Effectiveness of Bivalent mRNA COVID-19 Vaccines in Preventing SARS-CoV-2 Infection in Children and Adolescents Aged 5 to 17 Years.

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009.

BACKGROUND: Vaccine-strain herpes zoster (HZ) can occur after varicella vaccination. This study determined the number and proportion of HZ cases caused by vaccine-strain varicella zoster virus (VZV), assessed the positive predictive value of provider diagnosis of HZ, and computed HZ incidence rates in vaccinated and unvaccinated children. METHODS: We used electronic medical records to identify all office visits with an HZ diagnosis for children aged <18 years in a managed care plan. Providers collected skin specimens and completed a questionnaire. Specimens were tested by polymerase chain reaction to identify wild-type or vaccine-strain VZV. RESULTS: From May 2005 to September 2009, we enrolled 322 subjects. VZV was detected in 82% of specimens (84% wild-type, 15% vaccine-strain, 1% possible vaccine-wild-type recombinant). Among the 118 vaccinated subjects, VZV was detected in 70% (52% wild-type). The positive predictive value for provider diagnosis of "definite HZ" was 93% for unvaccinated and 79% for vaccinated children. The incidence of laboratory-confirmed HZ was 48 per 100,000 person-years in vaccinated children (both wild-type and vaccine-strain) and 230 per 100,000 person-years in unvaccinated children (wild-type only). CONCLUSIONS: HZ incidence in vaccinated children was 79% lower than in unvaccinated children. Among vaccinated children, half of HZ cases were due to wild-type VZV.

Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study.

BACKGROUND: Statins may have anti-inflammatory and immunomodulatory effects that could reduce the risk of mortality from influenza virus infections. METHODS: The Centers for Disease Control and Prevention's Emerging Infections Program conducts active surveillance for persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states. We analyzed data for hospitalized adults during the 2007-2008 influenza season to evaluate the association between receiving statins and influenza-related death. RESULTS: We identified 3043 patients hospitalized with laboratory-confirmed influenza, of whom 1013 (33.3%) received statins and 151 (5.0%) died within 30 days of their influenza test. Patients who received statins were more likely to be older, male, and white; to suffer from cardiovascular, metabolic, renal, and chronic lung disease; and to have been vaccinated against influenza that season. In a multivariable logistic regression model, administration of statins prior to or during hospitalization was associated with a protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval, .38-.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration. CONCLUSIONS: Statin use may be associated with reduced mortality in patients hospitalized with influenza.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Engaging Patient Advisory Committees to Inform a Genomic Cancer Risk Study: Lessons for Future Efforts.

Introduction The Cancer Health Assessments Reaching Many study seeks to reduce disparities in genomic care. Two patient advisory committees (PACs) were formed, 1 of English speakers and 1 of Spanish speakers, to vet study processes and materials. Stakeholder engagement in research is relatively new, and we know little about how stakeholders view their engagement. We wanted to learn how patient stakeholders viewed the process, to inform future patient engagement efforts. Methods Patients at 2 study sites were invited to serve on 2 PACs. We used an iterative engagement process to solicit and incorporate patient feedback. Much of the PAC feedback on study materials and processes was incorporated. Using surveys and exit interviews, we evaluated stakeholders' experiences as PAC members. Results Nearly all PAC members felt satisfied and included in the study decisions, but surveys and exit interviews suggested the need to improve communications. Discussion Although most believed their feedback was used, and most felt included in study decisions, some said they did not know whether their opinions were used to modify materials or approaches. This suggests the need to explain to patient stakeholders the extent to which their feedback was used and to inform them about the impact that other stakeholders, such as institutional review boards, have on decisions. Conclusion Our evaluation highlights the value of dedicating resources to stakeholder engagement. Although gathering patient feedback on study materials and processes introduced time constraints and complexity to our study, adaptations to materials and processes furthered study goals.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

