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Issue 44, November 1, 2022

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CDC Science Clips: Volume 14, Issue 44, November 1, 2022

This week, CDC Science Clips is pleased to feature articles from the Clinical Infectious Disease CDC sponsored supplement Anthrax Preparedness.

  • For many Americans, awareness of the threat posed by anthrax is closely tied to the attacks of October 2001 and November 2001 when 22 persons were diagnosed with anthrax from exposure to intentionally contaminated mail. That event highlighted the critical need to strengthen preparedness for this biothreat in the United States. Anthrax is a bacterial disease caused by Bacillus anthracis. The US Department of Health and Human Services designated B. anthracis as a tier 1 select agent, signifying that it presents the greatest risk of deliberate misuse with significant potential for mass causalities and poses a severe threat to public health and safety. (Honein & Hoffmaster, 2022)

The report consists of these components:

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Anthrax Preparedness
      1. Algorithms for the identification of anthrax meningitis during a mass casualty event based on a systematic review of systemic anthrax from 1880 through 2018
        Binney S, Person MK, Traxler RM, Cook R, Bower WA, Hendricks K.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S468-s477.
        BACKGROUND: During an anthrax mass casualty event, prompt identification of patients with anthrax meningitis is important. Previous research has suggested use of a screening tool based on neurological symptoms and signs. METHODS: Using historical anthrax patient data from 1880 through 2018, we analyzed risk factors for meningitis. We developed lists of symptoms and signs (ie, algorithms) for predicting meningitis with high sensitivity and specificity. We evaluated both single and paired algorithms as screening tools. RESULTS: A single algorithm with 1 or more neurological symptoms or signs identifying patients with likely meningitis achieved high sensitivity (86%; 95% confidence interval [CI], 71%-100%) and specificity (90%; 95% CI, 82%-98%). Pairing algorithms with the same symptoms and signs (severe headache, altered mental status, meningeal signs, and "other neurological deficits") improved specificity (99%; 95% CI, 97%-100%) but left 17.3% of patients in a middle "indeterminate" meningitis category and in need of additional diagnostic testing to determine likely meningitis status. Pairing algorithms with differing symptoms and signs also improved specificity over the single algorithm (92%; 95% CI, 85%-99%) but categorized just 2.5% of patients as indeterminate. CONCLUSIONS: Our study confirms prior research suggesting quick and reliable assessment of patients for anthrax meningitis is possible based on the presence or absence of certain symptoms and signs. A single algorithm was adequate; however, if we assumed low-resource diagnostic testing was feasible for some patients, pairing algorithms improved specificity. Pairing algorithms with differing symptoms and signs minimized the proportion of patients requiring additional diagnostics.

      2. Anthrax meningoencephalitis and intracranial hemorrhage
        Caffes N, Hendricks K, Bradley JS, Twenhafel NA, Simard JM.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S451-s458.
        The neurological sequelae of Bacillus anthracis infection include a rapidly progressive fulminant meningoencephalitis frequently associated with intracranial hemorrhage, including subarachnoid and intracerebral hemorrhage. Higher mortality than other forms of bacterial meningitis suggests that antimicrobials and cardiopulmonary support alone may be insufficient and that strategies targeting the hemorrhage might improve outcomes. In this review, we describe the toxic role of intracranial hemorrhage in anthrax meningoencephalitis. We first examine the high incidence of intracranial hemorrhage in patients with anthrax meningoencephalitis. We then review common diseases that present with intracranial hemorrhage, including aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, postulating applicability of established and potential neurointensive treatments to the multimodal management of hemorrhagic anthrax meningoencephalitis. Finally, we examine the therapeutic potential of minocycline, an antimicrobial that is effective against B. anthracis and that has been shown in preclinical studies to have neuroprotective properties, which thus might be repurposed for this historically fatal disease.

      3. Welder's Anthrax: A tale of 2 cases
        Hendricks K, Martines RB, Bielamowicz H, Boyer AE, Long S, Byers P, Stoddard RA, Taylor K, Kolton CB, Gallegos-Candela M, Roberts C, DeLeon-Carnes M, Salzer J, Dawson P, Brown D, Templeton-LeBouf L, Maves RC, Gulvik C, Lonsway D, Barr JR, Bower WA, Hoffmaster A.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S354-s363.
        Bacillus anthracis has traditionally been considered the etiologic agent of anthrax. However, anthrax-like illness has been documented in welders and other metal workers infected with Bacillus cereus group spp. harboring pXO1 virulence genes that produce anthrax toxins. We present 2 recent cases of severe pneumonia in welders with B. cereus group infections and discuss potential risk factors for infection and treatment options, including antitoxin.

      4. Clinical features of patients hospitalized for all routes of anthrax, 1880-2018: A systematic review
        Hendricks K, Person MK, Bradley JS, Mongkolrattanothai T, Hupert N, Eichacker P, Friedlander AM, Bower WA.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S341-s353.
        BACKGROUND: Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent. METHODS: We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period. RESULTS: Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0-4) for injection to 7 days (IQR, 4-9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin. CONCLUSIONS: This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores.

      5. Antitoxin use in the prevention and treatment of anthrax disease: A systematic review
        Hesse EM, Godfred-Cato S, Bower WA.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S432-s440.
        BACKGROUND: Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality. Although timely and appropriate antimicrobial therapy can reduce morbidity and mortality, the role of adjunctive therapies continues to be explored. METHODS: We searched 11 databases for articles that report use of anthrax antitoxins in treatment or prevention of systemic anthrax disease published through July 2019. We identified other data sources through reference search and communication with experts. We included English-language studies on antitoxin products with approval by the US Food and Drug Administration (FDA) for anthrax in humans, nonhuman primates, and rabbits. Two researchers independently reviewed studies for inclusion and abstracted relevant data. RESULTS: We abstracted data from 12 publications and 2 case reports. All 3 FDA-approved anthrax antitoxins demonstrated significant improvement in survival as monotherapy over placebo in rabbits and nonhuman primates. No study found significant improvement in survival with combination antitoxin and antimicrobial therapy compared to antimicrobial monotherapy. Case reports and case series described 25 patients with systemic anthrax disease treated with antitoxins; 17 survived. Animal studies that used antitoxin monotherapy as postexposure prophylaxis (PEP) demonstrated significant improvement in survival over placebo, with greatest improvements coming with early administration. CONCLUSIONS: Limited human and animal evidence indicates that adjunctive antitoxin treatment may improve survival from systemic anthrax infection. Antitoxins may also provide an alternative therapy to antimicrobials for treatment or PEP during an intentional anthrax incident that could involve a multidrug-resistant B. anthracis strain.

      6. Responding to the threat posed by anthrax: Updated evidence to improve preparedness
        Honein MA, Hoffmaster AR.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S339-s340.

      7. Postexposure prophylaxis and treatment of bacillus anthracis infections: A systematic review and meta-analyses of animal models, 1947-2019
        Kennedy JL, Bulitta JB, Chatham-Stephens K, Person MK, Cook R, Mongkolrattanothai T, Shin E, Yu P, Negron ME, Bower WA, Hendricks K.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S379-s391.
        BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

      8. Risk factors for severe cutaneous anthrax in a retrospective case series and use of a clinical algorithm to identify likely meningitis and evaluate treatment outcomes, Kyrgyz Republic, 2005-2012
        Kutmanova A, Zholdoshev S, Roguski KM, Sholpanbay Uulu M, Person MK, Cook R, Bugrysheva J, Nadol P, Buranchieva A, Imanbaeva L, Dzhangazieva A, Bower WA, Hendricks K.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S478-s486.
        BACKGROUND: US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment. METHODS: We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status. RESULTS: We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis. CONCLUSIONS: Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis.

      9. Survival of patient with hemorrhagic meningitis associated with inhalation anthrax
        Lombarte Espinosa E, Villuendas Usón MC, Arribas García J, Jado García I, Huarte Lacunza R, Zárate Chug P, Claraco Vega LM, Jesús Santed Andrés M, Ríos MJ, Cook R, Simard JM, Boyer AE, Rezusta A.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S364-s372.
        This report describes a 49-year-old male construction worker who acquired a Bacillus anthracis infection after working on a sheep farm. He experienced a severe respiratory infection, septic shock, and hemorrhagic meningoencephalitis with severe intracranial hypertension. After several weeks with multiple organ dysfunction syndrome, he responded favorably to antibiotic treatment. Three weeks into his hospitalization, an intracranial hemorrhage and cerebral edema led to an abrupt deterioration in his neurological status. A single dose of raxibacumab was added to his antimicrobial regimen on hospital day 27. His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered.

      10. Systematic review of in vitro antimicrobial susceptibility testing for bacillus anthracis, 1947-2019
        Maxson T, Kongphet-Tran T, Mongkolrattanothai T, Travis T, Hendricks K, Parker C, McLaughlin HP, Bugrysheva J, Ambrosio F, Michel P, Cherney B, Lascols C, Sue D.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S373-s378.
        Bacillus anthracis, the causative agent of anthrax, is a high-consequence bacterial pathogen that occurs naturally in many parts of the world and is considered an agent of biowarfare or bioterrorism. Understanding antimicrobial susceptibility profiles of B. anthracis isolates is foundational to treating naturally occurring outbreaks and to public health preparedness in the event of an intentional release. In this systematic review, we searched the peer-reviewed literature for all publications detailing antimicrobial susceptibility testing of B. anthracis. Within the set of discovered articles, we collated a subset of publications detailing susceptibility testing that followed standardized protocols for Food and Drug Administration-approved, commercially available antimicrobials. We analyzed the findings from the discovered articles, including the reported minimal inhibitory concentrations. Across the literature, most B. anthracis isolates were reported as susceptible to current first-line antimicrobials recommended for postexposure prophylaxis and treatment. The data presented for potential alternative antimicrobials will be of use if significant resistance to first-line antimicrobials arises, the strain is bioengineered, or first-line antimicrobials are not tolerated or available.

      11. Safety of antimicrobials for postexposure prophylaxis and treatment of Anthrax: A review
        Parker CM, Karchmer AW, Fisher MC, Muhammad KM, Yu PA.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S417-s431.
        BACKGROUND: Bacillus anthracis, the causative agent for anthrax, poses a potential bioterrorism threat and is capable of causing mass morbidity and mortality. Antimicrobials are the mainstay of postexposure prophylaxis (PEP) and treatment of anthrax. We conducted this safety review of 24 select antimicrobials to identify any new or emerging serious or severe adverse events (AEs) to help inform their risk-benefit evaluation for anthrax. METHODS: Twenty-four antimicrobials were included in this review. Tertiary data sources (e.g. Lactmed, Micromedex, REPROTOX) were reviewed for safety information and summarized to evaluate the known risks of these antimicrobials. PubMed was also searched for published safety information on serious or severe AEs with these antimicrobials; AEs that met inclusion criteria were abstracted and reviewed. RESULTS: A total of 1316 articles were reviewed. No consistent observations or patterns were observed among the abstracted AEs for a given antimicrobial; therefore, the literature review did not reveal evidence of new or emerging AEs that would add to the risk-benefit profiles already known from tertiary data sources. CONCLUSIONS: The reviewed antimicrobials have known and/or potential serious or severe risks that may influence selection when recommending an antimicrobial for PEP or treatment of anthrax. Given the high fatality rate of anthrax, the risk-benefit evaluation favors use of these antimicrobials for anthrax. The potential risks of antimicrobials should not preclude these reviewed antimicrobials from clinical consideration for anthrax but rather guide appropriate antimicrobial selection and prioritization across different patient populations with risk mitigation measures as warranted.

      12. Systematic review of hospital treatment outcomes for naturally acquired and bioterrorism-related anthrax, 1880-2018
        Person MK, Cook R, Bradley JS, Hupert N, Bower WA, Hendricks K.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S392-s401.
        BACKGROUND: Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical countermeasures against anthrax were based on in vitro data and expert opinion. However, a century of previously uncompiled observational human data that often includes treatment and outcomes is available in the literature for analysis. METHODS: We reviewed treatment outcomes for patients hospitalized with anthrax. We stratified patients by meningitis status, route of infection, and systemic criteria, then analyzed survival by treatment type, including antimicrobials, antitoxin/antiserum, and steroids. Using logistic regression, we calculated odds ratios and 95% confidence intervals to compare survival between treatments. We also calculated hospital length of stay. Finally, we evaluated antimicrobial postexposure prophylaxis (PEPAbx) using data from a 1970 Russian-language article. RESULTS: We identified 965 anthrax patients reported from 1880 through 2018. After exclusions, 605 remained: 430 adults, 145 children, and 30 missing age. Survival was low for untreated patients and meningitis patients, regardless of treatment. Most patients with localized cutaneous or nonmeningitis systemic anthrax survived with 1 or more antimicrobials; patients with inhalation anthrax without meningitis fared better with at least 2. Bactericidal antimicrobials were effective for systemic anthrax; addition of a protein synthesis inhibitor(s) (PSI) to a bactericidal antimicrobial(s) did not improve survival. Likewise, addition of antitoxin/antiserum to antimicrobials did not improve survival. Mannitol improved survival for meningitis patients, but steroids did not. PEPAbx reduced risk of anthrax following exposure to B. anthracis. CONCLUSIONS: Combination therapy appeared to be superior to monotherapy for inhalation anthrax without meningitis. For anthrax meningitis, neither monotherapy nor combination therapy were particularly effective; however, numbers were small. For localized cutaneous anthrax, monotherapy was sufficient. For B. anthracis exposures, PEPAbx was effective.

