Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations of currently available rapid antigen tests.

The effects of mutations in continuously emerging variants of SARS-CoV-2 are a major concern for the performance of rapid antigen tests. To evaluate the impact of mutations on 17 antibodies used in 11 commercially available antigen tests with emergency use authorization, we measured antibody binding for all possible Nucleocapsid point mutations using a mammalian surface-display platform and deep mutational scanning. The results provide a complete map of the antibodies' epitopes and their susceptibility to mutational escape. Our data predict no vulnerabilities for detection of mutations found in variants of concern. We confirm this using the commercial tests and sequence-confirmed COVID-19 patient samples. The antibody escape mutational profiles generated here serve as a valuable resource for predicting the performance of rapid antigen tests against past, current, as well as any possible future variants of SARS-CoV-2, establishing the direct clinical and public health utility of our system.

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 human immunodeficiency virus (HIV). 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 polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (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 people with HIV.

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.

[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.

Effectiveness of Psychotherapy for Community-Dwelling Vulnerable Older Adults with Depression and Care Needs: Findings from the PSY-CARE Trial.

BACKGROUND: For older adults with care needs, evidence for the effectiveness of psychotherapy on depression is scarce. METHODS: In PSY-CARE, a pragmatic randomized controlled trial, N = 197 home-living older adults with depression and care needs were randomized into outpatient psychotherapy or an active control condition. Residential psychotherapists offered age-sensitive cognitive-behavioral psychotherapy (at-home if needed). Control group participants received telephone counseling and a self-help guide. Outcomes were assessed at baseline (T1), after (T2), 3 months after (T3), and 12 months after the intervention (T4). RESULTS: There was a significant decrease in depressive symptoms across both arms with Cohen's d T4-T1 = .52 in the psychotherapy and .55 in the control group. Mixed models revealed no statistically significant difference in primary and secondary outcomes between interventions. Posthoc, we found control group participants with greater ADL limitations experienced significantly increased depressive symptoms compared to those reporting lower limitations. CONCLUSIONS: Interventions were successful in reducing depressive symptoms, even though treatment fidelity was decreased due to the COVID-19 pandemic. We could not demonstrate superior effectiveness of psychotherapy for older adults with care needs. CLINICAL IMPLICATIONS: Findings suggest that psychotherapy may be an important and superior treatment to circumvent aggravation of depression in older patients with high functional limitations. TRIAL REGISTRATION: The trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN55646265, February 15, 2019).

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.

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.

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.

Predictive Value of Isolated Symptoms for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children Tested During Peak Circulation of the Delta Variant.

BACKGROUND: Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms. METHODS: Participants aged <18 years presenting for clinical SARS-CoV-2 molecular testing in 6 sites in urban/suburban/rural Georgia (July-October, 2021; Delta variant predominant) were queried about individual symptoms. Participants were classified into 3 groups: asymptomatic, 1 symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the 3 groups were compared. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for isolated symptoms were calculated by fitting a saturated Poisson model. RESULTS: Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70-13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66-10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI, .52-1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively. CONCLUSIONS: With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value.

Evaluation of Recruitment Strategies for Home-Living Vulnerable Older Adults With Depression: Findings From a Randomized Controlled Psychotherapy Trial.

OBJECTIVE: Vulnerable older adults, such as physically impaired or care-dependent individuals, are vastly underrepresented in psychotherapy research. Improving their inclusion in randomized controlled trials is necessary to determine the effectiveness of psychotherapy in this population. This study is the first to systematically evaluate strategies to recruit home-living vulnerable older adults with clinically significant depression into a large randomized controlled psychotherapy trial. Potential participants were approached directly (self-referral) or via cooperation with gatekeepers (gatekeeper-referral). METHODS: Successful recruitment strategies and the person initiating the first contact with the study team were recorded. Recruitment strategies were compared with respect to the number of inquiries and inclusion rates, study personnel's time investment, and participant characteristics (sociodemographics, functional and cognitive status, depression and anxiety scores). RESULTS: Most of the N = 197 participants were included via gatekeeper-referral (80.5%, 95% confidence interval = [74.9, 86.1]), but time investment for gatekeeper-referrals was five times higher than for self-referral by media reports. Clinical psychologists and medical practitioners referred the largest proportion of participants (32.3% each) and referral by medical practitioners led to highest inclusion rates (55.6%; χ²(3) = 8.964, p <0.05). Most participants were referred from a hospital setting (50.3%), whereas referral numbers by medical practices were low (15.9%). Participants who initiated the first contact themselves had higher inclusion rates and were less functionally impaired. CONCLUSION: Including home-living vulnerable older adults into psychotherapy trials requires simultaneous implementation of diverse recruitment strategies. Medical practitioners and psychologists, especially in hospitals, are the most effective recruitment strategy, but self-referral via media is most cost-efficient in terms of time investment.