Given the potential worsening clinical severity of 2009 pandemic influenza A (H1N1) virus (pH1N1) infection from spring to fall 2009, we conducted a clinical case series among patients hospitalized with pH1N1 infection from September through October 2009. A case patient was defined as a hospitalized person who had test results positive for pH1N1 virus by real-time reverse-transcription polymerase chain reaction. Among 255 hospitalized patients, 34% were admitted to an intensive care unit and 8% died. Thirty-four percent of patients were children <18 years of age, 8% were adults ≥ 65 years of age, and 67% had an underlying medical condition. Chest radiographs obtained at hospital admission that had findings that were consistent with pneumonia were noted in 103 (46%) of 255 patients. Among 255 hospitalized patients, 208 (82%) received neuraminidase inhibitors, but only 47% had treatment started ≤ 2 days after illness onset. Overall, characteristics of hospitalized patients with pH1N1 infection in fall 2009 were similar to characteristics of patients hospitalized with pH1N1 infection in spring 2009, which suggests that clinical severity did not change substantially over this period.

Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United States, April-July 2009.

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009, United States.

During April 2009-June 2010, thirty-seven (0.5%) of 6,740 pandemic (H1N1) 2009 viruses submitted to a US surveillance system were oseltamivir resistant. Most patients with oseltamivir-resistant infections were severely immunocompromised (76%) and had received oseltamivir before specimen collection (89%). No evidence was found for community circulation of resistant viruses; only 4 (unlinked) patients had no oseltamivir exposure.

Adult hospitalizations for laboratory-positive influenza during the 2005-2006 through 2007-2008 seasons in the United States.

BACKGROUND: Rates of influenza-associated hospitalizations in the United States have been estimated using modeling techniques with data from pneumonia and influenza hospitalization discharge diagnoses, but they have not been directly estimated from laboratory-positive cases. METHODS: We calculated overall, age-specific, and site-specific rates of laboratory-positive, influenza-associated hospitalization among adults and compared demographic and clinical characteristics and outcomes of hospitalized cases by season with use of data collected by the Emerging Infections Program Network during the 2005-2006 through 2007-2008 influenza seasons. RESULTS: Overall rates of adult influenza-associated hospitalization per 100,000 persons were 9.9 during the 2005-2006 season, 4.8 during the 2006-2007 season, and 18.7 during the 2007-2008 season. Rates of hospitalization varied by Emerging Infections Program site and increased with increasing age. Higher overall and age-specific rates of hospitalization were observed during influenza A (H3) predominant seasons and during periods of increased circulation of influenza B. More than 80% of hospitalized persons each season had > or =1 underlying medical condition, including chronic cardiovascular and metabolic diseases. CONCLUSIONS: Rates varied by season, age, geographic location, and type/subtype of circulating influenza viruses. Influenza-associated hospitalization surveillance is essential for assessing the relative severity of influenza seasons over time and the burden of influenza-associated complications.

Influenza testing and antiviral prescribing practices among emergency department clinicians in 9 states during the 2006 to 2007 influenza season.

STUDY OBJECTIVE: Influenza causes significant widespread illness each year. Emergency department (ED) clinicians are often first-line providers to evaluate and make treatment decisions for patients presenting with influenza. We sought to better understand ED clinician testing and treatment practices in the Emerging Infections Program Network, a federal, state, and academic collaboration that conducts active surveillance for influenza-associated hospitalizations. METHODS: During 2007, a survey was administered to ED clinicians who worked in Emerging Infections Program catchment area hospitals' EDs. The survey encompassed the role of the clinician, years since completing clinical training, hospital type, influenza testing practices, and use of antiviral medications during the 2006 to 2007 influenza season. We examined factors associated with influenza testing and antiviral use. RESULTS: A total of 1,055 ED clinicians from 123 hospitals responded to the survey. A majority of respondents (85.3%; n=887) reported they had tested their patients for influenza during the 2006 to 2007 influenza season (Emerging Infections Program site range: 59.3 to 100%; P<.0001). When asked about antiviral medications, 55.7% (n=576) of respondents stated they had prescribed antiviral medications to some of their patients in 2006 to 2007 (Emerging Infections Program site range 32.9% to 80.3%; P<.0001). A positive association between influenza testing and prescribing antiviral medications was observed. Additionally, the type of hospital, location in which an ED clinician worked, and the number of years since medical training were associated with prescribing antiviral influenza medications. CONCLUSION: There is much heterogeneity in clinician-initiated influenza testing and treatment practices. Additional exploration of the role of hospital testing and treatment policies, clinicians' perception of influenza disease, and methods for educating clinicians about new recommendations is needed to better understand ED clinician testing and treatment decisions, especially in an environment of rapidly changing influenza clinical guidelines. Until influenza testing and treatment guidelines are better promulgated, clinicians may continue to test and treat influenza with inconsistency.

