The Internet of Things infrastructure connects a massive number of edge devices with an increasing demand for intelligent sensing and inferencing capability. Such data-sensitive functions necessitate energy-efficient and programmable implementations of Error Correction Codes (ECC) and decoders. The algorithmic flow of ECCs with concurrent accumulation and comparison types of operations are innately exploitable by neuromorphic architectures for energy efficient execution–an area that is relatively unexplored outside of machine learning applications. For the first time, we propose a methodology to map the hard-decision class of decoder algorithms on a neuromorphic architecture. We present the implementation of the Gallager B (GaB) decoding algorithm on a TrueNorth-inspired architecture that is emulated on the Xilinx Zynq ZCU102 MPSoC. Over this reference implementation, we propose architectural modifications at the neuron block level that result in a reduction of energy consumption by 31% with a negligible increase in resource usage while achieving the same error correction performance.
Background Social vulnerability impacts the transmission of SARS-CoV-2 (SCV2) among household contacts. Understanding these correlates can inform interventions to prevent infection among close contacts. We examined whether the social vulnerability index (SVI), a composite measure of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation, is associated with the risk of SCV2 infection among household contacts. Overall Social Vulnerability Index Diagram Methods We used data from a multi-site, prospective, case-ascertained household transmission study with daily nasal swabs for 10 days and RT-PCR testing to detect SCV2 infections in household contacts. Age and gender were self-reported and vaccination status was self-reported and verified. We mapped households to 2020 census tracts and the 2020 SVI (Figure 1). We examined the association between census tract-level SVI (in quartiles) and the risk of infection among household contacts using Poisson regression with generalized estimating equations, accounting for household clustering. Inclusion criteria for analysis in this study. Inclusion criteria for analysis in this study. Results Among 1,171 household contacts from 719 households, 67.4% developed SCV2 infection. After adjusting for the age of the contact and study site, contacts living in the most vulnerable SVI quartiles, Q3 (Incidence Rate Ratio [IRR] 1.19, 95% CI 1.01-1.40) and Q4 (IRR=1.18, 95% CI 1.00-1.40), had higher rates of infection compared to those living in the least vulnerable quartile (Q1) at the census tract level. To describe the effect of SVI accounting for vaccination, we performed a second regression adjusting for vaccine receipt among participants. We found that Q3 (IRR 1.19, 95% CI 1.01-1.40) still had higher rates of infection compared to those living in the least vulnerable quartile (Q1). Q4 was directionally consistent but confidence bounds crossed 1 (IRR=1.17, 95% CI 0.99-1.39). Conclusion Household contacts from census tracts with greater social vulnerability at the census tract level had a greater risk of SCV2 infection. These risks held even after accounting for vaccine receipt among participants. Future public health interventions should focus on reducing infection and transmission among individuals living in areas with higher social vulnerability beyond vaccination coverage. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member
Background Coccidioidomycosis is an endemic mycosis in the southwestern United States. While most infections are mild or asymptomatic, severe cases are associated with high morbidity and mortality. We aimed to evaluate the clinical outcomes of patients admitted to the intensive care unit (ICU) with proven culture-positive coccidioidomycosis. Methods After institutional review board approval, we retrospectively included ICU patients with positive Coccidioides spp. culture within a multi-healthcare system between 10/01/2017 – 07/01/2022. Clinical information was collected by chart review. Results Of the 392 hospital encounters with positive Coccidioides spp. culture, 145 patients required ICU stay. The median age was 51 (32-62), with 100 (68.9%) male, 56 (38.6%) White non-Hispanics, and 25 (17.2%) Blacks. Fifty-seven (39.3%) received azole antifungals before hospitalization. Seventy-two (49.7%) had another fungal, bacterial, or viral infection during their hospitalization, and 41 (28.3%) had extrapulmonary coccidioidomycosis. The majority, 131 (90.3%), received antifungal therapy during their hospital stay. The median hospital length of stay was 18 days (10-37). Almost half (48.3%) died during the study period, with liver cirrhosis and age ( >60 years) resulting in statistically significant mortality, 12/13 (92.3%), p-value < 