Concordance of self- and informant-rated depressive symptoms in nursing home residents with Dementia: cross-sectional findings.

BACKGROUND: Depression is highly prevalent in nursing home residents living with moderate to severe dementia. However, assessing depressive symptoms in residents with dementia can be challenging and may vary by rater perspective. We aimed to investigate the concordance of, and factors associated with self- and informant-rated depressive symptoms in nursing home residents with dementia. METHODS: Cross-sectional data was collected from N = 162 nursing home residents with dementia (age: 53-100; 74% women). Self-ratings were assessed with the Geriatric Depression Scale, while the depression and anxiety items of the Neuropsychiatric Inventory were used for informant-ratings. Cohen's Kappa was calculated to determine the concordance of both measures and of each with antidepressant medication. Multivariate associations with sociodemographic variables, self- and informant-rated quality of life, dementia stage, neuropsychiatric symptoms, functional status and antidepressant medication were analysed with linear mixed models and generalized estimating equations. RESULTS: Concordance between self- and single item informant-rated depressive symptoms was minimal (Cohen's Kappa = .22, p = .02). No concordance was found for self-reported depressive symptoms and the combined informant-rated depression-anxiety score. Self-reported depression was negatively associated with self-rated quality of life (ß = -.32; 95%CI: -.45 to -.19, p < .001), informant-rated quality of life (ß = -.25; 95%CI: -.43 to -.07, p = .005) and functional status (ß = -.16; 95%CI: -.32 to -.01, p = .04), whilst single item informant-rated depression revealed negative associations with informant-rated quality of life (ß = -.32; 95%CI: -.52 to -.13, p = .001) and dementia stage (ß = -.31; 95%CI: -.52 to -.10, p = .004). The combined informant-rated depression-anxiety score showed negative associations with self-rated quality of life (ß = -.12; 95%CI: -.22 to -.03, p = .01) and dementia stage (ß = -.37; 95%CI: -.67 to -.07, p = .02) and a positive association with neuropsychiatric symptoms (ß = .30; 95%CI: .10 to .51, p = .004). No concordance was found with antidepressant medication. CONCLUSIONS: In line with our expectations, low agreement and unique association patterns were found for both measures. These findings indicate that both instruments address different aspects of depression und underline the need for comprehensive approaches when it comes to detecting signs of clinically relevant depressive symptoms in dementia. TRIAL REGISTRATION: The trial was registered with the ISRCTN registry (Trial registration number: ISRCTN98947160 ).

A tablet-based intervention for activating nursing home residents with dementia: results from a cluster-randomized controlled trial.

OBJECTIVES: To investigate global and momentary effects of a tablet-based non-pharmacological intervention for nursing home residents living with dementia. DESIGN: Cluster-randomized controlled trial. SETTING: Ten nursing homes in Germany were randomly allocated to the tablet-based intervention (TBI, 5 units) or conventional activity sessions (CAS, 5 units). PARTICIPANTS: N = 162 residents with dementia. INTERVENTION: Participants received regular TBI (n = 80) with stimulating activities developed to engage people with dementia or CAS (n = 82) for 8 weeks. MEASUREMENTS: Apathy Evaluation Scale (AES-I, primary outcome), Quality of Life in Alzheimer's Disease scale, QUALIDEM scale, Neuropsychiatric Inventory, Geriatric Depression Scale, and psychotropic medication (secondary outcomes). Momentary quality of life was assessed before and after each activity session. Participants and staff were blinded until the collection of baseline data was completed. Data were analyzed with linear mixed-effects models. RESULTS: Levels of apathy decreased slightly in both groups (mean decrease in AES-I of .61 points, 95% CI -3.54, 2.33 for TBI and .36 points, 95% CI -3.27, 2.55 for CAS). Group difference in change of apathy was not statistically significant (ß = .25; 95% CI 3.89, 4.38, p = .91). This corresponds to a standardized effect size (Cohen's d) of .02. A reduction of psychotropic medication was found for TBI compared to CAS. Further analyses revealed a post-intervention improvement in QUALIDEM scores across both groups and short-term improvements of momentary quality of life in the CAS group. CONCLUSIONS: Our findings suggest that interventions involving tailored activities have a beneficial impact on global and momentary quality of life in nursing home residents with dementia. Although we found no clear advantage of TBI compared to CAS, tablet computers can support delivery of non-pharmacological interventions in nursing homes and facilitate regular assessments of fluctuating momentary states.

Mobility enhancement among older adults 75 + in rural areas: Study protocol of the MOBILE randomized controlled trial.

