Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students.

Background: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implementation in a college population. Methods: We enrolled an annual cohort of first-year undergraduates who completed daily electronic symptom diaries to identify index cases (ICs) with respiratory illness. Investigators then selected 5-10 potentially exposed, asymptomatic close contacts (CCs) who were geographically co-located to follow for infections. Symptoms and nasopharyngeal samples were collected for 5 days. Logistic regression model-based predictions for proportions of self-reported illness were compared graphically for the whole cohort sampling group and the CC group. Results: We enrolled 1379 participants between 2009 and 2015, including 288 ICs and 882 CCs. The median number of CCs per IC was 6 (interquartile range, 3-8). Among the 882 CCs, 111 (13%) developed acute respiratory illnesses. Viral etiology testing in 246 ICs (85%) and 719 CCs (82%) identified a pathogen in 57% of ICs and 15% of CCs. Among those with detectable virus, rhinovirus was the most common (IC: 18%; CC: 6%) followed by coxsackievirus/echovirus (IC: 11%; CC: 4%). Among 106 CCs with a detected virus, only 18% had the same virus as their associated IC. Graphically, CCs did not have a higher frequency of self-reported illness relative to the whole cohort sampling group. Conclusions: Establishing clusters by geographic proximity did not enrich for cases of viral transmission, suggesting that ICSS may be a less effective strategy to detect spread of respiratory infection.

Interfacility Transfer Outcomes Among Children With Complex Chronic Conditions: Associations Between Patient-Level and Hospital-Level Factors and Transfer Outcomes.

OBJECTIVES: Determine patient- and referring hospital-level predictors of transfer outcomes among children with 1 or more complex chronic conditions (CCCs) transferred to a large academic medical center. METHODS: We conducted a retrospective chart review of 2063 pediatric inpatient admissions from 2017 to 2019 with at least 1 CCC defined by International Classification of Diseases, Tenth Revision codes. Charts were excluded if patients were admitted via any route other than transfer from a referring hospital's emergency department or inpatient ward. Patient-level factors were race/ethnicity, payer, and area median income. Hospital-level factors included the clinician type initiating transfer and whether the referring-hospital had an inpatient pediatric ward. Transfer outcomes were rapid response within 24 hours of admission, Pediatric Early Warning Score at admission, and hours to arrival. Regression analyses adjusted for age were used to determine association between patient- and hospital-level predictors with transfer outcomes. RESULTS: There were no significant associations between patient-level predictors and transfer outcomes. Hospital-level adjusted analyses indicated that transfers from hospitals without inpatient pediatrics wards had lower odds of ICU admission during hospitalization (odds ratio, 0.46; 95% confidence interval, 0.22-0.97) and shorter transfer times (ß-coefficient, -2.54; 95% CI, -3.60 to -1.49) versus transfers from hospitals with inpatient pediatrics wards. There were no significant associations between clinician type and transfer outcomes. CONCLUSIONS: For pediatric patients with CCCs, patient-level predictors were not associated with clinical outcomes. Transfers from hospitals without inpatient pediatric wards were less likely to require ICU admission and had shorter interfacility transfer times compared with those from hospitals with inpatient pediatrics wards.

Evaluation of SARS-CoV-2 identification methods through surveillance of companion animals in SARS-CoV-2-positive homes in North Carolina, March to December 2020.

We collected oral and/or rectal swabs and serum from dogs and cats living in homes with SARS-CoV-2-PCR-positive persons for SARS-CoV-2 PCR and serology testing. Pre-COVID-19 serum samples from dogs and cats were used as negative controls, and samples were tested in duplicate at different timepoints. Raw ELISA results scrutinized relative to known negative samples suggested that cut-offs for IgG seropositivity may require adjustment relative to previously proposed values, while proposed cut-offs for IgM require more extensive validation. A small number of pet dogs (2/43, 4.7%) and one cat (1/21, 4.8%) were positive for SARS-CoV-2 RNA, and 28.6 and 37.5% of cats and dogs were positive for anti-SARS-CoV-2 IgG, respectively.

