Limited evidence of autocorrelation signaling upcoming affective episodes: a 12-month e-diary study in patients with bipolar disorder.

BACKGROUND: Increased autocorrelation (AR) of system-specific measures has been suggested as a predictor for critical transitions in complex systems. Increased AR of mood scores has been reported to anticipate depressive episodes in major depressive disorder, while other studies found AR increases to be associated with depressive episodes themselves. Data on AR in patients with bipolar disorders (BD) is limited and inconclusive. METHODS: Patients with BD reported their current mood via daily e-diaries for 12 months. Current affective status (euthymic, prodromal, depressed, (hypo)manic) was assessed in 26 bi-weekly expert interviews. Exploratory analyses tested whether self-reported current mood and AR of the same item could differentiate between prodromal phases or affective episodes and euthymia. RESULTS: A total of 29 depressive and 20 (hypo)manic episodes were observed in 29 participants with BD. Self-reported current mood was significantly decreased during the two weeks prior to a depressive episode (early prodromal, late prodromal), but not changed prior to manic episodes. The AR was neither a significant predictor for the early or late prodromal phase of depression nor for the early prodromal phase of (hypo)mania. Decreased AR was found in the late prodromal phase of (hypo)mania. Increased AR was mainly found during depressive episodes. CONCLUSIONS: AR changes might not be better at predicting depressive episodes than simple self-report measures on current mood in patients with BD. Increased AR was mostly found during depressive episodes. Potentially, changes in AR might anticipate (hypo)manic episodes.

[Chronobiological aspects of bipolar disorder]. / Chronobiologische Aspekte der bipolaren Störung.

BACKGROUND: Numerous symptoms of bipolar disorder are regulated by the circadian rhythm. Because of this association it is assumed that disruption of the circadian rhythm may be part of the pathomechanism of bipolar disorder. OBJECTIVES: A comparison and subsequent critical discussion of the current data situation on chronobiological aspects of bipolar disorder are presented. METHODS: A narrative literature search was carried out and the main findings are presented in a summarized form. RESULTS: There are a large number of animal and human studies investigating the connection between disorders of the circadian rhythm and bipolar disorder. Especially chronotype, the environmental factor light and sleep disorders seem to be associated with the development of bipolar disorder. CONCLUSIONS: The neurobiology of bipolar disorder shows numerous chronobiological aspects. There is evidence for a direct connection of disruption of the circadian rhythm and development and progression of bipolar disorder; however, at present there is no proof for the specificity of these findings for bipolar disorder. Future studies should consolidate the evidence on the impact of disorders of the circadian rhythm on the pathomechanism of bipolar disorder.

Movement disorders after hypoxic brain injury following cardiac arrest in adults.

BACKGROUND AND PURPOSE: Post-hypoxic movement disorders and chronic post-hypoxic myoclonus are rare complications after cardiac arrest in adults. Our study investigates the clinical spectrum, neuroimaging results, therapy and prognosis of these debilitating post-hypoxic sequelae. METHODS: This retrospective study included 72 patients from the neurological intensive care unit at a university hospital, who were diagnosed with hypoxic-ischaemic encephalopathy after cardiac arrest between January 2007 and September 2018. Clinical records were screened for occurrence of post-hypoxic movement disorders and chronic post-hypoxic myoclonus. Affected patients were further analysed for applied neuroprognostic tests, administered therapy and treatment response, and the outcome of these movement disorders and neurological function. RESULTS: Nineteen out of 72 screened patients exhibited post-hypoxic motor symptoms. Basal ganglia injury was the most likely neuroanatomical correlate of movement disorders as indicated by T1 hyperintensities and hypometabolism of this region in magnetic resonance imaging and positron emission tomography computed tomography. Levomepromazine and intrathecal baclofen showed first promising and mostly prompt responses to control these post-hypoxic movement disorders and even hyperkinetic storms. In contrast, chronic post-hypoxic myoclonus best responded to co-application of clonazepam, levetiracetam and primidone. Remission rates of post-hypoxic movement disorders and chronic post-hypoxic myoclonus were 58% and 50%, respectively. Affected patients seemed to present a rather good recovery of cognitive functions in contrast to the often more severe physical deficits. CONCLUSIONS: Post-hypoxic movement disorders associated with pronounced basal ganglia dysfunction might be efficiently controlled by levomepromazine or intrathecal baclofen. Their occurrence might be an indicator for a more unfavourable, but often not devastating, neurological outcome.