      13. Pre- and postlicensure animal efficacy studies comparing anthrax antitoxins
        Slay RM, Cook R, Hendricks K, Boucher D, Merchlinsky M.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S441-s450.
        BACKGROUND: The deliberate use of Bacillus anthracis spores is believed by the US government to be a high bioweapons threat. The first line of defense following potential exposure to B. anthracis spores would be postexposure prophylaxis with antimicrobials that have activity against B. anthracis. Additional therapies to address the effects of toxins may be needed in systemically ill individuals. Over the last 2 decades, the United States government (USG) collaborated with the private sector to develop, test, and stockpile 3 antitoxins: anthrax immunoglobulin intravenous (AIGIV), raxibacumab, and obiltoxaximab. All 3 products target protective antigen, a protein factor common to the 2 exotoxins released by B. anthracis, and hamper or block the toxins' effects and prevent or reduce pathogenesis. These antitoxins were approved for licensure by the United States Food and Drug Administration based on animal efficacy studies compared to placebo. METHODS: We describe USG-sponsored pre- and postlicensure studies that compared efficacy of 3 antitoxins in a New Zealand White rabbit model of inhalation anthrax; survival following a lethal aerosolized dose of B. anthracis spores was the key measure of effectiveness. To model therapeutic intervention, intravenous treatments were started following onset of antigenemia. RESULTS: In pre- and postlicensure studies, all 3 antitoxins were superior to placebo; in the postlicensure study, raxibacumab and obiltoxaximab were superior to AIGIV, but neither was superior to the other. CONCLUSIONS: These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment.

      14. Risk factors for death or meningitis in adults hospitalized for cutaneous anthrax, 1950-2018: A systematic review
        Thompson JM, Cook R, Person MK, Negrón ME, Traxler RM, Bower WA, Hendricks K.
        Clin Infect Dis. 2022 Oct 17;75(Supplement_3):S459-s467.
        BACKGROUND: Cutaneous anthrax accounts for approximately 95% of anthrax cases worldwide. About 24% of untreated patients die, and many cases are complicated by meningitis. Here, we explore clinical features of cutaneous disease associated with poor outcomes. METHODS: A systematic review identified 303 full-text articles published from 1950 through 2018 that met predefined inclusion criteria. Cases were abstracted, and descriptive analyses and univariate logistic regression were conducted to identify prognostic indicators for cutaneous anthrax. RESULTS: Of 182 included patients, 47 (25.8%) died. Previously reported independent predictors for death or meningitis that we confirmed included fever or chills; nausea or vomiting; headache; severe headache; nonheadache, nonmeningeal signs; leukocytosis; and bacteremia. Newly identified predictors included anxiety, abdominal pain, diastolic hypotension, skin trauma, thoracic edema, malignant pustule edema, lymphadenopathy, and evidence of coagulopathy (all with P < .05). CONCLUSIONS: We identified patient presentations not previously associated with poor outcomes.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. Use of leading practices in US hospital antimicrobial stewardship programs
        Stenehjem EA, Braun BI, Chitavi SO, Hyun DY, Schmaltz SP, Fakih MG, Neuhauser MM, Davidson LE, Meyer MJ, Tamma PD, Dodds-Ashley ES, Baker DW.
        Infect Control Hosp Epidemiol. 2022 Oct 13:1-8.
        OBJECTIVE: To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey. SETTING: Acute-care hospitals. PARTICIPANTS: ASP leaders. METHODS: Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs. RESULTS: Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100-399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001). CONCLUSIONS: Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.

    • Chronic Diseases and Conditions
      1. Impact of the national amyotrophic lateral sclerosis registry: Analysis of registry-funded research
        Rechtman L, Brenner S, Wright M, Ritsick M, Rahman F, Han M, Raymond J, Larson T, Horton DK, Mehta P.
        Ann Clin Transl Neurol. 2022 Oct 19.
        OBJECTIVE: This research aims to examine the impact of the National Amyotrophic Lateral Sclerosis (ALS) Registry-funded research activities. METHODS: Registry-funded research and related publications were identified through the National ALS Registry website, the National Institutes of Health (NIH) Reporter website, and verified by Principal Investigators. Key study characteristics (e.g., study population, sample size) and key impact features (e.g., risk factors) were abstracted and recorded on study abstraction forms. Descriptive statistics were used to analyze the volume, productivity, and findings of the Registry-funded research. RESULTS: Since 2012, the National ALS Registry funded 21 research projects. Of these, 14 were through extramural research grants and included in the analysis. These studies are often related to environmental, medical conditions, and genetic risk factors. On average, the funded grants produced 1 to 2 publications which were cited 114 times by other researchers. The relative citation ratio averaged 1.81 with a weighted relative citation ratio of 16.28. These studies supported the identification and confirmation of candidate risk factors. Environmental and occupational risk factors typically related to heavy metal exposure (e.g., lead, mercury) and agricultural chemicals (e.g., pesticides, herbicides), and the occupations associated with exposure to these substances were most frequently explored. INTERPRETATION: The National ALS Registry is a multifaceted research platform, one component of which is funded research. This Registry-funded research fills an essential gap in the overall ALS scientific community as it is difficult to prevent and treat a disease without a deeper understanding of its causes.

      2. Incidence, prevalence, and mortality of lupus nephritis: A population-based study over four decades-The Lupus Midwest Network (LUMEN)
        Hocaoglu M, Valenzuela-Almada MO, Dabit JY, Osei-Onomah SA, Chevet B, Giblon RE, Zand L, Fervenza FC, Helmick CG, Crowson CS, Duarte-García A.
        Arthritis Rheumatol. 2022 Oct 13.
        OBJECTIVES: There is paucity of population-based studies investigating the epidemiology of lupus nephritis (LN) in the US and long-term secular trends of the disease and its outcomes. We aimed to examine the epidemiology of LN in a well-defined eight-county region in the US. METHODS: Patients with incident LN between 1976 and 2018 (1976-2009 Olmsted County, 2010-2018 eight-county region) in Minnesota were identified. Age- and sex-specific incidence rates and point prevalence for four decades, adjusted to the projected 2000 US population, were reported. Standardized mortality ratios (SMR), survival rates, and time to end-stage renal disease (ESRD) were estimated. RESULTS: There were 72 patients with incident LN between 1976-2018. Mean age at diagnosis was 38.4 years (SD 16.24), 76% were female, and 69% non-Hispanic White. Average annual LN incidence between 1976 and 2018 was 1 per 100,000 population (95%CI 0.8-1.3) and highest in the 30-39 age group. Between 1976-1989 and 2000-2018 periods, overall incidence of LN increased from 0.7 to 1.3 per 100,000, but this was not statistically significant. Estimated LN prevalence increased from 16.8 in 1985 to 21.2 per 100,000 in 2015. LN had an SMR of 6.33 (95% CI 3.81-9.89) with no improvement in mortality gap in the last four decades. At 10 years, survival was 70%, and 13% had ESRD. CONCLUSION: The incidence and prevalence of LN in this area increased in the last four decades. LN patients have poor outcomes with high rates of ESRD and mortality rates six times that of the general population. This article is protected by copyright. All rights reserved.

      3. Health care utilization in systemic lupus erythematosus in the community: The Lupus Midwest Network
        Chevet B, Figueroa-Parra G, Valenzuela-Almada MO, Hocaoglu M, Vallejo S, Osei-Onomah SA, Giblon RE, Dabit JY, Chamberlain AM, Cornec D, Greenlund KJ, Barbour KE, Crowson CS, Duarte-García A.
        J Clin Rheumatol. 2022 Oct 1.
        OBJECTIVE: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population. METHODS: This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups. RESULTS: Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups. CONCLUSION: Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.

      4. Incidence of chronic kidney disease among adults with diabetes, 2015-2020
        Tuttle KR, Jones CR, Daratha KB, Koyama AK, Nicholas SB, Alicic RZ, Duru OK, Neumiller JJ, Norris KC, Ríos Burrows N, Pavkov ME.
        N Engl J Med. 2022 Oct 13;387(15):1430-1431.

    • Communicable Diseases
      1. Individual and household factors associated with non-disclosure of positive HIV status in a population-based HIV serosurvey
        Lawton J, Lavoie MC, Bashorun A, Dalhatu I, Ibrahim J, Agbakwuru C, Boyd M, Stafford K, Swaminathan M, Aliyu G, Charurat M.
        AIDS. 2022 Oct 14.
        OBJECTIVES: Non-disclosure of positive HIV status in population-based surveys causes underestimation of national HIV diagnosis and biases inferences about engagement in the care continuum. This study investigated individual and household factors associated with HIV non-disclosure to survey interviewers in Nigeria. DESIGN: Secondary analysis of a cross sectional population-based household HIV survey. METHODS: We analyzed data from adults aged 15-64 years who tested positive for HIV and had antiretroviral drugs (ARVs) in their blood from a nationally representative HIV sero-survey conducted in Nigeria in 2018. We considered ARV use as a proxy for knowledge of HIV diagnosis; thus, respondents who self-reported to be unaware of their HIV status were classified as non-disclosers. We estimated the associations between non-disclosure and various sociodemographic, clinical, and household characteristics using weighted logistic regression. RESULTS: Among 1,266 respondents living with HIV who were taking ARVs, 503 (40%) did not disclose their HIV status to interviewers. In multivariable statistical analyses, the adjusted odds of non-disclosure were highest among respondents aged 15-24 years, those with less than a primary school education, and those who were the only person living with HIV in their household. CONCLUSIONS: Non-disclosure of positive HIV status to survey personnel is common among adults who are receiving treatment in Nigeria. These findings highlight the importance of validating self-reported HIV status in surveys using biomarkers of ARV use. Meanwhile, it is crucial to improve disclosure by strengthening interview procedures and tailoring strategies towards groups that are disproportionately likely to underreport HIV diagnoses.

      2. Quantifying Mycobacterium tuberculosis transmission dynamics across global settings: a systematic analysis
        Smith J, Cohen T, Dowdy D, Shrestha S, Gandhi NR, Hill AN.
        Am J Epidemiol. 2022 Oct 13.
        The degree to which individual heterogeneity in the production of secondary cases ("superspreading") affects tuberculosis (TB) transmission has not been systematically studied. We searched for population-based or surveillance studies in which whole genome sequencing was used to estimate TB transmission and the size distributions of putative TB transmission clusters were enumerated. We fit cluster size distribution data to a negative binomial branching process model to jointly infer the transmission parameters $R$ (the reproductive number) and dispersion parameter, $k$, which quantifies the propensity of superspreading in a population (generally, lower values of $k$ ($<1.0$) suggest increased heterogeneity). Of 4,796 citations identified in our initial search, nine studies met inclusion criteria ($n=5$ all TB; $n=4$ drug resistant TB) from eight global settings. Estimated $R$ values (range: 0.10, 0.73) were below 1.0, consistent with declining epidemics in the included settings; estimated $k$ values were well below 1.0 (range: 0.02, 0.48), indicating the presence of substantial individual-level heterogeneity in transmission across all settings. We estimated that a minority of cases (range 2-31%) drive the majority (80%) of ongoing transmission at the population level. Identifying sources of heterogeneity and accounting for them in TB control may have a considerable impact on mitigating TB transmission.

      3. An evaluation of an enhanced model of integrating family planning into HIV treatment services in Zambia, April 2018 - June 2019
        Medley A, Tsiouris F, Pals S, Senyana B, Hanene S, Kayeye S, Casquete RR, Lasry A, Braaten M, Aholou T, Kasonde P, Chisenga T, Mweebo K, Harris TG.
        J Acquir Immune Defic Syndr. 2022 Oct 13.
        BACKGROUND: We designed and implemented an enhanced model of integrating family planning (FP) into existing HIV treatment services at six health facilities in Lusaka, Zambia. METHODS: The enhanced model included: improving FP documentation within HIV monitoring systems; training HIV providers in FP services; offering contraceptives within the HIV clinic; and facilitated referral to community-based distributors. Independent samples of women living with HIV (WLHIV) aged ≥16 years were interviewed pre- and post-intervention and their clinical data abstracted from medical charts. Logistic regression models were used to assess differences in key outcomes between the two time periods. RESULTS: A total of 629 WLHIV were interviewed pre-intervention and 684 post-intervention. Current FP use increased from 35% to 49% comparing the pre- and post-intervention periods (P=0.0025). Increased use was seen for injectables (15% vs. 25%, P<0.0001) and implants (5% vs. 8%, P>0.05) but not for pills (10% vs. 8%, P<0.05) or intra-uterine devices (1% vs. 1%, P >0.05). Dual method use (contraceptive + barrier method) increased from 8% to 18% (P=0.0003) while unmet need for FP decreased from 59% to 46% (P=0.0003). Receipt of safer conception counseling increased from 27% to 39% (P<0.0001). The estimated total intervention cost was $83,293 (2018 USD). CONCLUSIONS: Our model of FP/HIV integration significantly increased the number of WLHIV reporting current FP and dual method use, a met need for FP, and safer conception counseling. These results support continued efforts to integrate FP and HIV services to improve women's access to sexual and reproductive health services.