In-Person Instruction and Educational Outcomes of K-8 Students During the COVID-19 Pandemic.

OBJECTIVES: Quantify the relationship between district policy permitting in-person instruction and educational outcomes during the 2020 to 2021 academic year for kindergarten through eighth grade students. METHODS: An ecological, repeated cross-sectional analysis of grade-level proficiency of students enrolled in public school districts in North Carolina (n = 115 school districts) was conducted. Univariate and multivariate analyses were performed to evaluate the association between the proportion of the school year a district spent in-person and 2020 to 2021 end-of-year student proficiency in the district. We then fit a multivariable linear regression model, weighted by district size, and adjusted for district-level 2018 to 2019 proficiency and district-level factors (rural or urban, area deprivation). RESULTS: Compared to 2018 to 2019, there was a 12.1% decrease (95% confidence interval [CI]: 16.8-19.3) in mathematics and an 18.1% decrease (95% CI: 10.8-13.4) in reading proficiency across the state at the end of 2020 to 2021. Compared to a district that remained entirely remote for the 2020 to 2021 school year, a district offering full in-person instruction had 12% (95% CI: 11%-12.9%) and 4.1% (95% CI: 3.5%-4.8%) more students achieve grade-level proficiency in mathematics and reading, respectively. In-person instruction was associated with greater increases in mathematics proficiency than reading, and greater increases in elementary-level students' proficiency than middle school-level. CONCLUSIONS: The proportion of students achieving grade-level proficiency in 2020 to 2021 fell below prepandemic levels at each evaluated time point in the academic year. Increased time spent in-person by a school district was associated with an increased proportion of students achieving grade-level end-of-grade proficiency in both mathematics and reading.

Common Data Element Collection in Underserved School Communities: Challenges and Recommendations.

OBJECTIVES: To provide recommendations for future common data element (CDE) development and collection that increases community partnership, harmonizes data interpretation, and continues to reduce barriers of mistrust between researchers and underserved communities. METHODS: We conducted a cross-sectional qualitative and quantitative evaluation of mandatory CDE collection among Rapid Acceleration of Diagnostics-Underserved Populations Return to School project teams with various priority populations and geographic locations in the United States to: (1) compare racial and ethnic representativeness of participants completing CDE questions relative to participants enrolled in project-level testing initiatives and (2) identify the amount of missing CDE data by CDE domain. Additionally, we conducted analyses stratified by aim-level variables characterizing CDE collection strategies. RESULTS: There were 15 study aims reported across the 13 participating Return to School projects, of which 7 (47%) were structured so that CDEs were fully uncoupled from the testing initiative, 4 (27%) were fully coupled, and 4 (27%) were partially coupled. In 9 (60%) study aims, participant incentives were provided in the form of monetary compensation. Most project teams modified CDE questions (8/13; 62%) to fit their population. Across all 13 projects, there was minimal variation in the racial and ethnic distribution of CDE survey participants from those who participated in testing; however, fully uncoupling CDE questions from testing increased the proportion of Black and Hispanic individuals participating in both initiatives. CONCLUSIONS: Collaboration with underrepresented populations from the early study design process may improve interest and participation in CDE collection efforts.

Test-to-Stay in Kindergarten Through 12th Grade Schools After Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Test-to-stay (TTS) is a strategy to limit school exclusion following an exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the use of TTS within universally masked kindergarten through 12th grade (K-12) school settings following household SARS-CoV-2 exposure. METHODS: Three hundred twenty-two participants were enrolled. Serial rapid antigen testing was performed up to 15 days post-exposure. Analysis-eligible participants completed the 15-day testing protocol, tested positive any time during the testing window, or received a negative test on or after day 9. Primary outcomes included within-school tertiary attack rate (TAR) (test positivity among close contacts of positive TTS participants), and school days saved among TTS participants. RESULTS: Seventy-three of 265 analysis-eligible participants tested positive for SARS-CoV-2 (secondary attack rate of 28% [95% CI: 16-63%]). Among 77 within-school close contacts, 2 were positive (TAR = 3% [95% CI: 1-5%]). Participant absences were limited to 338 days, resulting in 82% of 1849 school days saved. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: TTS facilitates continued in-person learning and can greatly reduce the number of missed school days. CONCLUSIONS: Within universally masked K-12 schools, TTS is a safe alternative to school exclusion following household SARS-CoV-2 exposure.

