The Behavior and Mind Health (BeMIND) study: Methods, design and baseline sample characteristics of a cohort study among adolescents and young adults

Objectives: The Behavior and Mind Health (BeMIND) study is a population‐based cohort study of adolescents and young adults from Dresden, Germany. The aim is to investigate psychological and behavioral factors linked to a range of mental disorders and health behaviors and their interaction with social‐environmental and genetic/biologic factors. Methods: A random sample of 14–21 year olds was drawn from the population registry in 2015. The baseline investigation was completed 11/2015–12/2016 (N = 1,180). Assessments include standardized diagnostic interview, cognitive‐affective tasks, questionnaires, biosamples, and ecologic momentary assessment in real life with combined actigraphic/geographic monitoring. In the family study component, parents completed similar assessments and provided information on child's early development. Results: The participation rate (minimum response proportion) was 21.7%; the cooperation rate was 43.4%. Acceptance and completion of study components were high. General health data indicate that more than 80% reported no or only mild impairment due to mental or somatic health problems in the past year; about 20% ever sought treatment for mental health problems or chronic somatic illnesses, respectively. Conclusions: Data from BeMIND baseline and follow‐up investigations will provide novel insights into contributors to health and disease as adolescents grow into adulthood

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Density estimation via best L2L^2-approximation on classes of step functions

summary:We establish consistent estimators of jump positions and jump altitudes of a multi-level step function that is the best $L^2$-approximation of a probability density function $f$. If $f$ itself is a step-function the number of jumps may be unknown

Writing a discussion section: how to integrate substantive and statistical expertise

Abstract Background When discussing results medical research articles often tear substantive and statistical (methodical) contributions apart, just as if both were independent. Consequently, reasoning on bias tends to be vague, unclear and superficial. This can lead to over-generalized, too narrow and misleading conclusions, especially for causal research questions. Main body To get the best possible conclusion, substantive and statistical expertise have to be integrated on the basis of reasonable assumptions. While statistics should raise questions on the mechanisms that have presumably created the data, substantive knowledge should answer them. Building on the related principle of Bayesian thinking, we make seven specific and four general proposals on writing a discussion section. Conclusion Misinterpretation could be reduced if authors explicitly discussed what can be concluded under which assumptions. Informed on the resulting conditional conclusions other researchers may, according to their knowledge and beliefs, follow a particular conclusion or, based on other conditions, arrive at another one. This could foster both an improved debate and a better understanding of the mechanisms behind the data and should therefore enable researchers to better address bias in future studies

Evidence for the association between physiological and emotional states in adolescents and young adults without psychopathology under ecologically valid conditions

Well-powered studies on the physiological concomitants underlying affect and its regulation during emerging adulthood are warranted to provide novel insight into mental health. The association between autonomic nervous system activity and emotional states occurring under natural conditions in daily life was investigated in individuals (N = 549, age 14-21, females 45.6%) without any lifetime mental disorder from an epidemiological cohort study in Germany. Using ecological momentary assessment, mood and optimism/pessimism were assessed over 4 days simultaneously with continuous heart rate monitoring. Lower vagal activity was found in mood states accompanied by high arousal (wakefulness, mania) and greater vagal activity in mood states with low arousal (calmness, pessimism). Findings illustrate important associations between autonomic nervous system activity and mood in youth under ecologically valid conditions. Vagal activity presents a prominent pathway by which mood may influence physiological function or vice versa. In contrast to commonly performed laboratory assessments, the ambulatory assessment in participants' daily life allows an application of the results to the field

Reliability and Validity of a German Standardized Diagnostic Interview Module for ICD-11 Adjustment Disorder

The ICD-11 includes a new definition of adjustment disorder (AjD). The present study aimed to examine interrater reliability, internal consistency, and construct validity of a new diagnostic interview module to assess ICD-11 AjD. Data from two studies that used a standardized diagnostic interview assessment (i.e., DIA-X/M-CIDI and updated DIA-X-5) were used. For interrater reliability, agreement indicators (i.e., κ) were calculated using data from the DIA-X-5 test-retest study (N = 60). To examine internal consistency and construct validity, Cronbach's alpha values and the Kuder-Richardson correlation coefficient were computed along with confirmatory factor and latent class analyses (LCA), using data from the Zurich Adjustment Disorder Study (N = 330). Interrater reliability analyses found an adjusted kappa of 0.807 for the ICD-11 AjD diagnosis. Few items from the impairment criterion of the diagnostic algorithm performed poorly. The internal consistency was acceptable, Cronbach's αs = .43-.80; the lower-bound estimate resulted from the two-item preoccupation symptom pattern. However, both items were significantly associated, OR = 3.14, 95% CI [1.97, 4.99]. Regarding LCA results, a two-class model was favored. We found that 94.3% of all ICD-11 AjD cases belonged to Class 2, OR = 23.69, 95% CI [7.15, 79.54], which was associated with subjectively rated distress, OR = 2.18, 95% CI [1.57, 3.02], and the external measure of the Brief Symptom Inventory global severity index, OR = 2.18, 95% CI [1.57, 3.02]. Overall, the new AjD interview module provided a reliable, valid assessment of the ICD-11 diagnosis; confirmation by other studies is needed

