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Objectives Approximately 8 - 10 % of COVID-19 patients present with a serious clinical course and need for hospitalization, 8% of hospitalized patients need ICU-treatment. Currently, no causal therapy is available and treatment is purely supportive. The main reason for death in critically ill patients is acute respiratory failure. However, in a number of patients a severe hyperinflammatory response with excessively elevated proinflammatory cytokines causes vasoplegic shock resistant to vasopressor therapy. A new polystyrene-based hemoadsorber (CytoSorb®, Cytosorbents Inc., New Jersey, USA) has been shown to adsorb effectively cytokines and other middle molecular weight toxins this way reducing their blood concentrations. This has been routinely used in clinical practice in the EU for other conditions where a cytokine storm occurs and an observational study has just been completed on COVID-19 patients. We hypothesized that the extracorporeal elimination of cytokines in critically ill COVID-19 patients with suspected hyperinflammation and shock may stabilize hemodynamics and improve outcome. The primary endpoint is time until resolution of vasoplegic shock, which is a well implemented, clinically relevant endpoint in critical care studies. Trial design Phase IIb, multicenter, prospective, open-label, randomized, 1:1 parallel group pilot study comparing the additional use of “CytoSorb” to standard of care without “CytoSorb”. Participants Patients are recruited from the Intensive Care Units (ICUs) of 7 participating centers in Germany (approximately 10 ICUs). All patients aged 18- 80 with positive polymerase chain reaction (PCR) test for SARS-CoV-2, a C-reactive protein (CRP) ≥ 100 mg/l, a Procalcitonin (PCT) < 2 ng/l, and suspected cytokine storm defined via a vasoplegic shock (Norepinephrine > 0.2 μg/min/kg to achieve a Mean Arterial Pressure ≥ 65mmHg). Patients are included irrespective of indication for renal replacement therapy. Suspected or proven bacterial cause for vasoplegic shock is a contraindication. Intervention and comparator Within 24 hours after meeting the inclusion criteria patients will be randomized to receive either standard of care or standard of care and additional “CytoSorb” therapy via a shaldon catheter for 3-7 days. Filter exchange is done every 24 hours. If patients receive antibiotics, an additional dose of antibiotics is administered after each change of “CytoSorb” filter in order to prevent underdosing due to “CytoSorb” treatment. Main outcomes Primary outcome is time to resolution of vasoplegic shock (defined as no need for vasopressors for at least 8 hours in order to sustain a MAP ≥ 65mmHg) in days. Secondary outcomes are 7 day mortality after fulfilling the inclusion criteria, mortality until hospital discharge, Interleukin-6 (IL-6) measurement on day 1 and 3, need for mechanical ventilation, duration of mechanical ventilation, duration of ICU-stay, catecholamine dose on day 1/2/3 after start of “CytoSorb” and acute kidney injury. Randomization An electronic randomization will be performed using the study software secuTrial® administered by the Clinical Study Center (CSC) of the Charité – Universitätsmedizin Berlin, Germany. Randomization is done in blocks by 4 stratified by including center. Blinding (masking) The trial will be non-blinded for the clinicians and patients. The statistician will receive a blinded data set, so that all analyses will be conducted blinded. Numbers to be randomized (sample size) As this is a pilot study with the goal to examine the feasibility of the study design as well as the intervention effect, no formal sample size calculation was conducted. A total number of approximately 80-100 patients is planned (40-50 patients per group). Safety assessment is done after the inclusion of each 10 patients per randomization group. Trial Status Please see the study protocol version from April 24 2020. Recruitment of patients is still pending. Trial registration The study was registered on April 27 2020 in the German Registry of Clinical Trials (DRKS) under the number DRKS00021447 . Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Chronic neck pain is a highly prevalent condition. Learning a relaxation technique is recommended by numerous guidelines for chronic neck pain. Smartphone apps can provide relaxation exercises; however, their effectiveness, especially in a self-care setting, is unclear. The aim of this pragmatic randomized trial is to evaluate whether app-based relaxation exercises, including audio-based autogenic training, mindfulness meditation, or guided imagery, are more effective in reducing chronic neck pain than usual care alone. Smartphone owners aged 18 to 65 years with chronic (>12 weeks) neck pain and the previous week's average neck pain intensity ≥4 on the Numeric Rating Scale (0=no pain to 10=worst possible pain) were randomized into either an intervention group to practice app-based relaxation exercises or a control group (usual care and app for data entry only). For both groups, the follow-up data were collected using app-based diaries and questionnaires. The primary outcome was the mean neck pain intensity during the first 3 months based on daily measurements. Secondary outcomes included neck pain based on weekly measurements, pain acceptance, neck pain-related stress, sick-leave days, pain medication intake, and adherence, which were all measured until the 6-month follow-up. For the primary analysis, analysis of covariance adjusted for baseline neck pain intensity was used. We screened 748 participants and enrolled 220 participants (mean age 38.9, SD 11.3 years; mean baseline neck pain 5.7, SD 1.3 points). The mean neck pain intensity in both groups decreased over 3 months; however, no statistically significant difference between the groups was found (intervention: 4.1 points, 95% CI 3.8-4.4; control: 3.8 points, 95% CI 3.5-4.1; group difference: 0.3 points, 95% CI -0.2 to 0.7; P=.23). In addition, no statistically significant between-group differences regarding neck pain intensity after 6 months, responder rate, pain acceptance, pain medication intake, or sick-leave days were observed. There were no serious adverse events that were considered related to the trial intervention. In week 12, only 40% (44/110) of the participants in the intervention group continued to practice the exercises with the app. The study app did not effectively reduce chronic neck pain or keep the participants engaged in exercising in a self-care setting. Future studies on app-based relaxation interventions should take into account the most recent scientific findings for behavior change techniques. ClinicalTrials.gov NCT02019134; https://clinicaltrials.gov/ct2/show/NCT02019134. RR2-10.1186/1745-6215-15-490.