      4. Tachyarrhythmias during hospitalization for COVID-19 or multisystem inflammatory syndrome in children and adolescents
        Dionne A, Friedman KG, Young CC, Newhams MM, Kucukak S, Jackson AM, Fitzgerald JC, Smallcomb LS, Heidemann S, McLaughlin GE, Irby K, Bradford TT, Horwitz SM, Loftis LL, Soma VL, Rowan CM, Kong M, Halasa NB, Tarquinio KM, Schwarz AJ, Hume JR, Gertz SJ, Clouser KN, Carroll CL, Wellnitz K, Cullimore ML, Doymaz S, Levy ER, Typpo KV, Lansell AN, Butler AD, Kuebler JD, Zambrano LD, Campbell AP, Patel MM, Randolph AG, Newburger JW.
        J Am Heart Assoc. 2022 Oct 18;11(20):e025915.
        Background Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID-19-related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID-19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4-17.4] versus 10.0 [range, 5.4-14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID-19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.

      5. Initial implementation of HIV pre-exposure prophylaxis for people who are incarcerated in Zambia: a cross-sectional observational study
        Lindsay B, Nyirongo N, Mwango L, Toeque MG, Masumba C, Litongola JP, Sikanyika J, Kabombo H, Moyo M, Siachibila S, Mudenda J, Tembo K, Olowski P, Olufunso A, Muchinda E, Musonda B, Okuku J, Mwila A, Moonga CN, Herce ME, Claassen CW.
        Lancet HIV. 2022 Oct 12.
        BACKGROUND: There are over 23 000 incarcerated people in Zambia, a population which has higher HIV prevalence than the general population yet has no access to HIV prevention. To evaluate the feasibility of HIV pre-exposure prophylaxis (PrEP) implementation in Zambian criminal justice facilities, we offered PrEP services to incarcerated people and aimed to describe early implementation outcomes. METHODS: In this cross-sectional observational study, we implemented a PrEP programme between Oct 1, 2020, and March 31, 2021, supporting 16 criminal justice facilities in four Zambian provinces. Before implementation, we held stakeholder engagement meetings with Zambia Correctional Service officials to discuss PrEP benefits, and trained Zambia Correctional Service health-care workers in PrEP management using the national PrEP training package. People who were incarcerated and screened positive for substantial HIV risk by use of a standardised HIV risk assessment tool were offered voluntary HIV testing and counselling. Those who tested positive were linked to antiretroviral therapy, and those who tested negative and met national HIV prevention eligibility criteria were offered PrEP. We assessed PrEP uptake and used descriptive statistics to characterise programme beneficiaries and the cascade of PrEP services. FINDINGS: During the study period, we reached 12 367 people older than 15 years with HIV risk assessment and counselling, including 11 794 (95·4%) men and 573 (4·6%) women. Of these, 2610 people received HIV testing, with 357 (13·7%) testing HIV positive; positivity was significantly higher in women (20·6%) than men (13·2%, p=0·011). 1276 people were identified as HIV negative and PrEP eligible. Of these, 1190 (93·3%) initiated PrEP. The age group with the highest proportion reached and initiated on PrEP was those aged 25-29 years, representing 19·2% (2377 of 12 367) of all people reached and 24·1% (287 of 1190) of those who initiated PrEP. INTERPRETATION: Delivery of PrEP to people who are incarcerated is feasible with adequate resourcing and support to the criminal justice health system, and can result in high uptake among eligible individuals. Further assessment is needed of PrEP persistence and adherence, and the perceptions of people who are incarcerated regarding their HIV risk and preferences for combination HIV prevention services. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

      6. The effects of the COVID-19 pandemic on community respiratory virus activity
        Chow EJ, Uyeki TM, Chu HY.
        Nat Rev Microbiol. 2022 Oct 17.
        The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused substantial global morbidity and deaths, leading governments to turn to non-pharmaceutical interventions to slow down the spread of infection and lessen the burden on health care systems. These policies have evolved over the course of the COVID-19 pandemic, including after the availability of COVID-19 vaccines, with regional and country-level differences in their ongoing use. The COVID-19 pandemic has been associated with changes in respiratory virus infections worldwide, which have differed between virus types. Reductions in respiratory virus infections, including by influenza virus and respiratory syncytial virus, were most notable at the onset of the COVID-19 pandemic and continued in varying degrees through subsequent waves of SARS-CoV-2 infections. The decreases in community infection burden have resulted in reduced hospitalizations and deaths associated with non-SARS-CoV-2 respiratory infections. Respiratory virus evolution relies on the maintaining of a diverse genetic pool, but evidence of genetic bottlenecking brought on by case reduction during the COVID-19 pandemic has resulted in reduced genetic diversity of some respiratory viruses, including influenza virus. By describing the differences in these changes between viral species across different geographies over the course of the COVID-19 pandemic, we may better understand the complex factors involved in community co-circulation of respiratory viruses.

      7. Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort
        Vielot NA, François R, Huseynova E, González F, Reyes Y, Gutierrez L, Nordgren J, Toval-Ruiz C, Vilchez S, Vinjé J, Becker-Dreps S, Bucardo F.
        PLoS One. 2022 ;17(10):e0267689.
        BACKGROUND: Norovirus and sapovirus are important causes of childhood acute gastroenteritis (AGE). Breastfeeding prevents AGE generally; however, it is unknown if breastfeeding prevents AGE caused specifically by norovirus and sapovirus. METHODS: We investigated the association between breastfeeding and norovirus or sapovirus AGE episodes in a birth cohort. Weekly data on breastfeeding and AGE episodes were captured during the first year of life. Stools were collected from children with AGE and tested by RT-qPCR for norovirus and sapovirus. Time-dependent Cox models estimated associations between weekly breastfeeding and time to first norovirus or sapovirus AGE. FINDINGS: From June 2017 to July 2018, 444 newborns were enrolled in the study. In the first year of life, 69 and 34 children experienced a norovirus and a sapovirus episode, respectively. Exclusive breastfeeding lasted a median of 2 weeks, and any breastfeeding lasted a median of 43 weeks. Breastfeeding in the last week did not prevent norovirus (HR: 1.09, 95% CI: 0.62, 1.92) or sapovirus (HR: 1.00, 95% CI: 0.82, 1.21) AGE in a given week, adjusting for household sanitation, consumption of high-risk foods, and mother's and child's histo-blood group phenotypes. Maternal secretor-positive phenotype was protective against norovirus AGE, whereas child's secretor-positive phenotype was a risk factor for norovirus AGE. INTERPRETATION: Exclusive breastfeeding in this population was short-lived, and no conclusions could be drawn about its potential to prevent norovirus or sapovirus AGE. Non-exclusive breastfeeding did not prevent norovirus or sapovirus AGE in the first year of life. However, maternal secretor-positive phenotype was associated with a reduced hazard of norovirus AGE.

      8. Trends in HPV- and non-HPV-associated vulvar cancer incidence, United States, 2001-2017
        Mix JM, Gopalani SV, Simko S, Saraiya M.
        Prev Med. 2022 Oct 12;164:107302.
        Vulvar cancer incidence has been rising in recent years, possibly due to increasing exposure to human papillomavirus (HPV). We assessed incidence rates of HPV-associated and non-HPV-associated vulvar cancers diagnosed from 2001 to 2017 in the United States (US). Using population-based cancer registry data covering 99% of the US population, incidence rates were calculated and stratified by age, race/ethnicity, stage, geographic region, and histology. The average annual percent change in incidence per year were calculated using joinpoint regression. From 2001 to 2017, the incidence of HPV-associated vulvar cancers increased by 1.2% per year, most notably among women who were aged 50-59 years (2.6%), 60-69 years (2.4%), and ≥ 70 years (0.9%); of White (1.5%) and Black (1.1%) race; diagnosed at an early (1.3%) and late (1.8%) stage; and living in the Midwest (1.9%), Northeast (1.4%), and South (1.2%). Incidence increased each year for HPV-associated histologic subtypes including keratinizing (4.7%), non-keratinizing (6.0%), and basaloid (3.1%) squamous cell carcinomas (SCCs), while decreases were found in warty (2.7%) and microinvasive (5.5%) SCCs. HPV-associated vulvar cancer incidence increased overall and among women aged over 50 years while remaining stable among women younger than 50 years. The overall incidence for non-HPV-associated cancers was stable. Continued surveillance of HPV-associated cancers will allow us to monitor future trends as HPV vaccination coverage increases in the US.

    • Community Health Services
      1. Reaching transgender populations in Zambia for HIV prevention and linkage to treatment using community-based service delivery
        Mwango L, Toeque MG, Lindsay B, Tembo K, Sakala H, Reggee S, Malunga SM, Kabwe M, Kafunda I, Olufunso A, Mwila A, Okuku J, Kancheya N, Nkwemu K, Mumba D, Hachaambwa L, Sheneberger R, Blanco N, Lavoie MC, Stafford KA, Claassen CW.
        J Int AIDS Soc. 2022 Oct;25 Suppl 5(Suppl 5):e25995.
        INTRODUCTION: Transgender and gender-diverse communities in Zambia are highly vulnerable and experience healthcare differently than cisgender persons. The University of Maryland, Baltimore (UMB) supports projects in Zambia to improve HIV case-finding, linkage and antiretroviral treatment (ART) for Zambia's transgender community. We describe programme strategies and outcomes for HIV prevention, testing and ART linkage among transgender communities. METHODS: UMB utilizes a differentiated service delivery model whereby community health workers (CHWs) recruited from key populations (KPs) reach community members through a peer-to-peer approach, with the support of local transgender civil society organizations (CSOs) and community gatekeepers. Peer CHWs are trained and certified as HIV testers and psychosocial counsellors to offer counselling with HIV testing and prevention services in identified safe spaces. HIV-negative people at risk of HIV infection are offered pre-exposure prophylaxis (PrEP), while those who test positive for HIV are linked to ART services. CHWs collect data using the standardized facility and community tools and a dedicated DHIS2 database system. We conducted a descriptive analysis examining HIV testing and prevention outcomes using proportions and comparisons by time period and geographic strata. RESULTS: From October 2020 to June 2021, across Eastern, Lusaka, Western and Southern Provinces, 1860 transgender persons were reached with HIV prevention messages and services. Of these, 424 (23%) were tested for HIV and 78 (18%) tested positive. Of the 346 HIV-negative persons, 268 (78%) eligible transgender individuals were initiated on PrEP. ART linkage was 97%, with 76 out of the 78 transgender individuals living with HIV initiating treatment. Programme strategies that supported testing and linkage included peer CHWs, social network strategy testing, same-day ART initiation and local KP CSO support. Challenges included non-transgender-friendly environments, stigma and discrimination, the high transiency of the transgender community and the non-availability of transgender-specific health services, such as hormonal therapy. CONCLUSIONS: Peer KP CHWs were able to reach many members of the transgender community, providing safe HIV testing, PrEP services and linkage to care. Focusing on community gatekeepers and CSOs to disburse health messages and employ welcoming strategies supported high linkage to both PrEP and ART for transgender people in Zambia.

      2. BACKGROUND: Lost to follow-up (LTFUP) continues to threaten the sustainability of antiretroviral therapy (ART) benefits and success of ART programs. We determined the incidence and predictors of LTFUP among people living with HIV (PLHIV) on ART in Nyarugenge the Central Business District of Kigali city. METHODS: A cohort of PLHIV who initiated ART in 2018 was retrospectively studied for 24 months. Using health facility records, a person who had no record of contact with the health facility for at least three consecutive months was considered LTFUP. LTFUP incidence rates were computed, and the Fine-Gray's competing risk regression models were used to determine factors associated with time to first LTFUP. Generalized estimating equations (GEEs) were used to analyze repeated measurement outcomes of LTFUP and predictors of LTFUP. RESULTS: Of 950 participants, 581 (61.2%) were females and 866 (91.2%) were 15 to 49 years old. From 1,586.1 person years of observation (pyo), 148 participants got LTFUP for 451 times. The incidence rate to first event was 9.4 per 100 pyo (95%CI:7.9-10.9) and 31.8 per 100 pyo (95%CI:29.0-34.4) to multiple events. WHO stage, marital status, employment status and person to contact when PLHIV is not reachable were associated with time to first LTFUP event. However, an average participant with a contact person who was not a Community Health Worker (CHW) or a peer educator had higher incidence of LTUP (aIRR = 2.69, 95%CI: 1.43-5.06), an average single patients had higher incidence of LTFUP (aIRR = 1.74, 95%CI: 1.28-2.34) compared to married/co-habiting, and an average self-employed had higher incidence of LTFUP (aIRR = 1.51, 95%CI: 1.14-2.01) compared to participants employed by others. Furthermore, an average PLHIV living out-of-the health facility catchment area had higher incidence of LTFUP (aIRR = 1.55, 95%CI: 1.19-2.01) compared to an average PLHIV living in the health facility catchment area whereas, an average children initiated on first line had lower incidence of LTUP (aIRR = 0.43, 95%CI: 0.21-0.86) compared to adults. CONCLUSION: Using CHW and peer educators as contact persons can help to reduce LTFUP while, targeted sensitization and service delivery are needed for single, self-employed and, patients living out of the health facility catchment area.

