Persistent SARS-CoV-2 PCR Positivity Despite Anti-viral Treatment in Immunodeficient Patients.

PURPOSE: COVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious potential. While clinical trials have demonstrated promising outcomes using anti-SARS-CoV-2 medicines in immunocompetent hosts, their ability to achieve sustained viral clearance in immunodeficient patients remains unknown. We therefore aimed to study long-term virological outcomes in patients treated at our centre. METHODS: We followed up immunocompromised inpatients treated with casirivimab-imdevimab (Ronapreve) between September and December 2021, and immunocompromised patients who received sotrovimab, molnupiravir, nirmatrelvir/ritonavir (Paxlovid), or no treatment from December 2021 to March 2022. Nasopharyngeal swab and sputum samples were obtained either in hospital or in the community until sustained viral clearance, defined as 3 consecutive negative PCR samples, was achieved. Positive samples were sequenced and analysed for mutations of interest. RESULTS: We observed sustained viral clearance in 71 of 103 patients, none of whom died. Of the 32/103 patients where sustained clearance was not confirmed, 6 died (between 2 and 34 days from treatment). Notably, we observed 25 cases of sputum positivity despite negative nasopharyngeal swab samples, as well as recurrence of SARS-CoV-2 positivity following a negative sample in 12 cases. Patients were then divided into those who cleared within 28 days and those with PCR positivity beyond 28 days. We noted lower B cell counts in the group with persistent PCR positivity (mean (SD) 0.06 (0.10) ×109/L vs 0.22 (0.28) ×109/L, p = 0.015) as well as lower IgA (median (IQR) 0.00 (0.00-0.15) g/L vs 0.40 (0.00-0.95) g/L, p = 0.001) and IgM (median (IQR) 0.05 (0.00-0.28) g/L vs 0.35 (0.10-1.10) g/L, p = 0.005). No differences were seen in CD4+ or CD8+ T cell counts. Antiviral treatment did not impact risk of persistent PCR positivity. CONCLUSION: Persistent SARS-CoV-2 PCR positivity is common among immunodeficient individuals, especially those with antibody deficiencies, regardless of anti-viral treatment. Peripheral B cell count and serum IgA and IgM levels are predictors of viral persistence.

Ethnic-racial identity and ethnic-racial socialization competency: How minoritized parents "walk the talk".

OBJECTIVES: Ethnic-racial identity (ERI) has important implications for individual psychosocial functioning as well as familial processes. For example, parents' ERI can shape children's developmental contexts through ethnic-racial socialization (ERS). Yet, existing research has tended to focus on the content or frequency of socialization messages themselves rather than on internal factors like socialization competence. Such competence, as reflected through confidence, skills, and stress, represents critical dimensions that permeate the socialization process and can impact the delivery of messages. The present study examines whether parents' ERI (i.e., private regard, centrality, exploration) is related to perceptions of their socialization competence. METHOD: Data from 203 Black, 194 Asian American, and 188 Latinx parents (N = 585, Mage = 44.46 years, SD = 9.14, 59.70% mothers) of adolescents between the ages of 10-18 were collected via Qualtrics panels. RESULTS: Across all parents, private regard, centrality, and ethnic-racial exploration were positively associated with perceived confidence and skills in engaging in ERS. Regard was additionally associated with lower socialization stress. CONCLUSIONS: The results point to consistent benefits of ERI in helping parents navigate ERS, furthering the understanding of ERI's developmental implications through parents' comfort with and ability to "walk the talk" with their children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Group education on the low FODMAP diet improves gastrointestinal symptoms but neither anxiety or depression in irritable bowel syndrome.

