National Action Plan for Adverse Drug Event Prevention: Recommendations for Safer Outpatient Opioid Use.

INTRODUCTION: Adverse drug events (ADEs) have been highlighted as a major patient safety and public health challenge by the National Action Plan for Adverse Drug Event Prevention (ADE Action Plan), which was released by the Office of Disease Prevention and Health Promotion (ODPHP) in August 2014. The ADE Action Plan focuses on surveillance, evidence-based prevention, incentives, and oversights, additional research needs as well as possible measures and metrics to track progress of ADE prevention within three drug classes: anticoagulants, diabetes agents, and opioids.Objectives and Recommendations. With outpatient opioid prescriptions being a great concern among many healthcare providers, this article focuses on recommendations from the ADE Action Plan to help guide safer opioid use in healthcare delivery settings. Its aim is to discuss current federal methods in place to prevent opioid ADEs while also providing evidence to encourage providers and hospitals to innovate new systems and practices to increase prevention.

Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug Event Prevention.

BACKGROUND: Adverse drug events (ADEs) are important contributors to preventable morbidity and mortality, comprising one third of all hospital adverse events. In response to growing evidence detailing the high prevalence of ADEs, particularly among vulnerable older adults, Congress requested that the Secretary of the Department of Health and Human Services (HHS) convene a Federal Interagency Steering Committee to establish a National Action Plan to focus on ADE prevention. In August 2014, the Office of Disease Prevention and Health Promotion released the final version of the National Action Plan for Adverse Drug Event Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan and the Patient Protection and Affordable Care Act by providing guidance on tracking and preventing ADEs, as well as describing evidence-based tools and resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal Interagency Steering Committee focused the Action Plan on ADEs that are clinically significant, account for the greatest number of measurable harms as identified by using existing surveillance tools, and are largely preventable. As such, the decision was made to target three medication classes: anticoagulants, diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action Plan is organized around four key areas: surveillance; evidence-based prevention; payment, policy incentives, and oversight; and research opportunities to advance medication safety. CONCLUSION: One measure of the ADE Action Plan's success will be the wider dissemination of information and educational resources to providers and patients (or consumers) regarding the risks associated with medications. Future Action Plan iterations are likely to consider other high-priority medication classes and update the recommendations.

Hepatitis B testing and access to care among racial and ethnic minorities in selected communities across the United States, 2009-2010.

UNLABELLED: Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B. CONCLUSION: These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care.

Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans.

UNLABELLED: Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assessed associations between 67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR, 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007). CONCLUSION: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted.

Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up.

UNLABELLED: Persistence of seropositivity conferred by hepatitis A vaccine administered to children <2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. One hundred ninety-seven infants and young children were randomized into three groups to receive a two-dose hepatitis A vaccine: group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age. Within each group, infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years after the second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after the second dose. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV-negative and anti-HAV-positive mothers, respectively, and 4% of group 3 children born to anti-HAV-negative mothers. At 10 years, children born to anti-HAV-negative mothers in group 3 had the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence interval, 71-133 mIU/mL) and children born to anti-HAV-positive mothers in group 1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after the second dose). CONCLUSION: The seropositivity induced by hepatitis A vaccine given to children <2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV.

Prospects for prophylactic and therapeutic vaccines against hepatitis C virus.

Natural cross-protective immunity is induced after spontaneous clearance of primary hepatitis C virus (HCV) infection. Although this suggests that effective prophylactic vaccines against HCV are possible, there are still several areas that require further study. Current data indicate that, at best, vaccine-induced immunity may not completely prevent HCV infection but rather prevent persistence of the virus. However, this may be an acceptable goal, because chronic persistence of the virus is the main cause of pathogenesis and the development of serious liver conditions. Therapeutic vaccine development is also highly challenging; however, strategies have been pursued in combination with current or new treatments in an effort to reduce the costs and adverse effects associated with antiviral therapy. This review summarizes the current state of HCV vaccines and the challenges faced for future development and clinical trial design.

Evolving epidemiology of hepatitis C virus in the United States.

The impact of hepatitis C virus (HCV) infection on health and medical care in the United States is a major problem for infectious disease physicians. Although the incidence of HCV infection has declined markedly in the past 2 decades, chronic infection in 3 million or more residents now accounts for more disease and death in the United States than does human immunodeficiency virus (HIV)/AIDS. Current trends in the epidemiology of HCV infection include an apparent increase in young, often suburban heroin injection drug users who initiate use with oral prescription opioid drugs; infections in nonhospital healthcare (clinic) settings; and sexual transmission among HIV-infected persons. Infectious disease physicians will increasingly have the responsibility of diagnosing and treating HCV patients. An understanding of how these patients were infected is important for determining whom to screen and treat.

