Septic Return Flow Pathlines, Endpoints, and Flows Based on the Urban Miami-Dade Groundwater Model.

Miami-Dade County (MDC) has over 112,000 septic systems, some of which are at risk of compromise due to water table rise associated with sea level rise. MDC is surrounded by protected water bodies, including Biscayne Bay, with environmentally sensitive ecosystems and is underlain by highly transmissive karstic limestone. The main objective of the study is to provide first estimates of the locations and magnitudes of septic return flows to discharge endpoints. This is accomplished by leveraging MDC's county-scale surface-groundwater model using pathline analysis to estimate the transport and discharge fate of septic system flows under the complex time history of groundwater flow response to pumping, canal management, storms, and other environmental factors. The model covers an area of 4772 km2 in Southeast Florida. Outputs from the model were used to create a 30-year (2010 to 2040) simulation of the spatial-temporal pathlines from septic input locations to their termination points, allowing us to map flow paths and the spatial distribution of the septic flow discharge endpoints under the simulated conditions. Most septic return flows were discharged to surface water, primarily canals 52,830 m3/d and Biscayne Bay (5696 m3/d), and well fields (14,066 m3/d). Results allow us to identify "hotspots" to guide water quality sampling efforts and to provide recommendations for septic-to-sewer conversion areas that should provide most benefit by reducing nutrient loading to water bodies.

Attentional Bias, Pupillometry, and Spontaneous Blink Rate: Eye Characteristic Assessment Within a Translatable Nicotine Cue Virtual Reality Paradigm.

Background: Incentive salience processes are important for the development and maintenance of addiction. Eye characteristics such as gaze fixation time, pupil diameter, and spontaneous eyeblink rate (EBR) are theorized to reflect incentive salience and may serve as useful biomarkers. However, conventional cue exposure paradigms have limitations that may impede accurate assessment of these markers. Objective: This study sought to evaluate the validity of these eye-tracking metrics as indicators of incentive salience within a virtual reality (VR) environment replicating real-world situations of nicotine and tobacco product (NTP) use. Methods: NTP users from the community were recruited and grouped by NTP use patterns: nondaily (n=33) and daily (n=75) use. Participants underwent the NTP cue VR paradigm and completed measures of nicotine craving, NTP use history, and VR-related assessments. Eye-gaze fixation time (attentional bias) and pupillometry in response to NTP versus control cues and EBR during the active and neutral VR scenes were recorded and analyzed using ANOVA and analysis of covariance models. Results: Greater subjective craving, as measured by the Tobacco Craving Questionnaire-Short Form, following active versus neutral scenes was observed (F1,106=47.95; P<.001). Greater mean eye-gaze fixation time (F1,106=48.34; P<.001) and pupil diameter (F1,102=5.99; P=.02) in response to NTP versus control cues were also detected. Evidence of NTP use group effects was observed in fixation time and pupillometry analyses, as well as correlations between these metrics, NTP use history, and nicotine craving. No significant associations were observed with EBR. Conclusions: This study provides additional evidence for attentional bias, as measured via eye-gaze fixation time, and pupillometry as useful biomarkers of incentive salience, and partially supports theories suggesting that incentive salience diminishes as nicotine dependence severity increases.

Seasonal human coronavirus humoral responses in AZD1222 (ChaAdOx1 nCoV-19) COVID-19 vaccinated adults reveal limited cross-immunity.

Background: Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now widespread; however, the degree of cross-immunity between SARS-CoV-2 and endemic, seasonal human coronaviruses (HCoVs) remains unclear. Methods: SARS-CoV-2 and HCoV cross-immunity was evaluated in adult participants enrolled in a US sub-study in the phase III, randomized controlled trial (NCT04516746) of AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination for one-year. Anti-HCoV spike-binding antibodies against HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63 were evaluated in participants following study dosing and, in the AZD1222 group, after a non-study third-dose booster. Timing of SARS-CoV-2 seroconversion (assessed via anti-nucleocapsid antibody levels) and incidence of COVID-19 were evaluated in those who received AZD1222 primary-series by baseline anti-HCoV titers. Results: We evaluated 2,020/21,634 participants in the AZD1222 group and 1,007/10,816 in the placebo group. At the one-year data cutoff (March 11, 2022) mean duration of follow up was 230.9 (SD: 106.36, range: 1-325) and 94.3 (74.12, 1-321) days for participants in the AZD1222 (n = 1,940) and placebo (n = 962) groups, respectively. We observed little elevation in anti-HCoV humoral titers post study-dosing or post-boosting, nor evidence of waning over time. The occurrence and timing of SARS-CoV-2 seroconversion and incidence of COVID-19 were not largely impacted by baseline anti-HCoV titers. Conclusion: We found limited evidence for cross-immunity between SARS-CoV-2 and HCoVs following AZD1222 primary series and booster vaccination. Susceptibility to future emergence of novel coronaviruses will likely persist despite a high prevalence of SARS-CoV-2 immunity in global populations.

Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study.

BACKGROUND: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated. METHODS: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2. INTERPRETATION: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants. FUNDING: AstraZeneca.

Clinical Utility of Remote Camera Video Head Impulse Testing Children Less Than 3 Years.

The purpose of this case report is to highlight both the feasibility and clinical utility of remote camera video head impulse testing (vHIT) in children <3 years. Five cases are described where remote camera vHIT was used to quantify ear specific semicircular function in children at risk for vestibular dysfunction. Remote camera vHIT is a helpful clinical tool for quantifying ear specific semicircular function in children between 6 and 31 months. Remote camera vHIT is feasible and provides ear specific information regarding semicircular canal function, which can be used to augment or validate the presence of vestibular dysfunction in children <3 years. Laryngoscope, 2024.

Influence of Pregnancy Intention on Postpartum Contraceptive Choice at an Urban Academic Medical Center.

OBJECTIVE: This study aimed to describe postpartum contraception preferences in the context of pregnancy intention (PI). STUDY DESIGN: A prospective cohort study analyzing postpartum contraceptive choice (PCC) in 431 postpartum women who delivered at a single academic medical center. PCC in women with an unintended or mistimed pregnancy was compared to contraceptive choice in women with an intended pregnancy using the adapted National Survey of Family Growth categorization. Mistimed and unintended pregnancies were grouped for analysis. Generalized linear modeling estimated the relative influence of PI on PCC adjusting for maternal age, race, and parity. RESULTS: Nearly three out of four (71.9%) pregnancies were mistimed or unintended. These pregnancies were more likely in women who were non-Hispanic Black (62.3%), unmarried (86.3%), 18 to 24 years (51.3%), and insured by Medicaid or Medicare (82.1%), compared to women with an intended pregnancy, p-value <0.001. Women with mistimed or unintended pregnancy were 83% more likely to choose highly effective, user-independent methods compared to any other or no method, adjusted relative risk (aRR) = 1.83 (95% confidence interval [CI]: 1.36, 2.47), and more likely to desire voluntary sterilization, aRR = 2.70 (95% CI: 1.58, 4.59). Additionally, women with these pregnancies were 56% more likely to use user-independent methods compared to user-dependent methods, aRR = 1.56 (95% CI: 1.18, 2.06). CONCLUSION: Women with mistimed or unintended pregnancies are 83% more likely to choose highly effective postpartum contraception or voluntary sterilization, and thus initiatives are necessary to increase access and affordability to these methods before hospital discharge after delivery. KEY POINTS: · Nearly three out of four pregnancies in this study were mistimed or unintended.. · Women with mistimed or unintended pregnancies are more likely to choose highly effective postpartum contraception or voluntary sterilization.. · Public health initiatives to improve access to family planning services and postpartum contraception, including surgery for bilateral tubal ligation before discharge from the hospital postdelivery, are important areas of focus to help attenuate the rates of unintended pregnancy in the United States..

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

The effects of standing foot-transmitted vibration on self-reported discomfort ratings.

BACKGROUND: Occupational foot-transmitted vibration (FTV) exposure is common in industries like mining, construction, and agriculture, often leading to acute and chronic injuries. Vibration assessments require technical expertise and equipment which can be costly for employers to perform. Alternatively, researchers have observed that self-reported discomfort can be used as an effective indicator of injury risk. OBJECTIVE: This study aimed to investigate the effect of standing FTV exposure on self-reported ratings of discomfort, and whether these subjective ratings differed by body area and exposure frequency. METHODS: Participants (n = 30) were randomly exposed to standing FTV at six frequencies (25, 30, 35, 40, 45, and 50 Hz) for 20-45 seconds. Following each exposure, participants rated discomfort on a scale of 0-9 in four body areas: head and neck (HN), upper body (UB), lower body (LB), and total body. RESULTS: Results indicated that participants experienced the most discomfort in the LB at higher frequencies (p < 0.001), consistent with the resonance of foot structures. The HN discomfort tended to decrease as the exposure frequency increased, although not statistically significant (p > 0.0167). The UB discomfort remained relatively low across all frequencies. CONCLUSIONS: The study suggests a potential connection between resonant frequencies and discomfort, potentially indicating injury risk. Although self-reported discomfort is insufficient for directly assessing injury risk from FTV, it provides a simple method for monitoring potential musculoskeletal risks related to vibration exposure at resonant frequencies. While professional vibration assessment remains necessary, self-reported discomfort may act as an early indicated of vibration-induced injuries, aiding in implementing mitigation strategies.