[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.

[Ambulatory monitoring and digital phenotyping in the diagnostics and treatment of bipolar disorders]. / Ambulantes Monitoring und digitale Phänotypisierung in Diagnostik und Therapie bipolarer Erkrankungen.

BACKGROUND: Reliable and valid diagnostics and treatment of bipolar disorders and affective episodes are subject to extensive, especially methodological limitations in the clinical practice. OBJECTIVE: The use of smartphones and mobile sensor technology for improvement in diagnostics and treatment of bipolar disorders. METHODS: Critical discussion of current research on the use of ambulatory monitoring and digital phenotyping with bipolar disorders. RESULTS: In many studies the observation periods were too short and the sensors applied were too inaccurate to enable reliable and valid detection of behavioral changes in the context of affective episodes. CONCLUSION: The clarification and operationalization of psychopathological constructs to allow for the measurement of objectively observable and ascertainable behavioral changes during depressive and (hypo)manic states are essential for the successful application of modern mobile technologies in the diagnostics and treatment of bipolar disorders.

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.

[Guideline-adherent psychiatric psychotherapeutic treatment of bipolar disorders : Which resources are needed?] / Leitliniengerechte psychiatrisch-psychotherapeutische Behandlung bei bipolaren Störungen : Welche Ressourcen werden dafür benötigt?

In this article the guideline-adherent psychiatric psychotherapeutic treatment of patients with bipolar disorders is outlined and the required resources are estimated. Based on the core recommendations of the S3 guidelines for diagnostics and treatment of bipolar disorders published in 2012, inpatient treatment needs in hours per week and per patient are determined for both manic and bipolar depressive episodes. The resulting staffing requirements are estimated on this basis. In summary, for guideline-adherent inpatient psychiatric psychotherapeutic treatment the additional needs regarding the physician/psychotherapeutic domain add up to 44 min per patient and week during a manic episode and 88 min for patients with bipolar depression when compared to current psychiatry staffing regulations.

Symptom characteristics of depressive episodes prior to the onset of mania or hypomania.

OBJECTIVE: Depressive episodes are typically the initial presentation of bipolar disorder. The evidence as to whether depressive episodes occurring in persons who later convert to bipolar disorder are symptomatically distinct from episodes of unipolar depression remains controversial. As there are crucial differences in the therapeutic management, symptom profiles indicating subsequent bipolar conversion may aid in appropriate treatment. METHOD: A representative community sample of originally N = 3021 adolescents and young adults aged 14-24 years at baseline was assessed up to four times over 10 years. Assessment of symptoms was conducted by clinically trained interviewers using the standardized M-CIDI. Symptom profiles of depressive episodes were compared via logistic regression between subjects that subsequently developed (hypo-)manic episodes (n = 35) or remained unipolar depressive (n = 659). RESULTS: Initial depression amongst prospective converters was characterized by significantly increased suicidality (odds ratio, OR = 2.31), higher rates of feelings of worthlessness and excessive guilt (OR = 2.52), complete loss of pleasure (OR = 2.53) and diurnal variation (OR = 4.30). No differences were found for hyperphagia, hypersomnia and psychomotor alterations. CONCLUSION: Findings suggest that the symptom profile of initial depressive episodes may be useful in the identification of subjects with an elevated risk for the subsequent conversion to bipolar disorder.