SARS-CoV-2 Screening Testing Programs for Safe In-person Learning in K-12 Schools.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening testing is a recommended mitigation strategy for schools, although few descriptions of program implementation are available. METHODS: Kindergarten through 12th grade (K-12) students and staff practicing universal masking during the delta and omicron variant waves from five schools in Durham, North Carolina and eight schools in Kansas City, Missouri participated; Durham's program was structured as a public health initiative facilitated by school staff, and Kansas City's as a research study facilitated by a research team. Tests included school-based rapid antigen or polymerase chain reaction testing, at-home rapid antigen testing, and off-site nucleic acid amplification testing. RESULTS: We performed nearly 5700 screening tests on more than 1600 K-12 school students and staff members. The total cost for the Durham testing program in 5 public charter K-12 schools, each with 500-1000 students, was $246 587 and approximately 752 h per semester; cost per test was $70 and cost per positive result was $7076. The total cost for the Kansas City program in eight public K-12 schools was $292 591 and required approximately 537 h in personnel time for school-based testing; cost per test was $132 and cost per positive result was $4818. SARS-CoV-2 positivity rates were generally lower (0-16.16%) than rates in the community (2.7-36.47%) throughout all testing weeks. CONCLUSIONS AND RELEVANCE: Voluntary screening testing programs in K-12 schools are costly and rarely detect asymptomatic positive persons, particularly in universally masked settings. CLINICAL TRIAL REGISTRATION: NCT04831866.

Effects of Structural Variations on Antibacterial Properties for Conjugated Diynes Generated through Glaser Hay Couplings.

Antibiotic resistance is a growing problem facing global societies today. Many new antibiotics are derivatized versions of already existing antibiotics, which allows for antibiotic resistance to arise. To combat this issue, new antibiotics with different core structures need to be elucidated. Asymmetrical polyacetylenes have been isolated from natural products and they have previously been demonstrated to exhibit antimicrobial and antibacterial activity; however, their synthetic preparation has not made them easily amenable to rapid derivatization for SAR studies. Using a combination of solution and solid-supported chemistries, an array of diynes inspired by a known natural product were prepared and assessed for antibacterial activity. Ultimately, several compounds were identified with improved activity in bacterial viability assays. Moreover, some compounds were discovered that displayed a degree of specificity for E. coli over P. fluorescens and vice versa. These new compounds show promise, and further investigation is needed to pinpoint the specific structural components that elicit biological activity.

Test-to-Stay After SARS-CoV-2 Exposure: A Mitigation Strategy for Optionally Masked K-12 Schools.

OBJECTIVES: We evaluated the impact of a test-to-stay (TTS) program on within-school transmission and missed school days in optionally masked kindergarten through 12th grade schools during a period of high community severe acute respiratory syndrome coronavirus 2 transmission. METHODS: Close contacts of those with confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for enrollment in the TTS program if exposure to a nonhousehold contact occurred between November 11, 2021 and January 28, 2022. Consented participants avoided school exclusion if they remained asymptomatic and rapid antigen testing at prespecified intervals remained negative. Primary outcomes included within-school tertiary attack rate (test positivity among close contacts of positive TTS participants) and school days saved among TTS participants. We estimated the number of additional school-acquired cases resulting from TTS and eliminating school exclusion. RESULTS: A total of 1675 participants tested positive or received at least 1 negative test between days 5 and 7 and completed follow-up; 92% were students and 91% were exposed to an unmasked primary case. We identified 201 positive cases. We observed a tertiary attack rate of 10% (95% confidence interval: 6%-19%), and 7272 (89%) of potentially missed days were saved through TTS implementation. We estimated 1 additional school-acquired case for every 21 TTS participants remaining in school buildings during the entire study period. CONCLUSIONS: Even in the setting of high community transmission, a TTS strategy resulted in substantial reduction in missed school days in optionally masked schools.

