[Methodology of the guideline update on bipolar disorders and perspective on future updates]. / Methodik des Leitlinien-Updates Bipolare Störungen und Ausblick auf künftige Aktualisierungen.

Since 2012 a German guideline for the diagnosis and therapy of bipolar disorders has been available at the S3 level defined by the Association of the Scientific Medical Societies in Germany. This has now been updated in a revision process and since May 2019 available under the AWMF number 038-019. In order to maintain the high quality of the guidelines it was necessary to review and evaluate studies published since the first release, which is reflected in the number of 20 new and 29 amended recommendations and statements. This article discusses the recently finalized revision process and provides a perspective on future updates.

[A review of the update of the German S3-guideline on diagnostics and therapy of bipolar disorders 2019]. / Überblick über Neuerungen der überarbeiteten und aktualisierten Leitlinie zur Diagnostik und Therapie bipolarer Störungen 2019.

Since the first publication of the guideline in 2012, which included critically reviewed evidence up to 2010, several hundred articles with new evidence were published and some topics of the clinical consensus needed to be reconsidered. Therefore, it was urgently necessary to revise the guideline to bring them up to date. In this article important revisions and updates are presented and the chances and limitations of the development of the guidelines and their implementation are discussed.

Sleep spindles in bipolar disorder - a comparison to healthy control subjects.

OBJECTIVE: Bipolar disorder is a severe mental disorder for which currently no reliable biomarkers exist. It has been shown that patients with schizophrenia but not with unipolar depression have a reduced density of fast sleep spindles during N2 sleep. The aim of this study was to assess fast sleep spindle density in euthymic patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 24) and healthy control subjects (n = 25) were assessed using all-night polysomnography. Sleep spindles within stage N2 sleep were identified by visual inspection and subdivided into fast (>13 Hz) and slow (≤13 Hz) spindles. All spindles were subsequently characterised by density, frequency, amplitude, duration and coherence. RESULTS: Euthymic patients with bipolar disorder were found to have a reduced density and a lower mean frequency of fast spindles. Slow spindle density and frequency did not differ between groups. There were no differences regarding amplitude, duration or coherence. CONCLUSIONS: A reduction in fast spindle density during N2 sleep points towards thalamic dysfunction as a potential neurobiological mechanism of relevance in bipolar disorder. In addition, a reduced sleep spindle density could be interpreted as a common endophenotype shared with schizophrenia but not unipolar depression and may - if replicated - be of utility in early recognition and risk stratification.

[Quality of reporting in studies on bipolar disorders: implications for the development of guidelines]. / "Quality of reporting" in Studien zur bipolaren Störung : Folgen für die Leitlinienentwicklung.

BACKGROUND: Selective publishing as well as inadequate reporting of clinical trials entail a risk of bias in clinical decision making. Therefore the CONSORT statement was introduced to improve the quality of reporting of randomized controlled trials (RCT). This study aimed to assess the quality of reporting of RCTs on pharmacological treatment of bipolar disorder in relation to publication period and endorsement of publication guidelines. METHODS: In the context of the development of the German evidence and consensus-based S3 guidelines for diagnosis and therapy of bipolar disorders a systematic literature search was carried out to identify all RCTs published between 2000 and 2010 relevant to the pharmacological treatment of bipolar disorders. An adapted checklist based on the CONSORT statement was used to assess the quality of reporting. RESULTS: A total of 134 RCTs were included in this analysis. Of the 72 checklist items, 43% were generally reported adequately (reported in ≥ 75% of all trials) and 25% inadequately (reported in < 25% of all trials). Reporting was generally poor for randomization, effect size (reported in 22%) and number needed to treat (NNT 16%). No consistent trend could be shown for improvement in quality of reporting over time or for journals that do or do not endorse the URM (uniform requirements for manuscripts submitted to biomedical journals). CONCLUSIONS: Clinical investigators as well as editors and reviewers should be further encouraged to follow publication guidelines otherwise trials have to be downgraded or excluded from systematic evaluations.

Antitumor agents XLV: Bisbrusatolyl and brusatolyl esters and related compounds as novel potent antileukemic agents.

A series of new bisbrusatolyl and brusatolyl esters and related compounds were synthesized and tested for in vivo antileukemia activity against a quassinoid sensitive strain of P-388 lymphocytic leukemia in BDF1 mice. The bisbrusatolyl malonate, succinate, glutarate, adipate, and sebacate were as active or more active than brusatol. The C-3 esters of brusatol and bruceantin were also found to be as active or more active than brusatol or bruceantin in general. The free hydroxyl groups at C-11 and C-12 as well as the enone double bond in ring A of both bisbrusatolyl and brusatolyl esters are required for antileukemic activity. The presence of a double bond in the ester side chain contributes to the enhanced activity of these esters.

A model for ionization mechanisms in field desorption mass spectrometry.

The apparent discrepancy between theory and experimental practices in field desorption mass spectrometry has encouraged a study attempting to focus theoretical concepts more clearly into forms recognizable to the chemical investigator. Preliminary results indicate that best anode temperature for many compounds is independent of the applied voltage throughout the range available on the Varian MAT CH-5 double focusing mass spectrometer with the electron impact-field ionization-field desorption combined source. Studies of mass transfer indicate that desorption of the sample at the best anode temperature occurs in the absence of the applied field and at a rate which is indistinguishable from the rate of desorption in the presence of the field. These results and other observations, have led us to postulate a new mechanism of ion formation, involving chemical attachment reactions in a thin fluidized system. Clearly, the role of the field in this technique must be the subject of continued study.