A single-arm pilot of MyInspiration: a novel digital resource to support spiritual needs of patients undergoing cancer-directed surgery.

PURPOSE: This study aimed to assess the feasibility, acceptability, and satisfaction associated with the MyInspiration intervention, a digital spiritual support tool for patients undergoing cancer surgery. Additionally, we evaluated changes in spiritual well-being and the ability to find meaning in their experience with cancer before and after the intervention. METHODS: This was a prospective, single-arm pilot study. Feasibility and acceptability were assessed by ratio of participants who completed all assessments among individuals who had signed consent forms. Satisfaction was assessed with 5 Likert-style questions around user experience. Patient spiritual well-being and finding meaning in their experience with cancer were measured at baseline and post-intervention. RESULTS: Forty patients were enrolled, the majority of whom were female (80.0%) and diagnosed with breast cancer (52.5%), with an average age of 54.4 years (SD = 13.7, range 29.0-82.0). Regarding feasibility and acceptability, 76.9% of patients who consented to participate completed the full study protocol. In assessing satisfaction, 59% of patients were satisfied with the overall experience of MyInspiration. There was no difference in spiritual well-being pre-/post-intervention. There was a difference in pre (M = 1.95, SD = .95) and post (M = 2.23, SD = .86) scores relative to "finding meaning in the cancer experience" with a mean difference of 0.28 (p = 0.008). CONCLUSION: MyInspiration was feasible and acceptable to patients, and the majority were satisfied with the tool. The intervention was associated with changes in patients' ability to find meaning within their cancer experience. A randomized control trial is needed to evaluate the efficacy of the tool in a broader population of patients with cancer.

Mediation of antitumor activity by AZD4820 oncolytic vaccinia virus encoding IL-12.

Oncolytic viruses are engineered to selectively kill tumor cells and have demonstrated promising results in early-phase clinical trials. To further modulate the innate and adaptive immune system, we generated AZD4820, a vaccinia virus engineered to express interleukin-12 (IL-12), a potent cytokine involved in the activation of natural killer (NK) and T cells and the reprogramming of the tumor immune microenvironment. Testing in cultured human tumor cell lines demonstrated broad in vitro oncolytic activity and IL-12 transgene expression. A surrogate virus expressing murine IL-12 demonstrated antitumor activity in both MC38 and CT26 mouse syngeneic tumor models that responded poorly to immune checkpoint inhibition. In both models, AZD4820 significantly upregulated interferon-gamma (IFN-γ) relative to control mice treated with oncolytic vaccinia virus (VACV)-luciferase. In the CT26 study, 6 of 10 mice had a complete response after treatment with AZD4820 murine surrogate, whereas control VACV-luciferase-treated mice had 0 of 10 complete responders. AZD4820 treatment combined with anti-PD-L1 blocking antibody augmented tumor-specific T cell immunity relative to monotherapies. These findings suggest that vaccinia virus delivery of IL-12, combined with immune checkpoint blockade, elicits antitumor immunity in tumors that respond poorly to immune checkpoint inhibitors.

Factors Associated with Maternal Morbidity among Black Women in the United States.