Excess Clinical Comorbidity Among HIV-Infected Patients Accessing Primary Care in US Community Health Centers.

OBJECTIVES: As the life expectancy of people infected with human immunodeficiency virus (HIV) infection has increased, the spectrum of illness has evolved. We evaluated whether people living with HIV accessing primary care in US community health centers had higher morbidity compared with HIV-uninfected patients receiving care at the same sites. METHODS: We compared data from electronic health records for 12 837 HIV-infected and 227 012 HIV-uninfected patients to evaluate the relative prevalence of diabetes mellitus, hypertension, chronic kidney disease, dyslipidemia, and malignancies by HIV serostatus. We used multivariable logistic regression to evaluate differences. Participants were patients aged ≥18 who were followed for ≥3 years (from January 2006 to December 2016) in 1 of 17 community health centers belonging to the Community Health Applied Research Network. RESULTS: Nearly two-thirds of HIV-infected and HIV-uninfected patients lived in poverty. Compared with HIV-uninfected patients, HIV-infected patients were significantly more likely to be diagnosed and/or treated for diabetes (odds ratio [OR] = 1.18; 95% confidence interval [CI], 1.22-1.41), hypertension (OR = 1.38; 95% CI, 1.31-1.46), dyslipidemia (OR = 2.30; 95% CI, 2.17-2.43), chronic kidney disease (OR = 4.75; 95% CI, 4.23-5.34), lymphomas (OR = 4.02; 95% CI, 2.86-5.67), cancers related to human papillomavirus (OR = 5.05; 95% CI, 3.77-6.78), or other cancers (OR = 1.25; 95% CI, 1.10-1.42). The prevalence of stroke was higher among HIV-infected patients (OR = 1.32; 95% CI, 1.06-1.63) than among HIV-uninfected patients, but the prevalence of myocardial infarction or coronary artery disease did not differ between the 2 groups. CONCLUSIONS: As HIV-infected patients live longer, the increasing burden of noncommunicable diseases may complicate their clinical management, requiring primary care providers to be trained in chronic disease management for this population.

The risk of salmonellae shedding by dogs fed Salmonella-contaminated commercial raw food diets.

Twenty-eight research dogs were enrolled to determine the prevalence of salmonellae shedding after consumption of 1 Salmonella-contaminated commercial raw food diet meal. Sixteen dogs were exposed to Salmonella-contaminated commercial raw food diets and 12 to Salmonella-free commercial raw food diets. Seven of the exposed dogs shed salmonellae 1-7 days after consumption of Salmonella-contaminated raw food diets. None of the dogs fed Salmonella-free diets shed salmonellae. No clinical signs were observed in either group. Five of the 7 dogs shed the same serotypes as those recovered from food samples used for feeding. Results showed the same serotypes and antimicrobial resistance pattern in 2 of the 7 shedders. Dogs fed Salmonella-contaminated raw food diets can shed salmonellae and may, therefore, be a source of environmental contamination potentially leading to human or animal illness.

Positive Predictive Value of ICD-9 Code for Herpes Zoster Among Children During the Varicella Vaccine Era.

We examined the positive predictive value of the herpes zoster ICD-9 diagnosis code 053 in the Kaiser Permanente Northwest integrated health plan. Among children 0-17 years old, the positive predictive value was 87.1% (95% confidence interval: 84.2-89.6) and 96.8% (95% confidence interval: 95.0-98.1) during the years 1997-2002 and 2005-2009, respectively, using chart review of the medical record as the diagnostic standard.

