The Impact of Video-Based Microinterventions on Attitudes Toward Mental Health and Help Seeking in Youth: Web-Based Randomized Controlled Trial.

BACKGROUND: Mental health (MH) problems in youth are prevalent, burdening, and frequently persistent. Despite the existence of effective treatment, the uptake of professional help is low, particularly due to attitudinal barriers. OBJECTIVE: This study evaluated the effectiveness and acceptability of 2 video-based microinterventions aimed at reducing barriers to MH treatment and increasing the likelihood of seeking professional help in young people. METHODS: This study was entirely web based and open access. The interventions addressed 5 MH problems: generalized anxiety disorder, depression, bulimia, nonsuicidal self-injury, and problematic alcohol use. Intervention 1 aimed to destigmatize and improve MH literacy, whereas intervention 2 aimed to induce positive outcome expectancies regarding professional help seeking. Of the 2435 participants who commenced the study, a final sample of 1394 (57.25%) participants aged 14 to 29 years with complete data and sufficient durations of stay on the video pages were randomized in a fully automated manner to 1 of the 5 MH problems and 1 of 3 conditions (control, intervention 1, and intervention 2) in a permuted block design. After the presentation of a video vignette, no further videos were shown to the control group, whereas a second, short intervention video was presented to the intervention 1 and 2 groups. Intervention effects on self-reported potential professional help seeking (primary outcome), stigma, and attitudes toward help seeking were examined using analyses of covariance across and within the 5 MH problems. Furthermore, we assessed video acceptability. RESULTS: No significant group effects on potential professional help seeking were found in the total sample (F2,1385=0.99; P=.37). However, the groups differed significantly with regard to stigma outcomes and the likelihood of seeking informal help (F2,1385=3.75; P=.02). Furthermore, separate analyses indicated substantial differences in intervention effects among the 5 MH problems. CONCLUSIONS: Interventions to promote help seeking for MH problems may require disorder-specific approaches. The study results can inform future research and public health campaigns addressing adolescents and young adults. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023110; https://drks.de/search/de/trial/DRKS00023110.

Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial.

OBJECTIVES: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown. METHODS: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months. RESULTS: CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS. DISCUSSION: Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.

Reasons for non-participation of children and adolescents in a large-scale school-based mental health project.

Background: Non-participation in mental health studies is an under-explored but very important topic. Investigating reasons for non-participation holds promise for the planning of future study designs and recruitment strategies. This study aimed at investigating reasons for children and adolescents (C&A) not participating in a school-based mental health research project. Methods: Data collection took place within the school-based recruitment of a large-scale multi-site project ("ProHEAD-Promoting Help-seeking using E-technology for Adolescents") in Germany. Participants were N = 534 C&A aged ≥ 12 years attending secondary schools. The present cross-sectional study analyzed anonymous survey data of C&A who themselves or whose parents, respectively, did not provide written consent to participate in the mental health research project. The questionnaire consisted of 14 items covering potential reasons for non-participation, and four free text fields. Besides descriptive statistics, free text field answers were analyzed using qualitative content analysis. Results: Students indicated an average of M = 2.94 (SD = 1.75) reasons for their non-participation in the project. In the descriptive analysis of indicated items, the three most frequently reported reasons for non-participation included students reporting to not be concerned by the topic "mental health" (n = 290, 54.3%), not having returned the consent form to the teacher (n = 175, 32.8%), and not having time for participation (n = 149, 27.9%). In the qualitative content analysis, the most frequently assigned categories were organizational reasons (n = 216, 57.1%), general disinterest in study participation (n = 139, 36.8%), and personal attitudes toward the topic "mental health" (n = 84, 22.2%), such as not being concerned with the topic "mental health" (n = 23, 6.1%) or being too concerned with the topic "mental health" (n = 16, 4.2%). Conclusion: The study provides unique insights into reasons for C&A and their caregivers not participating in a large federally funded mental health research project. The results suggest that in order to increase participation rates, stigma should be reduced, parents as well as teachers should be involved where possible, and the use of incentives might be helpful. The study highlights the importance of assessing reasons for non-participation, especially in online intervention studies on mental health.