An investigation of bloodborne pathogen transmission due to multipatient sharing of insulin pens.

On January 30, 2009, nursing staff at a military hospital in Texas reported that single-patient use insulin pens were used on multiple patients. An investigation was initiated to determine if patient-to-patient bloodbome transmission occurred from the practice. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) testing was offered to patients hospitalized from August 2007 to January 2009 and prescribed insulin pen injections. Virus from HCV-infected patients' sera was sequenced and compared for relatedness. An anonymous survey was administered to nurses. Of 2,113 patients prescribed insulin pen injections, 1,501 (71%) underwent testing; 6 (0.4%) were HIV positive, 6 (0.4%) were hepatitis B surface antigen positive, and 56 (3.7%) had HCV antibody. No viral sequences from 10 of 28 patients with newly diagnosed and 12 of 28 patients with preexisting HCV infection were closely related. Of 54 nurses surveyed, 74% reported being trained on insulin pen use, but 24% believed nurses used insulin pens on more than one patient. We found no clear evidence of bloodborne pathogen transmission. Training of hospital staff on correct use of insulin pens should be prioritized and their practices evaluated. Insulin pens should be more clearly labeled for single-patient use.

Leveraging lessons learned from the COVID-19 pandemic for HIV.

The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.

Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission.

Genotypic distribution of hepatitis B virus (HBV) among acute cases of HBV infection, selected United States counties, 1999-2005.

BACKGROUND: Knowledge of the genotypic distribution of hepatitis B virus (HBV) facilitates epidemiologic tracking and surveillance of HBV infection as well as prediction of its disease burden. In the United States, HBV genotyping studies have been conducted for chronic but not acute hepatitis B. METHODS: Serum samples were collected from patients with acute hepatitis B cases reported from the 6 counties that participated in the Sentinel Counties Study of Acute Viral Hepatitis from 1999 through 2005. Polymerase chain reaction followed by nucleotide sequencing of a 435-base pair segment of the HBV S gene was performed, and the sequences were phylogenetically analyzed. RESULTS: Of 614 patients identified with available serum samples, 75% were infected with genotype A HBV and 18% were infected with genotype D HBV. Thirty-two percent of genotype A sequences constituted a single subgenotype A2 cluster. The odds of infection with genotype A (vs with genotype D) were 5 times greater among black individuals than among Hispanic individuals (odds ratio [OR], 5; 95% confidence interval [CI], 2.3-10.7). The odds of infection with genotype A were 49, 8, and 4 times greater among patients from Jefferson County (Alabama), Pinellas County (Florida), and San Francisco (California), respectively, than among those living in Denver County (Colorado). Genotype A was less common among recent injection drug users than it was among non-injection drug users (OR, 0.2; 95% CI, 0.1-0.4). CONCLUSIONS: HBV genotype distribution was significantly associated with ethnicity, place of residence, and risk behavior.

The two faces of hepatitis E virus.

Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%-21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration-approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world.

Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in Northern Uganda.

BACKGROUND: Outbreaks of infection with hepatitis E virus (HEV) are frequently attributed to contaminated drinking water, even if direct evidence for this is lacking. METHODS: We conducted several epidemiologic investigations during a large HEV infection outbreak in Uganda. RESULTS: Of 10,535 residents, 3218 had HEV infection; of these, 2531 lived in households with >1 case. HEV was not detected in drinking water or zoonotic sources. Twenty-five percent of cases occurred > or = 8 weeks after onset of hepatitis in an index case in the household. Households with > or = 2 cases were more likely to have a member(s) who attended a funeral, had close contact with a jaundiced person, or washed hands in a common basin with others (P < .05 for all). CONCLUSIONS: A high attack rate in households, lack of a common source of infection, and poor hygienic practices in households with > or = 2 cases suggest person-to-person transmission of HEV during this outbreak.

Hepatitis E epidemic, Uganda.

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

Prevalence of anaemia among pregnant women in South-East China, 1993-2005.

OBJECTIVE: To report the prevalence of anaemia by demographic characteristics and its secular trend over 13 years for south-east Chinese pregnant women, and to determine the focus of anaemia prevention in Chinese pregnant women. DESIGN: Prospective study of the data on Hb concentration and other demographic information from a large-scale population-based perinatal health surveillance system in south-east China. SETTING: Fourteen cities or counties in Jiangsu and Zhejiang provinces. SUBJECTS: A total of 467 057 prenatal women who had participated in the perinatal health-care surveillance system and delivered babies from 1 January 1993 to 31 December 2005 and had a record of Hb in all three pregnancy trimesters. RESULTS: The overall prevalence of anaemia among pregnant women was 39.6 % from 1993 to 2005. Anaemia prevalence increased from the first (29.6 %) to the second (33.0 %) and third (56.2 %) trimesters. The prevalence of anaemia was higher in villagers, in women with less education and in women with higher gravidity or parity. The prevalence of anaemia in all of the trimesters was higher in the spring, summer and autumn and lower in the winter. The prevalence decreased from 1993 to 2005, from 53.3 % to 11.4 % for the first trimester, 45.6 % to 22.8 % for the second trimester and 64.6 % to 44.6 % for the third trimester. CONCLUSIONS: The prevalence of anaemia among pregnant women in Jiangsu and Zhejiang provinces decreased substantially from 1993 to 2005. However, anaemia in the third trimester is still a severe public health problem among pregnant women in these areas.