BACKGROUND: The low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is an effective dietitian-led treatment for irritable bowel syndrome (IBS). An increasing demand of IBS patient referrals has warranted group FODMAP education led by specialist dietitians. Psychological co-morbidities are common in IBS, although how the low FODMAP diet influences psychological outcomes is not understood. The present study aimed to evaluate symptom related outcomes of the diet following group education and assess its effect on psychological profiles. METHODS: An observational, prospective study was conducted in 55 IBS patients who attended FODMAP Restriction and FODMAP Reintroduction group sessions. Data were collected at baseline and follow-up after FODMAP Restriction and analysed using descriptive and McNemar's tests. Primary outcome was evaluated by IBS Symptom Severity Score (IBS-SSS). Secondary psychological outcomes included anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and risk of eating disorder questionnaire (SCOFF). RESULTS: After FODMAP Restriction, 27 of 55 (54%) patients reported clinically relevant symptom improvement, as defined by a reduction in the IBS-SSS ≥50 points, whereas no differences were recorded in the proportion of patients identified with clinical anxiety (p = 1.000) or clinical depression (p = 0.375). Positively, no increased risk of an eating disorder was observed. CONCLUSIONS: The present study provides data supporting the efficacy of the low FODMAP diet in IBS patients who attended dietitian led group education settings in tertiary care. Clinically significant improvements in gastrointestinal symptoms were observed, although with no impact on clinical levels of anxiety, depression or the risk of an eating disorder.

Correlates of Ethnicity-related Dating Preferences among Asian American Adolescents across the High School Years.

Ethnicity-related dating preferences among Asian American adolescents and the links between preferences (i.e., for a same-ethnic dating partner) and ethnic identity centrality and regard, American identity centrality and regard, parent-adolescent closeness, and perceptions of discrimination were investigated. Data from 175 self-identified Asian American high school students were collected yearly for four consecutive years. Higher levels of ethnic identity centrality and regard and parent-adolescent closeness averaged across four years were associated with preferring a same-ethnic partner. Moreover, foreign-born adolescents were less likely to prefer a same-ethnic partner when they encountered a higher than average level of discrimination on any given year. Results highlight variability in the developmental and individual-level factors that shape how adolescents navigate their dating relationships.

The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.

NMDA receptor-dependent synaptic plasticity has been proposed to be important for encoding of memories. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist, MK-801, has been found to impair performance on tests of memory. Interpretation of some of these findings has, however, been complicated by the fact that the drug-state of animals has differed during encoding and tests of memory. Therefore, it is possible that MK-801 may result in state-dependent retrieval or expression of memory rather than actually impairing encoding itself. We tested this hypothesis in mice using tests of object recognition memory with a 24-hour delay between the encoding and test phase. Mice received injections of either vehicle or MK-801 prior to the encoding phase and the test phase. In Experiment 1, a low dose of MK-801 (0.01 mg/kg) impaired performance when the drug-state (vehicle or MK-801) of mice changed between encoding and test, but there was no significant effect of MK-801 on encoding. In Experiment 2, a higher dose of MK-801 (0.1 mg/kg) failed to impair object recognition memory when mice received the drug prior to both encoding and test compared to mice that received vehicle. MK-801 did not affect object exploration, but it did induce locomotor hyperactivity at the higher dose. These results suggest that some previous demonstrations of MK-801 effects may reflect a failure to express or retrieve memory due to the state-dependency of memory rather than impaired encoding of memory.

Foreigner objectification, English proficiency, and adjustment among youth and mothers from Latinx American backgrounds.

OBJECTIVES: Understanding the experience of foreigner objectification is relevant given the possibility of ethnocentrism, xenophobia, and mistrust of immigrants in the United States. The present study examines main and interactive effects of objectification and English proficiency on developmental outcomes among immigrant mothers and children. METHOD: Our study includes 173 youth from Latinx backgrounds (52% female, Mage = 12.86 years, SD = .68; 87% United States-born) and their mothers (Mage = 38.26 SD = 5.65; all foreign-born) from emerging immigrant contexts. RESULTS: Bivariate and regression analyses suggest that lower English proficiency was associated with more objectification for youth; whereas higher English proficiency was associated with more objectification for mothers. For youth only, English proficiency was positively correlated with American identity. For both parents and youth, foreigner objectification was linked with negative psychological outcomes (e.g., mothers' depressive symptoms, youths' low self-esteem). CONCLUSIONS: Being subjected to assumptions that challenge individuals' social status can be psychologically harmful. Nuanced developmental variation, and implications regarding the dual role of objectification and English proficiency are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Coping and Culture: The Protective Effects of Shift-&-Persist and Ethnic-Racial Identity on Depressive Symptoms in Latinx Youth.

