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BACKGROUND: The choice of imaging modality—the use of whole-body computed tomography (WB-CT) versus a step-wise diagnostic procedure—in injured children is controversial. In this study we availed ourselves of data from the TR-DGU, the trauma registry of the German Society for Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie), to investigate whether the use of WB-CT improves the outcome. METHODS: The TR-DGU data from the period 2012–2021 were evaluated. A three-stage analysis began with comparison of children with adults aged ≤ 50 years. As a second step, the observed and expected mortality in children with WB-CT was compared with the mortality in children without WB-CT. Finally, predictors of the use of WB-CT were identified so that a propensity score analysis of matched pairs could be performed. RESULTS: A total of 65 092 patients were included, 4573 children (7%) and 60 519 adults (93%), with differences in accident type and injury pattern. Comparison of the ratio of observed to expected mortality revealed no difference between the two groups of children (standardized mortality ratio 0.97 with WB-CT, 0.95 without WB-CT). In adults, however, there was an advantage for the WB-CT group. The propensity score analysis of 1101 matched pairs showed identical mortality in the two groups (3.9% with WB-CT, 4.0% without WB-CT). CONCLUSION: The TR-DGU data show no benefit of WB-CT compared with step-wise diagnosis in the care of severely injured children. In view of the radiation exposure involved, with the danger of inducing malignancy, the benefits and risks of the use of WB-CT in children should be weighed up carefully in team discussions.

This paper studies the problem of siting renewable power generation assets using large amounts of climatological data while accounting for their spatiotemporal complementarity. The problem is cast as a combinatorial optimisation problem selecting a pre-specified number of sites so as to minimise the number of simultaneous low electricity production events that they experience relative to a pre-specified reference production level. It is shown that the resulting model is closely related to submodular optimisation and can be interpreted as generalising the well-known maximum coverage problem. Both deterministic and randomised algorithms are discussed, including greedy, local search and relaxation-based heuristics as well as combinations of these algorithms. The usefulness of the model and methods is illustrated by a realistic case study inspired by the problem of siting onshore wind power plants in Europe, resulting in instances featuring over ten thousand candidate locations and ten years of hourly-sampled meteorological data. The proposed solution methods are benchmarked against a state-of-the-art mixed-integer programming solver and several algorithms are found to consistently produce better solutions at a fraction of the computational cost. The physical nature of solutions provided by the model is also investigated, and all deployment patterns are found to be unable to supply a constant share of the electricity demand at all times. Finally, a cross-validation analysis shows that, except for an edge case, the model can successfully and reliably identify deployment patterns that perform well on previously unseen climatological data from historical data spanning a small number of weather years.

Attention Deficit Hyperactivity Disorder (ADHD) negatively impacts Quality of Life (QoL) in adults. Earlier studies on pharmacological treatment have shown short-term beneficial effects on QoL. No data are available on long-term effects on multimodal psychosocial and/or pharmacological interventions. The Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (Plac) (2 × 2 factorial design over a period of 52 weeks). Change of QoL was measured after three months of intensive treatment, after 26 weeks, and after one year of maintenance treatment, using the Quality of life enjoyment and satisfaction questionnaire (Q-LES-Q, eight subscales). A follow-up was performed 1.5 years after treatment completion. Q-LES-Q scores were analyzed descriptively (means and confidence intervals). A linear regression model was used to test for significant differences between the four treatment arms. The full analysis set comprised 419 patients. Q-LES-Q scores increased between baseline and the end of treatment across all Q-LES-Q subscales (with exception of stable scores in the physical health/activities subscale in the CM + Plac group) and remained stable improved at follow-up. Regression analyses did not show any significant differences between the four treatment conditions. COMPAS is the first study to demonstrate stable and long-term improvements of QoL after multimodal treatment regardless of medication with MPH or Placebo, and regardless of structured GPT or individual CM. Trial registration: ISRCTN54096201.

Introduction The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo (PLAC) in combination with cognitive behavioral group psychotherapy (GPT) or individual clinical management (CM) over the period of 1 year. Here, we report results on treatment safety. Methods MPH and PLAC were flexibly dosed. Among 433 randomized patients, adverse events (AEs) were documented and analyzed on an “as received” basis during week 0–52. Electrocardiogram data were recorded at baseline and week 24. Results Comparing 205 patients who received ≥1 dose of MPH with 209 patients who received PLAC, AEs occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8%), dry mouth (15 vs. 4.8%), palpitations (13 vs. 3.3%), gastrointestinal infection (11 vs. 4.8%), agitation (11 vs. 3.3%), restlessness (10 vs. 2.9%), hyperhidrosis, tachycardia, weight decrease (all 6.3 vs. 1.9%), depressive symptom, influenza (both 4.9 vs. 1.0%), and acute tonsillitis (4.4 vs. 0.5%). Syncope occurred significantly more often in the PLAC group (2.4 vs. 0%). Clinically relevant ECG changes occurred very rarely in both groups. Serious AEs were rare and without a significant group difference. The comparison of 206 patients treated with GPT versus 209 patients who received CM revealed no major differences. Serious AE classified as psychiatric occurred in 5 cases in the CM group and in 1 case in the GPT group. Conclusion In this so far longest-running clinical trial, methylphenidate treatment was safe and well-tolerated.

