Safety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years.

BACKGROUND AND OBJECTIVES: Limited postauthorization safety data for the Pfizer-BioNTech coronavirus disease 2019 vaccination among children ages 5 to 11 years are available, particularly for the adverse event myocarditis, which has been detected in adolescents and young adults. We describe adverse events observed during the first 4 months of the United States coronavirus disease 2019 vaccination program in this age group. METHODS: We analyzed data from 3 United States safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health effects; the Vaccine Adverse Events Reporting System (VAERS), the national spontaneous reporting system comanaged by the Centers for Disease Control and Prevention and Food and Drug Administration; and the Vaccine Safety Datalink, an active surveillance system that monitors electronic health records for prespecified events, including myocarditis. RESULTS: Among 48 795 children ages 5 to 11 years enrolled in v-safe, most reported reactions were mild-to-moderate, most frequently reported the day after vaccination, and were more common after dose 2. VAERS received 7578 adverse event reports; 97% were nonserious. On review of 194 serious VAERS reports, 15 myocarditis cases were verified; 8 occurred in boys after dose 2 (reporting rate 2.2 per million doses). In the Vaccine Safety Datalink, no safety signals were detected in weekly sequential monitoring after administration of 726 820 doses. CONCLUSIONS: Safety findings for Pfizer-BioNTech vaccine from 3 United States monitoring systems in children ages 5 to 11 years show that most reported adverse events were mild and no safety signals were observed in active surveillance. VAERS reporting rates of myocarditis after dose 2 in this age group were substantially lower than those observed among adolescents ages 12 to 15 years.

Safety Monitoring of COVID-19 Vaccine Booster Doses Among Persons Aged 12-17 Years - United States, December 9, 2021-February 20, 2022.

As of February 20, 2022, only BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine has been authorized for use in persons aged 12-17 years in the United States (1). The Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for Pfizer-BioNTech vaccine on December 9, 2021, to authorize a homologous* booster dose for persons aged 16-17 years ≥6 months after receipt of dose 2 (1). On January 3, 2022, authorization was expanded to include persons aged 12-15 years, and for all persons aged ≥12 years, the interval between dose 2 and booster dose was shortened to ≥5 months (1). To characterize the safety of Pfizer-BioNTech booster doses among persons aged 12-17 years (adolescents), CDC reviewed adverse events and health impact assessments during the week after receipt of a homologous Pfizer-BioNTech booster dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. During December 9, 2021-February 20, 2022, approximately 2.8 million U.S. adolescents received a Pfizer-BioNTech booster dose.† During this period, receipt of 3,418 Pfizer-BioNTech booster doses were reported to v-safe for adolescents. Reactions were reported to v-safe with equal or slightly higher frequency after receipt of a booster dose than after dose 2, were primarily mild to moderate in severity, and were most frequently reported the day after vaccination. VAERS received 914 reports of adverse events after Pfizer-BioNTech booster dose vaccination of adolescents; 837 (91.6%) were nonserious and 77 (8.4%) were serious. Health care providers, parents, and adolescents should be advised that local and systemic reactions are expected among adolescents after homologous Pfizer-BioNTech booster vaccination, and that serious adverse events are rare.

National Estimates of Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Hospitalized Patients in the United States.

BACKGROUND: Treating patients with infections due to multidrug-resistant pathogens often requires substantial healthcare resources. The purpose of this study was to report estimates of the healthcare costs associated with infections due to multidrug-resistant bacteria in the United States (US). METHODS: We performed retrospective cohort studies of patients admitted for inpatient stays in the Department of Veterans Affairs healthcare system between January 2007 and October 2015. We performed multivariable generalized linear models to estimate the attributable cost by comparing outcomes in patients with and without positive cultures for multidrug-resistant bacteria. Finally, we multiplied these pathogen-specific, per-infection attributable cost estimates by national counts of infections due to each pathogen from patients hospitalized in a cohort of 722 US hospitals from 2017 to generate estimates of the population-level healthcare costs in the US attributable to these infections. RESULTS: Our analysis cohort consisted of 16 676 patients with community-onset infections and 172 712 matched controls and 8246 patients with hospital-onset infections and 66 939 matched controls. The highest cost was seen in hospital-onset invasive infections, with attributable costs (95% confidence intervals) ranging from $30 998 ($25 272-$36 724) for methicillin-resistant Staphylococcus aureus to $74 306 ($20 377-$128 235) for carbapenem-resistant (CR) Acinetobacter. The highest attributable costs for community-onset invasive infections were seen in CR Acinetobacter ($62 396; $20 370-$104 422). Treatment of these infections cost an estimated $4.6 billion ($4.1 billion-$5.1 billion) in 2017 in the US for community- and hospital-onset infections combined. CONCLUSIONS: We found that antimicrobial-resistant infections led to substantial healthcare costs.

Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017.

BACKGROUND: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. METHODS: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa. RESULTS: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases. CONCLUSIONS: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.).

Evaluating guideline adherence regarding empirical vancomycin use in patients with neutropenic fever.

OBJECTIVE: The purpose of this study was to evaluate the use of empirical vancomycin for patients with neutropenic fever (NF) with regard to adherence to treatment guidelines. METHODS: Adult patients with a diagnosis of neutropenia, who met the definition of NF as per treatment guidelines, were identified. Use of vancomycin was evaluated as part of empirical therapy and again after 72h. Outcomes were assessed using descriptive statistics, the Chi-square or Fisher's exact test, and univariate exact logistic regression analyses. RESULTS: Sixty-four patients were included. Overall, inappropriate empirical vancomycin use was observed in more than 30% of patients. Of 35 patients with indications for empirical vancomycin, only 68% received it. At 72h, appropriate vancomycin continuation, de-escalation, or discontinuation occurred in 21 of 33 patients. On univariate regression, hematological malignancy was associated with appropriate empirical vancomycin prescribing, whether initiating or withholding (odds ratio 4.0, 95% confidence interval 1.31-12.1). No variable was independently associated with inappropriate continuation at 72h. CONCLUSIONS: There is poor guideline adherence to vancomycin prescribing as empirical therapy and at 72-h reassessment in patients with NF. Further efforts are needed to foster a more rational use of vancomycin in patients with NF.

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease.

The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima-media thickness (CIMT), endothelial markers, C-reactive protein (CRP), homocysteine, and lipids. Among 332 articles screened, 28 were included (39,498 participants). Study designs varied: 18 cross-sectional, 9 cohort, and 1 clinical trial. Compared with healthy controls and people with HIV or HCV monoinfection, individuals with HIV/HCV coinfection had statistically significant lower levels of lipids and CRP and higher levels of endothelial markers (sICAM-1 and sVCAM-1), CIMT, homocysteine, and IL-6. One study found the odds of carotid plaque in coinfected individuals was 1.64 (0.91-2.94) compared with healthy controls, and another study showed the prevalence of vascular plaques (carotid and femoral) in coinfected individuals was higher compared with HIV monoinfected individuals (44% vs 14%, P = 0.04). Biomarkers of CVD have different patterns of association with HIV/HCV coinfection compared with monoinfection and healthy controls. Prospective studies are needed to confirm the predictive value of these biomarkers for clinical CVD risk among coinfected individuals.

Like Peas and Carrots: Combining Wellness Policy Implementation With Classroom Education for Obesity Prevention in the Childcare Setting.