Accuracy of the pacemaker-mediated tachycardia algorithm in Boston Scientific devices.

INTRODUCTION: The incidence of pacemaker-mediated tachycardia (PMT) varies as a function of patient characteristics, device programming and algorithm specificities. We investigated the efficacy of the Boston Scientific algorithm by reviewing PMT episodes in a large device population. METHODS: In this multicenter study, we included 328 patients implanted with a Boston Scientific device: 157 non-dependent patients with RYTHMIQ™ activated (RYTHMIQ group), 76 patients with permanent AV-conduction disorder (AV-block group) and 95 Cardiac Resynchronization Therapy patients (CRT group). For each patient, we reviewed the last 10 remote monitoring-transmitted EGMs diagnosed as PMT. RESULTS: We analyzed 784 PMT episodes across 118 patients. In the RYTHMIQ group, the diagnosis of PMT was correct in most episodes (80%) of which 69% was directly related to the prolongation of the AV-delay associated with the RYTHMIQ algorithm. The usual triggers for PMT were also observed (PVC 16%, PAC 9%). The remainder of the episodes (20%) in RYTHMIQ patients and most episodes of AV-block (66%) and CRT patients (74%) were incorrectly diagnosed as PMT during sinus tachycardia at the maximal tracking rate. The inappropriate intervention of the algorithm during exercise causes non-conducted P-waves, loss of CRT (sustained in six patients) and may have been pro-arrhythmogenic in one patient (induction of ventricular tachycardia). CONCLUSION: Algorithms to minimize ventricular pacing can occasionally have unintended consequences such as PMT. The PMT algorithm in Boston Scientific devices is associated with a high rate of incorrect PMT diagnosis during exercise resulting in inappropriate therapy with non-conducted P-waves, loss of CRT and limited risk of pro-arrhythmic events.

Does lithium reduce acute suicidal ideation and behavior? A protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode.

BACKGROUND: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE. METHODS/DESIGN: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome. DISCUSSION: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02039479.

[Is there an increased risk for renal tumors during long-term treatment with lithium?]. / Gibt es bei der Lithiumlangzeitbehandlung ein erhöhtes Risiko für Nierentumoren?

Lithium salts are the recommended first-line treatment (gold standard) in national and international treatment guidelines for acute and maintenance treatment of affective disorders, such as bipolar disorders. Lithium has also been shown to have a unique protective effect against suicide in patients suffering from affective disorders. Despite the well-known acute and long-term adverse effects lithium therapy can be safely administered if patients are properly educated and carefully monitored. A recent study from France now shows that patients with severely impaired renal function who had been treated with lithium salts for more than 10 years could have an increased risk for kidney tumors (benign and malignant). This resulted in an adjustment concerning information within the package leaflet by European authorities. The authors of this article reflect the currently available data in order to better understand and handle this new finding and to warn about uncritical reactions including withdrawal of lithium in successfully treated patients. This article provides clinical recommendations to provide further insight relating to the risk of kidney cancer in long-term lithium therapy.

[Ketamine as antidepressant: the current study situation]. / Ketamin als Antidepressivum : Die aktuelle Studienlage.

The treatment of depressive episodes is characterized by a delay in response of antidepressant medications and high rates of therapeutic failure. In recent years several open and five controlled trials have demonstrated the antidepressant efficacy of ketamine for major depression. In addition a recent study established the utility of nasal ketamine which may render the necessity of intravenous administration obsolete. The current state of evidence is reviewed and discussed.

'One also needs a bit of trust in the doctor ... ': a qualitative interview study with pancreatic cancer patients about their perceptions and views on information and treatment decision-making.

