Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

Prevention of Hepatitis A Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020.

HEPATITIS A IS A VACCINE-PREVENTABLE, COMMUNICABLE DISEASE OF THE LIVER CAUSED BY THE HEPATITIS A VIRUS (HAV). THE INFECTION IS TRANSMITTED VIA THE FECAL-ORAL ROUTE, USUALLY FROM DIRECT PERSON-TO-PERSON CONTACT OR CONSUMPTION OF CONTAMINATED FOOD OR WATER. HEPATITIS A IS AN ACUTE, SELF-LIMITED DISEASE THAT DOES NOT RESULT IN CHRONIC INFECTION. HAV ANTIBODIES (IMMUNOGLOBULIN G [IGG] ANTI-HAV) PRODUCED IN RESPONSE TO HAV INFECTION PERSIST FOR LIFE AND PROTECT AGAINST REINFECTION; IGG ANTI-HAV PRODUCED AFTER VACCINATION CONFER LONG-TERM IMMUNITY. THIS REPORT SUPPLANTS AND SUMMARIZES PREVIOUSLY PUBLISHED RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) REGARDING THE PREVENTION OF HAV INFECTION IN THE UNITED STATES. ACIP RECOMMENDS ROUTINE VACCINATION OF CHILDREN AGED 12-23 MONTHS AND CATCH-UP VACCINATION FOR CHILDREN AND ADOLESCENTS AGED 2-18 YEARS WHO HAVE NOT PREVIOUSLY RECEIVED HEPATITIS A (HEPA) VACCINE AT ANY AGE. ACIP RECOMMENDS HEPA VACCINATION FOR ADULTS AT RISK FOR HAV INFECTION OR SEVERE DISEASE FROM HAV INFECTION AND FOR ADULTS REQUESTING PROTECTION AGAINST HAV WITHOUT ACKNOWLEDGMENT OF A RISK FACTOR. THESE RECOMMENDATIONS ALSO PROVIDE GUIDANCE FOR VACCINATION BEFORE TRAVEL, FOR POSTEXPOSURE PROPHYLAXIS, IN SETTINGS PROVIDING SERVICES TO ADULTS, AND DURING OUTBREAKS.

The CAPACITI Decision-Support Tool for National Immunization Programs.

OBJECTIVES: Immunization programs in low-income and middle-income countries (LMICs) are faced with an ever-growing number of vaccines of public health importance recommended by the World Health Organization, while also financing a greater proportion of the program through domestic resources. More than ever, national immunization programs must be equipped to contextualize global guidance and make choices that are best suited to their setting. The CAPACITI decision-support tool has been developed in collaboration with national immunization program decision makers in LMICs to structure and document an evidence-based, context-specific process for prioritizing or selecting among multiple vaccination products, services, or strategies. METHODS: The CAPACITI decision-support tool is based on multi-criteria decision analysis, as a structured way to incorporate multiple sources of evidence and stakeholder perspectives. The tool has been developed iteratively in consultation with 12 countries across Africa, Asia, and the Americas. RESULTS: The tool is flexible to existing country processes and can follow any type of multi-criteria decision analysis or a hybrid approach. It is structured into 5 sections: decision question, criteria for decision making, evidence assessment, appraisal, and recommendation. The Excel-based tool guides the user through the steps and document discussions in a transparent manner, with an emphasis on stakeholder engagement and country ownership. CONCLUSIONS: Pilot countries valued the CAPACITI decision-support tool as a means to consider multiple criteria and stakeholder perspectives and to evaluate trade-offs and the impact of data quality. With use, it is expected that LMICs will tailor steps to their context and streamline the tool for decision making.

Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus influenzae Type b Conjugate, and Hepatitis B Vaccine, and Guidance for Use in Infants.