Serum cytokines predict efficacy and toxicity, but are not useful for disease monitoring in lung cancer treated with PD-(L)1 inhibitors.

Introduction: PD-(L)1 inhibitors (IO) have improved the prognosis of non-small-cell lung cancer (NSCLC), but more reliable predictors of efficacy and immune-related adverse events (irAE) are urgently needed. Cytokines are important effector molecules of the immune system, whose potential clinical utility as biomarkers remains unclear. Methods: Serum samples from patients with advanced NSCLC receiving IO either alone in the first (1L, n=46) and subsequent lines (n=50), or combined with chemotherapy (ICT, n=108) were analyzed along with age-matched healthy controls (n=15) at baseline, after 1 and 4 therapy cycles, and at disease progression (PD). Patients were stratified in rapid progressors (RP, progression-free survival [PFS] <120 days), and long-term responders (LR, PFS >200 days). Cytometric bead arrays were used for high-throughput quantification of 20 cytokines and other promising serum markers based on extensive search of the current literature. Results: Untreated NSCLC patients had increased levels of various cytokines and chemokines, like IL-6, IL-8, IL-10, CCL5, G-CSF, ICAM-1, TNF-RI and VEGF (fold change [FC]=1.4-261, p=0.026-9x10-7) compared to age-matched controls, many of which fell under ICT (FC=0.2-0.6, p=0.014-0.002), but not under IO monotherapy. Lower baseline levels of TNF-RI were associated with longer PFS (hazard ratio [HR]= 0.42-0.54; p=0.014-0.009) and overall survival (HR=0.28-0.34, p=0.004-0.001) after both ICT and IO monotherapy. Development of irAE was associated with higher baseline levels of several cytokines, in particular of IL-1ß and angiogenin (FC=7-9, p=0.009-0.0002). In contrast, changes under treatment were very subtle, there were no serum correlates of radiologic PD, and no association between dynamic changes in cytokine concentrations and clinical outcome. No relationship was noted between the patients' serologic CMV status and serum cytokine levels. Conclusions: Untreated NSCLC is characterized by increased blood levels of several pro-inflammatory and angiogenic effectors, which decrease under ICT. Baseline serum cytokine levels could be exploited for improved prediction of subsequent IO benefit (in particular TNF-RI) and development of irAE (e.g. IL-1ß or angiogenin), but they are not suitable for longitudinal disease monitoring. The potential utility of IL-1/IL-1ß inhibitors in the management and/or prevention of irAE in NSCLC warrants investigation.

Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™: An antigen-detecting point-of-care device for SARS-CoV-2.

PURPOSE: Rapid antigen-detecting tests (Ag-RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transform pandemic control. Thus far, sensitivity (≤ 85%) of lateral-flow assays has limited scale-up. Conceivably, microfluidic immunofluorescence Ag-RDTs could increase sensitivity for SARS-CoV-2 detection. METHODS: This multi-centre diagnostic accuracy study investigated performance of the microfluidic immunofluorescence LumiraDx™ assay, enrolling symptomatic and asymptomatic participants with suspected SARS-CoV-2 infection. Participants collected a supervised nasal mid-turbinate (NMT) self-swab for Ag-RDT testing, in addition to a professionally collected nasopharyngeal (NP) swab for routine testing with reverse transcriptase polymerase chain reaction (RT-PCR). Results were compared to calculate sensitivity and specificity. Sub-analyses investigated the results by viral load, symptom presence and duration. An analytical study assessed exclusivity and limit-of-detection (LOD). In addition, we evaluated ease-of-use. RESULTS: The study was conducted between November 2nd 2020 and 4th of December 2020. 761 participants were enrolled, with 486 participants reporting symptoms on testing day. 120 out of 146 RT-PCR positive cases were detected positive by LumiraDx™, resulting in a sensitivity of 82.2% (95% CI 75.2-87.5%). Specificity was 99.3% (CI 98.3-99.7%). Sensitivity was increased in individuals with viral load ≥ 7 log10 SARS-CoV2 RNA copies/ml (93.8%; CI 86.2-97.3%). Testing against common respiratory commensals and pathogens showed no cross-reactivity and LOD was estimated to be 2-56 PFU/mL. The ease-of-use-assessment was favourable for lower throughput settings. CONCLUSION: The LumiraDx™ assay showed excellent analytical sensitivity, exclusivity and clinical specificity with good clinical sensitivity using supervised NMT self-sampling. TRIAL REGISTRATION NUMBER AND REGISTRATION DATE: DRKS00021220 and 01.04.2020.