0.001, and 31/43 (72.1%) p-value =0.001, respectively. Mechanical ventilation and/or intravenous vasopressor support was associated with a high risk of mortality 66/113 (58.4%, p-value=< 0.001). Failure to receive antifungal therapy before ICU admission was associated with increased mortality, 46/70 (65.7%, p-value=0.002). Conclusion Patients with coccidioidomycosis admitted to the ICU face an increased risk of mortality. Risk factors associated with ICU mortality include advanced age, cirrhosis, and delay in the administration of antifungal therapy. Future studies are needed to evaluate these risks further. Disclosures Tirdad Zangeneh, DO, AiCuris: Grant/Research Support Mohanad Al-Obaidi, MD, MPH, La Jolla Pharmaceuticals: Honoraria
Background An estimated 1-3% of children with SARS-CoV-2 infection will develop Post-COVID Conditions (PCC). This study evaluates mRNA COVID-19 vaccine impact on likelihood of PCC in children. Methods A multi-site cohort of children enrolled 7/21/2021-9/1/2022 underwent weekly SARS-CoV-2 screening tests and were surveyed via self- or parental report 12/1/2022-5/31/2023 regarding PCC (defined as ≥1 new or on-going symptoms lasting ≥ 1 month after infection). Multivariable logistic regression was performed to estimate the occurrence of PCC by vaccination status among children aged 5–17 years whose first PCR-confirmed SARS-CoV-2 infection occurred in-study with Omicron variant, who completed the survey >60 days from infection, and who were vaccine age-eligible at time of infection per ACIP recommendations. Vaccination status was categorized as vaccinated (at least primary series completed >14 days before infection) and unvaccinated (no vaccine doses before infection). Vaccination status was verified through vaccine registry and/or medical records. Results Of 622 participants surveyed, 5% (n=28) had PCC (Table 1) and 67% (n=474) were vaccinated (Table 2). Surveys were completed a median (IQR) of 203.7 days (119.0–293.0) after infection. Children with non-Hispanic Black race/ethnicity and good/fair/poor self-rated baseline health were more likely to report PCC. Children aged 12-18 years, Non-Hispanic Asian and White children, those reporting symptomatic SARS-CoV-2 infection, and those with excellent/very good self-rated baseline health were more likely to report vaccination When comparing children with and without PCC symptoms, COVID-19 mRNA vaccination was associated with a decreased likelihood of >1 PCC symptom (aOR 0.66, 95% CI 0.43-0.99), >2 PCC symptoms (aOR 0.52, 95% 0.32-0.83), and respiratory PCC symptoms (aOR 0.53, 95% CI 0.33-0.87) (Table 3). Figure 1.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages ≥50 (N=564,303)Figure 2.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 18-49 (N=292,818)Figure 3.Relative Risk of Post-COVID Conditions among Patients who Received Paxlovid, Ages 12-17 (N=17,178) Conclusion In this study, mRNA COVID-19 vaccination appeared to be protective against PCC in children following Omicron SARS-CoV-2 infection. The adjusted ORs correspond to an estimated 34%, 48%, and 47% reduced likelihood of >1, >2, and respiratory PCC symptoms among vaccinated children, respectively. These findings support COVID-19 vaccination for children and may encourage increased pediatric vaccine uptake. Disclosures Lisa Gwynn, MBA, MSPH, Merck: Honoraria
Background Severe COVID-19 predicts increased risk of Post-COVID conditions (PCC). However, the impact of mild COVID-19 in non-hospitalized patients on development of PCC is less clear. Methods We recruited individuals with mild SARS-CoV-2 (SCV2) infection from 7 US sites into a household transmission study, Sep. 2021–Dec. 2022. Index cases and their household contacts (HHC) were enrolled ≤6 days after the index case tested positive for SCV2. At baseline, participants provided sociodemographic, clinical and vaccine history, and dried blood spot for antibody detection. Participants completed daily symptom and medication diaries and collected nasal swabs for quantitative PCR (qPCR) for 10 days as well as a 90-day survey including the PROMIS® Global Health measure of physical, mental, and social health. We defined PCC as presence of ≥1 symptom (Table 1) most or almost all of the time 90 days post enrollment (Fig. 1). We calculated the proportion of PCC among adults with SCV2 infection and evaluated factors associated with PCC using Chi-squared, Student’s t-test, or binary logistic regression, as applicableTable 1:Individual symptoms and symptom clusters occurring most of the time or almost all the time at 90-day follow-up among adults who had Post-COVID (PCC) conditions At 90-days after enrollment, participants were asked how often they experience a list of 17 symptoms with response options of never, sometimes, most of the time, almost all the time. Those who responded most or