Shift-&-persist is a coping strategy that has been shown to lead to positive health outcomes in low-SES youth but has not yet been examined with respect to psychological health. This study tests whether the shift-&-persist coping strategy works in tandem with ethnic-racial identity to protect against depressive symptoms in the face of two uncontrollable stressors: economic hardship and peer discrimination. In a sample of 175 Latinx youth (51.4% female; Mage = 12.9), shift-&-persist buffered the positive relation between economic hardship and depressive symptoms. In terms of peer discrimination, among youth who reported little use of shift and persist, discrimination was related to higher depressive symptoms, whereas youth who reported higher amounts of shift and persist (at and above the mean) were protected and did not evidence this association. However, among youth with high ethnic-racial identity, shift-&-persist failed to protect against the deleterious association between peer discrimination and depressive symptoms. These findings suggest that shift-&-persist is protective for Latinx youth, although the context in which it is protective changes based on the racialized/non-racialized nature of the stressor.

The use of charcoal in modified cigarette filters for mainstream smoke carbonyl reduction.

Carbonyls are harmful and potentially harmful constituents (HPHCs) in mainstream cigarette smoke (MSS). Carbonyls, including formaldehyde and acrolein, are carcinogenic or mutagenic in a dose-dependent manner. Past studies demonstrate significant reduction of HPHCs by charcoal filtration. However, limits of charcoal filtration and cigarette design have not yet been investigated in a systematic manner. Objective data is needed concerning the feasibility of HPHC reduction in combustible filtered cigarettes. This systematic study evaluates the effect of charcoal filtration on carbonyl reduction in MSS. We modified filters of ten popular cigarette products with predetermined quantities (100-400 mg) of charcoal in a plug-space-plug configuration. MSS carbonyls, as well as total particulate matter, tar, nicotine, carbon monoxide (TNCO), and draw resistance were quantified. Significant carbonyl reductions were observed across all cigarette products as charcoal loading increased. At the highest charcoal loadings, carbonyls were reduced by nearly 99%. Tar and nicotine decreased modestly (<20%) compared to reductions in carbonyls. Increased draw resistance was significant at only the highest charcoal loadings. This work addresses information gaps in the science base that can inform the evaluation of charcoal filtration as an available technological adaptation to cigarette design which reduces levels of carbonyls in MSS.

In Situ Derivatization and Quantification of Seven Carbonyls in Cigarette Mainstream Smoke.

Carbonyls, especially aldehydes, are a group of harmful volatile organic compounds that are found in tobacco smoke. Seven carbonyls are listed on the FDA's harmful and potential harmful constituents list for tobacco or tobacco smoke. Carbonyls have reactive functional groups and thus are challenging to quantitatively measure in cigarette smoke. The traditional method of measuring carbonyls in smoke involves solvent-filled impinger trapping and derivatization. This procedure is labor-intensive and generates significant volumes of hazardous waste. We have developed a new method to efficiently derivatize and trap carbonyls from mainstream smoke in situ on Cambridge filter pads. The derivatized carbonyls are extracted from the pads and subsequently quantified by ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry. The new method has been validated and applied to research and commercial cigarettes. Carbonyl yields from research cigarettes are comparable to those from other published literature data. With a convenient smoke collection apparatus, a 4 min sample analysis time, and a low- or submicrogram detection limit, this new method not only simplifies and speeds the detection of an important class of chemical constituents in mainstream smoke but also reduces reactive losses and provides a more accurate assessment of carbonyl levels in smoke. Excellent accuracy (average 98%) and precision (14% average relative standard deviation in research cigarettes) ensure this new method's sufficient fidelity to characterize conventional combusted tobacco products, with potential application toward new or emerging products.

We got this: Evaluating racial socialization competency among diverse ethnic-racial groups.