      3. Examining the multilevel barriers to pharmacy-based HIV prevention and treatment services
        Crawford ND, Lewis CF, Moore R, Pietradoni G, Weidle P.
        Sex Transm Dis. 2022 Nov 1;49(11S Suppl 2):S22-s25.

      4. A commentary on recent successes and challenges for home STI specimen collection, for point-of-care test usage close to the home, and implications of COVID-19 self-tests for future STI self-test development.

    • Disaster Preparedness and Emergency Services
      1. Characterizing emergency supply kit possession in the United States during the COVID-19 pandemic - 2020-2021
        Schnall AH, Kieszak S, Hanchey A, Heiman H, Bayleyegn T, Daniel J, Stauber C.
        Disaster Med Public Health Prep. 2022 Oct 17:1-29.
        BACKGROUND: In the immediate aftermath of a disaster, household members may experience lack of support services and isolation from one another. To address this, a common recommendation is to promote preparedness through the preparation of an emergency supply kit (ESK). The goal was to characterize ESK possession on a national level to help the Centers for Disease Control and Prevention (CDC) guide next steps to better prepare for and respond to disasters and emergencies at the community level. METHODS: The authors analyzed data collected through Porter Novelli's ConsumerStyles surveys in Fall 2020 (n=3,625) and Spring 2021 (n=6,455). RESULTS: ESK ownership is lacking. Overall, while most respondents believed that an ESK would help their chance of survival, only a third have one. Age, gender, education level, and region of the country were significant predictors of kit ownership in a multivariate model. In addition, there was a significant association between level of preparedness and ESK ownership. CONCLUSIONS: These data are an essential starting point in characterizing ESK ownership and can be used to help tailor public messaging, inform work with partners to increase ESK ownership, and guide future research.

      2. Scientific value of the sub-cohort of children in the World Trade Center Health Registry
        Brackbill RM, Butturini E, Cone JE, Ahmadi A, Daniels RD, Farfel MR, Kubale T.
        Int J Environ Res Public Health. 2022 Sep 30;19(19).
        The World Trade Center Health Registry (WTCHR) was established in 2002 as a public health resource to monitor the health effects from the World Trade Center (WTC) disaster. We evaluated the representativeness of the WTC youth population (&lt;18 years on 11 September 2001) by comparing the distributions of age, gender, race/ethnic groups, and income to 2000 census data for the matched geographic area, including distance from disaster. There were 2379 WTCHR enrolled children living in Lower Manhattan south of Canal Street on 11 September 2001, along with 752 enrolled students who attended school in Lower Manhattan but were not area residents. The WTCHR sub-group of children who were residents was similar to the geographically corresponding census population on age and sex. Black and Hispanic children are moderately overrepresented at 0.9% and 2.4% in the WTCHR compared to 0.8% and 1.7% in census population, respectively, while lower-income households are slightly under-represented, 28.8% in the WTCHR and 30.8% for the corresponding census information. Asian children appear underrepresented at 3.0% participation compared to 6.3% in the census. While the demographics of WTCHR youth are somewhat skewed, the gaps are within expected patterns of under-representation observed in other longitudinal cohorts and can be effectively addressed analytically or through targeted study design.

    • Disease Reservoirs and Vectors
      1. Anaplasmosis is increasingly common in the United States, with cases being reported over an expanding geographic area. To monitor for changes in risk of human infection, the U.S. Centers for Disease Control and Prevention monitors the distribution and abundance of host-seeking vector ticks (Ixodes scapularis and Ixodes pacificus) and their infection with Anaplasma phagocytophilum. While several variants of A. phagocytophilum circulate in I. scapularis, only the human-active variant (Ap-ha) appears to be pathogenic in humans. Failure to differentiate between human and non-human variants may artificially inflate estimates of the risk of human infection. Efforts to differentiate the Ap-ha variant from the deer variant (Ap-V1) in ticks typically rely on traditional PCR assays coupled with sequencing of PCR products. However, laboratories are increasingly turning to Next Generation Sequencing (NGS) to increase testing efficiency, retain high sensitivity, and increase specificity compared with traditional PCR assays. We describe a new NGS assay with novel targets that accurately segregate the Ap-ha variant from other non-human variants and further identify unique clades within the human and non-human variants. Recognizing that not all investigators have access to NGS technology, we also developed a PCR assay based on one of the novel targets so that variants can be visualized using agarose gel electrophoresis without the need for subsequent sequencing. Such an assay may be used to improve estimates of human risk of developing anaplasmosis in North America.

    • Environmental Health
      1. Consensus on the key characteristics of immunotoxic agents as a basis for hazard identification
        Germolec DR, Lebrec H, Anderson SE, Burleson GR, Cardenas A, Corsini E, Elmore SE, Kaplan BL, Lawrence BP, Lehmann GM, Maier CC, McHale CM, Myers LP, Pallardy M, Rooney AA, Zeise L, Zhang L, Smith MT.
        Environ Health Perspect. 2022 Oct;130(10):105001.
        BACKGROUND: Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents. OBJECTIVES: The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs. METHODS: A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity. DISCUSSION: KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.

      2. Viable norovirus persistence in water microcosms
        Shaffer M, Huynh K, Costantini V, Bibby K, Vinjé J.
        Environ Sci Technol Lett. 2022 .
        Human noroviruses are one of the leading causes of acute gastroenteritis worldwide. Based on quantitative microbial risk assessments, norovirus contributes the greatest infectious risk of any pathogen from exposure to sewage-contaminated water; however, these estimates have been based upon molecular (i.e., RNA-based) data as human norovirus has remained largely unculturable in the laboratory. Current approaches to assess the environmental fate of noroviruses rely on the use of culturable surrogate viruses and molecular methods. Human intestinal enteroids (HIEs) are an emerging cell culture system capable of amplifying viable norovirus. Here, we applied the HIE assay to assess both viable norovirus and norovirus RNA persistence in surface, tap, and deionized water microcosms. Viable norovirus decreased to below the detection limit in tap and deionized water microcosms and was measured in a single replicate in the surface water microcosm at study conclusion (28 days). Conversely, the norovirus RNA signal remained constant over the duration of the study, even when viable norovirus was below the limit of detection. Our findings demonstrate the disconnect between current environmental norovirus detection via molecular methods and viability as assessed through the HIE assay. These results imply that molecular norovirus monitoring is not inherently representative of infectious norovirus. © 2022 American Chemical Society.

      3. Why are noise exposure guidelines so complex?
        Eichwald J, Themann CL, Kardous CC, Carroll Y.
        Hear J. 2022 ;75(10):18-21.

      4. The Environmental Health Nexus: A communication hub
        Khan A, Lynch J.
        J Environ Health. 2022 ;85(3):34-35.

      5. Blood lead levels among Afghan children in the United States, 2014-2016
        Pezzi C, Kumar GS, Lee D, Cabanting N, Kawasaki B, Kennedy L, Aguirre J, Titus M, Ford R, Mamo B, Urban K, Hughes S, Payton C, Altshuler M, Montour J, Jentes ES.
        Pediatrics. 2022 Oct 18.

      6. Traffic as a barrier to walking safely in the United States: Perceived reasons and potential mitigation strategies
        Soto GW, Whitfield GP, Webber BJ, Omura JD, Chen TJ, Zaganjor H, Rose K.
        Prev Med Rep. 2022 Dec;30:102003.
        Motor vehicle traffic is commonly cited as a barrier to walking, but national level perceptions of traffic characteristics that negatively influence walking and potential traffic mitigation strategies remain unclear. The objectives of this study were to describe perceptions of (1) traffic characteristics that make walking unsafe in the United States and (2) potential mitigation strategies to address these concerns among those who report traffic as a barrier to walking. Data were from FallStyles, a nationwide internet panel survey conducted in October 2019 (n = 3,284 adults). Respondents reported if traffic makes walking unsafe where they live; those who answered yes were then asked about traffic characteristics that make walking unsafe (number of vehicles, speed of vehicles, distracted or impaired driving, types of vehicles, and other reasons) and potential mitigation strategies (new or improved sidewalks, crosswalks, pedestrian signals, street lighting, things that slow vehicles down, separating the sidewalk from the road, fewer vehicle lanes, and other). Prevalence of responses was assessed overall and by select sociodemographic and geographic characteristics, and by walking status. Nearly 25% of US adults reported that traffic is a barrier to walking where they live. Of these, 79% selected vehicle speed as a contributing traffic characteristic, and 57% indicated new or improved sidewalks as a potential mitigation strategy. These top responses were shared across all sociodemographic, geographic, and walking behavior subgroups. Speed reduction efforts and built environment enhancements such as sidewalks may alleviate pedestrian safety concerns. Promotion campaigns may be needed to bring awareness to such changes.

    • Health Behavior and Risk
      1. Public willingness to engage with COVID-19 contact tracing, quarantine, and exposure notification
        Liccardi I, Alekseyev J, Woltz VL, McLean JE, Zurko ME.
        Public Health Rep. 2022 Oct 18:333549221125891.
        OBJECTIVES: We conducted a survey to understand how people's willingness to share information with contact tracers, quarantine after a COVID-19 exposure, or activate and use a smartphone exposure notification (EN) application (app) differed by the person or organization making the request or recommendation. METHODS: We analyzed data from a nationally representative survey with hypothetical scenarios asking participants (N = 2157) to engage in a public health action by health care providers, public health departments, employers, and others. We used Likert scales and ordered logistic regression to compare willingness to take action based on which person or organization made the request, and we summarized findings by race and ethnicity. RESULTS: The highest levels of willingness to engage in contact tracing (adjusted odds ratio [aOR] = 1.74; 95% CI, 1.55-1.96), quarantine (aOR = 1.91; 95% CI, 1.69-2.15), download/activate an EN app (aOR = 1.30; 95% CI, 1.16-1.46), and notify other EN users (aOR = 1.43; 95% CI, 1.27-1.60) were reported when the request came from the participant's personal health care provider rather than from federal public health authorities. When compared with non-Hispanic White participants, non-Hispanic Black participants reported significantly higher levels of willingness to engage in contact tracing (aOR = 1.32; 95% CI, 1.18-1.48), quarantine (aOR = 1.49; 95% CI, 1.37-1.63), download/activate an EN app (aOR = 2.19; 95% CI, 2.01-2.38), and notify other EN users (aOR = 1.63; 95% CI, 1.49-1.79). CONCLUSIONS: Partnering with individuals and organizations perceived as trustworthy may help influence people expressing a lower level of willingness to engage in each activity, while those expressing a higher level of willingness to engage in each activity may benefit from targeted communications.

    • Health Economics
      1. OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

    • Health Equity and Health Disparities
      1. Severity of COVID-19 hospitalization outcomes and patient disposition differ by disability status and disability type
        Clarke KE, Hong K, Schoonveld M, Greenspan AI, Montgomery M, Thierry JM.
        Clin Infect Dis. 2022 Oct 19.
        BACKGROUND: Systemic inequities may place people with disabilities at higher risk of severe COVID-19 illness or lower likelihood to be discharged home after hospitalization. We examined whether severity of COVID-19 hospitalization outcomes and disposition differ by disability status and disability type. METHODS: In a retrospective analysis of April 2020-November 2021 hospital-based administrative data among 745,375 people hospitalized with COVID-19 from 866 US hospitals, people with disabilities (n = 120,360) were identified via ICD-10-CM codes. Outcomes compared by disability status included intensive care admission, invasive mechanical ventilation (IMV), in-hospital mortality, 30-day readmission, length of stay, and disposition (discharge to home, long-term care facility (LTCF), or skilled nursing facility (SNF). RESULTS: People with disabilities had increased risks of IMV (aRR: 1.05; 95%CI: 1.03-1.08) and in-hospital mortality (1.04; 1.02-1.06) compared to those with no disability; risks were higher among people with intellectual and developmental disabilities (IDD) (IMV [1.34; 1.28-1.40], mortality [1.31; 1.26-1.37]) or mobility disabilities (IMV [1.13; 1.09-1.16], mortality [1.04; 1.01-1.07]). Risk of readmission was increased among people with any disability (1.23; 1.20-1.27) and each disability type. Risks of discharge to a LTCF (1.45, 1.39-1.49) or SNF (1.78, 1.74-1.81) were increased among community-dwelling people with each disability type. CONCLUSIONS: Severity of COVID-19 hospitalization outcomes vary by disability status and type; IDD and mobility disabilities were associated with higher risks of severe outcomes. Disparities such as differences in discharge disposition by disability status require further study which would be facilitated by standardized data on disability. Increased readmission across disability types indicates a need to improve discharge planning and support services.