Background The aim of the trial was to investigate the effect of a hypnotherapeutic group program in healthy persons with increased levels of perceived stress. Methods In a randomized controlled multicenter trial participants with a self-assessed subjective stress level ≥ 40 mm on a visual analogue scale (0–100 mm; VAS) for the previous week and a stable state of health were randomized to either 5 weekly sessions of 120-min duration of a hypnotherapeutic group program for stress reduction and improved stress coping plus 5 hypnosis audiorecords for individual practice at home plus an educational booklet for stress coping (hypnosis group) versus an educational booklet only (control group). The primary outcome parameter was the VAS stress level for the previous week after 5 weeks. Secondary outcome parameters included the VAS stress level after 12 weeks, perceived stress (CPSS), depression (ADS-K), self efficacy (SWE) and quality of life (SF 36) after 5 weeks and 12 weeks. Analysis of covariance with a significance level of 5% using the full analysis set was used for analysis; the model included treatment (fixed effect), VAS baseline value (fixed covariate), and center (random effect). Results A total of 95 participants were randomized; 47 (40 female, 45 ± 13.4 years of age) were allocated to the hypnosis group, and 48 (41 female, 46.9 ± 14.3 years) were allocated to the control group. Regarding VAS stress level after 5 weeks, the adjusted VAS mean in the hypnosis group was 41.8 mm [95% confidence interval (CI): 35.2; 48.4] compared to 62.9 mm [56.2; 69.7] in the control group, and the group difference was − 21.2 mm [− 30.1; − 12.2] ( P  < 0.001). After 12 weeks, the stress intensity on the VAS showed a between-group difference of − 14.7 mm [− 25.1; − 4.4] ( P  = 0.006), and the adjusted means were 41.1 mm [33.4; 48.8] in the hypnosis group and 55.9 mm [48.4; 63.5] in the control group. Improvements were also reported for CPSS, SF-36, SWE and ADS-K after 5 and 12 weeks. Conclusion Compared to the control group, the hypnosis group showed reduced perceived stress after 5 and 12 weeks. Trial registration ClinicalTrials.gov NCT03525093 ; date of registration: May 15, 2018.

IntroductionTo understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.MethodsWe used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex–puberty interaction terms and conducted a one-stage individual participant data meta-analysis.ResultsGirls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.DiscussionWe found an incidence ‘sex shift’ in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.

While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study’s aim was to examine whether levels of serum Lp(a) are associated with lung function in a dataset of relatively healthy older adults. We used longitudinal data collected at two time points 7.4 ± 1.5 years apart from 679 participants (52% women, 68 [65–71] years old) from the Berlin Aging Study II (BASE-II). Multiple linear regression models adjusting for covariates were applied to examine the association between Lp(a) and lung function. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were higher in both men and women with higher Lp(a) levels. However, since this association between lung function parameters and Lp(a) was not supported by Mendelian randomization analyses using recent genome-wide association study data, these relationships should be investigated in future work, as the observed differences are, in part, considerable and potentially clinically relevant.

