Implementation of a novel program to support colorectal cancer screening in a community health center consortium before and after the onset of COVID-19: a qualitative study of stakeholders' perspectives.

BACKGROUND: In 2017, the San Francisco Cancer Initiative (SF CAN) established the Colorectal Cancer (CRC) Screening Program to provide technical assistance and financial support to improve CRC screening processes, and outcomes in a consortium of community health centers (CHCs) serving low-income communities in San Francisco. The purpose of this study was twofold: to evaluate the perceived influence of the support provided by the CRC Screening Program's Task Force on CRC screening processes and outcomes in these settings and to identify facilitators and barriers to SF CAN-supported CRC screening activities before and after the onset of the COVID-19 pandemic. METHODS: Semi-structured key informant interviews were conducted with consortium leaders, medical directors, quality improvement team members, and clinic screening champions. Interviews were audio-recorded, professionally transcribed, and analyzed for themes. The Consolidated Framework for Implementation Research (CFIR) was used to develop the interview questions and organize the analysis. RESULTS: Twenty-two participants were interviewed. The most commonly cited facilitators of improved screening processes included the expertise, funding, screening resources, regular follow-up, and sustained engagement with clinic leaders provided by the task force. The most salient barriers identified were patient characteristics, such as housing instability; staffing challenges, such as being understaffed and experiencing high staff turnover; and clinic-level challenges, such as lack of ability to implement and sustain formalized patient navigation strategies, and changes in clinic priorities due to the COVID-19 pandemic and other competing health care priorities. CONCLUSIONS: Implementing CRC screening programs in a consortium of CHCs is inherently challenging. Technical assistance from the Task Force was viewed positively and helped to mitigate challenges both before and during the pandemic. Future research should explore opportunities to increase the robustness of technical assistance offered by groups such as SF CAN to support cancer screening activities in CHCs serving low-income communities.

New Injury Patterns in Pediatric Supracondylar Fractures During COVID-19: Beds Are the New Monkey Bars.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic drastically altered children's activity patterns. Our goal was to investigate how COVID-19 affected demographics, injury characteristics, treatment patterns, follow-up, and outcomes in pediatric supracondylar humerus (SCH) fractures. METHODS: This was an Institutional Review Board-approved retrospective analysis of patients undergoing surgery for a SCH fracture from May to November 2019 (pre-COVID-19) and from May to November 2020 (during COVID-19) at 2 tertiary children's hospitals. Demographic information, injury characteristics, hospital course, and follow-up data were collected and compared. RESULTS: SCH fractures decreased by >50% from 2019 (149) to 2020 (72). Children in the 2020 cohort were younger (mean 5.2 y old) compared with 2019 (6.0 y old) ( P =0.019). Mechanism of injury was significantly different in 2020 ( P <0.001), as the proportion of trampoline and furniture fractures increased from 8% and 17% to 15% and 33%, respectively. The proportion of playground and monkey bar fractures decreased from 20% and 17% to 3% and 4%, respectively. Distribution of Gartland type and neurovascular injury rates were similar in 2019 and 2020 ( P =0.411 and 0.538). Time from emergency department admission to the operating room and duration of hospital admission were both unchanged from 2019 to 2020 ( P =0.864 and 0.363). The duration of postoperative follow-up in 2019 was 94.5 days compared with 72.8 days in 2020 ( P =0.122), as more pandemic patients were lost to follow up (22.5% vs. 35.2%, P =0.049). CONCLUSIONS: The demographics, mechanism of injury, and follow-up practices of pediatric SCH fractures changed significantly during the pandemic, likely because of school closures and lock-downs changing activity patterns. Different mechanisms of injury affected younger patients and reflected the new ways children played. Trampoline-related and furniture-related injuries overtook the classic playground falls as primary mechanism of injury. Despite the need for COVID-19 testing, there was no delay in time to the operating room. Hospitalization duration did not change, yet postoperative follow-up was shorter, and more patients were lost to follow up. Despite these stressors, outcomes remained excellent in most children. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

Virus exposure and neurodegenerative disease risk across national biobanks.

With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk. Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations. The largest effect association was between viral encephalitis exposure and Alzheimer's disease. Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.

Vaccine-based clinical protection against SARS-CoV-2 infection and the humoral immune response: A 1-year follow-up study of patients with multiple sclerosis receiving ocrelizumab.