      2. Changes in racial and ethnic disparities in glucose-lowering drug utilization and HbA1c in US adults with diabetes: 2005-2018
        Li P, Zhang P, Guan D, Guo J, Zhang Y, Pavkov ME, Bullard KM, Shao H.
        Diabetes Obes Metab. 2022 Oct 17.
        OBJECTIVE: To examine changes in racial and ethnic disparities in glucose-lowering drugs (GLD) use and HbA1c in US adults with diabetes from 2005 to 2018. METHODS: We conducted pooled cross-sectional analysis using data from the 2005-2018 Medical Expenditure Panel Surveys, and the 2005-2018 National Health and Nutrition Examination Survey. Individuals ≥ 18 years with diabetes were included. Racial and ethnic disparities in 1) newer non-insulin GLDs use; 2) insulin analogs use; 3) non-insulin GLDs adherence; 4) insulin adherence, and 5) glucose management, along with 6) the proportion of the disparities explained by potential contributing factors were measured. RESULTS: From 2005 to 2018, racial and ethnic disparities persisted in newer GLDs use, non-insulin GLDs adherence, insulin analogs use, and glucose management. In 2018, compared with non-Hispanic White adults, non-Hispanic Black, Hispanic, and other race/ethnicity groups had lower rates of using newer GLDs (adjusted risk ratio (aRR): 0.44, 0.52, 0.64, respectively; p<0.05 for all) and insulin analogs (aRR: 0.93, 0.89, 0.95, respectively; p<0.05 for all except other group), lower non-insulin GLDs adherence (proportion of days covered (PDC): -4.5%, -5.6%, -4.3%, respectively; p<0.05 for all), higher HbA1c (0.29%, 0.32%, 0.02%, respectively; p<0.05 for all except other group), and similar insulin adherences. Socioeconomic and health status were the main contributors to these disparities. CONCLUSIONS: Our findings provide evidence of racial and ethnic disparities in newer GLD use and quality of care in glucose management. Our study results can inform decision-makers of the current status of racial and ethnic disparities and identify ways to reduce these disparities. This article is protected by copyright. All rights reserved.

      3. Social determinants of cancer risk among American Indian and Alaska Native populations: An evidence review and map
        Melkonian SC, Crowder J, Adam EE, White MC, Peipins LA.
        Health Equity. 2022 ;6(1):717-728.
        OBJECTIVES: To explore current literature on social determinants of health (SDOH) and cancer among American Indian and Alaska Native (AI/AN) populations. METHODS: We searched Ovid MEDLINE(®), CINAHL, and PsycINFO databases for articles published during 2000 to 2020, which included terms for SDOH and cancer occurrence in AI/AN populations. We derived the data extraction elements from the PROGRESS-Plus framework. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Equity extension guided the evidence map. RESULTS: From 2180 screened articles, 297 were included. Most were observational (93.9%), employed a cross-sectional design (83.2%), were categorized as cancer occurrence and surveillance research (62%), and included no cancer-related risk factors (70.7%). Race, gender, and place were the most frequently included PROGRESS-Plus categories. Religion, relationship features, and characteristics of discrimination were least common. Only 12% of articles mentioned historical/current trauma or historical context. CONCLUSIONS: Gaps exist in our understanding of SDOH as drivers of cancer disparities in AI/AN populations. Future studies in health equity science may incorporate historical and cultural factors into SDOH frameworks tailored for AI/AN populations.

      4. HIV stigma and health care discrimination experienced by Hispanic or Latino persons with HIV - United States, 2018-2020
        Padilla M, Patel D, Beer L, Tie Y, Nair P, Salabarría-Peña Y, Henny KD, Thomas D, Dasgupta S.
        MMWR Morb Mortal Wkly Rep. 2022 Oct 14;71(41):1293-1300.
        Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*(,)(†)(,)(§) (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.(¶) The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination.

    • Immunity and Immunization
      1. Neutralizing antibody responses in patients hospitalized with SARS-CoV-2 Delta or Omicron infection
        Linderman SL, Lai L, Bocangel Gamarra EL, Lau MS, Edupuganti S, Surie D, Tenforde MW, Chappell JD, Mohr NM, Gibbs KW, Steingrub JS, Exline MC, Shapiro NI, Frosch AE, Qadir N, Davis-Gardner ME, McElrath MJ, Lauring AS, Suthar MS, Patel MM, Self WH, Ahmed R.
        J Clin Invest. 2022 Oct 18.
        Humoral and cellular immune responses contribute to overall protective immunity against SARS-CoV-2 with neutralizing antibody playing a key role in preventing viral infection. This is evident from the large number of Omicron infections in vaccinated and convalescent patients since antibodies induced after vaccination or infection by the ancestral WA1 strain do not neutralize Omicron variants efficiently (1, 2). This has led to the FDA recommendation for inclusion of the Omicron variant in bivalent COVID-19 vaccines. However, issues have been raised about the value of adding Omicron to the vaccine based on data showing only modest differences between antibody responses after booster immunization with Omicron versus WA1 (3, 4). Also, a recent study has shown that booster responses to Omicron infection are impacted by previous SARS-CoV-2 infections (5). Thus, having additional information on the types of neutralizing antibody responses induced after infection with different SARS-CoV-2 variants will be helpful in addressing this important issue. Here we report live virus neutralization titers against WA1, Delta, BA.1, BA.2 and BA.5 variants in serum samples collected from hospitalized patients infected with SARS-COV-2 Delta or Omicron strains. Blood samples were collected from 187 patients hospitalized with acute COVID-19 between July 2021 - March 2022 at 8 U.S. hospitals (Supplemental Methods). 26% of these patients were immunocompromised, the details of which are given in Supplemental Table 1. The majority (69%) of these patients were sequence confirmed for Delta or Omicron infection and the remaining were classified according to calendar period of circulation. Patients were either unvaccinated (n=80) or vaccinated with COVID-19 mRNA vaccine (n=100) or adenovirus vector vaccine (n=7) before infection. Unvaccinated Delta infected patients made a highly biased neutralizing antibody response towards the infecting Delta strain with lower titers against WA1 (6-fold) and strikingly lower titers against BA.1 (60-fold) and BA.2 (22-fold) (Figure 1A). In vaccinated Delta patients the neutralization titers were similar between Delta and WA1 but were again much lower against BA.1 (17-fold) and BA.2 (9-fold) (Figure 1B). Thus, both unvaccinated and vaccinated Delta infected patients made significantly lower neutralizing antibody responses to Omicron (as determined by Wilcoxon rank sums test). A strikingly different pattern was seen in Omicron infected patients irrespective of their vaccination history with a more favorable neutralizing antibody response to BA.1 and BA.2. While BA.1 and BA.2 neutralizing titers were modestly lower in vaccinated compared to unvaccinated Omicron patients, there was a clear trend for a broader and more balanced antibody response with similar neutralization titers to Delta, BA.1, and BA.2 (Figures 1C, 1D). Importantly, the ratio of BA.1 to WA1 neutralizing titers was significantly higher in Omicron patients compared to Delta patients in both unvaccinated (19-fold) and vaccinated (11-fold) patients (Figure 1E, 1F). This analysis of the ratio between neutralizing antibody to Omicron versus WA1 within a given individual nicely documents that Omicron infection favors Omicron specific antibody responses. These Omicron neutralizing antibodies could have emerged from either de novo naïve B cells or from cross-reactive memory B cells. Given the importance of the currently dominant BA.5 strain we then tested neutralization against BA.5. Note that our samples were collected prior to dominance of BA.5 and most of our patients were infected with BA.1 (Supplemental Table 1). In the subset of Omicron patient samples that we analyzed, there was detectable neutralization of BA.5 but it was lower than for BA.1. and BA.2 in both vaccinated and unvaccinated patients (Figure 1G, 1H, Supplemental Figure 1). This reduced neutralization activity against BA.5 in patients infected with BA.1 suggests that it is better to have BA.5 than BA.1 in the vaccine. In summary, our results show that Omicron infection of unvaccinated or vaccinated patients induces a more proportional and balanced neutralizing antibody response to Omicron variants supporting the recent decision to include Omicron in the bivalent SARS-CoV-2 vaccine. However, it remains to be seen how these findings from infection will translate to vaccination. Our results are from hospitalized patients with high levels of infected cells and antigen that would have efficiently induced a primary response to Omicron in addition to selectively recruiting Omicron reactive memory B cells. It is possible that a single immunization with the Omicron bivalent vaccine may not be sufficient and that two doses may be needed to give the desired antibody response (6). Future studies should address this issue, and it will also be interesting to see how the bivalent vaccine works in people who have already been infected with an Omicron strain.

    • Injury and Violence
      1. Association of 7 million+ tweets featuring suicide-related content with daily calls to the Suicide Prevention Lifeline and with suicides, United States, 2016-2018
        Niederkrotenthaler T, Tran US, Baginski H, Sinyor M, Strauss MJ, Sumner SA, Voracek M, Till B, Murphy S, Gonzalez F, Gould M, Garcia D, Draper J, Metzler H.
        Aust N Z J Psychiatry. 2022 Oct 14:48674221126649.
        OBJECTIVE: The aim of this study was to assess associations of various content areas of Twitter posts with help-seeking from the US National Suicide Prevention Lifeline (Lifeline) and with suicides. METHODS: We retrieved 7,150,610 suicide-related tweets geolocated to the United States and posted between 1 January 2016 and 31 December 2018. Using a specially devised machine-learning approach, we categorized posts into content about prevention, suicide awareness, personal suicidal ideation without coping, personal coping and recovery, suicide cases and other. We then applied seasonal autoregressive integrated moving average analyses to assess associations of tweet categories with daily calls to the US National Suicide Prevention Lifeline (Lifeline) and suicides on the same day. We hypothesized that coping-related and prevention-related tweets are associated with greater help-seeking and potentially fewer suicides. RESULTS: The percentage of posts per category was 15.4% (standard deviation: 7.6%) for awareness, 13.8% (standard deviation: 9.4%) for prevention, 12.3% (standard deviation: 9.1%) for suicide cases, 2.4% (standard deviation: 2.1%) for suicidal ideation without coping and 0.8% (standard deviation: 1.7%) for coping posts. Tweets about prevention were positively associated with Lifeline calls (B = 1.94, SE = 0.73, p = 0.008) and negatively associated with suicides (B = -0.11, standard error = 0.05, p = 0.038). Total number of tweets were negatively associated with calls (B = -0.01, standard error  = 0.0003, p = 0.007) and positively associated with suicide, (B = 6.4 × 10(-5), standard error  = 2.6 × 10(-5), p = 0.015). CONCLUSION: This is the first large-scale study to suggest that daily volume of specific suicide-prevention-related social media content on Twitter corresponds to higher daily levels of help-seeking behaviour and lower daily number of suicide deaths. PREREGISTRATION: As Predicted, #66922, 26 May 2021.

      2. BACKGROUND: Globally, adolescent girls and young women (AGYW) are disproportionately impacted by economic, demographic, and social factors associated with a wide range of negative outcomes. OBJECTIVE: The objective of this study was to use latent class analysis (LCA) to identify groupings of AGYW in Lesotho based on patterns of gendered risk factors, and to assess the association between the identified groupings and intimate partner violence (IPV) and low educational attainment. PARTICIPANTS AND SETTING: Data were from the 2018 Lesotho Violence Against Children and Youth Survey. AGYW reported gendered risk factors: teen pregnancy, child marriage, intergenerational sex, early sexual debut, being HIV positive, transactional sex, endorsement of one or more negative traditional gender norms, and one or more norms supportive of violence against women. METHODS: LCA identified latent classes of eight gendered risk factors. Multivariable logistic regression assessed associations between latent classes and IPV victimization and low educational attainment. RESULTS: A three-class solution was selected, and classes were named as: Low Risk class, Behavioral Risk class, and Attitudinal Risk class. Odds of low educational attainment and IPV were higher in the Attitudinal Risk class than the Low Risk class. Odds of low educational attainment and IPV were higher in the Behavioral Risk class than the Low Risk class and the Attitudinal Risk class. CONCLUSIONS: In Lesotho, gendered risk factors form distinct classes that have variable associations with low educational attainment and IPV. LCA can be an important approach to better understand the complicated relationship gendered risk factors have with each other and with certain outcomes, to further elucidate the influence that gender has on the health of AGYW and to provide more targeted prevention programming.

      3. Implementation of active injury management (AIM) in youth with acute concussion: A randomized controlled trial
        Thomas D, Erpenbach H, Hickey RW, Waltzman D, Haarbauer-Krupa J, Nelson LD, Patterson CG, McCrea M, Collins M, Kontos AP.
        Contemp Clin Trials. 2022 Oct 14:106965.
        BACKGROUND: Nearly 2 million youth seek acute medical care following concussion in the U.S. each year. Current standard of care recommends rest for the first 48 h after a concussion. However, research suggests that prolonged rest may lengthen recovery time especially for patients with certain risk profiles. Research indicates that physical activity and behavioral management interventions (sleep, stress management) may enhance recovery. To date, there is limited empirical evidence to inform acute (<72 h) concussion recommendations for physical activity and behavioral management in adolescents. OBJECTIVE: To determine the effectiveness of physical activity and behavioral management for acute concussion in adolescents and young adults, and to evaluate the role of patient characteristics on treatment response. METHODS: This multicenter prospective randomized controlled trial will determine which combination of physical activity and behavioral management is most effective for patients 11-24 years old who present to the emergency department or concussion clinic within 72 h of injury. Participants are randomized into: 1) rest, 2) physical activity, 3) mobile health application (mHealth) behavioral management, or 4) physical activity and mHealth app conditions. Assessments at enrollment, 3-5 days, 14 days, 1 month, and 2 months include: concussion symptoms, balance, vestibular-ocular and cognitive assessments, quality of life, and recovery time. Somatic symptoms and other risk factors are evaluated at enrollment. Compliance with treatment and symptoms are assessed daily using actigraph and daily self-report. The primary study outcome is symptoms at 14 days. CONCLUSION: Prescribed physical activity and behavioral management may improve outcomes in youth following acute concussion.