almost all the time to at least one of the listed symptoms and tested positive for SARS-CoV-2 during enrollment or daily swabbing were defined as having PCC. Constitutional symptoms include fever, fatigue, and dizziness/lightheadedness; Neuropsychiatric symptoms include brain fog, change in mood, problems sleeping, tingling/numbness, and dizziness/lightheadedness; Respiratory symptoms include cough and dyspnea; Cardiovascular symptoms include chest pain and dizziness/lightheadedness; Gastrointestinal symptoms include change in taste/smell, vomiting, constipation, and diarrhea.Figure 1.Flow chart of participants who tested positive for SARS-CoV-2 and completed a 90-day survey for Post-COVID conditions (PCC) Results Among 532 adults with SCV2 who completed a 90-day survey, 326 (61.3%) were female, mean age was 47.4 years (SD 16.8), and 89 (17%) met PCC definition. Among people with PCC, the most common symptoms were neuropsychiatric (60%), fatigue (35%), respiratory (34%), and sleep problems (30%; Table 1); 41% reported ≥ 2 symptoms and 23% reported ≥ 3. HHC had lower odds of PCC compared to index cases (OR 0.6, 95% CI 0.4, 0.9), college graduates had higher odds of PCC compared to non-graduates (OR 1.7, 95% CI 1.0, 2.9) and participants with comorbidities had twice the odds of PCC compared to those without (95% CI 1.2, 3.4; Table 2). There were no significant associations between viral load, antibodies, or treatment during acute illness and PCC (Table 3). PCC was associated with higher odds of reporting poor/fair quality of life (OR 7.8, 95%CI 2.9, 21.3), physical health (OR 8.2, 95%CI 4.2, 16.3), mental health (OR 4.9, 95%CI 2.7, 8.9), and social satisfaction (OR 4.9, 95%CI 2.5, 9.6).Table 2:Characteristics of adult participants who had SARS-CoV-2 infection and who did and did not develop Post-COVID conditions (PCC)* at 90-day follow upSCV2: SARS-CoV-2; OR: Odds ratio; CI: Confidence interval * PCC defined as presence of ≥ 1 of the following symptoms most or all of the time, 90 days after enrollment: fever, fatigue or post-exertional malaise, weight loss, mood changes, headache, tingling/numbness, change in ability to smell/taste, cough, shortness of breath, chest pain/palpitations, lightheadedness/dizziness, syncope, change in appetite, nausea, vomiting, diarrhea, constipation, or sleep disturbance. † Ref: Reference category ‡ Data on ethnicity available for 514 participants (83 with PCC and 431 without PCC). Data on level of education available for 523 participants (85 with PCC and 438 without PCC). Data on current cigarette smoking and medical comorbidities available for 524 participants (84 with PCC and 440 without PCC).Table 3:Virologic, immunologic and treatment characteristics of adult participants who had SARS-CoV-2 infection and who did and did not develop Post-COVID conditions (PCC)* at 90-day follow upSCV2: SARS-CoV-2; OR: Odds ratio; CI: Confidence interval, Ref.: Reference category *Fully vaccinated defined as having received at least two doses of a COVID vaccine (inclusive of all mRNA, vector, or nanoparticle COVID vaccines) † History of COVID prior to the SARS-CoV-2 infection that qualified the participant for study enrollment. ‡ Data on viral variant available for 526 participants (88 with PCC and 438 without PCC). Conclusion In this household transmission study, 17% of ambulatory adults with COVID-19 reported PCC symptoms 90 days after acute infection. Index cases, people with comorbidities, and college graduates had higher odds of PCC. Disclosures Michelle Floris-Moore, MD, MS, Viiv Healthcare: Advisor/Consultant Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Lisa Saiman, MD MPH, Merck & Co., Inc,: Grant/Research Support|Merck & Co., Inc,: Member, DSMB|Pfizer, Inc: Member, DSMB Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support
Background Antibiotic resistance has worsened since the start of the COVID-19 pandemic because of overstrained healthcare and laboratory systems, disrupted antimicrobial stewardship programs, and overuse of antibiotics. Community-based antibiotic use during the pandemic in the United States (US) and Mexico, including the socially vulnerable border region, is poorly characterized and does not account for non-prescription antibiotic use. The goal of this study was to assess the association between antibiotic use and infection with, or worry about, COVID-19 in the US and Mexico. Results for Univariate and Multiple Logistic Regression Analysis for Antibiotic Use with Worry about COVID-19 (n=618) as a Predictor during the COVID-19 Pandemic. a=High school diploma or equivalent including GED, b=4-year, and c=Household income in previous year before taxes, d=Other includes multiple races, e= adjusted for only significant covariates: COVID-19 infection status, age, race, education, and country of residence. Acronyms: AIN=American