Implementation of AZD7442 (Tixagevimab/Cilgavimab) COVID-19 Pre-exposure Prophylaxis (PrEP) in the Largest Health Maintenance Organization in Israel: Real-world Uptake and Sociodemographic and Clinical Characteristics Across Immunocompromised Patient Groups.

INTRODUCTION: AZD7442 is a combination of two neutralizing antibodies (tixagevimab/cilgavimab) with demonstrated efficacy in reducing the risk of symptomatic coronavirus disease 2019 (COVID-19) among individuals at high risk of severe COVID-19 ≤ 6 months after administration. On February 15, 2022, the Israeli Ministry of Health (IMoH) authorized the administration of 300 mg AZD7442 as pre-exposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2 infection among immunocompromised individuals aged ≥ 12 years. This study describes the real-world uptake of AZD7442 in Israel. METHODS: This descriptive, observational study analyzed data from Israel's largest health maintenance organization, Clalit Health Services (CHS). Individuals were assessed for AZD7442 eligibility between February 13 and December 11, 2022, and were included if they were aged ≥ 12 years, had ≥ 1 year of continuous CHS membership, had ≥ 1 moderate or severe immunocompromising condition, and were eligible for AZD7442 per IMoH recommendations during this time frame. RESULTS: Overall, 19,161 AZD7442-eligible individuals with immunocompromising conditions were identified during the study period; 2829 (14.8%) received AZD7442. A higher proportion of individuals receiving AZD7442 were older (aged ≥ 65 years), male, not current smokers and residents in large cities; required more physician visits (> 50 visits); and had ≥ 1 COVID-19 hospitalization over 12 months, while uptake was lowest among ultra-orthodox Jewish individuals. AZD7442 uptake was also higher among individuals with multiple comorbidities (Charlson Comorbidity Index ≥ 5), including hypertension, diabetes and chronic kidney disease. In specific immunocompromised types, AZD7442 uptake was highest among individuals with lung transplantation (41%), primary immunodeficiency (32%), bone marrow transplantation (29%) and multiple myeloma (25%) or those receiving anti-CD20 therapy (26%) and was lowest in individuals with lymphoma (8%). CONCLUSION: These results show AZD7442 uptake among the eligible population of Israel in 2022 was relatively low, at 14.8%. Uptake was generally higher among immunocompromised individuals who may be perceived to be frail or at highest risk of COVID-19 infection and complications, although at 25-41%, further improvements in uptake would be more impactful. These results also indicate there is opportunity to expand AZD7442 uptake across immunocompromised groups and ensure more equitable uptake among some other sociodemographic groups. Overall, this study will help inform and reassess future implementation strategies for vulnerable populations.

Development and Validation of a Colorectal Cancer Prediction Model: A Nationwide Cohort-Based Study.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) is critical to increasing survival rates. Computerized risk prediction models hold great promise for identifying individuals at high risk for CRC. In order to utilize such models effectively in a population-wide screening setting, development and validation should be based on cohorts that are similar to the target population. AIM: Establish a risk prediction model for CRC diagnosis based on electronic health records (EHR) from subjects eligible for CRC screening. METHODS: A retrospective cohort study utilizing the EHR data of Clalit Health Services (CHS). The study includes CHS members aged 50-74 who were eligible for CRC screening from January 2013 to January 2019. The model was trained to predict receiving a CRC diagnosis within 2 years of the index date. Approximately 20,000 EHR demographic and clinical features were considered. RESULTS: The study includes 2935 subjects with CRC diagnosis, and 1,133,457 subjects without CRC diagnosis. Incidence values of CRC among subjects in the top 1% risk scores were higher than baseline (2.3% vs 0.3%; lift 8.38; P value < 0.001). Cumulative event probabilities increased with higher model scores. Model-based risk stratification among subjects with a positive FOBT, identified subjects with more than twice the risk for CRC compared to FOBT alone. CONCLUSIONS: We developed an individualized risk prediction model for CRC that can be utilized as a complementary decision support tool for healthcare providers to precisely identify subjects at high risk for CRC and refer them for confirmatory testing.

Indirect protection of children from SARS-CoV-2 infection through parental vaccination.

Children not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may still benefit from vaccines through protection from vaccinated contacts. We estimated the protection provided to children through parental vaccination with the BNT162b2 vaccine. We studied households without prior infection consisting of two parents and unvaccinated children, estimating the effect of parental vaccination on the risk of infection for unvaccinated children. We studied two periods separately-an early period (17 January 2021 to 28 March 2021; Alpha variant, two doses versus no vaccination) and a late period (11 July 2021 to 30 September 2021; Delta variant, booster dose versus two vaccine doses). We found that having a single vaccinated parent was associated with a 26.0 and a 20.8% decreased risk in the early and late periods, respectively, and having two vaccinated parents was associated with a 71.7 and a 58.1% decreased risk, respectively. Thus, parental vaccination confers substantial protection on unvaccinated children in the household.