An outbreak of hepatitis A among primary and secondary contacts of an international adoptee.

The Advisory Committee on Immunization Practices recommends that susceptible people traveling to developing countries receive hepatitis A vaccine or immune globulin prior to departure. Until 2009, the recommendations did not address non-traveling family members or other close contacts of international adoptees. We report an outbreak of hepatitis A in 2008 that occurred in Maine. Eight members of an extended family developed hepatitis A following the arrival of an asymptomatic infant from Ethiopia who was brought to the United States by an adoption agency. Two children in the family attended an elementary school where five additional cases of hepatitis A were subsequently identified. Only three (1%) of 208 students at the school had previously been immunized against hepatitis A. This outbreak highlights the need to immunize household members and other close contacts of families adopting children from countries where hepatitis A is endemic, as well as all children at one year of age.

Iron, folate, and B(12) deficiencies and their associations with anemia among women of childbearing age in a rural area in Northern China.

OBJECTIVE: To assess the prevalence of folate, vitamin B(12), and iron deficiencies and their associations with anemia among women of childbearing age in northern China, an area with a reported high incidence of neural tube defects. METHODS: Plasma folate, vitamin B(12), ferritin, and hemoglobin levels were measured among 1,671 non-pregnant women of childbearing age from Xianghe County, Hebei Province, China in June 2004. RESULTS: Geometric means [95 % confidence interval (CI)] of plasma concentrations were 9.3 (4.0, 21.6) nmol/L for folate, 213.1 (82.4, 550.9) pmol/L for vitamin B(12), 17.4 (1.1, 278.6) microg/L for ferritin, and 129.9 (104.6, 161.4) g/L for hemoglobin (Hb). Approximately 24 % of women had biochemical evidence of folate deficiency (<6.8 nmol/L), 21.4 % were deficient (<148 pmol/L) in vitamin B(12), 30.2 % had iron depletion (<15 microg/L), and anemia (Hb < 120 g/L) was detected among 15.4 % of women. Of the three nutrients, only iron depletion (ferritin < 15 microg/L) was independently associated with anemia (adjusted odds ratio = 6.4, 95 % CI 4.8, 8.6). CONCLUSIONS: Although there were substantial proportions of folate and vitamin B(12) deficiencies among women of childbearing age in northern China, iron deficiency was the most important contributor to anemia.

Engineering immunity for next generation HIV vaccines: The intersection of bioengineering and immunology.

Bioengineering approaches grounded in immunology have the potential for the discovery and development of a successful HIV vaccine. The overarching goal is to engineer immunity through a fusion of immunology with bioengineering to create novel strategies for the design, development and delivery of vaccines based on the controlled modulation of the immune system. To foster these collaborations, the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Biomedical Imaging and Bioengineering (NIBIB) brought together a group of experts (see Table 1) from these diverse fields for a workshop in September 2018 to: (1) engage the engineering, immunology, and HIV vaccinology communities to dialogue on the topic of an HIV vaccine and; (2) generate a framework of new and innovative research avenues to explore in HIV vaccinology between knowledge stakeholders and problem solvers.

Low-Dose Radiation Therapy (LDRT) for COVID-19: Benefits or Risks?

The limited impact of treatments for COVID-19 has stimulated several phase 1 clinical trials of whole-lung low-dose radiation therapy (LDRT; 0.3-1.5 Gy) that are now progressing to phase 2 randomized trials worldwide. This novel but unconventional use of radiation to treat COVID-19 prompted the National Cancer Institute, National Council on Radiation Protection and Measurements and National Institute of Allergy and Infectious Diseases to convene a workshop involving a diverse group of experts in radiation oncology, radiobiology, virology, immunology, radiation protection and public health policy. The workshop was held to discuss the mechanistic underpinnings, rationale, and preclinical and emerging clinical studies, and to develop a general framework for use in clinical studies. Without refuting or endorsing LDRT as a treatment for COVID-19, the purpose of the workshop and this review is to provide guidance to clinicians and researchers who plan to conduct preclinical and clinical studies, given the limited available evidence on its safety and efficacy.