Indian or Alaskan Native, MXN= Mexican peso, NHPI=Native Hawaiian or Pacific Islander, OR= odds ratio, SD=standard deviation, USD= US Dollars. Significant findings in bold. Methods An online cross-sectional survey with monetary incentive was deployed through Amazon Mechanical Turk to adults in the US and Mexico with enhanced recruitment through flyers at clinics and COVID-19 testing sites in the border regions of the US and Mexico (defined as within 100km of the border). Responses (n=981) were collected from 8/8/2020 to 8/4/2021. Logistic regression models were specified to model any (prescription and non-prescription) antibiotic use for “flu- or COVID-like” symptoms since March 2020. Predictors of interest were history of laboratory-confirmed SARS-CoV-2 infection and general worry about COVID-19. Models were adjusted for sex, age, ethnicity, race, education, income, insurance status, and country of residence. Results A total of 688 participants were used in the analysis, excluding 293 who did not answer the antibiotic use question. 29% reported already being infected and 78% reported being worried about COVID-19. After adjusting for significant covariates, those who reported a history of infection and worries about COVID-19 at the time of the survey had increased odds of using antibiotics for flu- or COVID-like symptoms: OR=26.7 (95% CI: 12.5-49.2) and OR=7.6 (95% CI: 3.6-16.4), respectively. Conversely, residing in Mexico decreased the odds of antibiotic use for those who had concerns about COVID-19: OR=0.3 (95% CI: 0.1-0.6) in adjusted models. Conclusion Findings suggest that worry about COVID-19 drove higher odds of antibiotic use, which could potentially be attributed to uncertainty, misinformation, and political turmoil during this time period. The relationships did not appear to be affected by sex, ethnicity, income, and insurance which suggests more research is needed. Disclosures All Authors: No reported disclosures
Background Considerable reductions in antimicrobial stewardship efforts have been attributed to the COVID-19 pandemic, especially among low-resourced healthcare facilities, such as long-term care settings. Our study objectives were to (1) assess the appropriateness of antibiotic prescriptions for urinary (UTI) and respiratory tract infections (RTI) using standardized infection definitions, known as the McGeer criteria, and (2) to determine whether the prescribing practices differed prior to and during the COVID-19 pandemic. Methods We employed a HIPPA-compliant REDCap data collection tool to abstract Electronic Medical Record data from an Arizona-based, Skilled Nursing Facility between March 2019 and January 2022. Clinical and microbiologic infection characteristics were abstracted to determine whether indications for antibiotic prescriptions met the McGeer criteria for UTI and RTI. The frequency and proportion of antibiotic prescriptions for suspected infections that did not meet McGeer criteria were compared for the time period prior to and during the COVID-19 pandemic. Results 388 total antibiotic events prescribed for UTI and RTI infections between March 2019 – January 2022 were analyzed (Figure 1). 61% (n=14) and 78% (n=154) of UTI prescriptions did not meet McGeer criteria prior to and during the COVID-19 pandemic, respectively. 70% (n=14) of RTI antibiotic prescriptions prior to the pandemic and 60% (n=89) of antibiotic events during the pandemic were not in accordance with McGeer criteria (Table 1) (Figure 2). Flow diagram to demonstrate Electronic Medical Record abstraction analysis inclusion criteria Note: a suspected infection was defined as a laboratory order (e.g., urine analysis, chest x-ray), or an antibiotic prescription Frequency and percent of UTI and RTI antibiotic prescriptions that did not meet McGeer criteria, prior to and during the COVID-19 pandemic Note: suspected infections from March 01, 2019 - January 25, 2020 are considered “pre-pandemic,” and January 26, 2020 – January 23, 2022 are considered “during pandemic” *The McGeer criteria differentiate infection definitions based on the presence or absence of an indwelling catheter Antibiotic prescription accordance with McGeer criteria from March 2019 – January 2022 Conclusion Despite consorted efforts to improve antimicrobial stewardship infrastructure, the majority of antibiotic prescribing for UTIs and RTIs prior to the pandemic did not meet McGeer criteria. This trend also persisted during the pandemic, indicating a need for increased stewardship practices that can operate concurrently with future public health threats. Disclosures All Authors: No reported disclosures
