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Objectives. We examined HCV exposure prevalence and predictors among persons in the United States born during 1945–1965. Methods. With data from the 1999–2008 National Health and Nutrition Examination Survey, we calculated the proportion of persons born during 1945–1965 who tested positive for HCV antibody (anti-HCV) and analyzed the prevalence by sociodemographic and behavioral risk factors. Results. Anti-HCV prevalence in the 1945–1965 birth cohort was 3.2% (95% confidence interval [CI] = 2.8%, 3.8%), substantially higher than among other adults (0.9%). Within the cohort, anti-HCV prevalence was higher among non-Hispanic Blacks (6.4%; 95% CI = 5.3%, 7.7%), persons with injection drug use histories (56.8%; 95% CI = 48.4%, 64.8%), and persons with elevated alanine aminotransferase levels (12.7%; 95% CI = 10.7%, 15.1%). Injection drug use (adjusted odds ratio = 98.4; 95% CI = 58.8, 164.5) was the strongest anti-HCV prevalence predictor. Among anti-HCV–positive persons, 57.8% reported having 2 or more alcoholic drinks daily. Conclusions. With the high prevalence of HCV among persons born during 1945–1965, the increasing morbidity and mortality associated with HCV, and reductions in liver cancer and HCV-related mortality when HCV is eradicated, it is critically important to identify persons with HCV and link them to appropriate care.

Objective. Hepatitis B virus (HBV) infection continues to be a public health threat in the United States. As many as 2.2 million people are infected, approximately 70% of whom are foreign-born, and fewer than one-third are aware of their infection. We launched an HBV testing and linkage-to-care initiative among foreign-born people. Methods. As part of the Hepatitis Testing and Linkage to Care (HepTLC) initiative, which promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites, nine U.S. programs in seven states conducted HBV screening from October 2012 to September 2014. The nine programs partnered with health-care centers and community-based organizations to recruit foreign-born people recommended for HBV testing. We assessed patient characteristics, region of origin, risk factors, hepatitis B surface antigen (HBsAg) status, and referral to medical care. Results. Of 23,144 participants tested for HBV, 1,317 (5.7%) were HBsAg positive. Of these, the median age was 47 years, 1,205 (91%) had at least one risk factor for HBV infection, 1,117 (85%) received posttest counseling, 1,098 (83%) were referred to care, and 606 (46%) attended a first medical appointment. The proportion of HBsAg-positive participants by region of origin included Africa (10%, 206/2,129), Western Pacific (6%, 616/9,673), Eastern Mediterranean (5%, 174/3,337), Southeast Asia (5%, 191/3,891), South America (2%, 6/252), Eastern Europe (2%, 6/262), and North America (1%, 17/1,936). Conclusion. Community-based HBV testing initiatives can identify substantial numbers of people with chronic HBV infection, inform them of their infection status, and provide posttest counseling and linkage to care. However, strategies are needed to improve linkage to HBV-directed medical care for foreign-born individuals living with chronic HBV infection.

Objective. In 2012, CDC's Division of Viral Hepatitis launched a public health initiative to increase hepatitis B virus (HBV) and hepatitis C virus (HCV) infection testing for those at risk and to improve linkage to medical care for those infected. We describe testing outcomes of previously unidentified people at risk for HBV and HCV infection and the lessons learned while linking patients to care. Methods. CDC's Hepatitis Testing and Linkage to Care (HepTLC) initiative provided 34 financial awards to U.S. organizations that serve people at risk for viral hepatitis, 25 of which focused on HCV and nine of which focused on HBV. Grantees offered testing and test result notification to people at risk for HBV and/or HCV infection, as well as counseling, referral, and verification or notification of linkage to care for people with positive test results. We entered demographic data, self-reported risk factors, country of origin (for HBV), and testing outcomes into a confidential database. Results. The 34 grantees tested 87,860 people at more than 260 sites in 17 states. Of the 23,144 people tested for HBV, 1,317 (6%) were positive. Of the 64,716 people tested for HCV, 57,570 (89%) received an HCV antibody (anti-HCV) test, of whom 7,580 (13%) tested anti-HCV positive. Of the 4,765 people who received an HCV RNA test, 3,449 (72%) tested positive. Of the 4,766 people who tested positive for either HBV or HCV infection, 2,116 (44%) were linked to care. Conclusion. Interventions targeting people at risk for HBV and HCV infection reached a substantial number of people for whom testing is recommended and identified a large proportion of those who had previously unrecognized infection. Patient navigation was critical for follow-up and linkage to care.

