National Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2023.

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.

A Comparison of Montreal Cognitive Assessment Scores among Individuals with Normal Hearing and Cochlear Implants.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a cognitive screening tool that has 4 of 10 test items heavily dependent on auditory input, potentially leaving hearing-impaired (HI) individuals at a disadvantage. Previous work found that HI individuals scored lower than normal-hearing (NH) individuals on the MoCA, potentially attributed to the degraded auditory signals negatively impacting the ability to commit auditory information to memory. However, there is no research comparing how cochlear implant (CI) recipients perform on the MoCA relative to NH and HI individuals. This study aimed to (1) examine the effect of implementing three different hearing-adjusted scoring methods for a group of age-matched CI recipients and NH individuals, (2) determine if there is a difference between the two groups in overall scores and hearing-adjusted scores, and (3) compare scores across our CI and NH data to the published HI data for all scoring methods. We hypothesized that (1) scores for CI recipients would improve with implementation of the hearing-adjusted scoring methods over the original method, (2) CI recipients would score lower than NH participants for both original and adjusted scoring methods, and (3) the difference in scores between NH and CI listeners for both adjusted and unadjusted scores would be greater than that reported in the literature between NH and HI individuals due to the greater severity of hearing loss and relatively poor spectral resolution of CIs. DESIGN: A total of 94 adults with CIs and 105 adults with NH were initially enrolled. After age-matching the two groups and excluding those who self-identified as NH but failed a hearing screening, a total of 75 CI participants (mean age 61.2 y) and 74 NH participants (mean age 58.8 y) were administered the MoCA. Scores were compared between the NH and CI groups, as well as to published HI data, using the original MoCA scoring method and three alternative scoring methods that excluded various auditory-dependent test items. RESULTS: MoCA scores improved for all groups when two of the three alternative scoring methods were used, with no significant interaction between scoring method and group. Scores for CI recipients were significantly poorer than those for age-matched NH participants for all scoring methods. CI recipients scored better than the published data for HI individuals; however, the HI group was not age matched to the CI and NH groups. CONCLUSIONS: MoCA scores are only partly affected by the potentially greater cognitive processing required to interpret degraded auditory signals. Even with the removal of the auditory-dependent items, CI recipients still did not perform as well as the age-matched NH group. Importantly, removing auditory-dependent items significantly and fundamentally alters the test, thereby reducing its sensitivity. This has important limitations for administration and interpretation of the MoCA for people with hearing loss.

The Effects of Substance Misuse on Auditory and Vestibular Function: A Systematic Review.

BACKGROUND: Chronic substance misuse is an ongoing and significant public health concern. Among a myriad of health complications that can occur, substance misuse potentially causes ototoxic effects. Case reports, retrospective chart data, and a few cohort studies suggest that certain prescription opioids and illicit drugs can have either temporary or permanent effects on auditory and/or vestibular function. Given the steady rise of people with a substance-use disorder (SUD), it is of growing importance that audiologists and otolaryngologists have an insight into the potential ototoxic effects of substance misuse. OBJECTIVES: A systematic review was conducted to (1) synthesize the literature on the illicit drugs, prescription opioids, and alcohol misuse on the auditory and vestibular systems, (2) highlight common hearing and vestibular impairments for each substance class, and (3) discuss the limitations of the literature, the potential mechanisms, and clinical implications for clinicians who may encounter patients with hearing or vestibular loss related to substance misuse, and describe opportunities for further study. DESIGN: Systematic searches were performed via PubMed, Scopus, and Google Scholar, and the final updated search was conducted through March 30, 2022. Inclusion criteria included peer-reviewed articles, regardless of study design, from inception until the present that included adults with chronic substance misuse and hearing and/or vestibular complaints. Articles that focused on the acute effects of substances in healthy people, ototoxicity from already known ototoxic medications, the relationship between hearing loss and development of a SUD, articles not available in English, animal work, and duplicates were excluded. Information on the population (adults), outcomes (hearing and/or vestibular data results), and study design (e.g., case report, cohort) were extracted. A meta-analysis could not be performed because more than 60% of the studies were single-case reports or small cohort. RESULTS: The full text of 67 studies that met the eligibility criteria were selected for the review. Overall, 21 studies reported associations between HL/VL related to illicit drug misuse, 28 studies reported HL/VL from prescription opioids, and 20 studies reported HL/VL related to chronic alcohol misuse (2 studies spanned more than one category). Synthesis of the findings suggested that the misuse and/or overdose of amphetamines and cocaine was associated with sudden, bilateral, and temporary HL, whereas HL from the combination of a stimulant and an opioid often presented with greater HL in the mid-frequency range. Reports of temporary vertigo or imbalance were mainly associated with illicit drugs. HL associated with misuse of prescription opioids was typically sudden or rapidly progressive, bilateral, moderately severe to profound, and in almost all cases permanent. The misuse of prescription opioids occasionally resulted in peripheral VL, especially when the opioid misuse was long term. Chronic alcohol misuse tended to associate with high-frequency sudden or progressive sensorineural hearing loss, or retrocochlear dysfunction, and a high occurrence of central vestibular dysfunction and imbalance. CONCLUSIONS: Overall, chronic substance misuse associates with potential ototoxic effects, resulting in temporary or permanent hearing and/or vestibular dysfunction. However, there are notable limitations to the evidence from the extant literature including a lack of objective test measures used to describe hearing or vestibular effects associated with substance misuse, small study sample sizes, reliance on case studies, lack of controlling for confounders related to health, age, sex, and other substance-use factors. Future large-scale studies with prospective study designs are needed to further ascertain the role and risk factors of substance misuse on auditory and vestibular function and to further clinical management practices.

Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate.

The death-inducing signaling complex (DISC) initiates death receptor-induced apoptosis. DISC assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL only) or anti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation. Current models assume that c-FLIP directly competes with procaspase-8 for recruitment to FADD. Using a functional reconstituted DISC, structure-guided mutagenesis, and quantitative LC-MS/MS, we show that c-FLIPL/S binding to the DISC is instead a co-operative procaspase-8-dependent process. FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes with c-FLIPL/S via a hierarchical binding mechanism. Procaspase-8 activation is regulated by the ratio of unbound c-FLIPL/S to procaspase-8, which determines composition of the procaspase-8:c-FLIPL/S heterodimer. Thus, procaspase-8:c-FLIPL exhibits localized enzymatic activity and is preferentially an activator, promoting DED-mediated procaspase-8 oligomer assembly, whereas procaspase-8:c-FLIPS lacks activity and potently blocks procaspase-8 activation. This co-operative hierarchical binding model explains the dual role of c-FLIPL and crucially defines how c-FLIP isoforms differentially control cell fate.

A Culturally Specific Community Supported Agriculture (CSA) Program to Improve Diet in Immigrant Communities in Brooklyn, New York.

Anti-Asian and anti-immigrant sentiment has surged in the country in the last 3 years. Food insecurity is also on the rise; in our local needs assessment of n = 1,270 Asian American adults in New York City, accessing food was cited as the number 1 priority among those who needed help. Finally, racial discrimination and food access are related to fear of being attacked-driving feelings of safety and therefore willingness to travel for food. To combat these narratives and leveraging pivots by our community partners, we implemented a community-supported agriculture pilot program (n = 38) to assess whether culturally appropriate food access can improve diet and foster cross-cultural learning among immigrant families in Brooklyn, NY. Over a 20-week period from June to October 2022, participants received Chinese-specific produce and nutrition education. Participants reported eating more and a greater variety of vegetables and had higher vegetable intake measured via skin carotenoid scores. This pilot may inform the adaptation of nutrition interventions to reduce inequities in chronic diseases in immigrant communities.

The Effect of Fluid Resuscitation Timing in Early Sepsis Resuscitation.

PURPOSE: The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. METHODS: Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. RESULTS: Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance (P = .09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. CONCLUSIONS: We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating.

A National Survey of the Infrastructure and Scope of Practice for Gastroenterology Hospitalists.