Background The colonic microbiome plays a critical role in resisting the ingrowth of pathogenic microbes like Clostridioides difficile (C. difficile). Disruption of the microbiome by antibiotics is known to cause antibiotic-associated diarrhea (AAD) and C. difficile infection (CDI). Outpatient parenteral antimicrobial therapy (OPAT) reduces hospital length of stay and exposure to healthcare-associated pathogens which may decrease the incidence of CDI. Previous studies that compared patients who received metronidazole for non-CDI indications with those who did not found a reduction in CDI among patients who received metronidazole. The aim was to study the incidence of AAD and CDI in the OPAT patient population and compare the incidence rate between patients who received oral metronidazole for non-CDI indications with those who did not. Methods We retrospectively reviewed a cohort from our facility's OPAT program. We included adult patients (18 years or older) discharged to home or skilled nursing facility (SNF) on OPAT over a 2-year time span, regardless of diagnosis. Pregnant patients, patients with active CDI before starting OPAT, and those who were receiving an associated CDI treatment were excluded. Antibiotic-associated diarrhea was defined as 3 or more loose or watery stools per day with negative CDI testing or spontaneous improvement after stopping antibiotics. Community-onset and healthcare facility–associated CDI (CO-HCFA CDI) was defined as 3 or more watery stools per day with a positive stool C. difficile diagnostic test in the community or within the first 3 days of readmission, provided the diagnosis was made less than 4 weeks since discharge from a healthcare facility. Demographics of Patients Discharged on OPAT. Patients selected between June 1, 2018 and June 2020, grouped by whether or not they developed Clostridioides difficile infection (CDI). SD= standard deviation; Q1= 1st quartile; Q3= 3rd quartile. Results Of the 617 charts that met inclusion criteria, 31 had AAD and 3 had CO-HCFA CDI. Incidence of CO-HCFA CDI was < 1%; < 1 per 1000 person-day and incidence of AAD was 5.02%. The protective role of metronidazole could not be studied due to the rarity of CDI in this study. Patients with positive CDI after initiation of OPAT and associated characteristics. Conclusion Although our study was not able to answer our initial question when comparing the effect of metronidazole within OPAT groups and rates of CDI, our data is promising for showing low rates of CDI in patients receiving OPAT. This study demonstrates the putative benefits of OPAT with reduced CDI incidence regardless of use of anti-CDI drugs. Disclosures Tirdad Zangeneh, DO, AiCuris: Grant/Research Support
Background Epetraborole (EBO), an orally available bacterial leucyl transfer RNA synthetase inhibitor with potent activity against nontuberculous mycobacteria, is in clinical development for treatment-refractory MAC lung disease. The objective of the study was to evaluate EBO PK in adult subjects with varying degrees of renal impairment (RI) including end stage renal disease (ESRD) with intermittent hemodialysis (IHD). Methods Open-label, single-dose EBO 500 mg PO was given to subjects in 5 cohorts: normal renal function, mild, moderate, and severe RI, and ESRD-IHD (Table); ESRD subjects received a second 500 mg dose on Day 5 approximately 1 hour before receiving IHD. EBO and its inactive major metabolite (M3) concentrations in plasma, urine and dialysate were measured by validated LC-MS/MS methods. Plasma PK parameters were determined using non-compartmental methods and compared among cohorts using analysis of variance (ANOVA). Standard clinical and laboratory evaluations and treatment-emergent adverse events (TEAEs) were assessed. Results 40 subjects were enrolled (8/cohort). Subjects with RI did not exhibit quantitatively distinct EBO plasma PK profiles compared to those with normal renal function; AUC mean ratios were 110-140% in subjects with RI, and the mean ratios of maximum observed concentration (Cmax ) values did not exceed 116% (Table). The elimination half-life (t1/2) increased slightly from 9.3 to 11.0 h in ESRD subjects, and clearance decreased by about 30%. Renal elimination was not a major route of excretion (∼15% of dose over 72 h) for EBO, with mean renal clearance ranging from 4.24 L/h to 1.04 L/h. Metabolite M3 AUC increased 4-fold in subjects with severe RI, and t1/2 increased from 20 to 32 h. EBO was well tolerated; 7 subjects (17.5%) experienced at least 1 TEAE (11 events), all mild in severity except 1 moderately-severe TEAE of worsening anemia. There were no severe or serious TEAEs. Conclusion Minimal increases in plasma EBO exposures and similar t1/2 values were observed in subjects with varying degrees of RI, including ESRD-IHD. Single 500 mg doses of EBO were well tolerated in each RI cohort. Overall, these data suggest that no dose adjustment of EBO is needed in subjects with any degree of RI. Disclosures All Authors: No reported disclosures