OBJECTIVE: Non-Hispanic Black people (NHBP) have a three-fold higher rate of maternal mortality compared to other racial groups. Racial disparities in maternal morbidity are well-described; however, there are substantial differences in cultural, economic, and social determinants of health among racial groups. We thus sought to study the at-risk, non-Hispanic Black population as its own cohort to identify factors most associated with severe maternal morbidity (SMM). STUDY DESIGN: This is a population-based retrospective case-control study of all live births in the United States between 2017 and 2019 using birth records obtained from the National Center for Health Statistics. The primary outcome for this study was to determine demographic, social, medical, and obstetric factors associated with maternal morbidity among NHBP who did and did not experience an SMM event. Multivariable logistic regression was used to estimate the adjusted odds ratio between each individual factor and the outcome of SMM among NHBP. RESULTS: Of the 1,624,744 NHBP who delivered between 2017 and 2019, 1.1% experienced an SMM event defined as a composite of blood product transfusion, eclamptic seizure, intensive care unit admission, unplanned hysterectomy, and uterine rupture. The rates of these individual SMM events per 10,000 deliveries were 50, 40, 20, 5, and 4 among NHBP, respectively. Among NHBP, factors associated in multivariable regression analysis with SMM in order of strength of association included cesarean delivery, earlier gestational age at delivery, preeclampsia, induction of labor, chronic hypertension, prior preterm birth, lower educational attainment, multifetal gestation, advanced maternal age, pregestational diabetes, and cigarette smoking. The population attributable fraction for cesarean delivery, preterm birth, and pregnancy-induced hypertensive disease for the outcome of SMM were 0.46, 0.23, and 0.07, respectively. CONCLUSION: The three factors most associated with SMM among NHBP are potentially avoidable or modifiable by aggressive screening, prevention, and treatment of preeclampsia and preterm birth as well as reducing cesarean rates in this population. KEY POINTS: · The rate of SMM in NHBP may be modifiable.. · NHBP have a three-fold higher rate of maternal mortality.. · Preeclampsia, preterm birth, and cesarean sections are most associated with maternal morbidity..

Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

Effect of Paxlovid Treatment During Acute COVID-19 on Long COVID Onset: An EHR-Based Target Trial Emulation from the N3C and RECOVER Consortia.

Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,352 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. We estimated overall PASC incidence using a computable phenotype. We also measured the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.98, 95% confidence interval [CI] 0.95-1.01). However, it had a protective effect on cognitive (RR = 0.90, 95% CI 0.84-0.96) and fatigue (RR = 0.95, 95% CI 0.91-0.98) symptom clusters, which suggests that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms.

The Use of Brief Mindfulness Interventions in the Context of Perioperative Care.

The purpose of this review was to synthesize and categorize the literature on the use of brief mindfulness interventions for both patients and physicians across the spectrum of perioperative care. Web-based discovery services and discipline-specific databases were queried. Brief mindfulness interventions were defined as sessions lasting 30 min or less on any single occasion, with a total practice accumulation not exceeding 100 min per week, and a duration of up to 4 weeks. Study screening and data extraction were facilitated through the Covidence software platform. After screening 1047 potential studies, 201 articles were identified based on initial abstract and title screening; 10 studies ultimately met inclusion criteria. All ten studies were published between 2019 and 2023; most (n = 9) reports focused on patients (total joint arthroplasty, n = 3; stereotactic breast biopsy, n = 2; minimally invasive foregut surgery, n = 1; septorhinoplasty, n = 1; cardiac surgery, n = 1; and other/multiple procedures, n = 1); one studied investigated mindfulness interventions among surgeons. The duration of the interventions varied (3 min to 29 min). The most common issue that the mindfulness intervention aimed to address was pain (n = 6), followed by narcotic use (n = 3), anxiety (n = 2), delirium (n = 1), or patient satisfaction (n = 1). While most studies included a small sample size and had inconclusive results, brief mindfulness interventions were noted to impact various health-related outcomes, including mental health outcomes, anxiety, and pain perception. Mindfulness interventions may be a scalable, low-cost, time-limited intervention that has the potential to optimize well-being and surgical outcomes broadly construed.

Outbreak of Anthrax in Livestock with Human Occupational Exposures - Minnesota, 2023.

In July 2023, the Minnesota Department of Health (MDH) was notified of possible occupational exposures to anthrax during an outbreak in animals. In consultation with the Centers for Disease Control and Prevention, MDH epidemiologists created a questionnaire that assessed exposure risks and helped determine individual illness monitoring and antibiotic post-exposure prophylaxis needs. This investigation and the resources developed for it could be useful in future scenarios where there are occupational exposures to naturally occurring anthrax.

Which factors influence the approach to shared decision-making among surgeons performing complex operations?

