a 150 patient "Validation" cohort using repeat-sub-sampling validation of the testing dataset with 1000 iterations each to assess model detection accuracy. RESULTS: Seven miRNAs (miR-21, miR-29c, miR-122, miR-192, miR-346, miR-372, and miR-374a) were selected based upon P value, area under the curve (AUC), fold change, and biological plausibility. Area under the curve (±95% confidence interval) for "Test" cohort comparisons were 0.91 (0.85-0.96) between all neoplasia and controls, 0.79 (0.70-0.88) between colorectal neoplasia and other cancers, and 0.98 (0.96-1.0) between CRC and colorectal adenomas. In our "Validation" cohort, our mathematical model predicted blinded sample identity with 69% to 77% accuracy, 67% to 76% accuracy, and 86% to 90% accuracy for each comparison, respectively. CONCLUSIONS: Our plasma miRNA assay and prediction model differentiate colorectal neoplasia from patients with other neoplasms and from controls with higher sensitivity and specificity compared with current clinical standards.

Hepatitis A Infections Among Food Handlers in the United States, 1993-2011.

We reviewed news reports of hepatitis A virus (HAV)-infected food handlers in the United States from 1993 to 2011 using the LexisNexis® search engine. Using U.S. news reports, we identified 192 HAV-infected food handlers who worked while infectious; of these HAV-infected individuals, 34 (18%) transmitted HAV to restaurant patrons. News reports of HAV-infected food handlers declined from 1993 to 2011. This analysis suggests that universal childhood vaccination contributed to the decrease in reports of HAV-infected food handlers, but mandatory vaccination of this group is unlikely to be cost-effective.

Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012.

UNLABELLED: The number of persons with chronic hepatitis B virus (HBV) infection in the United States is affected by diminishing numbers of young persons who are susceptible because of universal infant vaccination since 1991, offset by numbers of HBV-infected persons migrating to the United States from endemic countries. The prevalence of HBV infection was determined by serological testing and analysis among noninstitutionalized persons age 6 years and older for: antibody to hepatitis B core antigen (anti-HBc), indicative of previous HBV infection; hepatitis B surface antigen (HBsAg), indicative of chronic (current) infection; and antibody to hepatitis B surface antigen (anti-HBs), indicative of immunity from vaccination. These prevalence estimates were analyzed in three periods of the National Health and Nutrition Examination Survey (NHANES): 1988-1994 (21,260 persons); 1999-2008 (29,828); and 2007-2012 (22,358). In 2011-2012, for the first time, non-Hispanic Asians were oversampled in NHANES. For the most recent period (2007-2012), 3.9% had anti-HBc, indicating approximately 10.8 (95% confidence interval [CI]: 9.4-12.2) million noninstitutionalized U.S. residents having ever been infected with HBV. The overall prevalence of chronic HBV infection has remained constant since 1999: 0.3% (95% CI: 0.2-0.4), and since 1999, prevalence of chronic HBV infection among non-Hispanic blacks has been 2- to 3-fold greater than the general population. An estimated 3.1% (1.8%-5.2%) of non-Hispanic Asians were chronically infected with HBV during 2011-2012, which reflects a 10-fold greater prevalence than the general population. Adjusted prevalence of vaccine-induced immunity increased 16% since 1999, and the number of persons (mainly young) with serological evidence of vaccine protection from HBV infection rose from 57.8 (95% CI: 55.4-60.1) million to 68.5 (95% CI: 65.4-71.2) million. CONCLUSION: Despite increasing immune protection in young persons vaccinated in infancy, an analysis of chronic hepatitis B prevalence in racial and ethnic populations indicates that during 2011-2012, there were 847,000 HBV infections (which included ~400,000 non-Hispanic Asians) in the noninstitutionalized U.S. POPULATION.

Housekeeping genes for studies of plasma microRNA: A need for more precise standardization.