Historically, research on racial socialization (RS) has centered on frequency, beliefs, and content of parent-child communications, with varied applications and implications across racial and ethnic subgroups. The Racial Socialization Competency Scale (RaSCS; Anderson et al., 2020) was developed to assess three dimensions of a novel construct, RS competency (confidence, skills, stress), among Black caregivers. In this article, we investigated the psychometric properties of the RaSCS across diverse ethnic-racial groups. Participants were 778 caregivers (Mage = 44.4 years) of youth between the ages of 10 and 18 recruited from across the United States. The sample was intentionally racially and ethnically diverse, with 26.1% identifying as Black, 24.2% identifying as Latinx, 24.9% identifying as Asian American, and 24.8% identifying as White. Confirmatory factor analyses replicated the previously identified structure of the RaSCS subscales, and scores were reliable. Multigroup measurement invariance analyses supported full scalar invariance across the four racial/ethnic subgroups for the Confidence, Skills, and General RS Stress subscales and partial scalar invariance for the Call to Action RS Stress subscale. These findings suggest that the RaSCS is an appropriate tool for assessing RS competency across racial and ethnic groups and that RS competency as a universal construct is relevant across groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association between prehospital physician clinical experience and discharge at scene - retrospective cohort study.

BACKGROUND: Clinical experience has been shown to affect many patient-related outcomes but its impact in the prehospital setting has been little studied. OBJECTIVES: To determine whether rates of discharge at scene, handover to paramedics and supervision are associated with clinical experience. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective study, performed on all prehospital interventions carried out by physicians working in a mobile medical unit ("service mobile d'urgence et de réanimationË® [SMUR]) at Geneva University Hospitals between 1 January 2010 and 31 December 2019. The main exclusion criteria were phone consultations and major incidents with multiple casualties. EXPOSURE: The exposure was the clinical experience of the prehospital physician at the time of the intervention, in number of years since graduation. OUTCOME MEASURES AND ANALYSIS: The main outcome was the rate of discharge at scene. Secondary outcomes were the rate of handover to paramedics and the need for senior supervision. Outcomes were tabulated and multilevel logistic regression was performed to take into account the cluster effect of physicians. RESULTS: In total, 48,368 adult patients were included in the analysis. The interventions were performed by 219 different physicians, most of whom were male (53.9%) and had graduated in Switzerland (82.7%). At the time of intervention, mean (standard deviation [SD]) level of experience was 5.2 (3.3) years and the median was 4.6 (interquartile range [IQR]: 3.4-6.0). The overall discharge at scene rate was 7.8% with no association between clinical experience and discharge at scene rate. Greater experience was associated with a higher rate of handover to paramedics (adjusted odds ratio [aOR]: 1.17, 95% confidence interval [CI]: 1.13-1.21) and less supervision (aOR: 0.85, 95% CI: 0.82-0.88). CONCLUSION: In this retrospective study, there was no association between level of experience and overall rate of discharge at scene. However, greater clinical experience was associated with higher rates of handover to paramedics and less supervision.

Examining Multiracial Pride, Identity-based Challenges, and Discrimination: An Exploratory Investigation among Biracial Emerging Adults.

This study investigated the main and interactive effects of identity-based challenges, discrimination, and Multiracial pride on psychological distress in Biracial emerging adults. Additionally, we examined whether these associations may differ by Biracial sub-group (e.g., Black-White, Asian-White, Latinx-White, and minority-minority) given their unique racial experiences. Participants were 326 Biracial emerging adults (Mage = 19.57 years old; 75.2% female) recruited from three public universities in the United States for an online survey. For all Biracial groups, identity-based challenges were associated with greater psychological distress. After testing a series of competing multi-group regression models, results indicated that the relations between distress and our predictors: identity-based challenges, discrimination, and Multiracial pride do indeed differ across Biracial sub-group. The most apparent and unique differences were displayed by the Black-White Biracial sub-group. These findings highlight identity-based challenges as a unique risk in the Biracial population and suggest that a principled comparison between Biracial sub-groups is necessary to tease apart group-specific associations between these constructs and psychological distress.

Impact of Operator Medical Specialty on Endotracheal Intubation Rates in Prehospital Emergency Medicine-A Retrospective Cohort Study.

