[Structures, aims and needs of early career scientists at the German Center for Mental Health]. / Strukturen, Ziele und Bedürfnisse der Early Career Scientists am Deutschen Zentrum für Psychische Gesundheit.

BACKGROUND: Early career scientists (ECS) are agents of change and driving forces in the promotion of mental health. The German Center for Mental Health (DZPG) is a powerful initiative to guide and support careers in the field of mental health. OBJECTIVE: The DZPG aims to make investments to educate, engage, excite, and empower ECS in an interdisciplinary and interinstitutional scientific community. STRUCTURES, TOPICS AND INITIATIVES: To achieve this, the ECS Board at the DZPG plays a central role and consists of 18 elected ECS representatives. The ECS culture gives members the right of voice and embraces bottom-to-top ideas and acknowledges autonomy and co-determination. The DZPG academy was developed to facilitate communication and networking and encourage collaboration among ECS members. The DZPG also navigates several key issues, such as equality, diversity, inclusion, family friendliness and work-life balance, which are essential for a functioning research landscape. The DZPG also extends opportunities to ECS to develop skills and competencies that are essential for contemporary ECS. It complements nationwide support for ECS with funding opportunities, mental health support at work, careers advice and guidance activities. Importantly, the ECS Board is committed to patient and public involvement and engagement, scientific communication and knowledge transfer to multiple settings. CONCLUSION: The DZPG will contribute to fostering ECS training programs for student and academic exchanges, collaborative research, and pooling of resources to acquire grants and scholarships. It will also support the establishment of hubs for ECS networks and promote the expansion of international competence of ECS in Germany.

Gastrointestinal Acute Radiation Syndrome: Mechanisms, Models, Markers, and Medical Countermeasures.

There have been a number of reported human exposures to high dose radiation, resulting from accidents at nuclear power plants (e.g., Chernobyl), atomic bombings (Hiroshima and Nagasaki), and mishaps in industrial and medical settings. If absorbed radiation doses are high enough, evolution of acute radiation syndromes (ARS) will likely impact both the bone marrow as well as the gastrointestinal (GI) tract. Damage incurred in the latter can lead to nutrient malabsorption, dehydration, electrolyte imbalance, altered microbiome and metabolites, and impaired barrier function, which can lead to septicemia and death. To prepare for a medical response should such an incident arise, the National Institute of Allergy and Infectious Diseases (NIAID) funds basic and translational research to address radiation-induced GI-ARS, which remains a critical and prioritized unmet need. Areas of interest include identification of targets for damage and mitigation, animal model development, and testing of medical countermeasures (MCMs) to address GI complications resulting from radiation exposure. To appropriately model expected human responses, it is helpful to study analogous disease states in the clinic that resemble GI-ARS, to inform on best practices for diagnosis and treatment, and translate them back to inform nonclinical drug efficacy models. For these reasons, the NIAID partnered with two other U.S. government agencies (the Biomedical Advanced Research and Development Authority, and the Food and Drug Administration), to explore models, biomarkers, and diagnostics to improve understanding of the complexities of GI-ARS and investigate promising treatment approaches. A two-day workshop was convened in August 2022 that comprised presentations from academia, industry, healthcare, and government, and highlighted talks from 26 subject matter experts across five scientific sessions. This report provides an overview of information that was presented during the conference, and important discussions surrounding a broad range of topics that are critical for the research, development, licensure, and use of MCMs for GI-ARS.

Performance of the Xpert™ Mpox PCR assay with oropharyngeal, anorectal, and cutaneous lesion swab specimens.

Anorectal and oropharyngeal exposures are implicated in sexual transmission of mpox, but authorized assays in the United States are only validated with cutaneous lesion swabs. Diagnostic assays for anorectal and oropharyngeal swabs are needed to address potential future outbreaks. The Cepheid Xpert® Mpox is the first point-of-care assay to receive FDA emergency use authorization in the United States and would be a valuable tool for evaluating these sample types. Our exploratory study demonstrates 100 % positive agreement with our in-house PCR assay for natural positive anorectal and oropharyngeal specimens and 92 % sensitivity with low-positive spiked specimens. The Xpert® assay detected viral DNA in specimens not detected by our reference PCR assay from four participants with mpox DNA at other sites, suggesting it may be more sensitive at low viral loads. In conclusion, the validation of the Xpert® for oropharyngeal and anorectal sample types can be rapidly achieved if clinical need returns and prospective samples become available.