Mental Health, Social and Emotional Well-Being, and Perceived Burdens of University Students During COVID-19 Pandemic Lockdown in Germany.

Background: The COVID-19 pandemic has been affecting everyone's daily life in unknown measures since its outbreak. Nearly all Universities around the globe were affected. Further, young people and University students in particular, are known to be vulnerable for developing mental disorders. This study aims to examine the mental health social and emotional well-being and perceived burdens of University students during COVID-19 pandemic lockdown in Germany. Materials and Methods: This cross-sectional and anonymous online survey among University students assessed mental health status with standardized measures (depressive symptoms, alcohol and drug consumption, and eating disorder symptoms), attitudes toward the COVID-19 pandemic and perceived burdens, and social and emotional aspects of the pandemic (social support, perceived stress, loneliness, and self-efficacy). Results: In total, N = 3,382 German University students participated. Nearly half of the students (49%) reported that they are worried or very much worried about the COVID-19 pandemic. The majority supports the governmental lockdown measures (85%). A Patient Health Questionnaire-9 (PHQ-9) sum score of 10 or above, indicating clinically relevant depressive symptoms, was reported by 37% (n = 1,249). The PHQ-9 sum score was on average 8.66 (SD = 5.46). Suicidal thoughts were indicated by 14.5% of the participants. Levels of depressive symptoms differed significantly for the different self-rated income changes during the pandemic (increase, decrease, no change in income). Further, levels of depressive symptoms and suicidal ideation differed significantly for students from different faculties. Multiple regression analyses revealed that not being a parent, having no indirect social contact one or two times a week, higher perceived stress, higher experienced loneliness, lower social support, and lower self-efficacy significantly predicted higher scores of depressive symptoms, also higher hazardous alcohol use, and higher levels of eating disorder symptoms. Other aspects of lifestyle such as social and cultural activities, dating, and hobbies were reported to be negatively affected during the pandemic. Conclusion: The present study implies that University students are vulnerable and due to elevated depressive symptoms at risk, being hit hard by the pandemic, but are in general coping adaptively. Low-threshold online interventions promoting help-seeking and also targeting various mental health conditions might bridge the gap the COVID-19 pandemic opened up recently.

Clinical utility of multigene analysis in over 25,000 patients with neuromuscular disorders.

OBJECTIVE: Molecular genetic testing for hereditary neuromuscular disorders is increasingly used to identify disease subtypes, determine prevalence, and inform management and prognosis, and although many small disease-specific studies have demonstrated the utility of genetic testing, comprehensive data sets are better positioned to assess the complexity of genetic analysis. METHODS: Using high depth-of-coverage next-generation sequencing (NGS) with simultaneous detection of sequence variants and copy number variants (CNVs), we tested 25,356 unrelated individuals for subsets of 266 genes. RESULTS: A definitive molecular diagnosis was obtained in 20% of this cohort, with yields ranging from 4% among individuals with congenital myasthenic syndrome to 33% among those with a muscular dystrophy. CNVs accounted for as much as 39% of all clinically significant variants, with 10% of them occurring as rare, private pathogenic variants. Multigene testing successfully addressed differential diagnoses in at least 6% of individuals with positive results. Even for classic disorders like Duchenne muscular dystrophy, at least 49% of clinically significant results were identified through gene panels intended for differential diagnoses rather than through single-gene analysis. Variants of uncertain significance (VUS) were observed in 53% of individuals. Only 0.7% of these variants were later reclassified as clinically significant, most commonly in RYR1, GDAP1, SPAST, and MFN2, providing insight into the types of evidence that support VUS resolution and informing expectations of reclassification rates. CONCLUSIONS: These data provide guidance for clinicians using genetic testing to diagnose neuromuscular disorders and represent one of the largest studies demonstrating the utility of NGS-based testing for these disorders.