On December 21, 2018 the Food and Drug Administration (FDA) licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate (meningococcal protein conjugate) and hepatitis B (HepB) (recombinant) vaccine, DTaP-IPV-Hib-HepB (Vaxelis; MCM Vaccine Company),* for use as a 3-dose series in infants at ages 2, 4, and 6 months (1). On June 26, 2019, after reviewing data on safety and immunogenicity, the Advisory Committee on Immunization Practices (ACIP)† voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.§ This report summarizes the indications for DTaP-IPV-Hib-HepB and provides guidance for its use.

Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Persons Experiencing Homelessness.

Hepatitis A (HepA) vaccination is recommended routinely for children at age 12-23 months, for persons who are at increased risk for hepatitis A virus (HAV) infection, and for any person wishing to obtain immunity. Persons at increased risk for HAV infection include international travelers to areas with high or intermediate hepatitis A endemicity, men who have sex with men, users of injection and noninjection drugs, persons with chronic liver disease, person with clotting factor disorders, persons who work with HAV-infected primates or with HAV in a research laboratory setting, and persons who anticipate close contact with an international adoptee from a country of high or interme-diate endemicity (1-3). Persons experiencing homelessness are also at higher risk for HAV infection and severe infection-associated outcomes. On October 24, 2018, the Advisory Committee on Immunization Practices (ACIP)* recommended that all persons aged 1 year and older experiencing homelessness be routinely immunized against HAV. The ACIP Hepatitis Vaccines Work Group conducted a systematic review of the evidence for administering vaccine to persons experiencing homelessness, which included a set of criteria assessing the benefits and adverse events associated with vaccination. HepA vaccines are highly immunogenic, and >95% of immunocompetent adults develop protective antibody within 4 weeks of receipt of 1 dose of the vaccine (1). HAV infections are acquired primarily by the fecal-oral route by either person-to-person transmission or via ingestion of contaminated food or water. Among persons experiencing homelessness, effective implementation of alternative strategies to prevent exposure to HAV, such as strict hand hygiene, is difficult because of living conditions among persons in this population. Integrating routine HepA vaccination into health care services for persons experiencing homelessness can reduce the size of the at-risk population over time and thereby reduce the risk for large-scale outbreaks.

Recommendation of the Advisory Committee on Immunization Practices for Use of a Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for Mumps During an Outbreak.

A substantial increase in the number of mumps outbreaks and outbreak-associated cases has occurred in the United States since late 2015 (1,2). To address this public health problem, the Advisory Committee on Immunization Practices (ACIP) reviewed the available evidence and determined that a third dose of measles, mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During its October 2017 meeting, ACIP recommended a third dose of a mumps virus-containing vaccine* for persons previously vaccinated with 2 doses who are identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak. The purpose of the recommendation is to improve protection of persons in outbreak settings against mumps disease and mumps-related complications. This recommendation supplements the existing ACIP recommendations for mumps vaccination (3).

Update: Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Postexposure Prophylaxis and for Preexposure Prophylaxis for International Travel.

Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin (IG) effectively prevents infection with hepatitis A virus (HAV) when administered within 2 weeks of exposure. Preexposure prophylaxis against HAV infection through the administration of HepA vaccine or IG provides protection for unvaccinated persons traveling to or working in countries that have high or intermediate HAV endemicity. The Advisory Committee on Immunization Practices (ACIP) Hepatitis Vaccines Work Group conducted a systematic review of the evidence for administering vaccine for PEP to persons aged >40 years and reviewed the HepA vaccine efficacy and safety in infants and the benefits of protection against HAV before international travel. The February 21, 2018, ACIP recommendations update and supersede previous ACIP recommendations for HepA vaccine for PEP and for international travel. Current recommendations include that HepA vaccine should be administered to all persons aged ≥12 months for PEP. In addition to HepA vaccine, IG may be administered to persons aged >40 years depending on the provider's risk assessment. ACIP also recommended that HepA vaccine be administered to infants aged 6-11 months traveling outside the United States when protection against HAV is recommended. The travel-related dose for infants aged 6-11 months should not be counted toward the routine 2-dose series. The dosage of IG has been updated where applicable (0.1 mL/kg). HepA vaccine for PEP provides advantages over IG, including induction of active immunity, longer duration of protection, ease of administration, and greater acceptability and availability.