Introduction: Given the varying severity of coronavirus disease 2019 (COVID-19) and the rapid spread of Severe-Acute-Respiratory-Syndrome-Corona-Virus-2 (SARS-CoV-2), vaccine-mediated protection of particularly vulnerable individuals has gained increasing attention during the course of the pandemic. Methods: We performed a 1-year follow-up study of 51 ocrelizumab-treated patients with multiple sclerosis (OCR-pwMS) who received COVID-19 vaccination in 2021. We retrospectively identified 37 additional OCR-pwMS, 42 pwMS receiving natalizumab, 27 pwMS receiving sphingosine 1-phosphate receptor modulators, 59 pwMS without a disease-modifying therapy, and 61 controls without MS (HC). In OCR-pwMS, anti-SARS-CoV-2(S)-antibody titers were measured prior to the first and after the second, third, and fourth vaccine doses (pv2/3/4). The SARS-CoV-2-specific T cell response was analyzed pv2. SARS-CoV-2 infection status, COVID-19 disease severity, and vaccination-related adverse events were assessed in all pwMS and HC. Results: We found a pronounced and increasing anti-SARS-CoV-2(S)-antibody response after COVID-19 booster vaccinations in OCR-pwMS (pv2: 30.4%, pv3: 56.5%, and pv4 90.0% were antibody positive). More than one third of OCR-pwMS without detectable antibodies pv2 developed positive antibodies pv3. 23.5% of OCR-pwMS had a confirmed SARS-CoV-2 infection, of which 84.2% were symptomatic. Infection rates were comparable between OCR-pwMS and control groups. None of the pwMS had severe COVID-19. An attenuated humoral immune response was not associated with a higher risk of SARS-CoV-2 infection. Discussion: Additional COVID-19 vaccinations can boost the humoral immune response in OCR-pwMS and improve clinical protection against COVID-19. Vaccines effectively protect even OCR-pwMS without a detectable COVID-19 specific humoral immune response, indicating compensatory, e.g., T cell-mediated immunological mechanisms.

Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic.

Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) for programmable capture and concentration of specific RNAs from complex mixtures. The target bound TtCsm complex generates two cyclic oligoadenylates (i.e., cA3 and cA4) that allosterically activate ancillary nucleases. We show that both Can1 and Can2 nucleases cleave single-stranded RNA, single-stranded DNA, and double-stranded DNA in the presence of cA4. We integrate the Can2 nuclease with type III-A RNA capture and concentration for direct detection of SARS-CoV-2 RNA in nasopharyngeal swabs with 15 fM sensitivity. Collectively, this work demonstrates how type-III CRISPR-based RNA capture and concentration simultaneously increases sensitivity, limits time to result, lowers cost of the assay, eliminates solvents used for RNA extraction, and reduces sample handling.

Early anti-S antibody levels predict anti-SARS-CoV-2 neutralizing activity over 24 weeks in RA patients after SARS-CoV-2 mRNA vaccination

Objectives: Routine monitoring of vaccine-induced anti-S responses following mRNA based SARS-CoV-2 vaccination is not recommended routinely as uncertainties exist about the critical threshold of antibody levels that correlate to protection and the optimal timepoint for determination. In our study, anti-S antibody were analysed over 24 weeks following a standard two-dose regimen of mRNA based anti-SARS-CoV-2 vaccines and correlated to the development and persistence of neutralizing activity against SARSCoV- 2 in patients with rheumatoid arthritis (RA) on DMARD therapy compared to healthy controls (HC). Method(s): The RECOVER study was a prospective, controlled, monocentric study. Assessments were performed before vaccination, and at three, six, 12 and 24 weeks after the first vaccine dose. Result(s): In RA patients, anti-S responses developed slower and resulted in lower peak titers compared to HC. A potent neutralizing activity (NT50) as assessed by a SARS-CoV-2 pseudoneutralization assay was observed in 60.3 % of all 73 RA patients and in all 21 HC after 12 weeks. A significant correlation between peak anti-S levels two weeks after the second vaccine dose and the development of a persistent neutralizing activity against SARS-CoV-2 was observed at week 12 and week 24. The analysis of IgG, IgA, and IgM isotype responses to RBD, S1, S2, and N proteins revealed a delayed IgG response, while IgA and IgM responses were maintained, suggesting a delayed isotype switch in RA patients. Conclusion(s): Peak anti-S IgG levels two weeks after the second vaccine dose significantly predicted the development and persistence of a potent neutralizing activity against SARS-CoV-2 after 12 and 24 weeks. Our data suggest that the early determination of anti- S levels allows the timely identification of non- or poor-responding patients.