There is broad consensus that to improve the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), the various therapy options need to be tailored more precisely to the individual patient's needs and specific symptoms. This post-hoc analysis evaluates the multimodal effects of first-line medication (methylphenidate [MPH] vs placebo [PLB]) and psychotherapeutic (group psychotherapy [GPT] vs clinical management [CM]) treatments on the ADHD core symptoms inattention, hyperactivity and impulsivity. For the two-by-two factorial, observer-blinded, multicenter, randomized controlled Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS; ISRCTN54096201), 419 outpatients with ADHD were considered for analysis. ADHD symptoms were assessed by blind observer-rated and patient-rated Conners Adult ADHD Rating Scales before treatment (T1), 13 weeks (T2) and 26 weeks (T3) after T1, at treatment completion after 52 weeks (T4), and at follow-up (130 weeks, T5). MPH was superior to PLB in improving symptoms of inattention at almost all endpoints (observer-rated T2, T3, T4, T5; patient-rated T2, T3, T4), while a significant decrease in hyperactivity and impulsivity was at first found after 6 months of treatment. CM compared to GPT decreased inattention and impulsivity in the early treatment phase only (observer-rated T2, patient-rated T2, T3). In conclusion, while MPH seems to have a direct and sustained effect on inattention, premature medication discontinuation should particularly be avoided in patients with hyperactive-impulsive symptoms. Also, especially in high inattention and/or impulsivity presentations, initial individual patient management might be beneficial. Consequently, considering individual core symptom profiles may enhance the efficacy of treatments in adult ADHD.

The accurate representation of variable renewable generation (RES, e.g., wind, solar PV) assets in capacity expansion planning (CEP) studies is paramount to capture spatial and temporal correlations that may exist between sites and impact both power system design and operation. However, it typically has a high computational cost. This paper proposes a method to reduce the spatial dimension of CEP problems while preserving an accurate representation of renewable energy sources. A two-stage approach is proposed to this end. In the first stage, relevant sites are identified via a screening routine that discards the locations with little impact on system design. In the second stage, the subset of relevant RES sites previously identified is used in a CEP problem to determine the optimal configuration of the power system. The proposed method is tested on a realistic EU case study and its performance is benchmarked against a CEP set-up in which the entire set of candidate RES sites is available. The method shows great promise, with the screening stage consistently identifying 90% of the optimal RES sites while discarding up to 54% of the total number of candidate locations. This leads to a peak memory reduction of up to 41% and solver runtime gains between 31% and 46%, depending on the weather year considered., Comment: Accepted to PowerTech2021, Madrid, Spain

Background Surveillance testing within healthcare facilities provides an opportunity to prevent severe outbreaks of coronavirus disease 2019 (COVID-19). However, the quantitative impact of different available surveillance strategies and their potential to decrease the frequency of outbreaks are not well-understood. Methods We establish an individual-based model representative of a mental health hospital yielding generalizable results. Attributes and features of this facility were derived from a prototypical hospital, which provides psychiatric, psychosomatic and psychotherapeutic treatment. We estimate the relative reduction of outbreak probability for three test strategies (entry test, once-weekly test and twice-weekly test) relative to a symptom-based baseline strategy. Based on our findings, we propose determinants of successful surveillance measures. Results Entry Testing reduced the outbreak probability by 26%, additionally testing once or twice weekly reduced the outbreak probability by 49% or 67% respectively. We found that fast diagnostic test results and adequate compliance of the clinic population are mandatory for conducting effective surveillance. The robustness of these results towards uncertainties is demonstrated via comprehensive sensitivity analyses. Conclusions We conclude that active testing in mental health hospitals and similar facilities considerably reduces the number of COVID-19 outbreaks compared to symptom-based surveillance only.

Background Few data are available on the characteristics of inpatient treatment and subsequent outpatient treatment for depression in Germany. In this study, we aimed to characterize the inpatient and outpatient treatment phases, to determine the rates of readmission and mortality, and to identify risk factors. Methods We carried out a descriptive statistical analysis of routine administrative data from a large health-insurance carrier (BARMER). All insurees aged 18 to 65 who were treated in 2015 as inpatients on a psychiatry and psychotherapy service or on a psychosomatic medicine and psychotherapy service with a main diagnosis of depression were included in the analysis. Risk factors for readmission and death were determined with the aid of mixed logistic regression. Results Of the 22 893 patients whose data were analyzed, 78% had been hospitalized on a psychiatry and psychotherapy service and 22% on a psychosomatic medicine and psychotherapy service. The median length of hospital stay was 42 days. Follow-up care in the outpatient setting failed to conform with the recommendations of the pertinent guidelines in 92% of the patients with a main diagnosis of severe depression during hospitalization, and in 50% of those with moderate depression. 21% of the patients were readmitted within a year. The mortality at one year was 961 per 100 000 individuals (adjusted for the age and sex structure of the German population), or 3.4 times the mortality of the population at large. In the regression model, more treatment units during hospitalization and subsequent treatment with psychotherapy were associated with a lower probability of readmission, while longer hospitalization with subsequent pharmacotherapy or psychotherapy was associated with lower mortality. Conclusion The recommendations of the national (German) S3 guidelines for the further care of patients who have been hospitalized for depression are inadequately implemented at present in the sectored structures of in- and outpatient care in the German health care system. This patient group has marked excess mortality.