Risk assessment for infected endocarditis in Staphylococcus aureus bacteremia patients: When is transesophageal echocardiography needed?

AIMS: Echocardiography is the main technique for the diagnosis of endocarditis in patients with Staphylococcus aureus bacteremia (SAB), but a consensus about performing transthoracic echocardiography or transesophageal echocardiography (TEE) as first-line tests is currently lacking. Recently, a new scoring system has been proposed by Palraj et al. to guide the use of TEE in this population. Our aim was to validate this scoring system or modify it, if necessary. METHODS AND RESULTS: Data from SAB patients admitted from 2012 to 2014 were collected. We tested the Palraj scores to stratify patients' risk for endocarditis. Moreover, we analyzed our population to identify any other possible clinical predictors of endocarditis not included in the score. Endocarditis was diagnosed in 38 of 205 patients (18.5%). Palraj's score was effective in the detection of patients at high risk of endocarditis. In addition, we identified the presence of cardiac devices, prolonged bacteremia and intravenous drug abuse (IVDA) as elements strongly correlated with endocarditis. Two scoring systems (Day-1 and Day-5) were derived including IVDA as a variable. Using a Day-1 cut-off value ≥5 and a Day-5 cut-off value ≥2, the 'modified Palraj's score' showed sensitivities of 42.1% and 97.0% and specificities of 88.6% and 32.0% for Day-1 and Day-5 scores, respectively. CONCLUSION: We modify and expand upon an effective scoring system to identify SAB patients at high risk for endocarditis in order to guide use of TEE. The inclusion of IVDA in the criteria for the calculation of the scores improves its effectiveness.

Hip fracture in the elderly: a re-analysis of the EPIDOS study with causal Bayesian networks.

OBJECTIVES: Hip fractures commonly result in permanent disability, institutionalization or death in elderly. Existing hip-fracture predicting tools are underused in clinical practice, partly due to their lack of intuitive interpretation. By use of a graphical layer, Bayesian network models could increase the attractiveness of fracture prediction tools. Our aim was to study the potential contribution of a causal Bayesian network in this clinical setting. A logistic regression was performed as a standard control approach to check the robustness of the causal Bayesian network approach. SETTING: EPIDOS is a multicenter study, conducted in an ambulatory care setting in five French cities between 1992 and 1996 and updated in 2010. The study included 7598 women aged 75 years or older, in which fractures were assessed quarterly during 4 years. A causal Bayesian network and a logistic regression were performed on EPIDOS data to describe major variables involved in hip fractures occurrences. RESULTS: Both models had similar association estimations and predictive performances. They detected gait speed and mineral bone density as variables the most involved in the fracture process. The causal Bayesian network showed that gait speed and bone mineral density were directly connected to fracture and seem to mediate the influence of all the other variables included in our model. The logistic regression approach detected multiple interactions involving psychotropic drug use, age and bone mineral density. CONCLUSION: Both approaches retrieved similar variables as predictors of hip fractures. However, Bayesian network highlighted the whole web of relation between the variables involved in the analysis, suggesting a possible mechanism leading to hip fracture. According to the latter results, intervention focusing concomitantly on gait speed and bone mineral density may be necessary for an optimal prevention of hip fracture occurrence in elderly people.