BACKGROUND: Information about diagnosis, treatment options and prognosis has been emphasized as a key to empower cancer patients to make treatment decisions reflecting their values. However, surveys indicate that patients' preferences regarding information and treatment decision-making differ. In this qualitative interview study, we explored pancreatic cancer patients' perceptions and preferences on information and treatment decision-making. PATIENTS AND METHODS: Qualitative in-depth interviews with patients with pancreatic cancer. Purposive sampling and qualitative analysis were carried out. RESULTS: We identified two stages of information and treatment decision-making. Patients initially emphasize trust in their physician and indicate rather limited interest in details about surgical and medical treatment. In the latter stage of disease, patients perceive themselves more active regarding information seeking and treatment decision-making. All patients discuss their poor prognosis. Reflecting on their own situation, all patients interviewed pointed out that hope was an important driver to undergo further treatment also in advanced stages of the disease. Interviewees unanimously emphasized the difficulty of anticipating the time at which stopping cancer treatment would be the right decision. CONCLUSIONS: The findings can serve as starting point for reflection on professional decision-making in pancreatic cancer and larger representative surveys on ethical issues in treatment decision-making in pancreatic cancer.

[Unclear hepatopathy in a patient with atrial fibrillation]. / Unklare Hepatopathie bei einem Patienten mit Vorhofflimmern.

Although liver damage is a relatively rare adverse effect of oral anticoagulation with phenprocoumon, acute liver failure can be a serious treatment-associated complication. In this contribution, a patient with drug-induced liver failure during oral anticoagulation with phenprocoumon is presented. This case illustrates the need for close laboratory monitoring and suggests that phenrocoumon-induced liver damage should be considered along with other common complications of this treatment.

THz microscope for three-dimensional imaging with superconducting Josephson junctions.

Superconducting Josephson junctions have a wide range of applications ranging from quantum computing to voltage standards, and they may also be employed as versatile sensors for high-frequency radiation and magnetic fields. In this work, we present a unique measurement setup utilizing a single Josephson junction on a cantilever for high-resolution spatial measurements of spectroscopically resolved THz and microwave field distributions. This THz microscope can be utilized to measure power and frequency of electromagnetic radiation from ∼1 GHz to 5 THz. It may also be used to measure static magnetic fields and provide topological scans of samples. The samples can be both actively radiating or passively irradiated at either room temperature or cryogenic temperatures. We review the measurement setup of the THz microscope and describe the evaluation of its measurement data to achieve three-dimensional visualizations of the field distributions. The diverse capabilities of this unique tool are demonstrated by its different measurement modes with measurements of field distributions at 20 GHz and 1.4 THz, spectroscopically resolved THz measurements, and magnetic field measurements.

Determinants of glucose control in patients with chronic pancreatitis.

AIMS/HYPOTHESIS: Diabetes frequently develops in patients with chronic pancreatitis (CP). Partial pancreatectomy has emerged as a treatment option for such patients. We addressed whether the development of diabetes in CP patients is related to pancreatic beta cell area or clinical variables, and which factors predict the diabetes risk after partial pancreatectomy. METHODS: Fractional beta cell area was determined in pancreatic tissue samples obtained from 114 CP patients undergoing pancreatic surgery and related to measures of glucose control, as well as clinical and anthropometric data. Seventy-four patients without diabetes at the time of surgery were contacted again 2.5 +/- 1.0 years after partial pancreatectomy in order to obtain information about the post-operative development of diabetes. RESULTS: In the surgical samples in the whole cohort, pancreatic beta cell area was 0.40 +/- 0.06% in patients with and 0.64 +/- 0.06% in those without previously known diabetes (p = 0.039). There was an inverse non-linear relationship between pancreatic beta cell area and fasting glucose concentrations (r = 0.29) as well as HbA(1c) levels (r = 0.36). Nineteen out of 74 previously normoglycaemic patients (26%) developed diabetes over an average period of 2.5 years of follow-up. Pre-operative fasting glucose levels, HbA(1c) and BMI were identified as predictors of diabetes after partial pancreatectomy. However, pancreatic beta cell area did not differ in those who subsequently developed diabetes (0.66 +/- 0.15%) and those who did not (0.62 +/- 0.08%, p = 0.45). CONCLUSIONS/INTERPRETATION: Hyperglycaemia in CP patients is associated with reduced beta cell area. However, reduced beta cell area does not predict the development of diabetes, suggesting that other factors are more important determinants of alterations in glucose metabolism in patients with CP.