      4. OBJECTIVE: Describe rates of hip fracture-related emergency department (ED) visits, hospitalizations, and deaths among older adults (aged ≥65 years) in the United States. METHODS: Data from the 2019 Healthcare Cost and Utilization Project and National Vital Statistics System were used to calculate rates of hip fracture-related ED visits, hospitalizations, and deaths among older adults by select characteristics and mechanism of injury. RESULTS: In 2019, there were 318,797 ED visits, 290,130 hospitalizations, and 7731 deaths related to hip fractures among older adults. About 88% of ED visits and hospitalizations and approximately 83% of deaths related to hip fractures were caused by falls. Rates were highest among older adults living in rural areas and among those aged ≥85 years. DISCUSSION: Most hip fractures among older adults are fall-related. Healthcare providers can prevent falls among their older patients by screening for fall risk, assessing modifiable risk factors, and offering evidence-based interventions.

      5. Adverse childhood experiences during the COVID-19 pandemic and associations with poor mental health and suicidal behaviors among high school students - adolescent behaviors and experiences survey, United States, January-June 2021
        Anderson KN, Swedo EA, Trinh E, Ray CM, Krause KH, Verlenden JV, Clayton HB, Villaveces A, Massetti GM, Holditch Niolon P.
        MMWR Morb Mortal Wkly Rep. 2022 Oct 14;71(41):1301-1305.
        Social and educational disruptions during the COVID-19 pandemic have exacerbated concerns about adolescents' mental health and suicidal behavior. Data from the 2021 Adolescent Behaviors and Experiences Survey (ABES) indicate that 37.1% of U.S. high school students reported poor mental health during the COVID-19 pandemic, with 19.9% considering and 9.0% attempting suicide in the preceding year (1). Adverse childhood experiences (ACEs)* are associated with poor mental health and suicidal behaviors (2,3), and high prevalence of some ACEs have been documented during the pandemic (4). ACEs are preventable, potentially traumatic events that occur in childhood (ages 0-17 years) such as neglect, experiencing or witnessing violence, or having a family member attempt or die by suicide. Also included are aspects of a child's environment that can undermine their sense of safety, stability, and bonding. Associations between ACEs occurring during the pandemic and mental health or suicidal behaviors among U.S. high school students were examined using ABES data. Experience of one to two ACEs was associated with poorer mental health and increased suicidal behaviors, and these deleterious outcomes increased with additional ACE exposure. After adjusting for demographic characteristics, adolescents who reported four or more ACEs during the pandemic had a prevalence of poor current mental health four times as high as, and a prevalence of past-year suicide attempts 25 times as high as, those without ACEs during the pandemic. Experience of specific ACE types (e.g., emotional abuse) was associated with higher prevalences of poor mental health and suicidal behaviors. Prevention and intervention strategies (5), including early identification and trauma-informed mental health service and support provision, for ACEs and their acute and long-term impacts could help address the U.S. child and adolescent mental health and suicide crisis.(†).

      6. Retrospective analysis of ulnar collateral ligament reconstructions in major league baseball pitchers: A comparison of the "tall and fall" versus "drop and drive" pitching styles
        Beaudry MF, Beaudry AG, Bradley JP, Davis S, Baker BA, Holland G, Jacobson BR, Chetlin RD.
        Orthop J Sports Med. 2022 Oct;10(10):23259671221128041.
        BACKGROUND: Previous pilot research has investigated differences in elbow valgus torque between the "tall and fall" (TF) and "drop and drive" (DD) pitching styles. Whether one of these pitching styles is associated with a greater rate of ulnar collateral ligament reconstruction (UCLR) is currently unknown. PURPOSE: To determine the proportion of Major League Baseball (MLB) pitchers using the TF and DD pitching styles who underwent UCLR over a 10-year period. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The demographic characteristics of pitchers who underwent UCLR between 2007 and 2017 were obtained via the open-source database MLB Player Analysis Tommy John Surgery List. Other information, such as previous UCLR and pitching videos and graphics, was obtained from other open-source databases. A comprehensive, 2-dimensional, kinesiology-based multicomponent definition of each pitching style was formulated and used to categorize the included pitchers into the TF and DD groups. Statistical comparisons and contrasts were made using chi-square and Pearson correlation tests. RESULTS: Included were 223 MLB pitchers (mean ± SD age, 27.5 ± 3.6 years; body mass index [BMI], 27.6 ± 2.2; throwing velocity, 92.9 ± 2.6 mph [149.5 ± 4.2 km/h]) who underwent UCLR between 2007 and 2017. Of these pitchers, 162 were categorized as TF pitchers (72.6%) and 61 as DD pitchers (27.4%). Pitching velocity for injured pitchers was significantly correlated to BMI (P < .001). We found no significant associations of pitching style with year of UCLR (P = .941), BMI (P = .549), age (P = .647), handedness (P = .501), or average pitch velocity (P = .921). CONCLUSION: The study findings demonstrated that a higher proportion of UCL-injured MLB pitchers (72.6%) used the TF pitching style. Further research is needed to explore the potential association between pitching style and UCL injury.

    • Laboratory Sciences
      1. Strengthening laboratory biosafety in Liberia during the COVID-19 pandemic: Experience from the Global Laboratory Leadership Programme
        Malik S, Taweh FM, Freeman M, Dogba JB, Gwesa GO, Tokpah M, Gbondin PP, Kohar TH, Hena JY, MaCauley JA, Pierson A, Rayfield MA, Peruski LF, Albetkova A, Balish A.
        One Health. 2022 Dec;15:100442.
        BACKGROUND: The Global Laboratory Leadership Programme (GLLP) has biosafety and biosecurity as one of its core competencies and advocates for a One Health approach involving all relevant sectors across the human-animal-environment interface to empower national laboratory systems and strengthen health security. Decentralization of SARS-CoV-2 testing in Liberia coupled with an increase in the number of COVID-19 infections among laboratory professionals raised biosafety concerns. In response, a set of trainings on laboratory biosafety was launched for lab personnel across the country under the framework of the GLLP. The goal was to deliver a comprehensive package for laboratory biosafety in the context of SARS-CoV-2 through active learning. METHODS: Three one-day workshops were conducted between September and October 2020, training personnel from human, animal and environmental laboratories through a One Health approach. Concepts critical to laboratory biosafety were delivered in an interactive engagement format to ensure effective learning and retention of concepts. Pre- and post-training assessments were performed, and a paired t-test was used to assess knowledge gain. RESULTS: Of the 67 participants, 64 were from the human health sector, one from veterinary sector and two from environmental health sector. The average pre-test score was 41%. The main gaps identified were failure to acknowledge surgical antisepsis as a form of hand hygiene and recognition of PPE as the best risk control measure. The average post-test score was 75.5%. The mean difference of pre-test and post-test scores was statistically significant (p-value <0.001). Participants indicated satisfaction with the workshop content, mode of delivery and trainers' proficiency. CONCLUSIONS: The workshops were impactful as evidenced by significant improvement (34.5%) in the post-test scores and positive participant feedback. Repeated refresher trainings are vital to addressing the gaps, ensuring compliance, and promoting biosafety culture. GLLP's approach to cultivating multisectoral national laboratory leaders ready to take responsibility and ownership for capacity building provides a sustainable solution for attaining strong national laboratory systems better prepared for health emergencies and pandemics like COVID-19.

      2. Rodent studies investigating long-term effects following termination of hypertrophy-inducing loading have predominantly involved exposures such as synergist ablation and weighted wheel running or ladder climbing. This research yielded a spectrum of results regarding the extent of detraining in terms of muscle mass and myonuclei number. The studies were also limited in their lack of sensitive performance measures and indirect relatedness to resistance training. Our research group developed and validated a relevant rat model of resistance-type training that induces increased muscle mass and performance. The aim of the present study was to determine to what extent these features persist 3 months following the termination of this training. While performance returned to baseline, muscle mass remained elevated by 17% and a shift in distribution to larger muscle fibers persisted. A 16% greater total RNA and heightened mRNA levels of ribosomal protein S6 kinases implicated preserved transcriptional output and ribosomal content. Remodeling of muscle fiber nuclei was consistent with these findings - increased nuclear number and a distribution shift to a more circular nuclear shape. These findings indicate that muscle mass detrains at a slower rate than performance and implicates multiple forms of myonuclear remodeling in muscle memory.

      3. Improving the quality of HIV rapid testing in Ghana using the dried tube specimen-based proficiency testing program
        Nkrumah B, Iriemenam NC, Frimpong F, Kalou MB, Botchway B, Adukpo R, Jackson KG, Angra P, Whistler T, Adhikari AP, Ayisi-Addo S, Melchior MA.
        PLoS One. 2022 ;17(10):e0264105.
        BACKGROUND: The introduction of human immunodeficiency virus (HIV) antibody rapid testing (RT) in resource-limited settings has proven to be a successful intervention to increase access to prevention measures and improve timely linkage to care. However, the quality of testing has not always kept pace with the scale-up of this testing strategy. To monitor the accuracy of HIV RT test results, a national proficiency testing (PT) program was rolled out at selected testing sites in Ghana using the dried tube specimen (DTS) approach. METHODS: Between 2015 and 2018, 635 HIV testing sites, located in five regions and supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), were enrolled in the HIV PT program of the Ghana Health Service National AIDS/STI Control Programme. These sites offered various services: HIV Testing and Counselling (HTC), prevention of mother-to-child transmission (PMTCT) and Antiretroviral Treatment (ART). The PT panels, composed of six DTS, were prepared by two regional laboratories, using fully characterized plasma obtained from the regional blood banks and distributed to the testing sites. The results were scored by the PT providers according to the predefined acceptable performance criteria which was set at ≥ 95%. RESULTS: Seven rounds of PT panels were completed successfully over three years. The number of sites enrolled increased from 205 in round 1 (June 2015) to 635 in round 7 (December 2018), with a noticeable increase in Greater Accra and Eastern regions. The average participation rates of enrolled sites ranged from 88.0% to 98.0% across the PT rounds. By round 7, HTC (257/635 (40.5%)) and PMTCT (237/635 (37.3%)) had a larger number of sites that participated in the PT program than laboratory (106/635 (16.7%)) and ART (12/635 (1.9%)) sites. The average testing performance rate improved significantly from 27% in round 1 to 80% in round 7 (p < 0.001). The highest performance rate was observed for ART (100%), HTC (92%), ANC/PMTCT (90%) and Laboratory (89%) in round 5. CONCLUSION: The DTS PT program showed a significant increase in the participation and performance rates during this period. Sub-optimal performances observed was attributed to non-compliance to the national testing algorithm and testing technique. However, the implementation of review meetings, peer-initiated corrective action, supportive supervisory training, and mentorship proved impactful. The decentralized approach to preparing the PT panels ensured ownership by the region and districts.

    • Maternal and Child Health
      1. The role of intellectual disability with autism spectrum disorder and the documented cooccurring conditions: A population-based study
        Etyemez S, Esler A, Kini A, Tsai PC, DiRienzo M, Maenner M, Lee LC.
        Autism Res. 2022 Oct 17.
        Previous research has identified that patterns of cooccurring conditions (CoCs) associated with autism spectrum disorder (ASD) differ based on the presence of intellectual disability (ID). This study explored the association of documented CoCs among 8-year-old children with ASD and ID (ASD+ID, n = 2416) and ASD without ID (ASD-ID, n = 5372) identified by the Autism and Developmental Disabilities Monitoring Network, surveillance years (SYs) 2012 and 2014. After adjusting for demographic variables, record source, surveillance site, and SY, children with ASD+ID, as compared with children with ASD-ID, were more likely to have histories of nonspecific developmental delays and neurological disorders documented in their records but were less likely to have behavioral and psychiatric disorders. ID plays a key role on how children with ASD would experience other CoCs. Our results emphasize how understanding the pattern of CoCs in ASD+ID and ASD-ID can inform comprehensive and multidisciplinary approaches in assessment and management of children in order to develop targeted interventions to reduce possible CoCs or CoCs-related impairments. LAY SUMMARY: CoCs are common among children with either ASD or ID which can complicate diagnosis and treatment decisions. We compared these CoCs in children with ASD and ID and children with ASD without ID. Our results suggest that children with ASD and ID are more likely to have histories of nonspecific developmental delays and neurological disorders but were less likely to have behavioral and psychiatric conditions compared with children with ASD but not ID.