Objective. To compare measurements of thyroid and adrenal function between survivors and non-survivors in critical illness. Design and setting. Prospective, observational study at the medical/surgical intensive care unit (ICU) at Royal Infirmary of Edinburgh, Scotland. Patients. 163 patients admitted to the intensive care unit over a 4-month period. Interventions. We took blood samples within 1 h of ICU admission, and at 08:00 hours on the subsequent 2 days of ICU admission. We measured serum total (TT4) and free (fT4) thyroxine, total (TT3) and free (fT3) tri-iodothyronine, thyrotropin (TSH) and plasma cortisol concentrations. Measurements and results. TT3 and TT4 concentrations were significantly less in non-survivors than in survivors on admission and on day 1 but not on day 2. Cortisol concentrations were higher in non-survivors on admission and on day 1 but not on day 2. TSH, fT3 and fT4 concentrations did not differ significantly between survivors and non-survivors at any time. Only TT4 and cortisol were independent predictors of outcome. Prediction of outcome from the admission sample values was not better than using APACHE II scoring. Conclusions. Thyroid hormone and cortisol concentrations differ between survivors and non-survivors on admission to intensive care, but the values overlap. These differences do not allow accurate prediction of outcome from critical illness.

Background: Free thyroxine (FT4) assays may exhibit biases that are related to serum T4 binding capacity (sBC). We describe two tests that can be used to assess the presence and magnitude of sBC-dependent biases in FT4 assays. Methods: We used a direct equilibrium dialysis FT4 assay as the reference method and compared the results obtained with those of the FT4 assays under investigation, in patient sera having a wide range of sBC. We then compared the expected and observed FT4 results for sera diluted with an inert buffer. Because serum dilution causes a predictable decrease in sBC, an increasingly negative bias on progressive dilution is indicative of a sBC-dependent bias. Results: The automated FT4 assay investigated (Vitros FT4) showed no demonstrable sBC-dependent bias by either test. Conclusion: These two tests can be used to screen for sBC-dependent biases in FT4 assays.

This article informs physician assistants of an algorithm designed for primary care practice to guide the screening of patients for hepatitis B virus infection. The algorithm also provides guidance on evaluation, follow-up, and referral of patients who screen positive. The algorithm is a synthesis of several published, evidence-based practice guidelines and reports.

Using a specific RIA, we have investigated in patients and volunteers whether fasting, diminished hepatic clearance, hemoconcentration, or within-day biological variation might be responsible for the transient increases in plasma glutathione S-transferase (GST) concentration observed after anesthesia. GST concentration was measured in 44 healthy volunteers after an overnight fast and at 3, 6, and 24 h after the fasting sample. The concentration was significantly lower at 3 and 6 h after than in the fasting sample (P = 0.0019 and P = 0.015, respectively). The change in GST concentration caused by fasting was examined in 30 subjects by comparing pre- and postfasting values. Fasting had no significant effect on GST concentration overall (P = 0.4721), but two individuals showed a marked increase in GST concentration after fasting overnight. In a separate study of 10 patients, plasma amylase activity and plasma concentrations of GST and albumin were measured immediately before and 3 h after induction of halothane anesthesia. Although GST concentration was increased at 3 h in each of the 10 patients, plasma amylase activity and plasma albumin concentration were significantly decreased in all patients (P = 0.002). Apparently, increases in GST concentration after anesthesia do not result from incidental factors.

The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C virus (HCV)-infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDC's 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations.These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. RECOMMENDATION 1: Adults born during 1945-1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).

Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, an approach that provides guidance and tools to define the research questions, conduct the systematic review, assess the overall quality of the evidence, and determine strength of the recommendations. This report is intended to serve as a resource for health-care professionals, public health officials, and organizations involved in the development, implementation, and evaluation of prevention and clinical services. These recommendations will be reviewed every 5 years and updated to include advances in the published evidence.

Hepatitis C virus (HCV) infection is a complex public health problem, characterized by a high prevalence of chronic infection, an increasing burden of HCV-associated disease, low rates of testing and treatment, and the prospect of increasing incidence associated with the epidemic of injection drug use. Three-quarters of chronic HCV infections occur among persons born from 1945 through 1965. Prevention efforts are complicated by limited knowledge among health care professionals, persons at risk and in the public at large. At the Centers for Disease Control and Prevention, efforts to improve primary and secondary prevention effectiveness center on policy development, education and training initiatives, and applied research. This report provides a brief overview of some of these efforts, including the development of testing recommendations for the 1945–1965 birth cohort, research and evaluation studies in settings where persons who inject drugs receive services, and a national viral hepatitis education campaign that targets health care professionals, the public, and persons at risk.