BACKGROUND: Hospital-based specialty-trained physicians have become more prevalent with emerging data suggesting benefit in consult and procedure volume, reduced complication rates, and increased practice productivity. Interest in gastroenterology (GI) hospitalist programs has increased in recent years. However, little is known regarding the types of GI hospitalist models that currently exist. AIMS: To characterize the infrastructure of GI hospitalist models across the USA. METHODS: A 50-question survey was distributed to the GI Hospitalist Special Interest Group of the American Society for Gastrointestinal Endoscopy. Information on demographics, hospital infrastructure, and compensation were collected. RESULTS: 31 of 33 (94%) GI hospitalists completed the questionnaire. Respondents were mostly male (65%), white (48%) or Asian (42%). Most GI hospitalists spent at least half of their clinical time dedicated to the inpatient consultation service (73%), during which they had no other clinical duties. Most services had endoscopy suites with dedicated inpatient endoscopy rooms (66%), over 4 h allotted for procedures (83%), and were available on weekends (62%). Over half of GI hospitalists reported having outpatient duties, the most common being performance of direct access endoscopy (69%). Outside of clinical responsibilities, GI hospitalists were most frequently involved in clinical education or fellowship program leadership (48%). Most GI hospitalists were salaried with an incentive-based bonus based on work relative value units. CONCLUSION: GI hospitalist programs are varied throughout the USA but key commonalities exist between most programs.

Insulin edema: An untypical etiology of anasarca in a 19-year old female presenting to a pediatric emergency department.

Pulmonary edema and anasarca are both common findings in patients presenting to emergency departments (ED). The differential diagnosis for these conditions is very wide and requires an initially broad approach that considers multiple organ systems. Insulin edema has been previously described in multiple case reports as a likely cause of acutely developing edema in mostly type I diabetics either initiating or increasing the intensity of their insulin regimens. This case report describes a 19-year-old female with history of type I diabetes mellitus recently admitted to the hospital for diabetic ketoacidosis (DKA) presenting to a pediatric emergency department (ED) with dyspnea and weight gain. The patient had been reportedly poorly compliant on her insulin therapy before her last admission for DKA and had strictly begun to adhere to her insulin therapy in the interim. Her clinical presentation was notable for hypoxia requiring supplemental oxygen, bilateral lower extremity pitting edema, weight gain of 30 kg since discharge 9 days ago, a chest Xray displaying bilateral pulmonary edema and a work-up otherwise unrevealing for cardiac, renal, or liver etiologies. She was then admitted to the Pediatric Intensive Care Unit (PICU) on supplemental oxygen where through further evaluation she was determined to have insulin edema. This case details an unlikely etiology of anasarca and pulmonary edema, however diagnosing this condition highlights the broad diagnostic process that must be considered for any patient without known significant cardiac, renal, or liver history presenting with respiratory distress and anasarca especially on initial presentation to an emergency department.

Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine: Updated Interim Recommendations from the Advisory Committee on Immunization Practices - United States, December 2021.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.

Hearing and Vestibular Loss with Misuse of Opioids and Illicit Drugs: A Review of the Literature.

BACKGROUND: The purpose of this review was to summarize the literature regarding the effects of opioids and illicit drugs on the auditory and vestibular systems. METHODS: Data were sourced from published papers reporting hearing loss (HL) and/or vestibular loss (VL) following misuse or overdose of opioids or illicit drugs. Most papers consisted of retrospective single-case reports, with few retrospective reviews or prospective cohort studies. Search terms included variations of HL, VL, opioids, and illicit drugs. Search results yielded 51 articles published between 1976 and 2021. A total of 44 articles were reviewed after excluding studies that were not available in English (n = 3), only described acute effects in healthy cohorts (n = 3) or only described general health aspects in a group on methadone maintenance (n = 1). RESULTS: Sixteen studies reported ototoxicity from illicit drugs, 27 from prescription opioids, and 1 was unspecified. This review shows that HL associated with amphetamines and cocaine was typically sudden, bilateral, and temporary. HL from cocaine/crack and heroin often presented with greatest losses in the mid-frequency range. HL associated with opioids was typically sudden, bilateral, moderately severe to profound, and in most cases permanent. The literature is sparse regarding VL from illicit drugs and opioids. CONCLUSION: Practitioners who see patients for sudden or rapidly progressive HL or VL with no apparent cause should inquire about misuse of illicit drugs and opioids, particularly when the HL does not respond to steroid treatment.