Prevalence, Onset, and Course of Suicidal Behavior Among Adolescents and Young Adults in Germany

Suicidal behavior is a leading cause of death among adolescents and young adults. In light of the ideation-to-action framework, the delineation of frequency and temporal characteristics of such behavior during this developmental period is crucial.; To provide lifetime and 12-month prevalence estimates of suicidal behavior, including ideation, plan, and attempt, in adolescents and young adults of the general population, and to provide information about age at onset, temporal characteristics of suicidal behavior, including duration (number of years between onset and last occurrence) and frequency (number of episodes), and transition patterns across suicidal behaviors.; A cross-sectional epidemiological study was conducted in a random community sample of 1180 adolescents and young adults aged 14 to 21 years assessed in 2015 to 2016 in Dresden, Germany. Data analysis was performed from October 2018 to March 2019.; Lifetime and 12-month suicidal behavior (ideation, plan, and attempt) were assessed with a standardized diagnostic interview (Munich-Composite International Diagnostic Interview) by trained clinical interviewers. The onset, frequency, and duration of suicidal behavior were assessed by questionnaire.; Of the 1180 participants (495 male [weighted percentage, 51.7%]; mean [SD] age, 17.9 [2.3] years), 130 participants (10.7%; 95% CI, 9.0%-12.8%), 65 participants (5.0%; 95% CI, 3.9%-6.5%), and 41 participants (3.4%; 95% CI, 2.4%-4.7%) reported lifetime suicidal ideation, plan, and attempt, respectively. Any lifetime suicidal behavior was reported by 138 participants (11.5%; 95% CI, 9.7%-13.7%). Age-specific cumulative incidence estimates indicated an increase in suicidal behavior during adolescence, starting at age 10 years (<1%), increasing slightly until the age of 12 years (2.2%), and then increasing sharply thereafter until age 20 years (13.5%). There were different patterns among female and male participants for ideation, plan, and attempt, with an overall higher incidence among female participants for ideation (hazard ratio, 1.51; 95% CI, 1.02-2.22; P = .04), for plan (hazard ratio, 3.31; 95% CI, 1.72-6.36; P < .001), and, among those older than 14 years, for attempt (hazard ratio, 3.07; 95% CI, 1.11-8.49; P = .03). Of those with suicidal ideation, 66.0% reported persistent or recurrent ideation over more than 1 year with 75.0% reporting more than 1 episode. Of the participants with lifetime suicidal ideation, 47.0% reported a suicide plan and 23.9% reported a suicide attempt. The transition to suicide plan or attempt occurred mainly in the year of onset of suicidal ideation or plan; of those who transitioned, 74.9% transitioned from ideation to plan, 71.2% transitioned from ideation to attempt, and 85.4% transitioned from plan to attempt in the same year.; There is an urgent public health need for timely identification of suicidal behavior in adolescents and young adults to terminate persistent or recurrent suicidal tendencies and to interrupt the ideation-to-action transition

Analytical Validation of GFR_NMR: A Blood-Based Multiple Biomarker Assay for Accurate Estimation of Glomerular Filtration Rate

Accurate and precise monitoring of kidney function is critical for a timely and reliable diagnosis of chronic kidney disease (CKD). The determination of kidney function usually involves the estimation of the glomerular filtration rate (eGFR). We recently reported the clinical performance of a new eGFR equation (GFRNMR) based on the nuclear magnetic resonance (NMR) measurement of serum myo-inositol, valine, and creatinine, in addition to the immunoturbidometric quantification of serum cystatin C, age and sex. We now describe the analytical performance evaluation of GFRNMR according to the Clinical and Laboratory Standards Institute guidelines. Within-laboratory coefficients of variation (CV%) of the GFRNMR equation did not exceed 4.3%, with a maximum CV% for repeatability of 3.7%. Between-site reproducibility (three sites) demonstrated a maximum CV% of 5.9%. GFRNMR stability was demonstrated for sera stored for up to 8 days at 2–10°C and for NMR samples stored for up to 10 days in the NMR device at 6 ± 2°C. Substance interference was limited to 4/40 (10.0%) of the investigated substances, resulting in an underestimated GFRNMR (for glucose and metformin) or a loss of results (for naproxen and ribavirin) for concentrations twice as high as usual clinical doses. The analytical performances of GFRNMR, combined with its previously reported clinical performance, support the potential integration of this NMR method into clinical practice

5‑HTT genotype and inertia of negative affect in adolescents and young adults from the general population

The study aims to replicate the previous found association of 5-HTTLPR and inertia of negative affect in daily life of adolescents and young adults. Data of 877 adolescents (aged 14–21 years) of the Behavior and Mind Health (BeMIND) study (epidemiological cohort study, Dresden, Germany) were genotyped for 5-HTTLPR/rs25531, grouped into SS/SLG/SLA/ LGLA/LGLG vs. LALA, and provided ratings on negative affect items, depression and anxiety (Patient-Reported Outcomes Measurement Information System) eight times a day over 4 days. Multilevel regression models did not reveal an association of 5-HTTLPR genotype and inertia of negative affect, nor associations with inertia of anxiety or depression. Inertia of negative affect seems not to be a psychological mechanism through which 5-HTTLPR acts on psychopathology