Comparison of RT-PCR and antigen test sensitivity across nasopharyngeal, nares, and oropharyngeal swab, and saliva sample types during the SARS-CoV-2 omicron variant.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.529) variant viral load between the gold standard nasopharyngeal (NP) swab, mid-turbinate (MT)/anterior nasal swabs, oropharyngeal (OP) swabs, and saliva. MT, OP, and saliva samples from symptomatic individuals in Atlanta, GA, in January 2022 and longitudinal samples from a small familial cohort were tested by both RT-PCR and ultrasensitive antigen assays. Higher concentrations in the nares were observed in the familial cohort, but a dominant sample type was not found among 39 cases in the cross-sectional cohort. The composite of positive MT or OP assay for both RT-PCR and antigen assay trended toward higher diagnostic yield but did not achieve significant difference. Our data did not identify a singular preferred sample type for SARS-CoV-2 testing, but higher levels of saliva nucleocapsid, a trend toward higher yield of composite OP/MT result, and association of apparent MT or OP predominance with symptoms warrant further study.

Statin Use and All-Cause Mortality in Nursing Home Residents With and Without Dementia: A Retrospective Cohort Study Using Claims Data.

BACKGROUND AND OBJECTIVES: Little is known about the benefits of statin therapy in older adults with dementia. We aimed to evaluate the role of statin use for all-cause mortality in nursing home residents with and without dementia. METHODS: This retrospective cohort study used claims data collected between January 2015 and December 2019 from a German health and long-term care insurance provider. Propensity score-based Cox proportional hazards models were used to evaluate the association of statin use with all-cause mortality and adjusted for potential confounders in nursing home residents. Subgroup analyses were performed based on the presence or absence of atherosclerotic cardiovascular disease (ASCVD), statin intensity (low, moderate, high), dementia type, age, sex, and level of care required. RESULTS: A total of 282,693 participants were included in the study, of which 96,162 were matched. In total, 68.9% were women, and the mean age was 82.91 years (SD ±7.97). The average observation period was 2.25 years (SD ±1.35), and 54,269 deaths were recorded. Statin use in individuals with dementia resulted in lower all-cause mortality (hazard ratio [HR] 0.80, 95% CI 0.78-0.82, p < 0.001) compared with statin nonusers. Similarly, in individuals without dementia, statin use was associated with lower all-cause mortality (HR 0.73, 95% CI 0.71-0.76, p < 0.001) compared with statin nonusers. Similar findings were observed in subanalyses excluding participants with a history of ASCVD and across subgroups stratified by age, sex, care level required, and dementia type. Statin benefits were consistent among individuals with and without dementia. DISCUSSION: Statin benefits were consistent among individuals with and without dementia. Statin therapy may be continued in nursing home residents with dementia to mitigate the risk of all-cause mortality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that nursing home patients receiving statins have a lower mortality rate, whether they have a dementia diagnosis or not.

Intersectional analysis of social disparities in type 2 diabetes risk among adults in Germany: results from a nationwide population-based survey.

BACKGROUND: Differences in type 2 diabetes risk have been reported for several sociodemographic determinants including sex/gender or socioeconomic status. From an intersectional perspective, it is important to not only consider the role of social dimensions individually, but also their intersections. This allows for a deeper understanding of diabetes risk and preventive needs among diverse population groups. METHODS: As an intersectionality-informed approach, multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was used in a population-based sample of adults without known diabetes in Germany from the cross-sectional survey "Disease knowledge and information needs- Diabetes mellitus (2017)". Diabetes risk was assessed by the German Diabetes Risk Score (GDRS, range 0-122 points), estimating the individual risk of developing type 2 diabetes within the next 5 years based on established self-reported risk factors. Nesting individuals in 12 intersectional strata defined by combining sex/gender, educational level, and history of migration, we calculated measures to quantify the extent to which individual differences in diabetes risk were explained at strata level, and how much this was due to additive or multiplicative intersectional effects of social determinants. RESULTS: Drawing on data of 2,253 participants, we found good discriminatory accuracy of intersectional strata (variance partition coefficient = 14.00% in the simple intersectional model). Model-predicted GDRS means varied between 29.97 (corresponding to a "low risk" of < 2%) in women with high educational level and a history of migration, and 52.73 ("still low risk" of 2-5%) in men with low educational level without a history of migration. Variance in GDRS between strata was mainly explained by additive effects of social determinants (proportional change in variance to intersectional interaction model = 77.95%) with being male and having low educational level being associated with higher GDRS. There was no evidence of multiplicative effects in individual strata. CONCLUSIONS: Type 2 diabetes risk differed between intersectional strata and can to some extent be explained at strata level. The role of intersectional effects was minor and needs to be further investigated. Findings suggest a need for specific preventive measures targeted at large groups with increased diabetes risk, such as men and persons with low educational level.