OBJECTIVES: We evaluated an intervention combining policy training and technical assistance for childcare teachers with a nutrition education curriculum to improve (1) the knowledge and self-efficacy of childcare teachers in implementing obesity prevention policies and practices, (2) the quantity and quality of nutrition and physical activity education, and (3) the childcare wellness environment. METHODS: Thirteen teachers and 8 administrators (2 of whom were also teachers) from 8 childcare programs in Clarke County, Georgia, participated in the Healthy Child Care Georgia intervention during June-October 2015. The intervention included (1) training and technical assistance on obesity prevention policies, systems, and practices and (2) direct education by teachers using the Eat Healthy, Be Active curriculum. We assessed changes in program wellness policy adoption and teacher knowledge and self-efficacy from pre- to post-intervention through self-report questionnaires, interviews, and focus groups. RESULTS: Teachers' knowledge scores (maximum score = 100) rose significantly from a mean (SD) pre-intervention of 67.1 (14.6) to post-intervention of 83.2 (14.3) ( P < .001). The mean score for "teaching nutrition and activity to children" (maximum score = 105) rose significantly from 86.9 (8.2) to 93.5 (5.2) ( P = .011) and for "modeling and supporting children" (maximum score = 63) from 55.8 (5.1) to 59.5 (4.5) ( P = .015). The mean (SD) scores for breastfeeding and infant feeding policy/practice adoption (maximum score = 6) increased significantly from 2.5 (1.8) to 3.7 (1.9) ( P = .043) and for nutrition education policy/practice adoption (maximum score = 4) from 2.0 (1.3) to 3.3 (1.4) ( P = .019). The combined approach enhanced classroom nutrition education and improved the adoption of best practices. CONCLUSION: Future studies should examine the effects of using a combined approach to promote nutrition and physical activity policies and practices in the early care and education setting.

Implementation of Evidence-Based HIV Interventions for Gay, Bisexual, and Other Men Who Have Sex with Men.

The Centers for Disease Control and Prevention provides trainings to support implementation of five evidence-based HIV prevention interventions (EBIs) for men who have sex with men (MSM): d-up: Defend Yourself!; Many Men, Many Voices; Mpowerment; Personalized Cognitive Counseling; and Popular Opinion Leader. We evaluated trainees' implementation of these EBIs and, using multivariable logistic regression, examined factors associated with implementation. Approximately 43% of trainees had implemented the EBIs for which they received training. Implementation was associated with working in community-based organizations (vs. health departments or other settings); acquiring training for Mpowerment or Popular Opinion Leader (vs. Personalized Cognitive Counseling); having ≥3 funding sources (vs. one); and having (vs. not having) sufficient time and necessary EBI resources. Findings suggest that implementation may vary by trainee characteristics, especially those related to employment setting, EBI training, funding, and perceived implementation barriers. Efforts that address these factors may help to improve EBI implementation among trainees.

Sexual Behaviors, Healthcare Interactions, and HIV-Related Perceptions Among Adults Age 60 Years and Older: An Investigation by Race/Ethnicity.

BACKGROUND: Older adults are remaining sexually active for longer periods of time, underscoring the need to assess sexual activity patterns in this group and identify differences by race/ethnicity, some of which may have implications for the development and implementation of sexual risk reduction interventions. METHODS: Using data from the 2010 National Social Life, Health, and Aging Project, this study examined responses from 1,429 adults aged 60 years and older. Multinomial logistic regression compared sexual behaviors, health-related indicators, interactions with healthcare professionals, and HIV-related perceptions across participants' race/ethnicity. RESULTS: Approximately 81% of participants self-reported as non-Hispanic white, 10.59% as African American, and 8.05% as Hispanic. On average, participants were 69.9 years of age. In the previous year, 49.3% of participants engaged in sexual intercourse; only 3% used condoms. The majority of participants (83.1%) visited a physician at least twice in the previous year, 30.9% had discussed sex with a physician since turning 50, and 14.2% had been tested for HIV. Relative to non-Hispanic whites, African Americans were more likely to be divorced (OR=3.23, P<0.001) or widowed (OR=2.90, P<0.001); have more lifetime sexually transmitted infection (STI) diagnoses (OR=1.67, P=0.030); and have paid for sex (OR=2.83, P=0.002). Although African Americans had greater perceived risk for HIV infection (OR=1.66, P=0.046), they were less likely to have discussed sex with a physician since turning 50 (OR=0.45, P=0.009). CONCLUSION: Contextualized interventions to improve patient-provider communication and proactive screening behaviors in sexually-active and aging African Americans are needed.

A Comparative Systematic Review of the Optimal CD4 Cell Count Threshold for HIV Treatment Initiation.