The Effect of Body Mass Index and Weight-Adjusted Fluid Dosing on Mortality in Sepsis.

PURPOSE: The Surviving Sepsis Campaign guidelines recommend 30 mL/kg of fluids within 3 hours (30by3) of sepsis-induced hypoperfusion, but a national mandate released an allowance for dosing based on ideal instead of actual body weight (IBW/ABW) for obese patients. This study aims to determine the dose-effect of 30by3 for patients with severe sepsis or septic shock (SS/SS) with respect to body mass index (BMI) categories and secondarily, examine the clinical impact of IBW vs. ABW-based dosing. METHODS: Retrospective cohort study of adults (≥18 years; n = 1,032) with SS/SS presenting to an urban, tertiary-care emergency department. Models include MEDS score, antibiotic timing, lactate, renal and heart failure, among others. RESULTS: The cohort was 10.2% underweight and 28.7% obese. Overall mortality was 17.1% with 20.4% shock mortality. An exponential increase in mortality was observed for each 5 mL/kg under 30by3 for underweight (p = 0.02), but not obese patients. ABW vs IBW-30by3 dosing was reached in 80.0 vs 52.4% (underweight), 56.4 vs 56.9% (normal/overweight), and 23.3 vs 46.0% (obese). Across all BMI categories, there was increased mortality for not reaching ABW-based 30by3 dosing (OR 1.78, 95% CI 1.18-2.69) with no significant impact for IBW (OR 1.28, 95% CI 0.87 -1.91). The increased mortality for failing to reach ABW-dosed 30by3 remained for underweight patients ABW (OR 5.82, 95% CI 1.32-25.57) but not obese patients. Longer ICU stays were observed for not reaching 30by3 based on ABW (ß = 2.40, 95% CI 0.84-3.95) and IBW dosing (ß = 1.58, 95% CI 0.07-3.08) overall. This effect remained for obese and underweight (except IBW dosing) patients. CONCLUSIONS: An exponential, dose-effect increase in mortality was observed for underweight patients not receiving 30by3. Therefore, the mortality impact of under-dosing may be amplified using ABW for underweight patients. Fluid dosing did not impact mortality for obese patients, but we caution against deviation from guidelines without further studies.

Increased Mortality in Patients Undergoing Inpatient Endoscopy During the Early COVID-19 Pandemic.

BACKGROUND AND AIMS: The Coronavirus disease 2019 (COVID-19) pandemic led to the restructuring of most healthcare systems, but the impact on patients undergoing inpatient endoscopic procedures is unknown. We sought to identify factors associated with 30-day mortality among patients undergoing inpatient endoscopy before and during the first wave of the pandemic within an academic tertiary care center. METHODS: We studied patients who underwent inpatient endoscopic procedures from March 1-May 31 in 2020 (COVID-19 era), the peak of the pandemic's first wave across the care center studied, and in March 1-May 31, 2018 and 2019 (control). Patient demographics and hospitalization/procedure data were compared between groups. Cox regression analyses were conducted to identify factors associated with 30-day mortality. RESULTS: Inpatient endoscopy volume decreased in 2020 with a higher proportion of urgent procedures, increased proportion of patients receiving blood transfusions, and a 10.1% mortality rate. In 2020, male gender, further distance from hospital, need for intensive care unit (ICU) admission, and procedures conducted outside the endoscopy suite were associated with increased risk of 30-day mortality. CONCLUSIONS: Patients undergoing endoscopy during the pandemic had higher proportions of ICU admission, more urgent indications, and higher rates of 30-day mortality. Greater proportions of urgent endoscopy cases may be due to hospital restructuring or patient reluctance to seek hospital care during a pandemic. Demographic and procedural characteristics associated with higher mortality risk may be potential areas to improve outcomes during future pandemic hospital restructuring efforts.

Demographic Characteristics of Persons Vaccinated During the First Month of the COVID-19 Vaccination Program - United States, December 14, 2020-January 14, 2021.