BACKGROUND: Shared decision-making (SDM) aims to create a context in which patients and surgeons work together to explore treatment options and goals of care. The objective of the current study was to characterize demographic factors, behaviors, and perceptions of patient involvement among surgeons relative to SDM. METHODS: Using a cross-sectional survey methodology, surgeon demographics, behaviors, and perceptions of patient involvement were assessed. Surgeon approaches to SDM were measured using a 100-point scale ranging from 'patient-led' (0) to 'surgeon-led' (100). RESULTS: Among 241 respondents, most were male (n = 123, 67.2%) and White (n = 124, 69.3%); roughly one-half of surgeons had been in practice ≥10 years (n = 120, 52.4%). Surgeon approaches to SDM ranged from 0 to 81.0, with a median rating of 50.0 (IQR: 35.5, 62.0). Reported approaches to SDM were associated with years in practice, sharing information, and perceptions of patient involvement. Surgeons in practice 10 + years most frequently utilized a 'Shared, Patient-led' approach to SDM (27.5%), while individuals with less experience more often employed a 'Shared, Surgeon-led' approach (33.3%, p = 0.031). Surgeons with a 'Patient-led' approach perceived patient involvement as most important (M = 3.82, SD = 0.16), while respondents who had a 'Surgeon-led' approach considered this less important (M = 3.57, SD = 0.38; p < 0.001). CONCLUSION: Surgeon factors including demographics, behaviors, and perceptions of patient involvement influenced SDM approaches. SDM between patients and surgeons should strive to be more dynamic and tailored to each specific patient's needs to promote optimal patient-centered care.

Gaps in Patient-Centered Decision-Making Related to Complex Surgery: A Mixed-Methods Study.

INTRODUCTION: We sought to understand the perceptions of surgeons around patient preferred roles in decision-making and their approaches to patient-centered decision-making (PCDM). METHODS: A concurrent embedded mixed-methods design was utilized among a cohort of surgeons performing complex surgical procedures. Data were collected through online surveys. Associations between perceptions and PCDM approaches were examined. RESULTS: Among 241 participants, most respondents were male (67.2%) with an average age of 47.6 y (standard deviation = 10.3); roughly half (52.4%) had practiced medicine for 10 or more years. Surgeons most frequently agreed (94.2%) with the statement, "Patients prefer to make health decisions on their own after seriously considering their physician's opinion." Conversely, surgeons most frequently disagreed (73.0%) with the statement, "Patients prefer that their physician make health decisions for them." Nearly one-third (30.4%) of surgeon qualitative responses (n = 115) indicated that clinical/biological information would help them tailor their approach to PCDM. Only 12.2% of respondents indicated that they assess patient preferences regarding both decision-making and information needs. CONCLUSIONS: Surgeons most frequently agree that patients want to make their own health decisions after seriously considering their physicians opinion. A greater focus on what information surgeons should know before treatment decision-making may help optimize patient experience and outcomes related to complex surgical procedures.

HIV vaccines induce CD8+ T cells with low antigen receptor sensitivity.

Current HIV vaccines designed to stimulate CD8+ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8+ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8+ T cell response may require a vaccination strategy that drives further TCR clonal selection.

Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial).

INTRODUCTION: AZD7442 (tixagevimab/cilgavimab) comprises neutralising monoclonal antibodies (mAbs) that bind to distinct non-overlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Viral evolution during mAb therapy can select for variants with reduced neutralisation susceptibility. We examined treatment-emergent SARS-CoV-2 variants during TACKLE (NCT04723394), a phase 3 study of AZD7442 for early outpatient treatment of coronavirus disease 2019 (COVID-19). METHODS: Non-hospitalised adults with mild-to-moderate COVID-19 were randomised and dosed ≤ 7 days from symptom onset with AZD7442 (n = 452) or placebo (n = 451). Next-generation sequencing of the spike gene was performed on SARS-CoV-2 reverse-transcription polymerase chain reaction-positive nasopharyngeal swabs at baseline and study days 3, 6, and 15 post dosing. SARS-CoV-2 lineages were assigned using spike nucleotide sequences. Amino acid substitutions were analysed at allele fractions (AF; % of sequence reads represented by substitution) ≥ 25% and 3% to 25%. In vitro susceptibility to tixagevimab, cilgavimab, and AZD7442 was evaluated for all identified treatment-emergent variants using a pseudotyped microneutralisation assay. RESULTS: Longitudinal spike sequences were available for 461 participants (AZD7442, n = 235; placebo, n = 226) and showed that treatment-emergent variants at any time were rare, with 5 (2.1%) AZD7442 participants presenting ≥ 1 substitution in tixagevimab/cilgavimab binding sites at AF ≥ 25%. At AF 3% to 25%, treatment-emergent variants were observed in 15 (6.4%) AZD7442 and 12 (5.3%) placebo participants. All treatment-emergent variants showed in vitro susceptibility to AZD7442. CONCLUSION: These data indicate that AZD7442 creates a high genetic barrier for resistance and is a feasible option for COVID-19 treatment.