Implementing Adult Hepatitis B Immunization and Screening Using Electronic Health Records: A Practical Guide.

IMPORTANCE: Hepatitis B is a serious problem in the United States (US), with up to 2.4 million Americans living with a chronic infection. Only 26-32% of people living with hepatitis B in the US are diagnosed. Additionally, just 30% of all adults are vaccinated against the virus. In 2022, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) updated adult hepatitis B vaccination recommendations to include all adults aged 19-59 years and those 60 years and older with risk factors for hepatitis B. Subsequently, in 2023, the CDC recommended that all adults be screened at least one time in their lives. OBSERVATIONS: Electronic health record (EHR) tools (prompts, order sets, etc.) have proven to be an effective method of increasing hepatitis B screening and vaccination, but longstanding challenges and questions around hepatitis B vaccines and tests could prevent effectual EHR implementation. As the new recommendations directly impact providers who may have limited familiarity with hepatitis B, guidance on how to identify eligible patients and triggers, order sets to facilitate vaccine/test selection, and proper documentation and patient follow-up is necessary. CONCLUSIONS AND RELEVANCE: This communication offers a practical framework for health systems to build an effective EHR strategy for the updated adult hepatitis B recommendations. We also provide comprehensive responses to clinicians' questions that are frequently asked prior to screening or vaccinating for hepatitis B.

Causal inference in epidemiological studies with strong confounding.

One of the identifiability assumptions of causal effects defined by marginal structural model (MSM) parameters is the experimental treatment assignment (ETA) assumption. Practical violations of this assumption frequently occur in data analysis when certain exposures are rarely observed within some strata of the population. The inverse probability of treatment weighted (IPTW) estimator is particularly sensitive to violations of this assumption; however, we demonstrate that this is a problem for all estimators of causal effects. This is due to the fact that the ETA assumption is about information (or lack thereof) in the data. A new class of causal models, causal models for realistic individualized exposure rules (CMRIER), is based on dynamic interventions. CMRIER generalize MSM, and their parameters remain fully identifiable from the observed data, even when the ETA assumption is violated, if the dynamic interventions are set to be realistic. Examples of such realistic interventions are provided. We argue that causal effects defined by CMRIER may be more appropriate in many situations, particularly those with policy considerations. Through simulation studies, we examine the performance of the IPTW estimator of the CMRIER parameters in contrast to that of the MSM parameters. We also apply the methodology to a real data analysis in air pollution epidemiology to illustrate the interpretation of the causal effects defined by CMRIER.

Robust extraction of covariate information to improve estimation efficiency in randomized trials.

In randomized trials, investigators typically rely upon an unadjusted estimate of the mean outcome within each treatment arm to draw causal inferences. Statisticians have underscored the gain in efficiency that can be achieved from covariate adjustment in randomized trials with a focus on problems involving linear models. Despite recent theoretical advances, there has been a reluctance to adjust for covariates based on two primary reasons: (i) covariate-adjusted estimates based on conditional logistic regression models have been shown to be less precise and (ii) concern over the opportunity to manipulate the model selection process for covariate adjustments to obtain favorable results. In this paper, we address these two issues and summarize recent theoretical results on which is based a proposed general methodology for covariate adjustment under the framework of targeted maximum likelihood estimation in trials with two arms where the probability of treatment is 50%. The proposed methodology provides an estimate of the true causal parameter of interest representing the population-level treatment effect. It is compared with the estimates based on conditional logistic modeling, which only provide estimates of subgroup-level treatment effects rather than marginal (unconditional) treatment effects. We provide a clear criterion for determining whether a gain in efficiency can be achieved with covariate adjustment over the unadjusted method. We illustrate our strategy using a resampled clinical trial dataset from a placebo controlled phase 4 study. Results demonstrate that gains in efficiency can be achieved even with binary outcomes through covariate adjustment leading to increased statistical power.

Population-level effects of uninterrupted health insurance on services use among HIV-positive unstably housed adults.