Background Vitamin D levels may differ between migrant and non-migrant populations, especially among non-western immigrants living in a country with limited sun exposure such as Germany. This study examined serum vitamin D concentration and associated factors among Berliners with and without Turkish background. Methods Two samples (with and without Turkish roots) were recruited in the inner city of Berlin for a cross-sectional study assessing serum vitamin D concentration. Linear regression analyses were used to examine sociodemographic, lifestyle and medical factors associated with serum vitamin D levels. Results In the analyses, we included 537 subjects (39% men and 61% women, age 43.2 ± 12.5 (mean ± standard deviation) years) with and 112 without Turkish background (46% men and 54% women, age 46.7 ± 14.6 years). The Turkish sample had lower mean (95%-Confidence Interval) vitamin D levels than the non-Turkish sample: 22.7 nmol/L (21.5;23.9) vs 34.7 nmol/L (31.9;37.5), p  < 0.001. In the Turkish female subgroup, veiled women had considerably lower levels than unveiled women: 14.4 nmol/L (11.5;17.3) vs 24.9 nmol/L (23.1;26.7), p < 0.001. Multivariable regression analysis revealed that among the Berliners of Turkish descent, being active less than 150 min per day, and being overweight/obese were independently associated with a lower vitamin D concentration. In the non-migrant sample besides being overweight and obese, female sex was associated with lower vitamin D concentrations. Conclusions Serum vitamin D levels were considerably low in Berliners of Turkish descent, and especially in veiled women. Potentially modifiable factors of low vitamin D levels were high BMI and low physical activity. These findings should be considered in the development of future public health strategies for subpopulations with Turkish migration background.

Background: Nonspecific chronic neck pain (cNP) is common in adult violinists and violists and is often treated with osteopathic medicine (OM), although the effectiveness of this treatment has not been determined to date. This study aimed to evaluate the effectiveness and safety of OM in adult violinists and violists with cNP. Methods: In a two-armed randomized controlled single-center open trial, adult violinists and violists, including music students, with cNP (⩾12 weeks) were randomized to either five individualized OM sessions (OM group) or to no intervention (control group, CG) in the outpatient clinic for integrative medicine, Charité - Universitätsmedizin Berlin, Germany. All patients received a musicians’ medicine consultation and paracetamol on demand. The primary outcome parameter was the neck pain intensity on a visual analog scale (VAS, 0–100 mm, 0 = no pain, 100 = worst imaginable pain) after 12 weeks. Secondary outcomes included neck pain disability (Neck Disability Index, NDI, 0–100%) after 12 weeks. The last follow-up visit was after 52 weeks. Statistical analysis included analysis of covariance adjusted for respective baseline value. Results: Altogether, 62 outpatients were included [OM group (n = 28), CG (n = 34); 81% female; mean age, 41.6 ± 11.1 years; mean baseline neck pain, 55.9 ± 11.6 mm]. After 12 weeks, OM was associated with an improvement in the OM group versus the CG in neck pain on the VAS [14.6 mm (95% confidence interval 8.0; 21.2) versus 40.8 mm (34.7; 46.9), p < 0.001, Cohen’s d = 1.4], and neck pain disability as determined by the NDI [8.8% (6.7; 10.8) versus 17.2% (15.3; 19.1), p < 0.001]. Some improvements were maintained until 52 weeks of follow-up. No serious adverse events were observed. Conclusions: The results of this study suggest that OM might be effective in reducing pain intensity in adult violinists and violists with nonspecific cNP. Further studies should investigate the efficacy of OM in comparison with a sham procedure and with other effective therapy methods in high-quality multicenter trials. Trial registration: WHO Trial Registration https://apps.who.int/trialsearch/NoAccess.aspx?aspxerrorpath=/trialsearch/Trial2.aspx by German Clinical Trials Register DRKS00009258, Universal Trial Number (UTN): U1111-1173-5943.