Background Oseltamivir is the most common antiviral prescribed to treat influenza. There are limited data about oseltamivir receipt in uncomplicated influenza, including frequency of early discontinuation of oseltamivir. Methods Individuals who tested positive for influenza were identified from outpatient clinics, emergency departments, or surveillance testing at seven sites in the United States from December 2021–March 2023. Index cases and their household contacts (HHC) enrolled ≤6 days after the first illness in the household, completed symptom/medication logs, and collected nasal swabs for influenza testing daily for 10 days. Oseltamivir receipt was classified by daily logs (ever/never receipt, and duration of use: early discontinuation [1–2 days], 3–4 days, or ≥5 days) among eligible persons (Methods 1). Addresses linked to the 2020 Social Vulnerability Index by census tract. Odds of oseltamivir receipt were estimated using binomial regression with household clustering. Methods upload 1: Analytic flow diagram for assessment of use and discontinuation of oseltamivir in household settings, United States 2021-22 and 2022-23 influenza seasons. Discontinuation was defined as use for 1-2 days, compared to use for 3-4 or ≥5 days. If the participant reported oseltamivir on the first or last day of follow-up and did not report use for at least 3 days, the duration of oseltamivir usage was considered “censored” and discontinuation was not described. Results Of 737 household members, 142 individuals (90/235 index cases, 40/284 infected HHC, 12/218 uninfected HHC) reported oseltamivir. Oseltamivir receipt was more common among those recruited in 2022–23 vs. 2021–22 and by participants who self-reported pre-existing conditions vs. those who did not. Oseltamivir receipt was less common among children 5–11 vs. adults 18–49 years (Results 1). Individuals from the most vulnerable census tracts were least likely to receive oseltamivir (Results 2). Among symptomatic infected persons, oseltamivir was typically initiated within 2 days of symptoms (76%). Of 126 individuals whose duration of oseltamivir was not censored by the start or end of follow-up, 19% reported receipt on only 1-2 days, 17% for 3-4 days, and 63% for ≥5 days. Compared to those who reported ≥5 days of oseltamivir receipt, people who took oseltamivir for 1–2 days had similar reported symptoms, including gastrointestinal symptoms, on the first day of illness and first day of oseltamivir (Results 3). Results upload 1: Characteristics of individuals who did and did not report use of oseltamivir among individuals in households with a known influenza case, United States, 2021-22 and 2023-24 influenza seasons. Results Upload 2. Social vulnerability of individuals who did and did not report use of oseltamivir among individuals in geocoded households with a known influenza case, United States, 2021-22 and 2023-24 influenza seasons. Conclusion Over a third of index cases received oseltamivir, and receipt differed by age and social vulnerability status. In this analysis, early discontinuation was not associated with initial symptom burden or symptoms, including gastrointestinal side-effects, after initiating oseltamivir. Disclosures Edward Belongia, MD, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support
Background It is believed that as much as 80% of common infections are spread by the hands. Touching surfaces (fomites) contaminated with infectious microorganisms results in their transfer to the hands (fingers). Subsequent touching of the mouth, nose, or skin can result in their transmission. Disinfection of surfaces has been found to reduce such transmission. Unfortunately, highly touched surfaces (door knobs, escalator hand rails, buttons, etc.) can quickly become re-contaminated. Disinfectants which leave a residual can act as an additional barrier in between regular disinfection of surfaces, reducing the risk of transmission. The goal of this study was to assess the reduction in the transfer of bacteria and viruses from surfaces treated with a quaternary ammonium based disinfectant (Actizone F5® spray) that leaves a residual disinfectant capability for more than 24 hours. Methods Stainless steel and plastic coupons were treated with Actizone F5® spray and allowed to dry for 24 hours. The test microorganisms were then added to the surfaces and after 2, 5 or 10 minutes, the surface was touched with a finger. The number of microorganisms transferred to the finger was then quantified. The experiment was repeated with untreated coupons as a control. Results The degree of finger transfer was reduced by more than 99.99% by the treated coupons for Salmonella Typhimurium, MRSA, Acinetobacter baumannii, and Escherichia coli. Candida auris was reduced by > 99.99% on the stainless steel and ∼99.6% for the plastic coupons. Pseudomonas aeruginosa