This paper provides a detailed account of the impact of different offshore wind siting strategies on the design of the European power system. To this end, a two-stage method is proposed. In the first stage, a highly-granular siting problem identifies a suitable set of sites where offshore wind plants could be deployed according to a pre-specified criterion. Two siting schemes are analysed and compared within a realistic case study. These schemes essentially select a pre-specified number of sites so as to maximise their aggregate power output and their spatiotemporal complementarity, respectively. In addition, two variants of these siting schemes are provided, wherein the number of sites to be selected is specified on a country-by-country basis rather than Europe-wide. In the second stage, the subset of previously identified sites is passed to a capacity expansion planning (CEP) framework that sizes the power generation, transmission and storage assets that should be deployed and operated in order to satisfy pre-specified electricity demand levels at minimum cost. Results show that the complementarity-based siting criterion leads to system designs which are up to 5% cheaper than the ones relying the power output-based criterion when offshore wind plants are deployed with no consideration for country-based deployment targets. On the contrary, the power output-based scheme leads to system designs which are consistently 2% cheaper than the ones leveraging the complementarity-based siting strategy when such constraints are enforced. The robustness of the results is supported by a sensitivity analysis on offshore wind capital expenditure and inter-annual weather variability, respectively., Comment: Submitted to Applied Energy

Key Points Question What are the long-term results of multimodal treatment for adult attention-deficit/hyperactivity disorder (ADHD) when comparing cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) in combination with either methylphenidate or placebo? Findings In this follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, 256 adults participated in follow-up 1.5 years after the intervention ended. The severity of ADHD symptoms improved in all 4 prior treatment groups, with no significant difference found between GPT and CM, but methylphenidate was associated with a larger improvement in symptoms compared with placebo. Meaning Results from the COMPAS trial demonstrate an improvement of ADHD symptoms over 1.5 years in adults with ADHD after 1 year of treatment with methylphenidate plus either GPT or CM., This follow-up assessment of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a multicenter randomized clinical trial, evaluates the long-term efficacy of multimodal treatment for attention-deficit/hyperactivity disorder (ADHD)., Importance Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. Objective To evaluate the long-term efficacy of multimodal treatment for adult ADHD. Design, Setting, and Participants This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 × 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. Interventions After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. Main Outcomes and Measures The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. Results At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, which improved to adjusted means of 14.2 for the GPT arm and 14.7 for the CM arm at follow-up with no significant difference between groups (difference, −0.5; 95% CI, −1.9 to 0.9; P = .48). The adjusted mean decreased to 13.8 for the MPH arm and 15.2 for the placebo arm (difference, −1.4; 95% CI, −2.8 to −0.1; P = .04). As in the core study, MPH was associated with a larger reduction in symptoms than placebo at follow-up. These results remained unchanged when accounting for MPH intake at follow-up. Compared with participants in the CM arm, patients who participated in group psychotherapy were associated with less severe symptoms as measured by the self-reported ADHD Symptoms Total Score according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) of Conners Adult ADHD Rating Scale (AMD, −2.1; 95% CI, −4.2 to −0.1; P = .04) and in the subscale of reducing pure hyperactive symptoms, measured via the Diagnostic Checklist for the diagnosis of ADHD in adults (AMD, −1.3; 95% CI, −2.8 to 0.1; P = .08). Regarding the Clinical Global Impression scale assessment of effectiveness, the difference between GPT and CM remained significant at follow-up (odds ratio, 1.63; 95% CI, 1.03-2.59; P = .04). No differences were found for any comparison concerning depression as measured with the Beck Depression Inventory. Conclusions and Relevance Results from COMPAS demonstrate a maintained improvement in ADHD symptoms for adults 1.5 years after the end of a 52-week controlled multimodal treatment period. The results indicate that MPH treatment combined with GPT or CM provides a benefit lasting 1.5 years. Confirming the results of the core study, GPT was not associated with better results regarding the primary outcome compared with CM. Trial Registration isrctn.org Identifier: ISRCTN54096201

Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of “well weeks” (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99–1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

This paper proposes a systematic framework to assess the complementarity of renewable resources over arbitrary geographical scopes and temporal scales which is particularly well-suited to exploit very large data sets of climatological data. The concept of critical time windows is introduced, and a spatio-temporal criticality indicator is proposed, consisting in a parametrised family of scalar indicators quantifying the complementarity between renewable resources in both space and time. The criticality indicator is leveraged to devise a family of optimisation problems identifying sets of locations with maximum complementarity under arbitrary geographical deployment constraints. The applicability of the framework is shown in a case study investigating the complementarity between the wind regimes in continental western Europe and southern Greenland, and its usefulness in a power system planning context is demonstrated. Besides showing that the occurrence of low wind power production events can be significantly reduced on a regional scale by exploiting diversity in local wind patterns, results highlight the fact that aggregating wind power production sites located on different continents may result in a lower occurrence of system-wide low wind power production events and indicate potential benefits of intercontinental electrical interconnections.