In December 2020, two COVID-19 vaccines (Pfizer-BioNTech and Moderna) were authorized for emergency use in the United States for the prevention of coronavirus disease 2019 (COVID-19).* Because of limited initial vaccine supply, the Advisory Committee on Immunization Practices (ACIP) prioritized vaccination of health care personnel† and residents and staff members of long-term care facilities (LTCF) during the first phase of the U.S. COVID-19 vaccination program (1). Both vaccines require 2 doses to complete the series. Data on vaccines administered during December 14, 2020-January 14, 2021, and reported to CDC by January 26, 2021, were analyzed to describe demographic characteristics, including sex, age, and race/ethnicity, of persons who received ≥1 dose of COVID-19 vaccine (i.e., initiated vaccination). During this period, 12,928,749 persons in the United States in 64 jurisdictions and five federal entities§ initiated COVID-19 vaccination. Data on sex were reported for 97.0%, age for 99.9%, and race/ethnicity for 51.9% of vaccine recipients. Among persons who received the first vaccine dose and had reported demographic data, 63.0% were women, 55.0% were aged ≥50 years, and 60.4% were non-Hispanic White (White). More complete reporting of race and ethnicity data at the provider and jurisdictional levels is critical to ensure rapid detection of and response to potential disparities in COVID-19 vaccination. As the U.S. COVID-19 vaccination program expands, public health officials should ensure that vaccine is administered efficiently and equitably within each successive vaccination priority category, especially among those at highest risk for infection and severe adverse health outcomes, many of whom are non-Hispanic Black (Black), non-Hispanic American Indian/Alaska Native (AI/AN), and Hispanic persons (2,3).

County-Level COVID-19 Vaccination Coverage and Social Vulnerability - United States, December 14, 2020-March 1, 2021.

The U.S. COVID-19 vaccination program began in December 2020, and ensuring equitable COVID-19 vaccine access remains a national priority.* COVID-19 has disproportionately affected racial/ethnic minority groups and those who are economically and socially disadvantaged (1,2). Thus, achieving not just vaccine equality (i.e., similar allocation of vaccine supply proportional to its population across jurisdictions) but equity (i.e., preferential access and administra-tion to those who have been most affected by COVID-19 disease) is an important goal. The CDC social vulnerability index (SVI) uses 15 indicators grouped into four themes that comprise an overall SVI measure, resulting in 20 metrics, each of which has national and state-specific county rankings. The 20 metric-specific rankings were each divided into lowest to highest tertiles to categorize counties as low, moderate, or high social vulnerability counties. These tertiles were combined with vaccine administration data for 49,264,338 U.S. residents in 49 states and the District of Columbia (DC) who received at least one COVID-19 vaccine dose during December 14, 2020-March 1, 2021. Nationally, for the overall SVI measure, vaccination coverage was higher (15.8%) in low social vulnerability counties than in high social vulnerability counties (13.9%), with the largest coverage disparity in the socioeconomic status theme (2.5 percentage points higher coverage in low than in high vulnerability counties). Wide state variations in equity across SVI metrics were found. Whereas in the majority of states, vaccination coverage was higher in low vulnerability counties, some states had equitable coverage at the county level. CDC, state, and local jurisdictions should continue to monitor vaccination coverage by SVI metrics to focus public health interventions to achieve equitable coverage with COVID-19 vaccine.

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock.

BACKGROUND: Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes. METHODS: ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others. RESULTS: In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81-3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95-4.57; 12-h- OR 2.46, 95% CI 1.72-3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06-1.90), and renal failure (OR 2.57, 95% CI 1.50-4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58-1.29) or other outcomes. CONCLUSIONS: Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.

User Engagement Using an Etextbook: A Descriptive Study.

Engagement is an integral pedagogical component underpinning effective educational activities and is of importance for educators using online platforms. Carefully designed, technology-enabled learning resources can increase student engagement. We developed an open educational resource etextbook on vital sign measurement using an interactive and multimodal platform to facilitate student learning. The etextbook design was informed by experiential teaching-learning theory. Students progressed through the etextbook at their own pace, following pedagogy informed by the iterative process of read, observe, practice, and test, commonly used in nursing education. The etextbook was introduced as a required reading in a first-year health assessment course at one university and two colleges. In this project, we explored the level of engagement experienced by users of the etextbook. We conducted a descriptive study using the User Engagement Scale to measure students' degree of engagement using the etextbook. Results from participants (N = 455) who used the etextbook in the study indicated a high level of engagement. The responses to an open-ended item on the survey provided context to the results and shed light on effective design practices. Several recommendations for best practices in developing etextbooks are identified for educators to consider.