Prehospital endotracheal intubation (ETI) can be challenging, and the risk of complications is higher than in the operating room. The goal of this study was to compare prehospital ETI rates between anaesthesiologists and non-anaesthesiologists. This retrospective cohort study compared prehospital interventions performed by either physicians from the anaesthesiology department (ADP) or physicians from another department (NADP, for non-anaesthesiology department physicians). The primary outcome was the prehospital ETI rate. Overall, 42,190 interventions were included in the analysis, of whom 68.5% were performed by NADP. Intubation was attempted on 2797 (6.6%) patients, without any difference between NADPs and ADPs (6.5 versus 6.7%, p = 0.555). However, ADPs were more likely to proceed to an intubation when patients were not in cardiac arrest (3.4 versus 3.0%, p = 0.026), whereas no difference was found regarding cardiac arrest patients (65.2 versus 67.7%, p = 0.243) (p for homogeneity = 0.005). In a prehospital physician-staffed emergency medical service, overall ETI rates did not depend on the frontline operator's medical specialty background. ADPs were, however, more likely to proceed with ETI than NADPs when patients were not in cardiac arrest. Further studies should help to understand the reasons for this difference.

Votucalis, a Novel Centrally Sparing Histamine-Binding Protein, Attenuates Histaminergic Itch and Neuropathic Pain in Mice.

Votucalis is a biologically active protein in tick (R. appendiculatus) saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host's immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H1 and H2 receptors as well as central histamine H4 receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions.

Diagnostic Value of a SARS-CoV-2 Rapid Test Kit for Detection of Neutralizing Antibodies as a Point-of-Care Surveillance Test.

Detection and tracking of antibodies play an increasingly prominent role in population surveillance and implementation of public health measures to combat the current coronavirus disease 2019 (COVID-19) pandemic, with much attention placed on developing commercial serological assays as point-of-care diagnostic tools. While many rapid diagnostic tests (RDTs) that detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM antibodies have been evaluated, there is currently limited insight into detection of neutralizing antibodies (nAbs) by such modalities. Here, we evaluate performance characteristics of an RDT that detects SARS-CoV-2 IgG antibodies and, importantly, nAbs based on both infection- and vaccine-immunized cohorts by direct comparison to known antibody titers obtained from live virus microneutralization (VMN) assays. We further contextualize interpretations of band intensity of the RDT with reference to the World Health Organization (WHO) International Standard. We report a sensitivity of 94.37% and specificity of 92.50% for SARS-CoV-2 IgG detection and a sensitivity of 94.37% and specificity of 92.68% for nAbs. A limit of detection was determined as 3.125 IU/mL and 25.00 IU/mL, respectively, with reference to the WHO International Standard. We confirm that indication of nAb concentration, as elucidated by band intensity on the RDT, correlated with nAb titers defined by VMN assays and surrogate nAb assays. We additionally observe no cross-reactivity of the nAb test line to SARS-CoV-1 but report display of weak seropositivity for one sample on the SARS-CoV-2 IgG test line. Our study reveals promising performance characteristics of the assessed RDT, which implicates its usefulness in a wide range of diagnostic and epidemiological settings. IMPORTANCE In the ongoing coronavirus disease 2019 (COVID-19) pandemic, antibody tests play an increasingly important role in detecting previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and monitoring of response to vaccinations. In particular, neutralizing antibodies have recently been demonstrated to be highly predictive of immune protection against symptomatic infection. Our study is the first to evaluate a rapid diagnostic test based on samples acquired from both recovered COVID-19 patients and individuals vaccinated for SARS-CoV-2, which detects neutralizing antibodies in addition to SARS-CoV-2 IgG. We report promising sensitivity, specificity, and cross-reactivity profiles, which implicate its usefulness in a wide range of settings as a diagnostic point-of-care tool to aid in curbing transmission and reducing mortality caused by COVID-19 symptoms.

Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.

Background: Individuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients. Objectives: To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern. Methods: The outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022. Results: 22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave. Conclusions: Most individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts.

Endotracheal Intubation Success Rate in an Urban, Supervised, Resident-Staffed Emergency Mobile System: An 11-Year Retrospective Cohort Study.