Telehealth for the Longitudinal Management of Chronic Conditions: Systematic Review.

BACKGROUND: Extensive literature support telehealth as a supplement or adjunct to in-person care for the management of chronic conditions such as congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM). Evidence is needed to support the use of telehealth as an equivalent and equitable replacement for in-person care and to assess potential adverse effects. OBJECTIVE: We conducted a systematic review to address the following question: among adults, what is the effect of synchronous telehealth (real-time response among individuals via phone or phone and video) compared with in-person care (or compared with phone, if synchronous video care) for chronic management of CHF, chronic obstructive pulmonary disease, and T2DM on key disease-specific clinical outcomes and health care use? METHODS: We followed systematic review methodologies and searched two databases (MEDLINE and Embase). We included randomized or quasi-experimental studies that evaluated the effect of synchronously delivered telehealth for relevant chronic conditions that occurred over ≥2 encounters and in which some or all in-person care was supplanted by care delivered via phone or video. We assessed the bias using the Cochrane Effective Practice and Organization of Care risk of bias (ROB) tool and the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation. We described the findings narratively and did not conduct meta-analysis owing to the small number of studies and the conceptual heterogeneity of the identified interventions. RESULTS: We identified 8662 studies, and 129 (1.49%) were reviewed at the full-text stage. In total, 3.9% (5/129) of the articles were retained for data extraction, all of which (5/5, 100%) were randomized controlled trials. The CHF study (1/5, 20%) was found to have high ROB and randomized patients (n=210) to receive quarterly automated asynchronous web-based review and follow-up of telemetry data versus synchronous personal follow-up (in-person vs phone-based) for 1 year. A 3-way comparison across study arms found no significant differences in clinical outcomes. Overall, 80% (4/5) of the studies (n=466) evaluated synchronous care for patients with T2DM (ROB was judged to be low for 2, 50% of studies and high for 2, 50% of studies). In total, 20% (1/5) of the studies were adequately powered to assess the difference in glycosylated hemoglobin level between groups; however, no significant difference was found. Intervention design varied greatly from remote monitoring of blood glucose combined with video versus in-person visits to an endocrinology clinic to a brief, 3-week remote intervention to stabilize uncontrolled diabetes. No articles were identified for chronic obstructive pulmonary disease. CONCLUSIONS: This review found few studies with a variety of designs and interventions that used telehealth as a replacement for in-person care. Future research should consider including observational studies and studies on additional highly prevalent chronic diseases.

Test-to-Stay After Exposure to SARS-CoV-2 in K-12 Schools.

OBJECTIVES: We evaluated the safety and efficacy of a test-to-stay program for unvaccinated students and staff who experienced an unmasked, in-school exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serial testing instead of quarantine was offered to asymptomatic contacts. We measured secondary and tertiary transmission rates within participating schools and in-school days preserved for participants. METHODS: Participating staff or students from universally masked districts in North Carolina underwent rapid antigen testing at set intervals up to 7 days after known exposure. Collected data included location or setting of exposure, participant symptoms, and school absences up to 14 days after enrollment. Outcomes included tertiary transmission, secondary transmission, and school days saved among test-to-stay participants. A prespecified interim safety analysis occurred after 1 month of enrollment. RESULTS: We enrolled 367 participants and completed 14-day follow-up on all participants for this analysis. Nearly all (215 of 238, 90%) exposure encounters involved an unmasked index case and an unmasked close contact, with most (353 of 366, 96%) occurring indoors, during lunch (137 of 357, 39%) or athletics (45 of 357, 13%). Secondary attack rate was 1.7% (95% confidence interval: 0.6%-4.7%) based on 883 SARS-CoV-2 serial rapid antigen tests with results from 357 participants; no tertiary cases were identified, and 1628 (92%) school days were saved through test-to-stay program implementation out of 1764 days potentially missed. CONCLUSION: After unmasked in-school exposure to SARS-CoV-2, even in a mostly unvaccinated population, a test-to-stay strategy is a safe alternative to quarantine.