and antibiotic-resistant Klebsiella pneumoniae (CRE) were reduced by ∼98%. The transfer of human coronavirus 229E was reduced by 98.7% from the stainless steel surfaces. Conclusion Transfer of all the test microorganisms was reduced by the treated surfaces even after 24 hours, demonstrating residual activity. The transfer for some of the microorganisms was less from the ABS plastic than from the stainless steel surfaces. This may have been due to the attachment or spreading of the product on this type of surface, resulting in a less even coating. A longer contact time may result in significant reduction of these microorganisms. The relative humidity and short exposure time to the treated surfaces used in this study should probably be considered a worst case scenario. Disclosures Charles P. Gerba, PhD, □ Corning: Advisor/Consultant| □ Reckitt: Advisor/Consultant| □ Reckitt: Grant/Research Support| □ Savory: Grant/Research Support
Background Inappropriate use of antibiotics is a driver of antimicrobial resistance globally. The US-Mexico border region is medically underserved and socially vulnerable. This study aimed to assess knowledge, attitudes and practices (KAP) regarding antibiotic use during the COVID-19 pandemic among US residents, and to compare KAPs for those living in border versus non-border regions. Methods A cross-sectional online survey with monetary incentive was deployed to a sample of adults ≥18 years old through Amazon Mechanical Turk with enriched sampling in the US-Mexico border region (defined as residency within 100 km of the border). Surveys were completed from 8/8/2020 to 8/4/2021. KAP questions were aligned with published tools and COVID-19-specific questions were added. Of 602 respondents from the US, 590 (98%) had complete KAP data and were included in this analysis. Chi-square tests were performed to examine the association between KAPs related to antibiotic use and border residency status. Results Overall, for 6 of 8 knowledge items about antibiotic use, fewer than 50% of survey respondents answered correctly (Table 1). 50% of border residents versus 71% of non-border residents (p< 0.01) correctly agreed that “antibiotics should never be saved for the next time you get sick.” Conversely 44% of border residents, versus 31% of non-border residents (p=0.03), correctly disagreed with the statement “when I have a cold, I should take antibiotics to avoid getting a more serious illness.” There was no difference in knowledge about causes of antibiotic resistance by region of residency. Overall, 40% of respondents believed that their personal antibiotic use did not affect antibiotic resistance (Table 2). Finally 37% all respondents said they tried to obtain antibiotics, and 31% tried to obtain chloroquine or hydroxychloroquine, because of concerns about COVID-19 with no difference by region of residency. Table 1: Number and percentage of survey respondents answering correctly to knowledge questions regarding antibiotic use, stratified by residency within 100 kilometers of the US-Mexico border. Table 2: Number and percentage of survey respondants with attitudes consistent with antibiotic stewardship among United States (US) residents, stratified by residency within 100 kilometers of the US-Mexico border. Conclusion KAP findings from this survey suggest that knowledge about antibiotic use is low regardless of proximity to the US-Mexico border. Further, practices related to antibiotic and chloroquine or hydroxychloroquine seeking in the context of COVID-19 suggest a role for public-facing information campaigns regarding medication seeking during public health emergencies. Disclosures All Authors: No reported disclosures
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
For the past 30 years, the Brazilian Black movement has devoted efforts to unearthing the accomplishments, achievements, and history of hidden Black people in Brazilian history. In response to Black mobilization, the Brazilian government mandated in 2003 that schools across the country teach African and Afro-Brazilian history and culture. In this context, some Black activists are focused on how the erasure of Blackness in Brazilian-formed texts has shaped how Afro-Brazilians understand and think about their Black heritage. In this chapter, I combine Michel de Certeau’s (1984) notion of reading as poaching with the Brazilian poet and playwright Oswald de Andrade’s concept of cultural cannibalism (anthropophagy)—with its subversive potential and tactics of (re)appropriation—to examine Black activists’ use of critical reading to probe, reclaim, and reimagine that which was whited out from Brazilian history and Afro-Brazilian identity. Their use of critical reading provides a way to not only visualize the impact of colonization but share a greater story of Black resilience through time.