This paper proposes an optimisation-based framework to tackle long-term centralised planning problems of multi-sector, integrated energy systems including electricity, hydrogen, natural gas, synthetic methane and carbon dioxide. The model selects and sizes the set of power generation, energy conversion and storage as well as carbon capture technologies minimising the cost of supplying energy demand in the form of electricity, hydrogen, natural gas or synthetic methane across the power, heating, transportation and industry sectors whilst accounting for policy drivers, such as energy independence, carbon dioxide emissions reduction targets, or support schemes. The usefulness of the model is illustrated by a case study evaluating the potential of sector coupling via power-to-gas and carbon capture technologies to achieve deep decarbonisation targets in the Belgian context. Results, on the one hand, indicate that power-to-gas can only play a minor supporting role in cross-sector decarbonisation strategies in Belgium, as electrolysis plants are deployed in moderate quantities whilst methanation plants do not appear in any studied scenario. On the other hand, given the limited renewable potential, post-combustion and direct air carbon capture technologies clearly play an enabling role in any decarbonisation strategy, but may also exacerbate the dependence on fossil fuels.

Current global environmental challenges require vigorous and diverse actions in the energy sector. One solution that has recently attracted interest consists in harnessing high-quality variable renewable energy resources in remote locations, while using transmission links to transport the power to end users. In this context, a comparison of western European and Greenland wind regimes is proposed. By leveraging a regional atmospheric model specifically designed to accurately capture polar phenomena, local climatic features of southern Greenland are identified to be particularly conducive to extensive renewable electricity generation from wind. A methodology to assess how connecting remote locations to major demand centres would benefit the latter from a resource availability standpoint is introduced and applied to the aforementioned Europe-Greenland case study, showing superior and complementary wind generation potential in the considered region of Greenland with respect to selected European sites., Published in Elsevier Energy

Summary Mental health promotion programs (MHP) seek to reduce sub-syndromal symptoms of mental distress and enhance positive mental health. This study evaluates the long-term effects of a mindfulness-based MHP program (‘Life Balance’) provided by health coaches in a multi-site field setting on mental distress, satisfaction with life and resilience. Using a controlled design, propensity score matching was used to select a control group for participants of the MHP. The total study sample (N = 3624) comprised 83% women, with a mean age of 50 years. Data was collected via mailings 1 year after study entry. Results suggest participants experience reduced emotional distress at 12-month follow-up, with a medium between-group effect size (d = 0.40) for those participants who showed clinically relevant symptoms of mental distress at study entry. The effects of the program were more pronounced in participants with higher initial distress scores. New cases of psychopathological symptoms were prevented in 1 of 16 participants. Satisfaction with life and resilience were enhanced significantly. Our data suggest ‘Life Balance’ shows long-term effectiveness and indicate it is possible to design MHP programs that serve as both primary and indicated prevention, and that these programs can be applied on a population basis.

Background Staffing regulations have determined the number of qualified staff required for sufficient, appropriate and economical inpatient mental health care in Germany since 1991. This minimum level of structural quality will probably be abolished in the context of the convergence of hospital budgets starting in 2019. Aims and objectives The aim of this study was to analyze the current fulfilment of staffing regulations in terms of time per patient in a large nationwide sample. Material and methods The required minutes of staff time as defined by staffing regulations were calculated for each patient using the treatment classifications provided by a large nationwide database. The actual use of staff time was calculated on the basis of average costs published by the German Institute for Hospital Reimbursement. Both figures were compared to calculate the fulfilment of staffing regulations. Results The study included approximately 95,000 inpatient episodes from 46 psychiatric hospitals and departments with a total length of stay of almost 2.5 million days. On average, the weekly use of staff resources per patient was 190 min (10 %) below the requirements of the staffing regulations. The largest gap in absolute terms was found in nursing staff where the weekly time per patient was 189 min (14 %) below the requirements of the staffing regulations. Conclusion The convergence of psychiatric hospital budgets starts in 2019 below a level of funding required to fulfil staffing regulations. This would perpetuate inadequately funded structures and should initially be opposed with a demand for complete fulfilment of staffing regulations. Thereafter, a normative consent should be reached to define the resources required for current inpatient mental health care.

Background The effective utilization of staff resources is of decisive importance for the adequate, appropriate, and economical delivery of hospital services. The goal of this study was to determine the distribution of working time among doctors in a German university hospital-in particular, in terms of type of activities and time of day. Methods The distribution of working time was determined from 14-day samples taken in seven clinical departments of the Medical Center-University of Freiburg. In each 14-day sample, the activities being carried out at multiple, randomly chosen times were recorded. Results A total of 250 doctors (participation rate: 83%) took part in the study. A total of 20 715 hours of working time was analyzed, representing twelve years of full-time employment. Overall, 46% of working time in the inpatient sector was spent in direct contact with patients, with relevant differences among the participating clinical departments: for instance, the percentage of time taken up by patient contact was 35% in pediatrics and 60% in oral and maxillofacial surgery. Patient contact was highest (over 50% overall) in the period 8 a.m. to 12 noon. Conclusion The amount of working time taken up by activities other than direct patient contact was found to be lower than in previous studies. It remains unclear what distribution of working time is best for patient care and whether it would be possible or desirable to increase the time that doctors spend in direct contact with patients.