BACKGROUND: Maintaining mobility in old age is crucial for healthy ageing including delaying the onset and progress of frailty. However, the extent of an individuals´ mobility relies largely on their personal, social, and environmental resources as outlined in the Life-Space Constriction Model. Recent studies mainly focus on facilitating habitual out-of-home mobility by fostering one type of resources only. The MOBILE trial aims at testing whether tablet-assisted motivational counselling enhances the mobility of community-dwelling older adults by addressing personal, social, and environmental resources. METHODS: In the MOBILE randomized controlled trial, we plan to enrol 254 community-dwelling older adults aged 75 and older from Havelland, a rural area in Germany. The intervention group will receive a tablet-assisted motivational counselling at the participant´s home and two follow-up telephone sessions. Main focus of the counselling sessions lays on setting and adapting individual mobility goals and applying action planning and habit formation strategies by incorporating the personal social network and regional opportunities for engaging in mobility related activities. The control group will receive postal general health information. The primary mobility outcome is time out-of-home assessed by GPS (GPS.Rec2.0-App) at three points in time (baseline, after one month, and after three months for seven consecutive days each). Secondary outcomes are the size of the GPS-derived life-space convex hull, self-reported life-space mobility (LSA-D), physical activity (IPAQ), depressive symptoms (GDS), frailty phenotype, and health status (SF-12). DISCUSSION: The MOBILE trial will test the effect of a motivational counselling intervention on out-of-home mobility in community-dwelling older adults. Novel aspects of the MOBILE trial include the preventive multi-level intervention approach in combination with easy-to-use technology. The ecological approach ensures low-threshold implementation, which increases the benefit for the people in the region. TRIAL REGISTRATION: The MOBILE trial is prospectively registered at DRKS (Deutsches Register Klinischer Studien, German Registry of Clinical Trials) DRKS00025230 . Registered 5 May 2021.

Concordance of SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents.

Importance: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown. Objective: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers. Design, Setting, and Participants: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children's Healthcare of Atlanta system from July to August 2021. Exposures: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization. Results: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65). Conclusions and Relevance: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.

Correlation of SARS-CoV-2 Subgenomic RNA with Antigen Detection in Nasal Midturbinate Swab Specimens.

Among symptomatic outpatients, subgenomic RNA of severe acute respiratory syndrome coronavirus 2 in nasal midturbinate swab specimens was concordant with antigen detection but remained detectable in 13 (82.1%) of 16 nasopharyngeal swab specimens from antigen-negative persons. Subgenomic RNA in midturbinate swab specimens might be useful for routine diagnostics to identify active virus replication.

Unveiling the histopathologic spectrum of MRI-guided breast biopsies: an institutional pathological-radiological correlation.

PURPOSE: Breast magnetic resonance imaging (MRI) has high sensitivity but suffers from low specificity, resulting in many benign breast biopsies for MRI-detected lesions. We sought to compare histologic findings between patients who underwent MRI-guided breast biopsy versus biopsy via other imaging modalities as well as to examine features associated with malignancy in the MRI cohort to help inform MRI-biopsy practice. METHODS: A 2-year (2018-2019) retrospective review of breast biopsies at our enterprise was conducted. Biopsies were categorized as stereotactic, ultrasound, MRI, or palpation guided. Pathology was categorized as benign (further divided into nine categories), atypical, or malignant (subdivided into in situ and invasive carcinoma). Pathology was compared between biopsy groups. Clinical, pathologic, and imaging features were compared between pathology groups within the MRI cohort. RESULTS: 5828 biopsies from 4154 patients were reviewed, including 548 MRI-guided biopsies with stratification of MRI-biopsy pathology as follows: 69% benign, 13.8% atypical, and 17.2% malignant. Among benign MRI biopsies, there was higher frequency of "clustered cysts with papillary apocrine metaplasia" (56/548; 10.2%) and lower rate of fibroadenoma/fibroadenomatous change (55/548; 10%) compared to other modalities (158 or 3% and 1144 or 21.7% of 5280 biopsies, respectively). Multivariate analysis revealed indication of breast cancer (p < .0001), ipsilateral cancer (p < .0001) and rapid initial phase kinetics (p = .017) to remain significantly associated with malignant MRI-biopsy pathology. CONCLUSIONS: A concurrent or recent breast cancer diagnosis was most predictive of malignancy on MRI-guided breast biopsy. Combined MRI feature evaluation and radiologic-pathologic concordance activities may allow for prognostic refinement and improved risk stratification.

Recruiting general practitioners and patients with dementia into a cluster randomised controlled trial: strategies, barriers and facilitators.