Health services research consistently confirms the benefit of insurance coverage on the use of health services sought in the USA. However, few studies have simultaneously addressed the multitude of competing and unmet needs specifically among unstably housed persons. Moreover, few have accounted for the fact that hospitalization may lead to obtaining insurance coverage, rather than the other way around. This study used marginal structural models to determine the longitudinal impact of insurance coverage on the use of health services and antiretroviral therapy (ART) among HIV-positive unstably housed adults. The impact of insurance status on the use of health services and ART was adjusted for a broad range of confounders specific to this population. Among 330 HIV-positive study participants, both intermittent and continuous insurance coverage during the prior 3-12 months had strong and positive effects on the use of ambulatory care and ART, with stronger associations for continuous insurance coverage. Longer durations of continuous coverage were less robust in affecting emergency and inpatient care. Race and ethnicity had no significant influence on health services use in this low-income population when confounding due to competing needs was considered in adjusted analyses. Given that ambulatory care and ART are factors with substantial potential impact on the course of HIV disease, these data suggest that securing uninterrupted insurance coverage would result in large reductions in morbidity and mortality. Health care policy efforts aimed at increasing consistent insurance coverage in vulnerable populations are warranted.

Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma.

PURPOSE: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing a 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making in GEA. EXPERIMENTAL DESIGN: We evaluated a large cohort (n = 2,140 tests; 1,630 patients) of ctDNA-NGS results (including 369 clinically annotated patients). Patients were assessed for genomic alteration (GA) distribution and correlation with clinicopathologic characteristics and outcomes. RESULTS: Treatment history, tumor site, and disease burden dictated tumor-DNA shedding and consequent ctDNA-NGS maximum somatic variant allele frequency. Patients with locally advanced disease having detectable ctDNA postoperatively experienced inferior median disease-free survival (P = 0.03). The genomic landscape was similar but not identical to tissue-NGS, reflecting temporospatial molecular heterogeneity, with some targetable GAs identified at higher frequency via ctDNA-NGS compared with previous primary tumor-NGS cohorts. Patients with known microsatellite instability-high (MSI-High) tumors were robustly detected with ctDNA-NGS. Predictive biomarker assessment was optimized by incorporating tissue-NGS and ctDNA-NGS assessment in a complementary manner. HER2 inhibition demonstrated a profound survival benefit in HER2-amplified patients by ctDNA-NGS and/or tissue-NGS (median overall survival, 26.3 vs. 7.4 months; P = 0.002), as did EGFR inhibition in EGFR-amplified patients (median overall survival, 21.1 vs. 14.4 months; P = 0.01). CONCLUSIONS: ctDNA-NGS characterized GEA molecular heterogeneity and rendered important prognostic and predictive information, complementary to tissue-NGS.See related commentary by Frankell and Smyth, p. 6893.

Medication burden attributable to chronic co-morbid conditions in the very old and vulnerable.

OBJECTIVE: Polypharmacy is common in older patients but relationships between polypharmacy and common co-morbid conditions have not been elucidated. Our goal was to determine relationships between daily oral medication use and common co-morbid disease dyads and triads using comprehensive medication and diagnostic data from a national sample of nursing homes (NH). DESIGN: Retrospective, cross-sectional study. SETTING: Nationally representative sample of U.S. Nursing Homes. PARTICIPANTS: Nationally representative sample of long-term stay residents (n = 11734, 75% women) aged 65 years or older. MEASUREMENTS: Diagnosis and medication data were analyzed. Proportion of daily oral medication intake attributed to treatment of common two-(dyads) and three-disease (triad) combinations and "health maintenance" agents (vitamins, dietary supplements, stool softeners without related diagnoses) was determined. RESULTS: Older NH residents received slightly >8 oral medications/day with the number related to number of medical diagnoses (p < .0001). One third of chronic oral medication intake/day (excluding health maintenance agents) could be attributed to dyad combinations and about half to triad combinations despite an average of 5 other diagnoses. Triads were comprised of hypertension +/- arthritis +/- vascular disease, +/-depression, +/- osteoporosis +/- gastroesophageal reflux disease and +/- diabetes. Health maintenance agents accounted for 15-17% of daily oral medication intake (1.4 medications) such that almost two-thirds of daily oral medications were attributable to disease triads plus health maintenance. Fewer medications were prescribed for NH residents over age 85 (decreased ACE inhibitor and HMG CoA reductase inhibitor USE (p < .001)) while use of Alzheimer medications was higher (p < .01). CONCLUSIONS: A large fraction of daily oral medications were attributed to management of common co-morbid disease dyads and triads. Efforts to reduce polypharmacy and unwanted medication interactions could focus on regimens for common co-morbid dyads and triads in varying populations.