Background: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. Methods: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. Results: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. Limitations: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. Conclusion: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reelin, a master molecule for development and differentiation of the hippocampus. From postnatal day 1 (P1) to P14, mouse pups were subjected to one of the following treatments: nonhandling (NH), handling (H), maternal separation (MS), and early deprivation (ED) followed by immediate (P15) or delayed (P70) real time RT-PCR analysis of reelin mRNA expression. We show that at P15, reelin mRNA levels were significantly increased in male H and ED groups when compared with the NH group. In contrast, no stress-induced alterations of reelin mRNA expression were found in female animals. This sex difference in stress-mediated stimulation of reelin expression was maintained into adulthood, since at P70 intergroup differences were still found in male, but not in female mice. On the cellular level, however, we did not find any significant differences in cell densities of Reelin-immunolabeled neurons between treatment groups or sexes, but an overall reduction of Reelin-expressing neurons in the adult hippocampus when compared to P15. To address the question whether corticosterone mediates the stress-induced up-regulation of reelin gene expression, we used age-matched hippocampal slice cultures derived from male and female mouse pups. Quantitative determination of mRNA levels revealed that corticosterone treatment significantly up-regulated reelin mRNA expression in male, but not in female hippocampi. Taken together, these results show a sex-specific regulation of reelin gene expression by early life experience, most likely mediated by corticosterone.

ADHD is a serious risk factor for co-occurring psychiatric disorders and negative psychosocial consequences in adulthood. Previous trials on psychotherapeutic concepts for adult ADHD are based on behavioural (cognitive behavioural and dialectical behavioural) psychotherapeutic approaches and showed significant effects. The aim of our study group (COMPAS) is to carry out a first randomized and controlled multicentre study to evaluate the effects of a disorder tailored psychotherapy in adult ADHD compared to clinical management in combination with psychopharmacological treatment or placebo. A total of 448 adults with ADHD according to DSM-IV will be treated at seven university sites in Germany. In a four-arm design, patients are randomized to a manualized dialectical behavioural therapy (DBT) based group programme plus methylphenidate or placebo or clinical management plus methylphenidate or placebo with weekly sessions in the first 12 weeks and monthly sessions thereafter. Therapists are graduated psychologists or physicians. Treatment integrity is established by independent supervision. Primary endpoint (ADHD symptoms measured by the Conners Adult Rating Scale) is rated by interviewers blind to the treatment allocation. Intention-to-treat analysis will be performed within a linear regression model (Current Controlled Trials ISRCTN54096201). The trial is funded by the German Federal Ministry of Research and Education (01GV0606) and is part of the German network for the treatment of ADHD in children and adults (ADHD-NET).

Objective. Depressive disorders are of great medical and political significance. Although evidence-based guidelines have been published and educational initiatives have been launched to implement them, they are rarely actually used. The aim of the study was to implement clinical practice guidelines for outpatient care of depression using a practice-oriented and interdisciplinary approach. Design. Controlled clinical trial with a naturalistic design (data collection within routine practice) designed as a prospective pre-post study. Setting. Outpatient care. Participants. 29 general practitioners (intervention: 18; control: 11) and 15 psychiatrists (intervention: 11; control: 4). Overall, the treatment of 698 patients (two samples: pre: 361; post: 337) was documented. Intervention(s). Multifaceted intervention combining benchmarking, continuous medical education and interdisciplinary quality circles for the diagnosis and treatment of depressive disorders. Main outcome measures. Mixed-effects regression models for cluster-adjusted analysis of patients’ symptom reduction. Results. Although physicians in the intervention group improved their clinical effectiveness ( proportion of patients with response/remission) to a greater extent than physicians in the control group (intervention: 48.6% to 66.9%; control: 54.9% to 61.5%), cluster-adjusted analysis failed to prove a statistically significant effect of the intervention on the treatment outcome. Conclusions. Although no statistically significant improvements were found regarding the outcomes, the action programme provides important work, materials and results for an integrated treatment model for depression.

Background Relapses and rehospitalisations are common after acute inpatient treatment in depressive disorders. Interventions for stabilising treatment outcomes are urgently needed. Psychoeducational group interventions for relatives were shown to be suitable for improving the course of disease in schizophrenia and bipolar disorders. A small Japanese monocentre randomised controlled trial also showed promising results for depressive disorders. However, the evidence regarding psychoeducation for relatives of patients with depressive disorders is unclear. Methods/Design The study is conducted as a two-arm multisite randomised controlled trial to evaluate the incremental effect of a brief psychoeducational group intervention for relatives as a maintenance treatment on the course of disease compared to treatment as usual. Primary outcome is the estimated number of depression-free-days in patients within one year after discharge from inpatient treatment. 180 patients diagnosed with unipolar depressive disorders as well as one key relative per patient will be included during inpatient treatment and randomly allocated to the conditions at discharge. In the intervention group, relatives will participate in a brief psychoeducational group intervention following the patient’s discharge. The intervention consists of four group sessions lasting 90 to 120 min each. Every group session contains informational parts as well as structured training in problem-solving. In both study conditions, patients will receive treatment as usual. Patients as well as relatives will be surveyed by means of questionnaires at discharge and three, six, nine and twelve months after discharge. In addition to the primary outcome, several patient-related and relative-related secondary outcomes will be considered and health economics will be investigated. Discussion Our study will provide evidence on the incremental effect of a brief psychoeducational intervention for relatives as a maintenance treatment after inpatient depression treatment. Positive results may have a major impact on health care for depression. Trial registration German Clinical Trials Register (DRKS): DRKS00006819; Trial registration date: 2014 Oktober 31; Universal Trial Number (UTN): U1111-1163-5391