      2. Urinary phenols in early to mid-pregnancy and risk of gestational diabetes: A longitudinal study in a multiracial cohort
        Zhu Y, Hedderson MM, Calafat AM, Alexeeff SE, Feng J, Quesenberry CP, Ferrara A.
        Diabetes. 2022 Oct 13.
        Environmental phenols are ubiquitous endocrine disruptors and putatively diabetogenic. However, data during pregnancy are scant. We investigated the prospective associations between pregnancy phenols concentrations and gestational diabetes (GDM) risk. In a nested matched case-control study of 111 individuals with GDM and 222 non-GDM controls within the prospective PETALS cohort, urinary bisphenol A (BPA), BPA substitutes (bisphenol F, bisphenol S [BPS]), benzophenone-3, and triclosan were quantified during the first and second trimesters. Cumulative concentrations across the two times were calculated using the area under the curve (AUC). Multivariable conditional logistic regression examined the associations of individual phenols with GDM risk. We conducted mixture analysis using Bayesian kernel machine regression. We a priori examined effect modification by Asians/Pacific Islanders (A/PI) race/ethnicity due to the case-control matching and highest GDM prevalence among A/PI. Overall, first-trimester urinary BPS was positively associated with an increased risk of GDM [adjusted odds ratio comparing the highest versus lowest tertile aORT3 vs. T1 (95% CI)=2.12 (1.00-4.50)]. We identified associations among non-A/P, who had higher phenols concentrations than A/PI. Among non-A/PI, first-trimester BPA, BPS, and triclosan were positively associated with GDM risk [aORT3 vs. T1 (95% CI)=2.91 (1.05-8.02), 4.60 (1.55-13.70), 2.88 (1.11-7.45), respectively]. Triclosan in the second trimester and AUC were positively associated with GDM risk among non-A/PI (P <0.05). In mixture analysis, triclosan was significantly associated with GDM risk. Urinary BPS among all and BPA, BPS, and triclosan among non-A/PI were associated with GDM risk. Pregnant individuals should be aware of these phenols' potential adverse health effects.

    • Nutritional Sciences
      1. Advancing healthy food service in the United States: State food service guidelines policy adoption and implementation supports, 2015-2019
        Lowry-Warnock A, Strombom N, Mugavero K, Harris D, Blanck HM, Onufrak S.
        Am J Health Promot. 2022 Sep 30:8901171221123311.
        PURPOSE: Food service guidelines (FSG) policies can impact the nutritional quality of millions of meals sold or served to government employees, citizens in public places, or institutionalized persons. This study examines state FSG policies adopted January 1, 2015 to April 1, 2019, and uses a FSG Classification Tool (FSG Tool) to quantify alignment with nutrition recommendations for public health impact. DESIGN: Quantitative Content Analysis. SETTING: State Government Worksites and Facilities. PARTICIPANTS: 50 states and District of Columbia (D.C.) in the United States. MEASURES: Frequency of policies and percent alignment to FSG tool. ANALYSIS: FSG policies were identified using legal databases to assess state statutes, regulations, and executive orders. Content analysis and coding determined attributes of policies across 4 FSG Tool domains, (1) nutrition standards referenced; (2) behavioral design strategies encouraging selection of healthier offerings; (3) facility efficiency and environmental sustainability; and (4) FSG implementation supports. RESULTS: From 2015-2019, 5 FSG policies met study inclusion criteria. Four out of 5 policies earned a perfect nutrition score (100%) by referencing nutrition standards that align with the Dietary Guidelines for Americans (DGA) and are operationalized for use in food service venues. Four out of 5 policies included at least 1 implementation supports provision, such as naming an implementing agency, and 2 included provisions that encourage local food sourcing. CONCLUSION: From 2015-2019, overall FSG policy comprehensiveness scores ranged from 24% to 73%, with most policies referencing food and nutrition standards that align to national nutrition recommendations. Public health practitioners can educate decision makers on the potential impact of FSG policies on diet-related health outcomes and associated cost savings, as well as other important co-benefits that support locally grown products and environmental sustainability practices.

    • Occupational Safety and Health
      1. Perceptions of fatigue and safety climate pertaining to residency duty-hour restrictions
        Carr MM, Friedel J, O'Brien D, Foreman AM, Wirth O.
        Cureus. 2022 Sep;14(9):e28929.
        INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME), which sets the standards for residency training, instituted work-hour restrictions in 2003. Our purpose was to assess residents' perceptions of fatigue and local safety climate specific to these duty-hour restrictions. METHODS:  All residents (N=433) at one university were emailed a link to a survey in 2019. The survey included demographic details, on-call descriptors, an 18-point climate survey (CS), and the 33-point Chalder Fatigue Questionnaire (CFQ). The CS was adapted from a commonly used safety climate scale and intended to measure the respondent's perceptions of their program's attitudes and practices around resident duty-hour compliance. A Pearson correlational analysis was used to determine if there were associations between the variables. RESULTS:  Mean CS score was 12.89 (95% confidence interval, CI 12.32-13.46, N=164, 48.5%). Respondents were most likely to disagree with "Residents are told when they are at risk of working beyond ACGME duty-hour restrictions," where 57 (34.7%) disagreed or strongly disagreed. Mean CFQ score was 16.02 (95% CI 14.87-17.17, N=113, 26.1%). As the CS score improved, CFQ scores decreased indicating an inverse relationship between duty-hour climate and fatigue (r=-0.328, p<0.05). Having a protected post-call day off, and having either the Program Director, Chief Resident, or Senior Resident decide that a resident takes a post-call day off were all associated with higher CS scores.  Conclusion: We found that the CS had good internal consistency and evidence of construct validity. An inverse relationship between CS score and fatigue suggests that the level of fatigue is higher among residents in programs where residents perceived that ACGME duty-hour compliance was less important.

      2. Comparison of the observer, single-frame video and computer vision hand activity levels
        Radwin RG, Hu YH, Akkas O, Bao S, Harris-Adamson C, Lin JH, Meyers AR, Rempel D.
        Ergonomics. 2022 Oct 13:1-12.
        Observer, manual single-frame video, and automated computer vision measures of the Hand Activity Level (HAL) were compared. HAL can be measured three ways: 1) observer rating (HAL(O)), 2) calculated from single-frame multimedia video task analysis for measuring frequency (F) and duty cycle (D) (HAL(F)), or 3) from automated computer vision (HAL(C)). This study analyzed videos collected from three prospective cohort studies to ascertain HAL(O), HAL(F), and HAL(C) for 419 industrial videos. Although the differences for the three methods were relatively small on average (<1), they were statistically significant (p<.001). A difference between the HAL(C) and HAL(F) ratings within ±1 point on the HAL scale was the most consistent, where more than two thirds (68%) of all the cases were within that range and had a linear regression through the mean coefficient of 1.03 (R(2) =0.89). The results suggest that the computer vision methodology yields comparable results as single-frame video analysis. The ACGIH Hand Activity Level (HAL) was obtained for 419 industrial tasks using three methods: observation, calculated using single-frame video analysis and computer vision. The computer vision methodology produced results that were comparable to single-frame video analysis. eng

      3. Determining worker exposure to hazardous volatile organic compounds (VOCs) in air at levels exceeding the Permissible Exposure Limits and Recommended Exposure Limits established by the U.S. federal agencies of Occupational Safety and Health Administration (OSHA) and the National Institute for Occupational Safety and Health (NIOSH), respectively, will continue to be an important part of environmental and occupational health risk assessments. The purpose of this work was to develop a reliable analytical method for rapid and on-site assessments of occupational VOC exposures using field-capable thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) instrumentation (i.e. the HAPSITE® ER). The experiments involved in this study included determining TD-GC-MS parameters suitable for efficient analyte separation and quantitation on the HAPSITE® ER, determinations of analyte mass loadings that cause mass spectrometer detector saturations, generation of calibration curves, estimations of the limits of detection (LODs) and quantification (LOQs), as well as desorption efficiency and relative response factor repeatability. The LODs using Carbopack™ B and Tenax® TA sampling media were estimated and ranged from 0.2–1.9 ng and 0.045–0.3 ng, respectively. The LOQs using Carbopack™ B and Tenax TA sampling media were estimated and ranged from 1.0–6.3 ng and 0.2–1.1 ng, respectively. We have developed a reliable analytical method for chloroform, benzene, trichloroethylene, and heptane using field-portable HAPSITE® ER instrumentation and Tenax® TA sorbent media. Reliable and accurate methods were developed for chloroform and trichloroethylene using Carbopack™ B sorbent media, however, this particular sorbent hadlow desorption efficiency and insufficient repeatability in relative response factors for many analytes. Our current and ongoing work in determining the uptake rates for analytes on Tenax® TA sorbent media will make the methods described herein applicable for on-site occupational VOC exposure assessments of chloroform, benzene, trichloroethylene, and heptane using either passive or active air sampling techniques. © This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC 105, no copyright protection is available for such works under US Law.

      4. In search of a value proposition for COVID-19 testing in the work environment: A social marketing analysis
        Parvanta C, Caban-Martinez AJ, Cabral N, Ball CK, Moore KG, Eastlake A, Levin JL, Nessim DE, Thiese MS, Schulte PA.
        Int J Environ Res Public Health. 2022 Sep 30;19(19).
        BACKGROUND: This study examined employer experience with SARS-CoV-2 (COVID-19) asymptomatic testing through a social marketing lens. Social marketing uses commercial marketing principles to achieve socially beneficial ends including improved health and safety behavior. METHOD: Twenty employers across 11 occupational sectors were interviewed about implementation of COVID-19 testing from January through April 2021. Recorded transcripts were coded and analyzed using marketing's "Four P's": "product," "price," "place," "promotion." RESULTS: COVID-19 tests (product) were uncomfortable, were easily confused, and didn't solve problems articulated by employers. Testing was not widely available or didn't line up with shifts or locations (place). The perceived price, which included direct and associated costs (e.g., laboratory fees, productivity loss, logistical challenges) was high. Most crucially, the time to receive (PCR) results negated the major benefit of less time spent in quarantine and challenged employer trust. A potential audience segmentation strategy based on perceptions of exposure risk also emerged. CONCLUSIONS: This social marketing analysis suggests ways to improve the value proposition for asymptomatic testing through changes in product, price, and placement features in line with employers' expressed needs. Study findings can also inform creation of employee communication materials that balance perceived rewards of testing against perceived risks of exposure.

      5. Effect of cooling on static postural balance while wearing firefighter's protective clothing in hot environment
        Aljaroudi AM, Bhattacharya A, Strauch A, Quinn TD, Jon Williams W.
        Int J Occup Saf Ergon. 2022 Oct 19:1-20.
        PURPOSE: Postural imbalance can result from hyperthermia mediated muscular fatigue and is a major factor contributing to injuries from falling. The objective of this study was to investigate the effect of exercise-induced hyperthermia and the impact of cooling on postural balance while wearing firefighters' protective clothing (FPC) in a hot environment. METHODS: A portable force platform measured postural balance characterized by postural sway patterns using center of pressure metrics. Twelve healthy, physically fit males were recruited to stand on the force platform once with eyes open and once with eyes closed before and after treadmill exercise (40% V˙O(2max)) inside an environmental chamber under hot and humid conditions (30 °C and 70% relative humidity) while wearing FPC. Subjects participated in two randomly assigned experimental phases: control and cooling intervention. RESULTS: A significant increase in physiological responses and postural balance metrics was observed after exercising in the heat chamber while wearing FPC. Cooling resulted in a significant effect only on postural sway speed after exercise-induced hyperthermia. CONCLUSIONS: Hyperthermia can negatively alter postural balance metrics, which may lead to an increased likelihood of falling. The utilization of body cooling reduced the thermal strain but had limited impact on postural balance stability.

      6. Future of work in agriculture
        Howard J, Lincoln JM.
        J Agromedicine. 2022 Oct 18.

      7. Association of mRNA vaccination with clinical and virologic features of COVID-19 among US essential and frontline workers
        Thompson MG, Yoon SK, Naleway AL, Meece J, Fabrizio TP, Caban-Martinez AJ, Burgess JL, Gaglani M, Olsho LE, Bateman A, Lundgren J, Grant L, Phillips AL, Groom HC, Stefanski E, Solle NS, Ellingson K, Lutrick K, Dunnigan K, Wesley MG, Guenther K, Hunt A, Mak J, Hegmann KT, Kuntz JL, Bissonnette A, Hollister J, Rose S, Morrill TC, Respet K, Fowlkes AL, Thiese MS, Rivers P, Herring MK, Odean MJ, Yoo YM, Brunner M, Bedrick EJ, Fleary DE, Jones JT, Praggastis J, Romine J, Dickerson M, Khan SM, Lamberte JM, Beitel S, Webby RJ, Tyner HL.
        Jama. 2022 Oct 18;328(15):1523-1533.
        IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. EXPOSURES: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. MAIN OUTCOMES AND MEASURES: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. RESULTS: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/μL; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/μL, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). CONCLUSIONS AND RELEVANCE: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

      8. Increased all-cause mortality following occupational injury: a comparison of two states
        Boden LI, Asfaw A, Busey A, Tripodis Y, O'Leary PK, Applebaum KM, Stokes AC, Fox MP.
        Occup Environ Med. 2022 Oct 17.
        OBJECTIVES: To measure the impact of lost-time occupational injuries on all-cause mortality in Washington State and, using the same data elements and study design, to determine whether the estimated impact was similar to previous estimates for New Mexico. METHODS: We linked injuries in the Washington workers' compensation system with Social Security Administration data on earnings and mortality. We estimated Cox survival models of mortality for women and men with lost-time compared with medical-only injuries, adjusting for age, pre-injury earnings and industry. We used quantitative bias analysis to account for confounding by pre-injury smoking and obesity. RESULTS: The estimated mortality HR was 1.24 for women (95% CI 1.21 to 1.28) and 1.22 for men (95% CI 1.20 to 1.24). After adjusting for unmeasured pre-injury smoking and obesity, the estimated HR for women was 1.10, 95% simulation interval (SI) 1.00 to 1.21; for men, it was 1.15, 95% SI 1.04 to 1.27. CONCLUSIONS: All-cause mortality for Washington workers with lost-time injuries was higher than for those with medical-only injuries. Estimated HRs for Washington were consistent with those previously estimated for New Mexico, a less populous state with lower median wages and a different workers' compensation insurance mechanism. This suggests that the relationship between workplace injury and long-term mortality may be generalisable to other US states. These findings support greater efforts to enhance safety and to investigate factors that improve postinjury employment opportunities and long-term health. This association should be examined in additional locations, with different study conditions, or using additional data on pre-injury risk factors.