Tennessee's 3-Star Report: Using Available Data Systems to Reduce Missed Opportunities to Vaccinate Preteens.

All preteens should receive tetanus-diphtheria-pertussis vaccine (Tdap), quadrivalent meningococcal vaccine (Men-ACWY), and the human papillomavirus (HPV) cancer vaccine series. In Tennessee, HPV vaccination rates have stagnated at low levels for a decade. Three fundamental strategies to reduce missed opportunities for immunization include administering all recommended vaccines at the same visit, making strong recommendations for vaccines, and auditing and feedback. In Tennessee, during each summer, a surge of preteens visit local health departments (LHDs) to receive a required Tdap vaccine before entering seventh grade, presenting an opportunity to administer Men-ACWY and HPV. The Tennessee Immunization Program (TIP) coined the term "3-Star visit" for such encounters and developed a monthly report to track them using data from the Patient Tracking Billing Management Information System (PTBMIS) used by LHDs across Tennessee. Implementation of this quality improvement report has correlated with a substantial increase in 3-Star visits from 2013 to 2016, particularly during the summer months.

Neonatal sepsis in Egypt associated with bacterial contamination of glucose-containing intravenous fluids.

BACKGROUND: Rates of sepsis exceeding 50% in a neonatal intensive care unit (NICU) in Cairo, Egypt, were not controlled by routine antimicrobial therapy. We investigated these conditions in September 2001. METHODS: Case series and retrospective cohort studies were conducted on 2 groups of NICU infants admitted to an academic medical center between February 12 and July 31, 2001. Observation of clinical practices led us to culture in-use intravenous (i.v.) fluids and medications. We monitored rates of i.v. fluid contamination, clinical sepsis and mortality after interventions to establish new procedures for handling and disposal of i.v. fluids, infection control training and improved clinical laboratory capacity. RESULTS: Among infants in the retrospective cohort group, 88 (77%) of 115 had clinical sepsis, and 59 (51%) died. In the case series group, we documented the time of initial positive blood culture; 21 (64%) of 33 were septic <24 hours after birth. Klebsiella pneumoniae accounted for 24 (73%) of 33 isolates; 14 (58%) of 24 were extended spectrum beta-lactamase-producing and aminoglycoside-resistant. On admission, all neonates received glucose-containing i.v. fluids; i.v. bottles (500 mL) were divided among multiple infants. The i.v. fluids were prepared at the bedside; poor hand hygiene and poor adherence to aseptic techniques were observed. K. pneumoniae was isolated from 13 (65%) of 20 in-use glucose-containing i.v. fluids. Fluid contamination, sepsis and mortality rates declined significantly after intervention. CONCLUSION: Extrinsically contaminated i.v. fluids resulted in sepsis and deaths. Standard infection control precautions significantly improve mortality and sepsis rates and are prerequisites for safe NICU care.

Anthrax and the mail: the making of an educational video for mail workers.

The anthrax bioterrorist attacks in 2001 affected millions of people who process, sort, and deliver mail. To more effectively communicate information intended to protect the health of these workers, the Centers for Disease Control and Prevention produced a short-format educational video in December 2001 that targets this diverse group. This report illustrates how an educational video can be rapidly produced to translate and disseminate public health recommendations as part of a public health emergency response.