Psychische Gesundheitsstorungen nach Arbeitsunfallen stellen ein unterschatztes Problem dar. Im Rahmen einer multizentrischen Studie wurden 408 Patienten, die nach Arbeitsunfallen stationar chirurgisch behandelt werden mussten, mittels Screeningbogen in eine Nichtrisiko- (NR) und eine Hochrisikogruppe (HR) eingeteilt und auf ihre nachfolgenden psychischen Reaktionen hin untersucht (4 Messzeitpunkte, 15 Monate Nachbeobachtung). Untersucht wurden Art, Schwere und Haufigkeit psychischer Storungen nach korperlichen Traumen in ihren spontanen Verlaufen und ihren Auswirkungen auf die langfristige psychosoziale und berufliche Rehabilitation. Weibliches Geschlecht sowie eine positive Anamnese fur mindestens eine psychiatrische Diagnose in der Vorgeschichte scheinen Risikofaktoren fur die Zugehorigkeit zur HR-Gruppe zu sein. HR- und NR-Patienten unterschieden sich sowohl bei Studienbeginn als auch im Verlauf in vielen Untersuchungsmerkmalen. Die Ergebnisse unterstreichen erneut die hohe Relevanz dieser Gesundheitsstorungen. Besonderer Handlungsbedarf ergibt sich eindeutig fur die Gruppe der Hochrisikopatienten. In ihr zeigten sich uber den kompletten Beobachtungszeitraum von 15 Monaten deutlich ungunstigere korperliche, psychische und soziale Heilungsverlaufe. Auf diese spezielle, aber auch heterogene Untergruppe sollten sich die klinischen und wissenschaftlichen Bemuhungen zur Entwicklung wirksamer Formen der psychologischen Akutbetreuung und Nachsorge konzentrieren.

BackgroundAdherence to treatment guidelines enhances treatment outcome. However, in clinical practice many patients with depression do not receive appropriate treatment.AimsTo evaluate the treatment of depression in in-patients of German psychiatric hospitals with respect to treatment outcome and adherence to guidelines.MethodWe recruited 1202 in-patients with depression from ten different hospitals. Quality data concerning treatment were collected at admission, during the treatment course and at discharge.ResultsThe level of depression was significantly decreased and most patients were satisfied with treatment. Many aspects of the treatment routine adhered to guideline recommendations. Adherence to guidelines could be improved with respect to adjustment of antidepressant dosage, reduction of benzodiazepine prescription, enhanced use of electroconvulsive therapy and wider use of interpersonal therapy.ConclusionsThe study reveals a high standard of psychiatric treatment of in-patients with depression. Nevertheless there is still room for improvement. Differences between hospitals in adherence to guidelines indicates the need for individual application of quality management tools.

The Committee on Chronotherapeutics, delegated by the International Society for Affective Disorders (ISAD), makes the following recommendations after reviewing the evidence as of November 2004. (1) Wake therapy is the most rapid antidepressant available today: approximately 60% of patients, independent of diagnostic subtype, respond with marked improvement within hours. Treatment can be a single or repeated sleep deprivation, total (all night) or partial (second half of the night). Relapse can be prevented by daily light therapy, concomitant administration of SSRIs, lithium (for bipolar patients), or a short phase advance of sleep over 3 days following a single night of wake therapy. Combinations of these interventions show great promise. (2) Light therapy is effective for major depression--not only for the seasonal subtype. As an adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients, morning light hastens and potentiates the antidepressant response. Light therapy shows benefit even for patients with chronic depression of 2 years or more, outperforming their weak response to drugs. This method provides a viable alternative for patients who refuse, resist or cannot tolerate medication, or for whom drugs may be contraindicated, as in antepartum depression. (3) Given the urgent need for new strategies to treat patients with residual depressive symptoms, clinical trials of wake therapy and/or adjuvant light therapy, coupled with follow-up studies of long-term recurrence, are a high priority.

The neuropeptide substance P (SP) has been supposed to be involved in the etiopathology of affective disorders, mainly because of the finding of increased levels of SP in the cerebrospinal fluid of depressed patients and the preliminary evidence of antidepressant effects of SP-receptor antagonists in depressed patients. We investigated whether SP may induce changes of sleep, mood and neuroendocrine measures that are similar to those in depressed patients. In a double-blind, randomized cross-over design, 12 healthy young men were investigated in two blocks of three consecutive nights, in which SP or NaCl was intravenously infused during the third night. Polysomnographic recordings were obtained during all nights and blood samples were drawn every 30 min during the third night. Infusion of SP caused a significant worsening of the mood of the subjects, led to an increase of REM latency and time awake during the SP-infusion intervals, caused increased stage 1 sleep in the first part of the night, and led to increased cortisol and thyroid stimulating hormone levels and a trend for decreased growth hormone levels. These effects can be interpreted as evidence for a central arousing effect of SP. Further studies should focus on the effects of substance P in patients with depressive or other psychiatric disorders.