Integrated hydrologic models can simulate coupled surface and subsurface processes but are computationally expensive to run at high resolutions over large domains. Here we develop a novel deep learning model to emulate continental-scale subsurface flows simulated by the integrated ParFlow-CLM model. We compare convolutional neural networks like ResNet and UNet run autoregressively against our novel architecture called the Forced SpatioTemporal RNN (FSTR). The FSTR model incorporates separate encoding of initial conditions, static parameters, and meteorological forcings, which are fused in a recurrent loop to produce spatiotemporal predictions of groundwater. We evaluate the model architectures on their ability to reproduce 4D pressure heads, water table depths, and surface soil moisture over the contiguous US at 1km resolution and daily time steps over the course of a full water year. The FSTR model shows superior performance to the baseline models, producing stable simulations that capture both seasonal and event-scale dynamics across a wide array of hydroclimatic regimes. The emulators provide over 1000x speedup compared to the original physical model, which will enable new capabilities like uncertainty quantification and data assimilation for integrated hydrologic modeling that were not previously possible. Our results demonstrate the promise of using specialized deep learning architectures like FSTR for emulating complex process-based models without sacrificing fidelity.
Programmable photonic integrated circuits (PICs) are emerging as powerful tools for control of light, with applications in quantum information processing, optical range finding, and artificial intelligence. Low-power implementations of these PICs involve micromechanical structures driven capacitively or piezoelectrically but are often limited in modulation bandwidth by mechanical resonances and high operating voltages. Here we introduce a synchronous, micromechanically resonant design architecture for programmable PICs and a proof-of-principle 1×8 photonic switch using piezoelectric optical phase shifters. Our design purposefully exploits high-frequency mechanical resonances and optically broadband components for larger modulation responses on the order of the mechanical quality factor Qm while maintaining fast switching speeds. We experimentally show switching cycles of all 8 channels spaced by approximately 11 ns and operating at 4.6 dB average modulation enhancement. Future advances in micromechanical devices with high Qm, which can exceed 10000, should enable an improved series of low-voltage and high-speed programmable PICs.
During the recent pandemic of COVID-19 (SARS-CoV-2), influential public health agencies such as the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) have favored the view that SARS CoV-2 spreads predominantly via droplets. Many experts in aerobiology have openly opposed that stance, forcing a vigorous debate on the topic. In this review, we discuss the various proposed modes of viral transmission, stressing the interdependencies between droplet, aerosol, and fomite spread. Relative humidity and temperature prevailing determine the rates at which respiratory aerosols and droplets emitted from an expiratory event (sneezing, coughing, etc .) evaporate to form smaller droplets or aerosols, or experience hygroscopic growth. Gravitational settling of droplets may result in contamination of environmental surfaces (fomites). Depending upon human, animal and mechanical activities in the occupied space indoors, viruses deposited on environmental surfaces may be re-aerosolized (re-suspended) to contribute to aerosols, and can be conveyed on aerial particulate matter such as dust and allergens. The transmission of respiratory viruses may then best be viewed as resulting from dynamic virus spread from infected individuals to susceptible individuals by various physical states of active respiratory emissions, instead of the current paradigm that emphasizes separate dissemination by respiratory droplets, aerosols or by contaminated fomites. To achieve the optimum outcome in terms of risk mitigation and infection prevention and control (IPAC) during seasonal infection peaks, outbreaks, and pandemics, this holistic view emphasizes the importance of dealing with all interdependent transmission modalities, rather than focusing on one modality.
Approximately 50% of Americans have hypertension which significantly increases the risk of heart failure. In response to increased peripheral resistance in hypertension, intensified mechanical stretch in the myocardium induces cardiomyocyte hypertrophy and fibroblast activation to withstand increased pressure overload. This changes the structure and function of the heart leading to pathological cardiac remodeling and eventual progression to heart failure. In the presence of hypertensive stimuli, cardiac fibroblasts activate and differentiate to myofibroblast phenotype capable of enhanced extracellular matrix secretion in coordination with other cell types, mainly cardiomyocytes. Both systemic and local renin angiotensin/aldosterone system activation leads to increased angiotensin II stimulation of fibroblasts. Angiotensin II directly activates fibrotic signaling such as transforming growth factor /SMAD and mitogen activated protein kinase (MAPK) signaling to produce extracellular matrix comprised of collagens and matricellular proteins. With the advent of single cell RNA sequencing techniques, heterogeneity in fibroblast populations has been identified in the left ventricle in models of hypertension and pressure overload. The various clusters of fibroblasts reveal a range of phenotypes and activation states. Select antihypertensive therapies have been shown to be effective in limiting fibrosis with some having direct actions on cardiac fibroblasts. The present review will focus on the fibroblast-specific changes that occur in response to hypertension and pressure overload, the knowledge gained from single cell analyses, and the effect of antihypertensive therapies. Understanding the dynamics of hypertensive fibroblast population and their similarities and differences by sex is crucial for the advent of new targets and personalized medicine.
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