Increasing vaccinations through an on-site school-based education and vaccination program: A city-wide cluster randomized controlled trial.

Vaccination rates for mumps, measles, and rubella (MMR) and tetanus, diphtheria, pertussis, and polio (Tdap-IPV) fall short of global targets, highlighting the need for vaccination interventions. This study examines the effectiveness of a city-wide school-based educational vaccination intervention as part of an on-site vaccination program aimed at increasing MMR and Tdap-IPV vaccination rates versus on-site vaccination alone among sociodemographically diverse students from Berlin, Germany. The study was a 1:1 two-arm cluster randomized controlled trial, with schools randomly assigned to either the Educational Class Condition (ECC) or the Low-Intensity Information Condition (LIIC). Both received an on-site vaccination program, while students in the ECC received an additional educational unit. Primary outcomes were MMR and Tdap-IPV vaccination rates. In total, 6512 students from 25 randomly selected urban area secondary schools participated. For students providing their vaccination documents on the day of the intervention (2273, 34.9%), adjusted Poisson mixed models revealed significant between-group differences in favor of the ECC (MMR: logRR = 0.47, 95%CI [0.01,0.92], RR = 1.59; Tdap-IPV: logRR = 0.28, 95%CI [0.10,0.47], RR = 1.32). When adjusting for socioeconomic and migration background, between-group differences became non-significant for MMR but remained significant for Tdap-IPV. Findings suggest that educational, school-based on-site vaccination appears to be a promising strategy for increasing vaccination uptake in adolescents.

Effectiveness of a tablet-based intervention for people living with dementia in primary care-A cluster randomized controlled trial.

BACKGROUND: Primary care physicians (PCP) play a key role in the care of people living with dementia. However, the implementation and practicability of the German S3 Dementia Guideline in primary care remain unclear. The main objective of the present study was to evaluate an intervention for improving guideline-based dementia care in primary care. DESIGN: A two-arm, 9-month follow-up cluster-randomized controlled trial with two parallel groups. SETTING: 28 primary care practices in Berlin and the surrounding area in Germany. PARTICIPANTS: A total of N = 28 PCP, N = 91 people living with dementia, and N = 88 informal caregivers participated in the trial. INTERVENTION: A tablet-based intervention to improve adherence to the German S3 Dementia Guideline in primary care was compared to a control group (care as usual plus a handbook on dementia). MeasurementsAdherence to dementia guideline (primary outcome) was measured on PCP' (23 items) and informal caregivers' level (19 items) with a self-developed checklist. Secondary outcomes (quality of life, neuropsychiatric symptoms, activities of daily living, general health status, depression, and caregiver burden) were measured with standardized assessments. Also, post-hoc per-protocol analyses were conducted. RESULTS: No differences in guideline adherence between the intervention and the control group were observed. Further, no significant impact of the intervention on secondary outcomes was detected. CONCLUSION: The DemTab Study did not improve self-reported guideline adherence in PCP. However, important implementation barriers such as lack of interoperability and low applicability of existing German S3 Dementia Guideline in the primary care setting were identified and are being discussed. TRIAL REGISTRATION: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413). Registered 01 April 2019, https://doi.org/10.1186/ISRCTN15854413.

The clinical effectiveness of mepolizumab treatment in severe eosinophilic asthma; outcomes from four years cohort evaluation.

BACKGROUND: Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. METHODS: we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. RESULTS: a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period.The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). CONCLUSIONS: mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity.