INTRODUCTION: Plasma microRNAs (miRNAs) are promising biomarkers for many forms of cancer in humans; however, a fundamental concern is the lack of standardization in current data acquisition and reporting. Part of this problem lies in the use of numerous, different housekeeping genes (HKG) for the acquisition of real-time polymerase chain reaction data. This existing practice of using different HKGs generally is accepted, but reproducibility of data for comparison and validation between different laboratories calls for improvement. The need for data reproducibility standardization is crucial. An ideal plasma HKG (1) should be expressed in all samples, (2) have medium-to-high levels of expression, and (3) have consistently measurable levels of expression. METHODS: Total RNA was extracted from 200-µL plasma samples via a modified miRNeasy (QIAGEN) extraction technique with yeast carrier. Total RNA purity was assessed with a Nanodrop 2000 spectrophotometer (Thermo Scientific). The cycle threshold (Ct) was fixed at 0.03 for all samples. We investigated 10 potential HKGs based both on reports in the literature and our previous data. The potential HKGs were Let-7a, Let-7d, Let-7g, miR-16, RNU6, RNU48, miR-191, miR-223, miR-484, and miR-520d-5p. Once all samples were run for each potential HKG, the mean Ct and SD was calculated for all sample groups, allowing for comparison among HKGs. RESULTS: We screened 380 miRNAs by using microfluidic array technology (Applied Biosystems) in a discovery cohort of 20 colorectal cancer (CRC) patients, 10 patients each with breast cancer (BC), lung cancer (LC), pancreatic cancer (PC), 11 patients with colorectal adenoma, and 12 controls. The mean Ct and SD was calculated for RNU6, miR-520d-5p, miR-16, miR-191, miR-223, and miR-484, which were expressed in all samples. Let-7a, Let-7d, Let-7g, and RNU48 were only expressed in 26%, 7%, 10%, and 8% of samples, respectively, and therefore were deemed to be insufficiently reliable HKGs. Only miRNAs with >50% expression were included in this statistical analysis. U6 and miR-520d-5p had the most consistent Ct as well as the least SD. The use of both RNU6 and 520d-5p as HKGs provided reliable results. CONCLUSION: Among HKGs that were expressed in all samples, we suggest that RNU6 and miR-520d-5p were the best candidates for HKGs for studies of plasma miRNA because of the consistent and high Ct in all samples and a very narrow, reproducible SD.

Assay reproducibility in clinical studies of plasma miRNA.

There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct) setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas) and 16 patients without any neoplasm (controls). Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy). We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4%) documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively). A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was negligible using modified miRNeasy. For standardized reporting, we recommend plasma extraction ≤ 12 h, using modified miRNeasy extraction and utilizing a 0.03 Ct.

Epidemiology of Acute Hepatitis B in the United States From Population-Based Surveillance, 2006-2011.

BACKGROUND: An estimated 20 000 new hepatitis B virus (HBV) infections occur each year in the United States. We describe the results of enhanced surveillance for acute hepatitis B at 7 federally funded sites over a 6-year period. METHODS: Health departments in Colorado, Connecticut, Minnesota, Oregon, Tennessee, 34 counties in New York state, and New York City were supported to conduct enhanced, population-based surveillance for acute HBV from 2006 through 2011. Demographic and risk factor data were collected on symptomatic cases using a standardized form. Serum samples from a subset of cases were also obtained for molecular analysis. RESULTS: In the 6-year period, 2220 acute hepatitis B cases were reported from the 7 sites. For all sites combined, the incidence rate of HBV infection declined by 19%, but in Tennessee incidence increased by 90%, mainly among persons of white race/ethnicity and those aged 40-49 years. Of all reported cases, 66.1% were male, 57.1% were white, 58.4% were aged 30-49 years, and 60.1% were born in the United States. The most common risk factor identified was any drug use, notably in Tennessee; healthcare exposure was also frequently reported. The most common genotype for all reported cases was HBV genotype A (82%). CONCLUSIONS: Despite an overall decline in HBV infection, attributable to successful vaccination programs, a rise in incident HBV infection related to drug use is an increasing concern in some localities.

Association of Employee Attributes and Exceptional Performance Rating at a National Center of the US Centers for Disease Control and Prevention, 2011.

CONTEXT: Employee performance evaluation motivates and rewards exceptional individual performance that advances the achievement of organizational goals. The Centers for Disease Control and Prevention (CDC) and its operating units evaluate employee performance annually and reward exceptional performance with a cash award or quality step increase in pay. A summary performance rating (SPR) of "exceptional" indicated personal achievements in 2011 that were beyond expectations described in the employee's performance plan. OBJECTIVE: To determine whether personal attributes and job setting of civil service employees were associated with an exceptional SPR in National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) in 2011. DESIGN: Data from the CDC 2011 performance management database collected in 2012 were analyzed in 2013 to identify SPR, personal attributes, and job settings of full-time civil service employees. Multivariate logistic regression controlled for confounding and stratified analysis detected effect modifiers of the association between receiving an exceptional SPR in 2011 and gender, race/ethnicity, education, job location, job series, grade level, years in grade, years of federal service, supervisory role, and NCHHSTP division. RESULTS: Among the 1037 employees, exceptional SPR was independently associated with: female gender (adjusted odds ratio: 1.7 [1.3, 2.3]), advanced degrees (doctorate: 1.7 [1.1, 2.5] master's: [1.1, 2.0]), headquarters location (2.8 [1.9, 4.1]), higher pay grade (3.3 [2.4, 4.5]) and years in grade (0-1 years: 1.7 [1.3, 2.4]; 2-4 years: 1.5 [1.1, 2.0]), division level (Division A: 5.0 [2.5, 9.9]; Division B: 5.5 [3.5, 8.8]), and supervisory status (at a lower-pay grade) (odds ratio: 3.7 [1.1, 11.3]). CONCLUSIONS: Exceptional SPR is independently associated with personal employee attributes and job settings that are not modifiable by interventions designed to improve employee performance based on accomplishments.