    • Occupational Safety and Health - Mining
      1. The integrity of unconventional shale gas well casings positioned in the abutment pillar of a longwall mine could be jeopardized by longwall-induced deformations. Under such scenarios, the surrounding fracture networks could provide pathways for gas flow into the mine creating safety concerns. To provide recommendations for developing guidelines that ensure a safe co-existence of longwall mining and unconventional shale gas production, this study evaluates the impact of parameters that could affect potential shale gas flow into the mine in the event of a casing breach using a discrete fracture network (DFN) model. These parameters are evaluated using a conceptualized DFN realization that is representative of the fractured zone in the overburden, and the range of parameter variations is within values validated with field measurements. The results show that a decrease in fracture aperture (potentially due to longwall-induced stress in the likely vicinity of the breach location) reduces the potential gas flow to the mine by a significantly higher proportion. A 50% decrease in the aperture of the fracture that directly transports the gas from the casing breach location reduces the gas flow to the mine by over 70%. Similarly, changes in the fracture water saturation level significantly affect the gas flow. In all cases, the potential gas flow to the mine is higher if the casing breach occurs at an increased gas well pressure. These findings provide critical information regarding the impact of each of the parameters associated with gas flow in the event of a shale gas casing breach near a longwall mine and could help towards the development of guidelines to ensure a safe coexistence of both industries. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

    • Physical Activity
      1. Association of muscle-strengthening and aerobic physical activity with mortality in US adults aged 65 years or older
        Webber BJ, Piercy KL, Hyde ET, Whitfield GP.
        JAMA Netw Open. 2022 Oct 3;5(10):e2236778.
        This cohort study uses national data to explore the dose-response association between guideline-recommended physical activity and mortality in older adults. eng

    • Social and Behavioral Sciences
      1. Impact of social isolation during the COVID-19 pandemic on mental health, substance use, and homelessness: Qualitative interviews with behavioral health providers
        Jeffers A, Meehan AA, Barker J, Asher A, Montgomery MP, Bautista G, Ray CM, Laws RL, Fields VL, Radhakrishnan L, Cha S, Christensen A, Dupervil B, Verlenden JV, Cassell CH, Boyer A, DiPietro B, Cary M, Yang M, Mosites E, Marcus R.
        Int J Environ Res Public Health. 2022 Sep 25;19(19).
        The United States is experiencing a syndemic of homelessness, substance use disorder, and mental health conditions, which has been further exacerbated by the COVID-19 pandemic. Although it is expected that mitigation strategies will curb community transmission of COVID-19, the unintended consequences of social isolation on mental health and substance use are a growing public health concern. Awareness of changing mental health and substance use treatment needs due to the pandemic is critical to understanding what additional services and support are needed during and post-pandemic, particularly among people experiencing homelessness who have pre-existing serious mental illness or substance use disorder. To evaluate these effects and support our understanding of mental health and substance use outcomes of the COVID-19 pandemic, we conducted a qualitative study where behavioral health providers serving people experiencing homelessness described the impact of COVID-19 among their clients throughout the United States. Behavioral health providers shared that experiencing social isolation worsened mental health conditions and caused some people to return to substance use and fatally overdose. However, some changes initiated during the pandemic resulted in positive outcomes, such as increased client willingness to discuss mental health topics. Our findings provide additional evidence that the social isolation experienced during the pandemic has been detrimental to mental health and substance use outcomes, especially for people experiencing homelessness.

      2. During the early months of COVID-19, many people in the US turned to charitable crowdfunding to seek and provide assistance. Little is known about the needs, hopes or experiences that motivated US pandemic crowdfunding and how these were correlated with campaign success. This study uses a mixed-methods data analysis of a randomised cluster sample of 919 US GoFundMe campaigns during the first 7 months of the pandemic. Overall, most campaigns performed poorly, and 38% got no donations at all. The largest proportion of campaigns aimed to address individual, acute financial struggles, often arising from considerable challenges accessing or qualifying for government assistance. These campaigns, as well as those involving campaigners and beneficiaries of colour, tended to be least successful. Qualitative thematic analysis revealed three key crowdfunding motivations that reflect individualistic, agentive responses to the pandemic: struggling, helping and adapting. These motivations reveal a shift away from social suffering and collective mobilisation and towards largely individualised efforts of survival as digital crowdfunding becomes a key domain of crisis response. Crowdfunding platforms are playing an increasingly important role in mediating and influencing individual and collective responses to crisis, which has important political ramifications for how societies perceive and address health emergencies.

    • Substance Use and Abuse
      1. Contraception claims by medication for opioid use disorder prescription status among insured women with opioid use disorder, United States, 2018
        Goyal S, Monsour M, Ko JY, Curtis KM, Whiteman MK, Coy KC, Cox S, Romero L.
        Contraception. 2022 Oct 12.
        OBJECTIVE(S): To understand how contraception method use differed between women prescribed and not prescribed medications for opioid use disorder (MOUD) among commercially-insured and Medicaid-insured women. STUDY DESIGN: IBM Watson Health MarketScan® Commercial Claims and Encounters database and the Multi-State Medicaid database were used to calculate the 1) crude prevalence and 2) adjusted odds ratios (adjusted for demographic characteristics) of using long-acting reversible or short-acting hormonal contraception methods or female sterilization compared with none of these methods (no method) in 2018 by MOUD status among women with OUD, aged 20 to 49 years, with continuous health insurance coverage through commercial insurance or Medicaid for ≥ six years. Claims data was used to define contraception use. Fisher exact test or χ(2) test with a p-value ≤ 0.0001, based on the Holm-Bonferroni method, and 95% confidence intervals were used to determine statistically significant differences for prevalence estimates and adjusted odds ratios, respectively. RESULTS: Only 41% of commercially-insured and Medicaid-insured women with OUD were prescribed MOUD. Medicaid-insured women with OUD prescribed MOUD had a significantly lower crude prevalence of using no method (71.1% vs 79.0%) and higher odds of using female sterilization (aOR, 1.33; 95% CI: 1.06 - 1.67 vs no method) than those not prescribed MOUD. Among commercially-insured women there were no differences in contraceptive use by MOUD status and 66% used no method. CONCLUSIONS: Among women with ≥ six years of continuous insurance coverage, contraceptive use differed by MOUD status and insurance. Prescribing MOUD for women with OUD can be improved to ensure quality care. IMPLICATIONS: Only two in five women with OUD had evidence of being prescribed MOUD, and majority did not use prescription contraception or female sterilization. Our findings support opportunities to improve prescribing for MOUD and integrate contraception and MOUD services to improve clinical care among women with OUD.

      2. Collaborative learning and response to opioid misuse and HIV prevention in Ukraine during war
        Altice FL, Bromberg DJ, Klepikov A, Barzilay EJ, Islam Z, Dvoriak S, Farnum SO, Madden LM.
        Lancet Psychiatry. 2022 Nov;9(11):852-854.

      3. Notes from the Field: Antihistamine Positivity and Involvement in Drug Overdose Deaths - 44 Jurisdictions, United States, 2019-2020
        Dinwiddie AT, Tanz LJ, Bitting J.
        MMWR Morb Mortal Wkly Rep. 2022 Oct 14;71(41):1308-1310.

      4. The role of depression in secondary HIV transmission among people who inject drugs in Vietnam: A mathematical modeling analysis
        Levintow SN, Pence BW, Sripaipan T, Ha TV, Chu VA, Quan VM, Latkin CA, Go VF, Powers KA.
        PLoS One. 2022 ;17(10):e0275995.
        BACKGROUND: Among people who inject drugs (PWID), depression burden is high and may interfere with HIV prevention efforts. Although depression is known to affect injecting behaviors and HIV treatment, its overall impact on HIV transmission has not been quantified. Using mathematical modeling, we sought to estimate secondary HIV transmissions and identify differences by depression among PWID. METHODS: We analyzed longitudinal data from 455 PWID living with HIV in Vietnam during 2009-2013. Using a Bernoulli process model with individual-level viral load and behavioral data from baseline and 6-month follow-up visits, we estimated secondary HIV transmission events from participants to their potentially susceptible injecting partners. To evaluate differences by depression, we compared modeled transmissions per 1,000 PWID across depressive symptom categories (severe, mild, or no symptoms) in the three months before each visit. RESULTS: We estimated a median of 41.2 (2.5th, 97.5th percentiles: 33.2-49.2) secondary transmissions from all reported acts of sharing injection equipment with 833 injecting partners in the three months before baseline. Nearly half (41%) of modeled transmissions arose from fewer than 5% of participants in that period. Modeled transmissions per 1,000 PWID in that period were highest for severe depressive symptoms (100.4, 80.6-120.2) vs. mild (87.0, 68.2-109.4) or no symptoms (78.9, 63.4-94.1). Transmission estimates fell to near-zero at the 6-month visit. CONCLUSIONS: Secondary transmissions were predicted to increase with depression severity, although most arose from a small number of participants. Our findings suggest that effective depression interventions could have the important added benefit of reducing HIV transmission among PWID.

    • Zoonotic and Vectorborne Diseases
      1. Procedure for spotted fever group Rickettsia isolation from limited clinical blood specimens
        Condit ME, Jones E, Biggerstaff BJ, Kato CY.
        PLoS Negl Trop Dis. 2022 Oct 14;16(10):e0010781.
        BACKGROUND: Current isolation techniques for spotted fever group Rickettsia from clinical samples are laborious and are limited to tissue, blood and blood derivatives with volumes ideally greater than 1 mL. We validated the use of simplified methodologies for spotted fever group Rickettsia culture isolation that overcome sample volume limitations and provide utility in clinical diagnostics and research studies. METHODOLOGY/PRINCIPAL FINDINGS: A modified cell culture method is evaluated for the isolation of Rickettsia ssp. from human diagnostic samples. Culture sampling method, culture platform, and growth phase analysis were evaluated to determine best practices for optimal culture isolation conditions. Rickettsial isolates (R. conorii, R. rickettsii, and R. parkeri) were grown in Vero E6 cells over a course of 5 to 7 days at low inoculum treatments (~40 bacterial copies) to standardize the sampling strategy at a copy number reflective of the bacteremia in acute diagnostic samples. This methodology was verified using small volumes (50 μL) of 25 unprocessed clinical whole blood, plasma, and serum samples from acute samples of patients suspected of having Rocky Mountain Spotted Fever, of which 10 were previously confirmed positive via the PanR8 qPCR assay, 13 had no detectable Rickettsia DNA by the PanR8 qPCR assay, and 2 were not previously tested; these samples resulted in the cultivation of 7 new R. rickettsii isolates. CONCLUSIONS/SIGNIFICANCE: We observed that rickettsial isolate growth in culture is reproducibly identified by real-time PCR testing of culture media within 72 hours after inoculation. Additionally, specimen sedimentation prior to isolation to remove red blood cells was found to decrease the amount of total viable organism available in the inoculum. A small volume culture method was established focusing on comparative qPCR detection rather than bacterial visualization, taking significantly shorter time to detect, and requiring less manipulation compared to traditional clinical isolate culture methods.

      2. An introduction to the Marburg virus vaccine consortium, MARVAC
        Cross RW, Longini IM, Becker S, Bok K, Boucher D, Carroll MW, Díaz JV, Dowling WE, Draghia-Akli R, Duworko JT, Dye JM, Egan MA, Fast P, Finan A, Finch C, Fleming TR, Fusco J, Geisbert TW, Griffiths A, Günther S, Hensley LE, Honko A, Hunegnaw R, Jakubik J, Ledgerwood J, Luhn K, Matassov D, Meshulam J, Nelson EV, Parks CL, Rustomjee R, Safronetz D, Schwartz LM, Smith D, Smock P, Sow Y, Spiropoulou CF, Sullivan NJ, Warfield KL, Wolfe D, Woolsey C, Zahn R, Henao-Restrepo AM, Muñoz-Fontela C, Marzi A.
        PLoS Pathog. 2022 Oct;18(10):e1010805.
        The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine "MARVAC" consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines.


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