Automatic facial reactions to emotional body expressions are not driven by emotional experience.

Perceiving emotional expressions automatically triggers a tendency to react with a matching facial expression. Although it is considered fundamental for healthy social interactions, the mechanism behind it is unclear. One prevalent explanation suggests that perceiving emotional expressions induces emotions in the observer and that it is these emotions that elicit the facial reactions. This study directly tested this hypothesis, investigating whether emotion elicitation is what drives the effect. Two experiments used a facial stimulus-response compatibility (SRC) paradigm-a widely used measure of the tendency to facially match emotional expressions-in which the irrelevant stimuli were happy and angry body postures. Reaction times were measured using facial electromyography. Experiment 1 replicated the known SRC effect to body postures using a simpler task with only one, prespecified, response. This established a novel variant of the paradigm in which the facial effects cannot be attributed to motor matching or response selection and which focuses specifically on the automatic components of the effect. Experiment 2 then added to this paradigm a habituation protocol and self-report ratings of affective valence. Results indicated that emotional body postures elicited limited emotional reactions, which were further habituated following repeated presentations. However, the facial SRC effect did not undergo such habituation, suggesting that reducing emotional reaction to observed expressions does not reduce the tendency to match those expressions. Our findings do not support the emotion elicitation hypothesis and suggest that automatic facial reactions to emotional body postures are not driven by emotional reactions to the stimuli. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Automatic facial reactions to facial, body, and vocal expressions: A stimulus-response compatibility study.

When perceiving emotional facial expressions there is an automatic tendency to react with a matching facial expression. A classic explanation of this phenomenon, termed the matched motor hypothesis, highlights the importance of topographic matching, that is, the correspondence in body parts, between perceived and produced actions. More recent studies using mimicry paradigms have challenged this classic account, producing ample evidence against the matched motor hypothesis. However, research using stimulus-response compatibility (SRC) paradigms usually assumed the effect relies on topographic matching. While mimicry and SRC share some characteristics, critical differences between the paradigms suggest conclusions cannot be simply transferred from one to another. Thus, our aim in the present study was to directly test the matched motor hypothesis using SRC. Specifically, we investigated whether observing emotional body postures or hearing emotional vocalizations produces a tendency to respond with one's face, despite completely different motor actions being involved. In three SRC experiments, participants were required to either smile or frown in response to a color cue, presented concurrently with stimuli of happy and angry facial (experiment 1), body (experiment 2), or vocal (experiment 3) expressions. Reaction times were measured using facial EMG. Whether presenting facial, body, or vocal expressions, we found faster responses in compatible, compared to incompatible trials. These results demonstrate that the SRC effect of emotional expressions does not require topographic matching. Our findings question interpretations of previous research and suggest further examination of the matched motor hypothesis.

Portraying emotions at their unfolding: a multilayered approach for probing dynamics of neural networks.

Dynamic functional integration of distinct neural systems plays a pivotal role in emotional experience. We introduce a novel approach for studying emotion-related changes in the interactions within and between networks using fMRI. It is based on continuous computation of a network cohesion index (NCI), which is sensitive to both strength and variability of signal correlations between pre-defined regions. The regions encompass three clusters (namely limbic, medial prefrontal cortex (mPFC) and cognitive), each previously was shown to be involved in emotional processing. Two sadness-inducing film excerpts were viewed passively, and comparisons between viewer's rated sadness, parasympathetic, and inter-NCI and intra-NCI were obtained. Limbic intra-NCI was associated with reported sadness in both movies. However, the correlation between the parasympathetic-index, the rated sadness and the limbic-NCI occurred in only one movie, possibly related to a "deactivated" pattern of sadness. In this film, rated sadness intensity also correlated with the mPFC intra-NCI, possibly reflecting temporal correspondence between sadness and sympathy. Further, only for this movie, we found an association between sadness rating and the mPFC-limbic inter-NCI time courses. To the contrary, in the other film in which sadness was reported to commingle with horror and anger, dramatic events coincided with disintegration of these networks. Together, this may point to a difference between the cinematic experiences with regard to inter-network dynamics related to emotional regulation. These findings demonstrate the advantage of a multi-layered dynamic analysis for elucidating the uniqueness of emotional experiences with regard to an unguided processing of continuous and complex stimulation.