Effect of the COVID-19 Pandemic on Chlamydial Infection Treatment in Women Discharged From an Urban Safety-Net Emergency Unit.

BACKGROUND: Chlamydia is the most frequently reported sexually transmitted infection. COVID-19 exacerbated the challenges in treating and preventing new Chlamydia trachomatis (CT) infections. This study examined the impact of COVID-19 on treating CT-positive patients discharged from a safety-net women's emergency unit. METHODS: This was a preretrospective and postretrospective cohort study. Chlamydia trachomatis -positive female patients seen in the women's emergency unit were evaluated. Patients discharged in 2019, the "pre-COVID-19" group, and those discharged in 2020, the "COVID-19" group, were compared. The primary outcome was CT treatment within 30 days, and secondary outcomes included prescription dispensation, repeat tests taken, and expedited partner treatment. A subgroup of patients discharged before treatment who entered a nurse-led follow-up program was also evaluated. RESULTS: Of the 1357 cases included, there were no differences in successful 30-day treatment (709 of 789 [89.9%] vs. 568 of 511 [89.9%], P = 0.969) or repeat positive CT test (74 of 333 [22.2%] vs. 46 of 211 [21.8%]), P = 0.36) between pre-COVID-19 and COVID-19. However, the patients who picked up their prescription (196 of 249 [78.7%] vs. 180 of 206 [87.4%], P = 0.021) and those who were prescribed expedited partner therapy (156 of 674 [23.1%] vs. 292 of 460 [63.5%], P < 0.001) increased. Findings in the subgroup of patients who entered the follow-up program were consistent with those in the full cohort. CONCLUSIONS: The COVID-19 pandemic did not change treatment patterns of CT-positive patients in this safety-net women's emergency unit. However, patients were more likely to pick up their medications during COVID-19. Despite the perseverance of these programs through the pandemic, most patients are discharged before positive results, and a fair amount remain untreated.

Expanding Access to Social Support in Primary Care via Telemedicine: A Pilot Study.

The coronavirus pandemic quickly exposed the need for efficient and widespread implementation of telehealth services. Additionally, it further unveiled the impact of social and environmental barriers to healthcare in underserved, rural populations. This in-practice pilot study tested the utility of a geographically centralized social worker providing services between a patient and a primary care provider via telecommunication at two high volume rural outpatient family practice clinics. Outcome measures included patient and provider satisfaction. Twenty-two telehealth social work encounters occurred spanning both adult and pediatric patients. Data collected from patients, primary care providers, and social work staff revealed positive feedback. The data from our small pilot study demonstrated that social work triage delivered via a tablet was an acceptable and valued resource in busy primary care practices.

Chemical modifications to mRNA nucleobases impact translation elongation and termination.

Messenger RNAs (mRNAs) serve as blueprints for protein synthesis by the molecular machine the ribosome. The ribosome relies on hydrogen bonding interactions between adaptor aminoacyl-transfer RNA molecules and mRNAs to ensure the rapid and faithful translation of the genetic code into protein. There is a growing body of evidence suggesting that chemical modifications to mRNA nucleosides impact the speed and accuracy of protein synthesis by the ribosome. Modulations in translation rates have downstream effects beyond protein production, influencing protein folding and mRNA stability. Given the prevalence of such modifications in mRNA coding regions, it is imperative to understand the consequences of individual modifications on translation. In this review we present the current state of our knowledge regarding how individual mRNA modifications influence ribosome function. Our comprehensive comparison of the impacts of 16 different mRNA modifications on translation reveals that most modifications can alter the elongation step in the protein synthesis pathway. Additionally, we discuss the context dependence of these effects, highlighting the necessity of further study to uncover the rules that govern how any given chemical modification in an mRNA codon is read by the ribosome.

Co-Created Messaging for Influenza Vaccination in a High-Risk Hispanic Community Provides Groundwork for COVID-19 Vaccine.