HIV and Hepatitis C Virus Screening Practices in a Geographically Diverse Sample of American Community Health Centers.

Because of the advent of highly effective treatments, routine screening for HIV and hepatitis C virus (HCV) has been recommended for many Americans. This study explored the perceived barriers surrounding routine HIV and HCV screening in a diverse sample of community health centers (CHCs). The Community Health Applied Research Network (CHARN) is a collaboration of CHCs, with a shared clinical database. In July, 2013, 195 CHARN providers working in 12 CHCs completed a survey of their attitudes and beliefs about HIV and HCV testing. Summary statistics were generated to describe the prevalence of HIV and HCV and associated demographics by CHCs. HIV and HCV prevalence ranged from 0.1% to 5.7% for HIV and from 0.1% to 3.7% for HCV in the different CHCs. About 15% of the providers cared for at least 50 individuals with HIV and the same was true for HCV. Two-thirds saw less than 10 patients with HIV and less than half saw less than 10 patients with HCV. Less than two-thirds followed USPHS guidelines to screen all patients for HIV between the ages of 13 and 64, and only 44.4% followed the guidance to screen all baby boomers for HCV. Providers with less HIV experience tended to be more concerned about routine screening practices. More experienced providers were more likely to perceive lack of time being an impediment to routine screening. Many US CHC providers do not routinely screen their patients for HIV and HCV. Although additional education about the rationale for routine screening may be indicated, incentives to compensate providers for the additional time they anticipate spending in counseling may also facilitate increased screening rates.

Patient-centered priorities for improving medication management and adherence.

OBJECTIVE: The Centers for Education and Research on Therapeutics convened a workshop to examine the scientific evidence on medication adherence interventions from the patient-centered perspective and to explore the potential of patient-centered medication management to improve chronic disease treatment. METHODS: Patients, providers, researchers, and other stakeholders (N = 28) identified and prioritized ideas for future research and practice. We analyzed stakeholder voting on priorities and reviewed themes in workshop discussions. RESULTS: Ten priority areas emerged. Three areas were highly rated by all stakeholder groups: creating tools and systems to facilitate and evaluate patient-centered medication management plans; developing training on patient-centered prescribing for providers; and increasing patients' knowledge about medication management. However, priorities differed across stakeholder groups. Notably, patients prioritized using peer support to improve medication management while researchers did not. CONCLUSION: Engaging multiple stakeholders in setting a patient-centered research agenda and broadening the scope of adherence interventions to include other aspects of medication management resulted in priorities outside the traditional scope of adherence research. PRACTICE IMPLICATIONS: Workshop participants recognized the potential benefits of patient-centered medication management but also identified many challenges to implementation that require additional research and innovation.

Patient-centered interventions to improve medication management and adherence: a qualitative review of research findings.

OBJECTIVE: Patient-centered approaches to improving medication adherence hold promise, but evidence of their effectiveness is unclear. This review reports the current state of scientific research around interventions to improve medication management through four patient-centered domains: shared decision-making, methods to enhance effective prescribing, systems for eliciting and acting on patient feedback about medication use and treatment goals, and medication-taking behavior. METHODS: We reviewed literature on interventions that fell into these domains and were published between January 2007 and May 2013. Two reviewers abstracted information and categorized studies by intervention type. RESULTS: We identified 60 studies, of which 40% focused on patient education. Other intervention types included augmented pharmacy services, decision aids, shared decision-making, and clinical review of patient adherence. Medication adherence was an outcome in most (70%) of the studies, although 50% also examined patient-centered outcomes. CONCLUSIONS: We identified a large number of medication management interventions that incorporated patient-centered care and improved patient outcomes. We were unable to determine whether these interventions are more effective than traditional medication adherence interventions. PRACTICE IMPLICATIONS: Additional research is needed to identify effective and feasible approaches to incorporate patient-centeredness into the medication management processes of the current health care system, if appropriate.