HIV infection is no longer characterized by high morbidity, rapid progression to AIDS, and death as when the infection was first identified. While anti-retroviral drugs have improved the outcome of AIDS patients, clinical research on the appropriate time to initiate therapy continues to evolve. Optimal therapy initiation would maximize the benefits of these drugs, while minimizing side effects and drug resistance. Recent 2013 WHO guidelines changed HIV therapy initiation from 350 cells/ µ L to 500 cells/ µ L. This systematic review provides an evidence-based comparison of starting treatment at >500 cells/ µ L with starting treatment at the range between 350 cells/ µ L and 500 cells/ µ L. An 11% increase in risk was detected from initiation therapy at the 350-500 cells/ µ L range (0.37 [0.26, 0.53]), when compared with starting treatment before 500 cells/ µ L (0.33 [0.22, 0.48]). Most individual study comparisons showed a benefit for starting treatment at 500 cells/ µ L in comparison with starting at the 350-500 cells/ µ L range with risks ranging from 19% to 300%, though a number of comparisons were not statistically significant. Overall, the study provides evidence based support for initiating anti retroviral therapy at cell counts >500 cells/ µ L wherever possible to prevent AIDS mortality and morbidity.

Electrotransformation of Bacillus mojavensis with fluorescent protein markers.

Gram-positive endophytic bacteria are difficult to transform. To study the interactions between Bacillus mojavensis and maize, a method was developed to transform the microbe by electroporation with three integration plasmids expressing green, cyan and yellow fluorescent proteins (GFP variants). GFP Transformations were verified by antibiotic selection, microscopy and amylase deficiency, based on incorporation of the plasmids through recombination with the amylase gene. Phenotypic expressions of endophytism and fungal antagonisms of the transformants were the same as wild type stains. This represents the first successful transformation of this endophytic species with GFP markers.

Functional studies of an HIV-1 encoded glutathione peroxidase.

In an alternate reading frame overlapping the viral envelope gene, HIV-1 has been shown to encoded a truncated glutathione peroxidase (GPx) module. Essential active site residues of the catalytic core regions of mammalian GPx sequences are conserved in the putative viral GPx (vGPx, encoded by the env-fs gene). Cells transfected with an HIV-1 env-fs construct show up to a 100% increase in GPx enzyme activity, and are protected against the loss of mitochondrial transmembrane potential and subsequent cell death induced by exogenous oxidants or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be more common in HIV-1-infected long-term non-progressors, as compared to HIV-1 isolates from patients developing AIDS. An antioxidant/antiapoptotic protective role of the vGPx is also consistent with the observation that -1 frameshifting induced by the HIV-1 env-fs sequence AAAAAGA (which contains a potential "hungry" arginine codon, AGA) increases during arginine deficiency, which has been associated with increased oxidative stress. Under arginine-limited conditions, nitric oxide synthase generates superoxide, which rapidly combines with NO to form peroxynitrite, which can cause activated T-cells to undergo apoptosis. Thus, biosynthesis of the HIV-1 GPx as an adaptive response to low arginine conditions might delay oxidant-induced apoptotic cell death, providing an enhanced opportunity for viral replication.

A -1 frameshift in the HIV-1 env gene is enhanced by arginine deficiency via a hungry codon mechanism.

Ribosomal frameshifting is used by various organisms to maximize protein coding potential of genomic sequences. It is commonly exploited by RNA viruses to overcome the constraint of their limited genome size. Frameshifting requires specific RNA structural features, such as a suitable heptanucleotide "slippery" sequence and an RNA pseudoknot. Previous genomic analysis of HIV-1 indicated the potential for several hidden genes encoded through frameshifting; one of these, overlapping the envelope gene, has an RNA pseudoknot just downstream from a slippery sequence, AAAAAGA that features an adenine quadruplet prior to a potential hungry arginine codon (AGA). This env-frameshift (env-fs) gene has been shown to encode a truncated glutathione peroxidase homologue, with both antioxidant and anti-apoptotic activities in transfected cells. Using a dual reporter cell-based frameshift assay, we demonstrate that the env-fs frameshift sequence is active in vitro. Furthermore, in arginine deficient media, env-fs frameshifting increased over 100% (p<0.005), consistent with the hypothesized hungry codon mechanism. As a response to arginine deficiency, increased expression of the antioxidant viral GPx gene (env-fs) by upregulation of frameshifting could be protective to HIV-infected cells, as a countermeasure to the increased oxidative stress induced by arginine deficiency (because NO is a known scavenger of hydroxyl radical).