Primary Care Engagement Among Individuals with Experiences of Homelessness and Serious Mental Illness: an Evidence Map.

BACKGROUND: Experiences of homelessness and serious mental illness (SMI) negatively impact health and receipt of healthcare. Interventions that promote the use of primary care services for people with both SMI and homelessness may improve health outcomes, but this literature has not been evaluated systematically. This evidence map examines the breadth of literature to describe what intervention strategies have been studied for this population, elements of primary care integration with other services used, and the level of intervention complexity to highlight gaps for future intervention research and program development. METHODS: We followed an a priori protocol developed in collaboration with clinical stakeholders. We systematically searched the published literature to identify interventions for adults with homelessness who also had SMI. We excluded case reports, editorials, letters, and conference abstracts. Data abstraction methods followed standard practice. Data were categorized into intervention strategies and primary care integration strategies. Then we applied the Complexity Assessment Tool for Systematic Reviews (iCAT_SR) to characterize intervention complexity. RESULTS: Twenty-two articles met our inclusion criteria evaluating 15 unique interventions to promote engagement in primary care for adults with experiences of homelessness and SMI. Study designs varied widely from randomized controlled trials and cohort studies to single-site program evaluations. Intervention strategies varied across studies but primarily targeted patients directly (e.g., health education, evidence-based interactions such as motivational interviewing) with fewer strategies employed at the clinic (e.g., employee training, multidisciplinary teams) or system levels (e.g., data sharing). We identified elements of primary care integration, including referral strategies, co-location, and interdisciplinary care planning. Interventions displayed notable complexity around the number of intervention components, interaction between intervention components, and extent to which interventions were tailored to specific patient populations. DISCUSSION: We identified and categorized elements used in various combinations to address the primary care needs of individuals with experiences of homeless and SMI.

Photoregulation of PRMT-1 Using a Photolabile Non-Canonical Amino Acid.

Protein methyltransferases are vital to the epigenetic modification of gene expression. Thus, obtaining a better understanding of and control over the regulation of these crucial proteins has significant implications for the study and treatment of numerous diseases. One ideal mechanism of protein regulation is the specific installation of a photolabile-protecting group through the use of photocaged non-canonical amino acids. Consequently, PRMT1 was caged at a key tyrosine residue with a nitrobenzyl-protected Schultz amino acid to modulate protein function. Subsequent irradiation with UV light removes the caging group and restores normal methyltransferase activity, facilitating the spatial and temporal control of PRMT1 activity. Ultimately, this caged PRMT1 affords the ability to better understand the protein's mechanism of action and potentially regulate the epigenetic impacts of this vital protein.

Application of the Solid-Supported Glaser-Hay Reaction to Natural Product Synthesis.

The Glaser-Hay coupling of terminal alkynes is a useful synthetic reaction for the preparation of polyynes; however, chemoselectivity issues have precluded its widespread utilization. Conducting the reaction on a solid-support provides a mechanism to alleviate the chemoselectivity issues and provide products in high purities and yields. Moreover, the polyyne core is a key component to several natural products. Herein, we describe the application of a solid-supported Glaser-Hay reaction in the preparation of several natural products. These compounds were then screened for antibacterial activity, illustrating the utility of the methodology.

Site-specific incorporation of a fluorescent terphenyl unnatural amino acid.

The site-specific incorporation of unnatural amino acids into proteins has a wide range of biological implications. Of particular interest is the incorporation of fluorescent probes as a mechanism to track protein function, transport, and folding. Thus, the development of a novel system for the incorporation of new fluorescent unnatural amino acids has significant utility. Specifically, we have elucidated an aminoacyl-tRNA synthetase capable of recognizing a terphenyl UAA derivative, and charging a cognate tRNA with this amino acid for protein incorporation. Moreover, we have successfully incorporated this fluorescent UAA into GFP at several key residues, demonstrating a novel means to modulate fluorescence within the protein.