Purpose: Influenza/pneumonia is the eighth leading cause of death in the United States. The 2020-2021 influenza season is predicted to be further impacted by COVID-19 infections. Historical data reflect disproportionate morbidity and mortality rates in the Hispanic population for influenza and COVID-19. Influenza vaccination rates remain low in the Hispanic community. We aim to improve vaccination through a community-led event, partnering with the Cristo Rey School Dallas, located in a zip code with a higher age-adjusted influenza/pneumonia mortality rate. A survey was administered to adults attending the Influenza vaccine event to understand attitudes and perceptions about influenza, vaccination, and effective messaging strategies for the campaign. Methods: Messaging was cocreated with student health ambassadors to promote immunization and delivered through trusted sources. The health department administered vaccines to individuals >age 3 at no cost. Adults were asked to complete a 19-question survey postvaccination offered in both English and Spanish. Results: Two hundred and forty-one of 394 (61.2%) participants completed the survey. Ninety-eight percent identified as Hispanic/Latino, and the majority of surveys were administered in Spanish. Among Spanish language participants, the church bulletins (57.3%) and Spanish language radio (30.5%) were reported to be most effective modes of messaging versus word of mouth (32.9%) and social media (26.3%) for English-speaking participants. Sixteen percent of participants surveyed had never received an influenza vaccine before this event. Conclusion: Cocreated messaging delivered by trusted sources in the Hispanic community led to a successful Influenza vaccine drive with the Dallas County health department.

Adolescents' Substance Use and Physical Activity Before and During the COVID-19 Pandemic.

Importance: Stay-at-home policies related to the COVID-19 pandemic could disrupt adolescents' substance use and physical activity. Objective: To compare adolescents' substance use and physical activity behaviors before and after stay-at-home restrictions. Design, Setting, and Participants: Ongoing prospective cohort study of tobacco use behaviors among ninth- and tenth-grade students enrolled at 8 public high schools in Northern California from March 2019 to February 2020 and followed up from September 2019 to September 2020. Race/ethnicity was self-classified from investigator-provided categories and collected owing to racial/ethnic differences in tobacco and substance use. Exposures: In California, a COVID-19 statewide stay-at-home order was imposed March 19, 2020. In this study, 521 six-month follow-up responses were completed before the order and 485 were completed after the order. Main Outcomes and Measures: The prevalence of substance use (ie, past 30-day use of e-cigarettes, other tobacco, cannabis, and alcohol) and physical activity (active ≥5 days/week) was compared at baseline and follow-up. A difference-in-difference approach was used to assess whether changes from baseline to 6-month follow-up varied if follow-up occurred after the stay-at-home order, adjusting for baseline behaviors and characteristics. All models were weighted for losses to follow-up using the inverse probability method. Weights were derived from a logistic regression model for having a follow-up response (dependent variable), as predicted by baseline characteristics and behaviors. Results: Of 1423 adolescents enrolled at baseline, 1006 completed 6-month follow-up (623 [62%] were female, and 492 [49%] were non-Hispanic White). e-Cigarette use declined from baseline to 6-month follow-up completed before the stay-at-home order (17.3% [89 of 515] to 11.3% [58 of 515]; McNemar χ2 = 13.54; exact P < .001) and 6-month follow-up completed after the stay-at-home order (19.9% [96 of 482] to 10.8% [52 of 482]; McNemar χ2 = 26.16; exact P < .001), but the extent of decline did not differ statistically between groups responding before vs after the stay-at-home order (difference-in-difference adjusted odds ratio, 0.84; 95% CI, 0.47-1.52; P = .58). In contrast, being physically active was unchanged from baseline if follow-up was before the order (53.7% [279 of 520] to 52.9% [275 of 520]; McNemar χ2 = 0.09; exact P = .82) but declined sharply from baseline if follow-up was after the order (54.0% [261 of 483] to 38.1% [184 of 483]; McNemar χ2 = 30.72; exact P < .001), indicating a pronounced difference in change from baseline after the stay-at-home order (difference-in-difference adjusted odds ratio, 0.49; 95% CI, 0.35-0.69; P < .001). Overall in the cohort, reported use of other tobacco, cannabis, and alcohol did not differ meaningfully before and after the order. Conclusions and Relevance: In this cohort, a reduction in e-cigarette use occurred independently of COVID-19 stay-at-home restrictions, but persistent cannabis and alcohol use suggest continued need for youth substance use prevention and cessation support. Declining physical activity during the pandemic is a health concern.

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.