Importance Chronic depression is a highly prevalent and disabling disorder. There is a recognized need to assess the value of long-term disorder-specific psychotherapy. Objective To evaluate the efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared with that of nonspecific supportive psychotherapy (SP). Design, Setting, and Participants A prospective, multicenter, evaluator-blinded, randomized clinical trial was conducted among adult outpatients with early-onset chronic depression who were not taking antidepressant medication. Patients were recruited between March 5, 2010, and October 16, 2012; the last patient finished treatment on October 14, 2013. Data analysis was conducted from March 5, 2014, to October 27, 2016. Interventions The treatment included 24 sessions of CBASP or SP for 20 weeks in the acute phase, followed by 8 continuation sessions during the next 28 weeks. Main Outcomes and Measures The primary outcome was symptom severity after 20 weeks (blinded observer ratings) as assessed by the 24-item Hamilton Rating Scale for Depression (HRSD-24). Secondary outcomes were rates of response (reduction in HRSD-24 score of ≥50% from baseline) and remission (HRSD-24 score ≤8), as well as self-assessed ratings of depression, global functioning, and quality of life. Results Among 622 patients assessed for eligibility, 268 were randomized: 137 to CBASP (96 women [70.1%] and 41 men [29.9%]; mean [SD] age, 44.7 [12.1] years) and 131 to SP (81 women [61.8%] and 50 men [38.2%]; mean [SD] age, 45.2 [11.6] years). The mean (SD) baseline HRSD-24 scores of 27.15 (5.49) in the CBASP group and 27.05 (5.74) in the SP group improved to 17.19 (10.01) and 20.39 (9.65), respectively, after 20 weeks, with a significant adjusted mean difference of –2.51 (95% CI, –4.16 to –0.86;P = .003) and a Cohendof 0.31 in favor of CBASP. After 48 weeks, the HRSD-24 mean (SD) scores were 14.00 (9.72) for CBASP and 16.49 (9.96) for SP, with an adjusted difference of –3.13 (95% CI, –5.01 to –1.25;P = .001) and a Cohendof 0.39. Patients undergoing CBASP were more likely to reach response (48 of 124 [38.7%] vs 27 of 111 [24.3%]; adjusted odds ratio, 2.02; 95% CI, 1.09 to 3.73;P = .03) or remission (27 of 124 [21.8%] vs 14 of 111 [12.6%]; adjusted odds ratio, 3.55; 95% CI, 1.61 to 7.85;P = .002) after 20 weeks. Patients undergoing CBASP showed significant advantages in most other secondary outcomes. Conclusions and Relevance Highly structured specific psychotherapy was moderately more effective than nonspecific therapy in outpatients with early-onset chronic depression who were not taking antidepressant medication. Adding an extended phase to acute psychotherapy seems promising in this population. Trial Registration clinicaltrials.gov Identifier:NCT00970437.

Background: In Germany, the one-month prevalence of post-traumatic stress disorder (PTSD) is in the range of 1% to 3%. Soldiers, persons injured in accidents, and victims of domestic violence increasingly seek medical help for symptoms of emotional stress. Days lost from work and monetary compensation for emotional disturbances are markedly on the rise. The term “PTSD” is commonly used uncritically and imprecisely, with too little regard for the existing diagnostic criteria. It is at risk of turning into a nonspecific collective term for emotional stress of any kind. Methods: We selectively reviewed the literature in the PubMed database and pertinent journals, with additional consideration of the recommendations and guidelines of medical societies from Germany and abroad. Results: The characteristic types of reactions seen in PTSD are nightmares and an intense, repetitive, intrusive “reliving” of the traumatic event(s). Emotional traumatization manifests itself not only as PTSD but also through major effects on other mental and somatic diseases. An early, trauma-focused behavioral therapeutic intervention involving several sessions, generally on an outpatient basis, can prevent the development of PTSD. The most important components of effective treatment are a focus on the particular trauma experienced and confrontation with the patient’s memories of the trauma. The best existing evidence is for cognitive therapy, behavioral therapy according to the exposure paradigm of Foa, and eye movement desensitization and reprocessing therapy. The most recent meta-analysis reveals effect strengths of g = 1.14 for all types of psychotherapy and g = 0.42 for all types of pharmacotherapy taken together (with considerable differences among psychotherapeutic methods and among drugs). The efficacy of psychodynamic therapy, systemic therapy, body-oriented therapy, and hypnotherapy has not been adequately documented in randomized controlled trials. Conclusion: PTSD can be precisely diagnosed and effectively treated when the diagnostic criteria and guideline recommendations are taken into account. Referral for trauma-focused psychotherapy should be considered if the acute symptoms persist for several weeks. ►Cite this as

Adult ADHD is a frequent psychiatric disorder affecting relevant aspects of an individual’s life. The aim of our study group was to carry out the first randomized controlled multicenter study to evaluate the effects of psychotherapy compared to clinical management in combination with psychopharmacological treatment with methylphenidate (MPH) or placebo (Plac) in a factorial four-arm design. Here, we present the enrollment procedure and description of adult ADHD patients recruited for the trial. Four hundred and thirty-three adult patients with ADHD were randomized at seven study sites in Germany to four treatment conditions: manualized dialectical-behavioral-therapy-based group psychotherapy (GPT) plus MPH or Plac, or clinical management (CM) including supportive counseling plus MPH or Plac with weekly sessions in the first 12 weeks and monthly sessions thereafter. Assessment for eligibility included standardized scales and instruments. After prescreening of 1,480 patients, 518 were evaluated for trial participation and 433 were randomized. The main reasons for prescreening failure were lack of interest in participating (n = 205), difficulties in meeting the time and effort requirements for participation (n = 186), and contraindications for psychopharmacological treatment with MPH (n = 194). The full analysis set (FAS) comprised 419 adult ADHD patients (mean age 35.2 years, males/females 1:1). Fifty-seven percent of the patients suffered from the combined ADHD subtype. Prevalence of at least one current or lifetime axis-I comorbidity was 66 %. Axis-II comorbidity rates was 18 % (patients with comorbid borderline and antisocial personality disorders were excluded). Our network was able to recruit an adult ADHD sample essentially comparable to community samples. A selection bias was created by excluding patients unable or unwilling to participate, or who had somatic and psychiatric contraindications for stimulant treatment (Current Controlled Trials ISRCTN54096201, Funding: Federal Ministry of Education and Research 01GV0606).