Standardization and Comparison of Emergency Use Authorized COVID-19 Assays and Testing Laboratories.

Motivation: The motivation for this work was the need to establish a predefined cutoff based on genome copies per ml (GE/ml) rather than Ct, which can vary depending on the laboratory and assay used. A GE/ml-based threshold was necessary to define what constituted 'low positives" for samples that were included in data sets submitted to the FDA for emergency use approval for SARS-CoV-2 antigen tests. Summary: SARS-CoV-2, the causal agent of the global COVID-19 pandemic, made its appearance at the end of 2019 and is still circulating in the population. The pandemic led to an urgent need for fast, reliable, and widely available testing. After December 2020, the emergence of new variants of SARS-CoV-2 led to additional challenges since new and existing tests had to detect variants to the same extent as the original Wuhan strain. When an antigen-based test is submitted to the Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) consideration it is benchmarked against PCR comparator assays, which yield cycle threshold (CT) data as an indirect indicator of viral load - the lower the CT, the higher the viral load of the sample and the higher the CT, the lower the viral load. The FDA mandates that 10-20% of clinical samples used to evaluate the antigen test have to be low positive. Low positive, as defined by the FDA, are clinical samples in which the CT of the SARS-CoV-2 target gene is within 3 CT of the mean CT value of the approved comparator test's Limit of Detection (LOD). While all comparator tests are PCR-based, the results from different PCR assays used are not uniform. Results vary depending on assay platform, target gene, LOD and laboratory methodology. The emergence and dominance of the Omicron variant further challenged this approach as the fraction of low positive clinical samples dramatically increased as compared to earlier SARS-CoV-2 variants. This led to 20-40% of clinical samples having high CT values and therefore assays vying for an EUA were failing to achieve the 80% Percent Positive Agreement (PPA) threshold required. Here we describe the methods and statistical analyses used to establish a predefined cutoff, based on genome copies per ml (GE/ml) to classify samples as low positive (less than the cutoff GE/ml) or high positive (greater than the cutoff GE/mL). CT 30 for the E gene target using Cobas® SARS-CoV-2-FluA/B platform performed at TriCore Reference Laboratories, and this low positive cutoff value was used for two EUA authorizations. Using droplet digital PCR and methods described here, a value 49,447.72 was determined as the GE/ml equivalent for the low positive cutoff. The CT cutoff corresponding to 49447.72 GE/ml was determined across other platforms and laboratories. The methodology and statistical analysis described here can now be used for standardization of all comparators used for FDA submissions with a goal towards establishing uniform criteria for EUA authorization.

Multisite mpox infection and viral dynamics among persons with HIV in metro-Atlanta.

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with HIV (PWH). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab PCR. Within-participant anatomic site of lowest Ct value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among PWH.

Deaf and hard-of-hearing patients are unsatisfied with and avoid German health care: Results from an online survey in German Sign Language.

BACKGROUND: Approximately 235,000 deaf and hard of hearing (DHH) people live in Germany. Due to communication barriers, medical care for this group is difficult in many respects. Especially in the case of acute illnesses, the possibilities of communication, e.g., through sign language interpreters, are limited. This study investigates the satisfaction of DHH patients with medical care in Germany in unplanned medical consultations. The aim of this study is to provide insights into DHH patient's perception of medical care, to identify barriers and avoidance behaviours that stem from fears, miscommunication, and prior experiences. METHODS: We obtained data from adult DHH participants between February and April 2022 throughout Germany via an online survey in German Sign Language. The responses of N = 383 participants (65% female, M = 44 years, SD = 12.70 years) were included in statistical analyses. Outcomes were convictions of receiving help, satisfaction with healthcare provision, and avoiding healthcare visits; further variables were concerns during healthcare visits, incidences of miscommunication, and a communication score. We calculated t-tests, ANOVAs, correlations, and linear and logistic regression analyses. RESULTS: Our main findings show that (1) DHH patients were unsatisfied with provided healthcare (M = 3.88; SD = 2.34; range 0-10); (2) DHH patients reported many concerns primarily about communication and treatment aspects when visiting a doctor; and (3) 57% of participants deliberately avoided doctor visits even though they experienced symptoms. Factors such as concerns during doctor's visits (B = -0.18; 95%CI: -0.34--0.02; p = .027) or miscommunication with medical staff (B = -0.19; 95%CI: -0.33-0.06; p = .006) were associated with satisfaction with medical care, while we found almost no associations with gender and location, and only few with age and education. CONCLUSIONS: Overall, our findings suggest that DHH patients are unsatisfied with provided healthcare, they deliberately avoid doctor visits, and they face various communication barriers. This study revealed several communication-related determinants of satisfaction with healthcare in DHH patients, such as incidences of miscommunication and the communication score. Communication-related barriers have high potential to be addressed in collaboration with the DHH community. To improve the medical care and the satisfaction with healthcare in DHH patients, training healthcare professionals, digital technologies, and other communication-enhancing interventions should be explored in future intervention studies.