Hepatitis C virus (HCV) infects an estimated 3.2 million persons in the U.S. [1]. Recent estimates indicate that in 2007, the mortality rate of HCV was 4.6 deaths per 100,000 population (n=15,106) [2]. Chronic HCV is a leading cause of hepatocellular carcinoma and its complications are a leading indication for liver transplantation [3, 4]. In addition, an estimated 39% to 85% of infected persons are unaware of their status [5, 6]. The National Health and Nutrition Examination Survey (NHANES), a national, multistage probability cluster sample of the U.S. civilian, noninstitutionalized population, collects information on HCV infection. Based on analyses of NHANES data published over the last decade [1], a birth cohort of persons with comparatively higher prevalence of HCV infection was identified. Persons born from 1945 through 1964 account for an estimated 65.6% of all persons infected with HCV [1]. The estimated prevalence of HCV infection in this birth cohort is 2.2 million. In 2010, the Institute of Medicine published a national strategy for the prevention and control of HCV and hepatitis B virus (HBV) [7]. In response, the Department of Health and Human Services (HHS) issued an action plan for the prevention, care and treatment of viral hepatitis [8]. The HHS Action Plan contains specific strategies and screening recommendations including: implementing routine HCV testing of all persons for whom it is recommended as part of standard of care in a reformed health care system and improving linkage to care and treatment for HCV-infected persons. In 1998, the Centers for Disease Control and Prevention (CDC) published recommendations for HCV screening among persons with behaviors, exposures, or clinically-defined risk indicators [9], which included: (1) persons who have ever injected drugs; (2) persons who received clotting factor concentrates produced before 1987, were ever on long-term hemodialysis, or had persistently abnormal alanine aminotransferase levels; (3) recipients of transfusions or organ transplants prior to July 1992; (4) healthcare workers after occupational exposures; and (5) children born to HCV-infected women. Following more than a decade of scientific advances, the Division of Viral Hepatitis (DVH) is updating the 1998 recommendations through a two-stage process. The first stage will focus on developing screening recommendations that can effectively target persons born from 1945 through 1965, a demographic that, as noted below, includes almost two-thirds of prevalent HCV infections. The second stage will entail a comprehensive update of the 1998 recommendations for HCV screening and prevention. Guidance will be targeted to clinicians and to professionals and agencies implementing HCV screening programs in community health centers, through health departments, and in other venues. To examine the evidence for a birth cohort screening strategy, DVH conducted a systematic review of HCV prevalence among persons born from 1945 through 1965. Seven databases were searched to capture peer-reviewed and grey literature from 1995 through 2011 including EMBASE, PubMed, and Cochrane. In addition to conducting a systematic review, DVH adopted the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for the development of these recommendations. GRADE provides standards for a rigorous, systematic and transparent approach to the development of recommendations in two parts: evaluating the quality of the evidence and assessing the strength of the recommendations. To lead and to provide input throughout the process, three advisory groups were developed: a DVH steering committee, a CDC Internal Work Group, and an External Work Group. The DVH Steering Committee, working with a GRADE methodology consultant, led the process, conducted the systematic reviews, and assessed the quality of the evidence. The Internal Work Group consisted of staff from all divisional units (e.g., i.e., Laboratory Branch, Epidemiology and Surveillance Branch, and Prevention Branch) of DVH. The External Work Group included representatives from federal agencies (e.g., Department of Veterans Affairs, Substance Abuse and Mental Health Services Administration), primary care provider organizations (e.g., American Medical Association, American Academy of Family Physicians), state and city health departments and advocacy groups (e.g., Adult Viral Hepatitis Prevention Coordinators, National Viral Hepatitis Roundtable), and medical specialty organizations (e.g., American Association for the Study of Liver Diseases, American Gastroenterological Association). Other experts including hepatologists, economists and guideline methodologists also participated. The Internal and External Work Groups were involved from the inception of the birth cohort guidelines development process through regular teleconferences, in-person meetings and a half-day GRADE workshop. All members disclosed academic and financial conflicts of interest using an established form from the International Committee of Medical Journal Editors (http://www.icmje.org/coi_disclosure.pdf). Both work groups provided input and reviewed the scope, key questions, analytic framework, outcomes, systematic review methods and findings. Summaries of the findings from the systematic review and the results of earlier work group determinations of evidence on patient-important outcomes were presented at a two-day consultation with members of both work groups in August 2011. Internal and External Work Group members reached a consensus on the strength of the recommendations by discussing the quality of available evidence, benefits versus harms, values and preferences, and cost implications. The drafted recommendations document is currently undergoing the Office of Management and Budget's Peer Review, CDC clearance, and public comment, which will allow input from the public at large. Publication of the birth cohort recommendation is expected in the Morbidity and Mortality Weekly Report (Recommendations and Reports) in 2012. In an effort to translate the recommendations into practice, dissemination, implementation, and evaluation activities will follow the release of the recommendations. Ongoing activities include the Know More Hepatitis campaign and the development of testing and counseling modules. These recommendations will be updated based on evaluation findings and new scientific research. The birth cohort recommendations were developed using a methodology focused on the quality of the evidence regarding the prevalence of HCV infection among persons born from 1945 through 1965 and an assessment of the potential harms and benefits of routine, one-time screening. A transparent, rigorous, and standardized methodology improves the likelihood of a well-supported recommendation that will have the intended public health impact: to reduce the burden of hepatitis C and HCV-associated disease.

We measured serum FT 4 by 2 analog RIA methods and a two-step method before and after a course of electroconvulsive therapy (ECT) for depressive illness; we investigated the possibility that any change in FT 4 was an artefact of altered concentrations of serum albumin or nonesterified free fatty acids (NEFA)