Background: Restless legs syndrome (RLS) is a usually chronic disorder accompanied by clinically relevant psychosocial impairment. To date, no psychologically based approach is available to improve the coping strategies and quality of life of RLS sufferers. Objective: To develop cognitive behavioural therapy tailored to this disorder (the RELEGS coping therapy programme) and present the results of this proof-of-concept study. Methods: Twenty-five patients (five men, 20 women; 15 medicated, 10 unmedicated; mean (SD) age 56.1 (12.3) years) with subjective psychosocial impairment due to RLS participated in one of three consecutive therapy groups. The severity scales (IRLS and RLS-6) indicated moderate to severe RLS symptoms at baseline. Exclusion criteria were secondary RLS, foreseeable change of RLS medication during the study period, serious physical or psychiatric comorbidity, and severe cognitive deficits. Each group took part in eight group sessions (90 min each with a break). Results: At the end of the treatment, both the RLS-related quality of life and the mental health status of the subjects had improved significantly (QoL-RLS scale: from 28.6 (12.8) to 23.4 (13.1); SCL-90-R: from 51.3 (37.0) to 45.9 (32.9)). The improvement remained at follow-up 3 months later. Subjective ratings of RLS severity had improved at the end of therapy and at follow-up. Psychometric scales not specific for RLS-related impairment remained unaffected by the treatment. Conclusions: The study establishes the feasibility and high acceptance of the newly devised therapy programme. The application of RLS-oriented specific psychological strategies is a step toward an integrated treatment approach in RLS.

Disturbances of events associated with intracellular signaling pathways have been suspected of involvement in the development or progression of affective disorders. Often, heterotrimeric G proteins are located at the beginning of these pathways as modulators of extracellular messages. For this reason, messenger RNA expression of three G protein alpha-subunits and of phosphatidylinositol-3 kinase (PI-3 K) regulatory subunit p85 was examined in granulocytes from patients with bipolar or unipolar affective disorder and compared to healthy controls. Messenger RNA expression of the G protein subunit alpha(q) and of p85 was identical in unipolar and bipolar patients and in controls. Furthermore, mRNAs of G protein subunits alpha(s) and alpha(i2) were not different in unipolar patients as compared to healthy controls. Alpha(s) mRNA, however, was markedly increased in bipolar patients. This increase was observed in lithium-treated (more than 12 months) and in unmedicated patients. Elevated levels of alpha(i2) mRNA in unmedicated bipolar patients did not reach statistical significance, whereas mRNA in bipolar patients receiving lithium was significantly above controls. Finally, long-term medication of unipolar patients with lithium had no influence on alpha(i2) mRNA levels. The data reveal elevated mRNA levels of G alpha(s) as a robust feature of bipolar affective disorder. Moreover, despite responsiveness of alpha(i2) gene expression to cAMP-related events, no substantial upregulation of alpha(i2) mRNA was observed in bipolar patients. The lack of alpha(i2) mRNA upregulation, hence, could be an additional abnormality in these patients. Even though lithium was able to reinstate this upregulation, there was no feedback downregulation of alpha(s). This strongly supports the notion of major disturbances of the cAMP signaling system in bipolar illness.

Periodic limb movements during sleep (PLMS), with or without symptoms of a restless legs syndrome (RLS), may cause sleep disturbances. The pharmacologic treatments of choice are dopaminergic drugs. Their use, however, may be limited due to tolerance development or rebound phenomena. Anecdotal observations have shown that oral magnesium therapy may ameliorate symptoms in patients with moderate RLS. We report on an open clinical and polysomnographic study in 10 patients (mean age 57 +/- 9 years; 6 men, 4 women) suffering from insomnia related to PLMS (n = 4) or mild-to-moderate RLS (n = 6). Magnesium was administered orally at a dose of 12.4 mmol in the evening over a period of 4-6 weeks. Following magnesium treatment, PLMS associated with arousals (PLMS-A) decreased significantly (17 +/- 7 vs 7 +/- 7 events per hour of total sleep time, p < 0.05). PLMS without arousal were also moderately reduced (PLMS per hour of total sleep time 33 +/- 16 vs 21 +/- 23, p = 0.07). Sleep efficiency improved from 75 +/- 12% to 85 +/- 8% (p < 0.01). In the group of patients estimating their sleep and/or symptoms of RLS as improved after therapy (n = 7), the effects of magnesium on PLMS and PLMS-A were even more pronounced. Our study indicates that magnesium treatment may be a useful alternative therapy in patients with mild or moderate RLS-or PLMS-related insomnia. Further investigations regarding the role of magnesium in the pathophysiology of RLS and placebo-controlled studies need to be performed.

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.