Sensitivity of rapid antigen tests against SARS-CoV-2 Omicron and Delta variants.

Rapid antigen tests (RATs) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of 10 commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using both individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR cycle threshold (CT) value (a rough proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Effect of swab pooling on the Accula point-of-care RT-PCR for SARS-CoV-2 detection.

Introduction: Swab pooling may allow for more efficient use of point-of-care assays for SARS-CoV-2 detection in settings where widespread testing is warranted, but the effects of pooling on assay performance are not well described. Methods: We tested the Thermo-Fisher Accula rapid point-of-care RT-PCR platform with contrived pooled nasal swab specimens. Results: We observed a higher limit of detection of 3,750 copies/swab in pooled specimens compared to 2,250 copies/swab in individual specimens. Assay performance appeared worse in a specimen with visible nasal mucous and debris, although performance was improved when using a standard laboratory mechanical pipette compared to the transfer pipette included in the assay kit. Conclusion: Clinicians and public health officials overseeing mass testing efforts must understand limitations and benefits of swab or sample pooling, including reduced assay performance from pooled specimens. We conclude that the Accula RT-PCR platform remains an attractive candidate assay for pooling strategies owing to the superior analytical sensitivity compared to most home use and point-of-care tests despite the inhibitory effects of pooled specimens we characterized.

Intersectional inequalities in the transition to grandparenthood and cognitive functioning: A longitudinal Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA).

Objectives: With aging societies, more people become vulnerable to experiencing cognitive decline. While normal aging is associated with a deterioration in certain cognitive abilities, little is known about how social determinants intersect to create late-life cognitive functioning inequalities. Simultaneously, the role of grandparenthood is central for older adults and their families. There are indications that social determinants intersect to modulate the effect of the transition to grandparenthood, but further evidence is needed. Our study investigates the relation of transition to grandparenthood with cognitive functioning and explores differences across intersectional strata. Methods: Using longitudinal data from the Survey of Health, Ageing and Retirement in Europe, we analyzed a sample of 19,953 individuals aged 50-85 without grandchildren at the baseline. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy to investigate cognitive functioning differences across 48 intersectional strata, defined by sex/gender, migration, education, and occupation. We allowed the impact of becoming a grandparent to vary across strata by including random slopes. Results: Intersectional strata accounted for 17.43% of the overall variance in cognitive functioning, with most of the stratum-level variation explained by additive effects of the stratum-defining characteristics. Transition to grandparenthood was associated with higher cognitive functioning, with a stronger effect for women. Stratum-level variation in the grandparenthood effect was modest. Discussion: This study highlights the importance of social determinants for understanding heterogeneities in the association of transition to grandparenthood with cognitive functioning. Adopting an intersectional lens is useful to decompose inequalities and derive tailored interventions to promote equal healthy aging.

Respiratory Coinfections in Children With SARS-CoV-2.