Projected Population Benefit of Increased Effectiveness and Coverage of Influenza Vaccination on Influenza Burden in the United States.

BACKGROUND: Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC). METHODS: For 3 influenza seasons (2011-12, 2015-16, and 2017-18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC. RESULTS: During the 2017-18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18-64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations. CONCLUSIONS: Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18-49 years.

Human Papillomavirus 16 Capsids Mediate Nuclear Entry during Infection.

Infectious human papillomavirus 16 (HPV16) L1/L2 pseudovirions were found to remain largely intact during vesicular transport to the nucleus. By electron microscopy, capsids with a diameter of 50 nm were clearly visible within small vesicles attached to mitotic chromosomes and to a lesser extent within interphase nuclei, implying nuclear disassembly. By confocal analysis, it was determined that nuclear entry of assembled L1 is dependent upon the presence of the minor capsid protein, L2, but independent of encapsidated DNA. We also demonstrate that L1 nuclear localization and mitotic chromosome association can occur in vivo in the murine cervicovaginal challenge model of HPV16 infection. These findings challenge the prevailing concepts of PV uncoating and disassembly. More generally, they document that a largely intact viral capsid can enter the nucleus within a transport vesicle, establishing a novel mechanism by which a virus accesses the nuclear cellular machinery.IMPORTANCE Papillomaviruses (PVs) comprise a large family of nonenveloped DNA viruses that include HPV16, among other oncogenic types, the causative agents of cervical cancer. Delivery of the viral DNA into the host cell nucleus is necessary for establishment of infection. This was thought to occur via a subviral complex following uncoating of the larger viral capsid. In this study, we demonstrate that little disassembly of the PV capsid occurs prior to nuclear delivery. These surprising data reveal a previously unrecognized viral strategy to access the nuclear replication machinery. Understanding viral entry mechanisms not only increases our appreciation of basic cell biological pathways but also may lead to more effective antiviral interventions.

Support for Transition from Adolescent to Adult Health Care Among Adolescents With and Without Mental, Behavioral, and Developmental Disorders - United States, 2016-2017.

Clinical guidelines recommend that primary care providers (PCPs) provide guidance and support to ensure a planned transition from pediatric to adult health care for adolescents, beginning at age 12 years (1). However, most adolescents do not receive the recommended health care transition planning (2). This is particularly concerning for adolescents with diagnosed mental, behavioral, and developmental disorders (MBDDs) (3), who account for approximately 20% of U.S. adolescents (4). Childhood MBDDs are linked to increased long-term morbidity and mortality; timely health care transition planning might mitigate adverse outcomes (5,6). CDC analyzed pooled, parent-reported data from the 2016 and 2017 National Survey of Children's Health (NSCH), comparing adolescents, aged 12-17 years, with and without MBDDs on a composite measure and specific indicators of recommended health care transition planning by PCPs. Overall, approximately 15% of adolescents received recommended health care transition planning: 15.8% (95% confidence interval [CI] = 14.1%-17.5%) of adolescents with MBDDs, compared with 14.2% (95% CI = 13.2%-15.3%) of adolescents without MBDDs. Relative to peers without MBDDs and after adjusting for age, adolescents with anxiety were 36% more likely to receive recommended health care transition planning, and those with depression were 69% more likely; adolescents with autism spectrum disorder (ASD) were 35% less likely to receive such transition planning, and those with developmental delay* were 25% less likely. Fewer than 20% of adolescents with MBDDs receiving current treatment met the transition measure. These findings suggest that a minority of adolescents with MBDDs receive recommended transition planning, indicating a potential missed public health opportunity to prevent morbidity and mortality in a population at high risk for health care disengagement (1). Improving access to comprehensive and coordinated programs and services,† as well as increasing provider training concerning adolescents' unique mental and physical health care needs (7), could help increase the number of adolescents benefiting from successful health care transitions (4).