OBJECTIVES: In the prehospital setting, endotracheal intubation (ETI) is sometimes required to secure a patient's airways. Emergency ETI in the field can be particularly challenging, and success rates differ widely depending on the provider's training, background, and experience. Our aim was to evaluate the ETI success rate in a resident-staffed and specialist-physician-supervised emergency prehospital system. METHODS: This retrospective study was conducted on data extracted from the Geneva University Hospitals' institutional database. In this city, the prehospital emergency response system has three levels of expertise: the first is an advanced life-support ambulance staffed by two paramedics, the second is a mobile unit staffed by an advanced paramedic and a resident physician, and the third is a senior emergency physician acting as a supervisor, who can be dispatched either as backup for the resident physician or when a regular Mobile Emergency and Resuscitation unit (Service Mobile d'Urgence et de Réanimation, SMUR) is not available. For this study, records of all adult patients taken care of by a second- and/or third-level prehospital medical team between 2008 and 2018 were screened for intubation attempts. The primary outcome was the success rate of the ETI attempts. The secondary outcomes were the number of ETI attempts, the rate of ETI success at the first attempt, and the rate of ETIs performed by a supervisor. RESULTS: A total of 3275 patients were included in the study, 55.1% of whom were in cardiac arrest. The overall ETI success rate was 96.8%, with 74.4% success at the first attempt. Supervisors oversaw 1167 ETI procedures onsite (35.6%) and performed the ETI themselves in only 488 cases (14.9%). CONCLUSION: A resident-staffed and specialist-physician-supervised urban emergency prehospital system can reach ETI success rates similar to those reported for a specialist-staffed system.

Evaluation of a Prehospital Rotation by Senior Residents: A Web-Based Survey.

The added value of prehospital emergency medicine is usually assessed by measuring patient-centered outcomes. Prehospital rotations might however also help senior residents acquire specific skills and knowledge. To assess the perceived added value of the prehospital rotation in comparison with other rotations, we analyzed web-based questionnaires sent between September 2011 and August 2020 to senior residents who had just completed a prehospital rotation. The primary outcome was the perceived benefit of the prehospital rotation in comparison with other rotations regarding technical and non-technical skills. Secondary outcomes included resident satisfaction regarding the prehospital rotation and regarding supervision. A pre-specified subgroup analysis was performed to search for differences according to the participants' service of origin (anesthesiology, emergency medicine, or internal medicine). The completion rate was of 71.5% (113/158), and 91 surveys were analyzed. Most senior residents found the prehospital rotation either more beneficial or much more beneficial than other rotations regarding the acquisition of technical and non-technical skills. Anesthesiology residents reported less benefits than other residents regarding pharmacological knowledge acquisition and confidence as to their ability to manage emergency situations. Simulation studies should now be carried out to confirm these findings.

Continual Trials Spontaneous Recognition Tasks in Mice: Reducing Animal Numbers and Improving Our Understanding of the Mechanisms Underlying Memory.

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioral noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioral noise and thus significantly reduces the numbers of rats required to retain statistical power. Here, we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object-location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognize OL combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use.

Chemical Characterization of Mainstream Smoke from SPECTRUM Variable Nicotine Research Cigarettes.

OBJECTIVE: Our objective was to characterize mainstream smoke constituent deliveries from SPECTRUM variable nicotine research cigarettes under 2 machine smoking regimens. SPECTRUM cigarettes are manufactured by the 22nd Century company for the National Institute on Drug Abuse, National Institutes of Health to contain varying (including reduced) levels of nicotine. METHODS: Mainstream smoke constituent deliveries of "tar," nicotine, carbon monoxide, tobacco-specific nitrosamines (N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)), benzo[a]pyrene, aromatic amines, and carbonyls were analyzed in 23 varieties of SPECTRUM cigarettes using ISO 17025 accredited methods. RESULTS: Data are presented as means and standard deviations of 5 replicates for all analytes. CONCLUSIONS: Under the ISO smoking regimen, mean levels of many smoke emissions for SPECTRUM varieties were comparable to the 3R4F research cigarette. Calculated SPECTRUM elasticity ranged from 1.6 to 4.0. Accordingly, under intense machine smoking conditions differences in emissions of SPECTRUM cigarettes were apparent. In addition, NNN increased with smoke nicotine while the same rate of change was not seen for NNK. It is important to monitor levels of chemicals of public health concern and regulatory interest as technologies emerge to reduce levels of nicotine or other targeted chemicals in tobacco products.