BACKGROUND: Recruitment of general practitioners (GPs) and their patients is reported as one of the most challenging steps when undertaking primary care research. The present paper describes the recruitment process of a cluster randomised controlled trial (cRCT) aiming to improve dementia care in the primary care setting. METHODS: Recruitment data was analysed descriptively using frequency tables to investigate comparisons of recruitment rates and results of different recruitment strategies as well as reasons for participation and non-participation of GPs, patients with dementia (PwD) and their caregivers. RESULTS: Over a period of 23 months, N = 28 GPs were successfully included in the cRCT. This represents an overall recruitment rate of 4.6%. The most efficient strategy in terms of high response and low labour-intensity involved the dissemination of calls for participation in a GP research network. Most frequently reported reasons for GP's participation were Improvement of patient's well-being (n = 22, 79%) followed by Interest in dementia research (n = 18, 64%). The most common reasons for non-participation were Lack of time (n = 71, 34%) followed by Not interested in participation (n = 63, 30%). On a patient level, N = 102 PwD were successfully recruited. On average, each GP referred about n = 7 PwD (range: 1-17; mdn = 6; IQR = 3.5) and successfully recruited about n = 4 PwD (range: 1-11; mdn = 3; IQR = 3.5). CONCLUSION: First, our findings propose GP research networks as a promising strategy to promote recruitment and participation of GPs and their patients in research. Second, present findings highlight the importance of including GPs and their interests in specific research topics in early stages of research in order to ensure a successful recruitment. Finally, results do not support cold calls as a successful strategy in the recruitment of GPs. TRIAL REGISTRATION: The trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413 ). Registered 01 April 2019.

Dementia care and the role of guideline adherence in primary care: cross-sectional findings from the DemTab study.

BACKGROUND: General practitioners (GPs) play a key role in the care of people with dementia (PwD). However, the role of the German Dementia Guideline in primary care remains unclear. The main objective of the present study was to examine the role of guideline-based dementia care in general practices. METHODS: A cross-sectional analysis of data obtained from the DemTab study was conducted. Descriptive analyses of sociodemographic and clinical characteristics for GPs (N = 28) and PwD (N = 91) were conducted. Adherence to the German Dementia Guideline of GPs was measured at the level of PwD. Linear Mixed Models were used to analyze the associations between adherence to the German Dementia Guideline and GP factors at individual (age, years of experience as a GP, frequency of utilization of guideline, perceived usefulness of guideline) and structural (type of practice, total number of patients seen by a participating GP, and total number of PwD seen by a participating GP) levels as well as between adherence to the German Dementia Guideline and PwD's quality of life. RESULTS: Self-reported overall adherence of GPs was on average 71% (SD = 19.4, range: 25-100). Adherence to specific recommendations varied widely (from 19.2 to 95.3%) and the majority of GPs (79.1%) reported the guideline as only partially or somewhat helpful. Further, we found lower adherence to be significantly associated with higher numbers of patients (γ10 = - 5.58, CI = - 10.97, - 0.19, p = .04). No association between adherence to the guideline and PwD's quality of life was found (γ10 = -.86, CI = - 4.18, 2.47, p = .61). CONCLUSION: The present study examined the role of adherence to the German Dementia Guideline recommendations in primary care. Overall, GPs reported high levels of adherence. However, major differences across guideline recommendations were found. Findings highlight the importance of guidelines for the provision of care. Dementia guidelines for GPs need to be better tailored and addressed. Further, structural changes such as more time for PwD may contribute to a sustainable change of dementia care in primary care. TRIAL REGISTRATION: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413 ). Registered 01 April 2019.

Nisin J, a Novel Natural Nisin Variant, Is Produced by Staphylococcus capitis Sourced from the Human Skin Microbiota.

The skin microbiota is thought to play a key role in host protection from infection. Nisin J is a novel nisin variant produced by Staphylococcus capitis APC 2923, a strain isolated from the toe web space area in a screening study performed on the human skin microbiota. Whole-genome sequencing and mass spectrometry of the purified peptide confirmed that S. capitis APC 2923 produces a 3,458-Da bacteriocin, designated nisin J, which exhibited antimicrobial activity against a range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes The gene order in the nisin J gene cluster (nsjFEGBTCJP) differs from that of other nisin variants in that it is lacking the nisin regulatory genes, nisRK, as well as the nisin immunity gene nisI Nisin J has 9 amino acid changes compared to prototypical nisin A, with 8 amino acid substitutions, 6 of which are not present in other nisin variants (Ile4Lys, Met17Gln, Gly18Thr, Asn20Phe, Met21Ala, Ile30Gly, Val33His, and Lys34Thr), and an extra amino acid close to the C terminus, rendering nisin J the only nisin variant to contain 35 amino acids. This is the first report of a nisin variant produced by a Staphylococcus species and the first nisin producer isolated from human skin.IMPORTANCE This study describes the characterization of nisin J, the first example of a natural nisin variant, produced by a human skin isolate of staphylococcal origin. Nisin J displays inhibitory activity against a wide range of bacterial targets, including MRSA. This work demonstrates the potential of human commensals as a source for novel antimicrobials that could form part of the solution to antibiotic resistance across a broad range of bacterial pathogens.