BACKGROUND: As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance. METHODS: We performed a retrospective analysis of all pediatric patients 0-21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children's Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021. We determined the proportion of patients with and without SARS-CoV-2 who had respiratory coinfections and performed Poisson regression to determine the likelihood of coinfection and its association with patient age. RESULTS: Of 19,199 respiratory panel tests performed, 1466 (7.64%) were positive for SARS-CoV-2, of which 348 (23.74%) also had coinfection with another pathogen. The most common coinfection was rhino/enterovirus (n = 230, 15.69%), followed by adenovirus (n = 62, 4.23%), and RSV (n = 45, 3.507%). Coinfections with SARS-CoV-2 were most commonly observed in the era of Delta (B.1.617.2) predominance (190, 54.60%), which coincided with periods of peak rhino/enterovirus and RSV transmission. Although coinfections were common among all respiratory pathogens, they were significantly less common with SARS-CoV-2 than other pathogens, with exception of influenza A and B. Children <2 years of age had the highest frequency of coinfection and of detection of any pathogen, including SARS-CoV-2. Among children with SARS-CoV-2, for every 1-year increase in age, the rate of coinfections decreased by 8% (95% CI, 6-9). CONCLUSIONS: Respiratory coinfections were common in children with SARS-CoV-2. Factors associated with the specific pathogen, host, and time period influenced the likelihood of coinfection.

SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 antigen self tests.

Widespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.

Cluster analysis of COVID-19 recovery center patients at a clinic in Boston, MA 2021-2022: impact on strategies for access and personalized care.

BACKGROUND: There are known disparities in COVID-19 resource utilization that may persist during the recovery period for some patients. We sought to define subpopulations of patients seeking COVID-19 recovery care in terms of symptom reporting and care utilization to better personalize their care and to identify ways to improve access to subspecialty care. METHODS: Prospective study of adult patients with prior COVID-19 infection seen in an ambulatory COVID-19 recovery center (CRC) in Boston, Massachusetts from April 2021 to April 2022. Hierarchical clustering with complete linkage to differentiate subpopulations was done with four sociodemographic variables: sex, race, language, and insurance status. Outcomes included ICU admission, utilization of supplementary care, self-report of symptoms. RESULTS: We included 1285 COVID-19 patients referred to the CRC with a mean age of 47 years, of whom 71% were female and 78% White. We identified 3 unique clusters of patients. Cluster 1 and 3 patients were more likely to have had intensive care unit (ICU) admissions; Cluster 2 were more likely to be White with commercial insurance and a low percentage of ICU admission; Cluster 3 were more likely to be Black/African American or Latino/a and have commercial insurance. Compared to Cluster 2, Cluster 1 patients were more likely to report symptoms (ORs ranging 2.4-3.75) but less likely to use support groups, psychoeducation, or care coordination (all p < 0.05). Cluster 3 patients reported greater symptoms with similar levels of community resource utilization. CONCLUSIONS: Within a COVID-19 recovery center, there are distinct groups of patients with different clinical and socio-demographic profiles, which translates to differential resource utilization. These insights from different subpopulations of patients can inform targeted strategies which are tailored to specific patient needs.

The development of a solid lipid nanoparticle (SLN)-based lacticin 3147 hydrogel for the treatment of wound infections.

Chronic wounds affect millions of people globally. This number is set to rise with the increasing incidence of antimicrobial-resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA), which impair the healing of chronic wounds. Lacticin 3147 is a two-peptide chain bacteriocin produced by Lactococcus lactis that is active against S. aureus including MRSA strains. Previously, poor physicochemical properties of the peptides were overcome by the encapsulation of lacticin 3147 into solid lipid nanoparticles. Here, a lacticin 3147 solid lipid nanoparticle gel is proposed as a topical treatment for S. aureus and MRSA wound infections. Initially, lacticin 3147's antimicrobial activity against S. aureus was determined before encapsulation into solid lipid nanoparticles. An optimised gel formulation with the desired physicochemical properties for topical application was developed, and the lacticin-loaded solid lipid nanoparticles and free lacticin 3147 aqueous solution were incorporated into separate gels. The release of lacticin 3147 from both the solid lipid nanoparticle and free lacticin gels was measured where the solid lipid nanoparticle gel exhibited increased activity for a longer period (11 days) compared to the free lacticin gel (9 days). Both gels displayed potent activity ex vivo against S. aureus-infected pig skin with significant bacterial eradication (> 75%) after 1 h. Thus, a long-acting potent lacticin 3147 solid lipid nanoparticle gel with the required physicochemical properties for topical delivery of lacticin 3147 to the skin for the potential treatment of S. aureus-infected chronic wounds was developed.

Sensitivity of Rapid Antigen Tests Against SARS-CoV-2 Omicron and Delta Variants.

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (C T ) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using C T value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.