Background/objectivesSleeping behavior and individual prospensity in sleep timing during a 24 h period, known as chronotypes, are underestimated factors, which may favor the development of obesity and metabolic diseases. Furthermore, melatonin is known to play an important role in circadian rhythm, but was also suggested to directly influence metabolism and bodyweight regulation. Since disturbed and shifted sleep rhythms have been observed in adolescents with obesity, this study aimed to investigate potential interactions between melatonin secretion, chronobiology, and metabolism. In addition, the influence of artificial light especially emitted by electronic devices on these parameters was of further interest.Subjects/methodsWe performed a cross-sectional study including 149 adolescents (mean age 14.7 ± 2.1 years) with obesity. Metabolic blood parameters (e.g., cholesterol, triglycerides, uric acid, and insulin) were obtained from patients and correlated with nocturnal melatonin secretion. Melatonin secretion was determined by measuring 6-sulfatoxymelatonin (MT6s), the major metabolite of melatonin in the first-morning urine, and normalized to urinary creatinine levels to account for the urinary concentration. Chronobiologic parameters were further assessed using the Munich ChronoType Questionnaire.ResultsSubjects with insulin resistance (n = 101) showed significantly lower nocturnal melatonin levels compared to those with unimpaired insulin secretion (p = 0.006). Furthermore, triglyceride (p = 0.012) and elevated uric acid levels (p = 0.029) showed significant associations with melatonin secretion. Patients with late chronotype showed a higher incidence of insulin resistance (p = 0.018). Moreover, late chronotype and social jetlag were associated with the time and duration of media consumption.ConclusionWe identified an association of impaired energy metabolism and lower nocturnal melatonin secretion in addition to late chronotype and increased social jetlag (misalignment of biological and social clocks) in adolescents with obesity. This might point towards a crucial role of chronotype and melatonin secretion as risk factors for the development of pediatric and adolescent obesity.

Objectives Our aim was to examine the effects of an early perinatal prevention program offered to mothers and families suffering from significant psychosocial burden. Methods All mothers giving birth in a Berlin university hospital during Jan-Aug 2013 were screened with a standardized 27-item questionnaire by trained staff. Mothers with a screening-score ≥ 3, who were not enrolled in other public support programs, were defined as psychosocially burdened. They received a detailed needs assessment and were followed up with counseling. When necessary, affected mothers were voluntarily guided through to specialized ‘early support’ institutions during the 12-month-intervention period. The historical control group (care-as-usual) consisted of children born at the same hospital the year before. At 12 months postnatally, we interviewed mothers in both groups to assess their stress burden and coping skills by Parenting Stress Index and assessed the current childcare condition. Differences between the groups were compared by multivariable logistic regression analyses adjusting for potential confounders. Results The intervention group and the control group included 225 and 157 families, respectively. After 12-months, mothers in the ‘early support’ intervention group had significantly less often depression (adjusted odds ratio 0.25, 95%-confidence interval 0.07–0.94), less often a disturbed relationship with the parenting partner (0.34, 0.10–1.14) and reported reduced stress due to the child’s demands (0.40, 0.15–1.10) compared to the control group. Childcare indicators did not differ between the 2 groups. Conclusions In mothers at high psychosocial risk, the ‘early support’ intervention program Babylotse-Plus seemed to reduce the occurrence of depression and several stress indicators in the first postnatal year.

Introduction Chronic subdural hematoma (cSDH) is a common condition in older adults that often requires neurosurgical evacuation. Postoperative delirium is a frequent and clinically relevant postoperative complication in this population. This study investigated whether burr hole craniotomy for cSDH performed under local anesthesia (LA) reduces the risk of postoperative delirium and complications compared to general anesthesia (GA). Methods The ABC-SDH trial was a single-center, open-label, phase 2, prospective randomized clinical trial conducted at a tertiary academic medical center between October 2023 and November 2024. Fifty consecutive patients with a confirmed diagnosis of cSDH underwent burr hole craniotomy performed under either LA or GA. Primary outcomes were postoperative delirium (Confusion Assessment Method, CAM) and complications rates until discharge, and the recruitment rate. Secondary outcomes included procedural times and clinical outcome measures at discharge and at 30-day follow-up. Results LA was associated with a significantly lower rate of postoperative delirium (4% vs. 32%, OR 0.09; 95%CI, 0.01–0.79; p  = 0.03; NNT = 4). Complications occurred in 8% (LA) versus 32% (GA) (OR 0.18, 95% CI 0.03–0.96; p  = 0.08). LA was also associated with significantly reduced procedural times (139.3 ± 53.0 vs. 196.0 ± 52.1 min; p  = 0.002). The severity of complications and functional outcomes were comparable between groups. Conclusion LA was associated with significantly lower rates of postoperative delirium and a shorter periprocedural duration compared to GA in patients undergoing cSDH evacuation. As the first prospective trial to systematically assess the incidence of delirium following burr hole craniotomy for cSDH, the ABC-SDH trial highlights the feasibility and safety of LA in a delirium-prone population.