Incidence of paroxysmal atrial tachycardias in patients treated with cardiac resynchronization therapy and continuously monitored by device diagnostics.

AIMS: Little is known about the incidence of paroxysmal atrial tachycardias (PAT) in patients with heart failure (HF). The availability of cardiac resynchronization therapy (CRT) devices with extended diagnostics for AT enables continuous monitoring of PAT episodes. The aim of the study was to assess the incidence over time of PAT in HF patients treated with CRT. METHODS AND RESULTS: Consecutive patients in NYHA functional class III or IV despite optimal drug therapy, QRS duration > or = 130 ms, left ventricular ejection fraction < or = 35%, and left ventricular end-diastolic dimension > or = 55 mm were eligible for enrolment. Patients with permanent or persistent atrial fibrillation (AF) were not included in the study. The first follow-up examination was performed 2 weeks after implantation, to optimize atrial sensing and CRT. Subsequent follow-up examinations were carried out 15 and 28 weeks after implantation, to collect the telemetric data. A total of 173 patients (67 +/- 11 years, M 116) were enrolled. Complete arrhythmia monitoring data were available from 120 patients over a mean follow-up of 183 +/- 23 days. Atrial tachycardia episodes were detected through telemetry in 25 of 120 patients (21%) during at least one follow-up examination. Atrial tachycardia episodes were recorded in 29 and 17% (P = NS) of patients with and without previous history of AF, respectively. CONCLUSION: More than 20% of the overall HF patient population treated with CRT suffer PAT episodes. Paroxysmal atrial tachycardia may interfere with response to CRT. Therefore, telemetric data may be relevant to drive the appropriate therapy in each patient.

[Mitoxantrone-related acute leukemia by multiple sclerosis. Case report and practical approach by unclear cytopenia]. / Mitoxantron-assoziierte akute Leukämie bei Multipler Sklerose. Fallbericht und praktisches Vorgehen bei unklaren Zytopenien.

BACKGROUND: Mitoxantrone is highly efficacious in the treatment of severe multiple sclerosis (MS). Mitoxantrone therapy-related acute leukemia (TRAL) has recently become the focus of interest. METHODS: A case report of fatal TRAL following mitoxantrone therapy is presented with a discussion on the differential diagnosis and risk factors. The interdisciplinary development of diagnostic and therapeutic algorithms is presented from a haematological and neurological point of view. RESULTS: We describe the case of a 34-year-old MS patient who developed TRAL following mitoxantrone therapy (cumulative dose 45 mg/m(2) body surface). The patient died from endocarditis. TRAL is a rare but potentially fatal complication of mitoxantrone therapy with a wide variation of reported incidence. Thus far, no specific risk factors relating for example to preceding therapy and treatment regimens have been identified. Frequent laboratory controls and early bone marrow aspiration are mandatory for suspected TRAL as the condition is potentially curable. CONCLUSIONS: TRAL needs to be considered in the risk-benefit assessment of mitoxantrone therapy, however, the exact incidence and risk factors (e.g. dosage, treatment regimen) are still unclear. The risks are controllable under close surveillance and early diagnosis is important for prognosis. Future investigations need to concentrate on identification of potential risk factors.

Subject specificity of the correlation between large-scale structural and functional connectivity.

Structural connectivity (SC), the physical pathways connecting regions in the brain, and functional connectivity (FC), the temporal coactivations, are known to be tightly linked. However, the nature of this relationship is still not understood. In the present study, we examined this relation more closely in six separate human neuroimaging datasets with different acquisition and preprocessing methods. We show that using simple linear associations, the relation between an individual's SC and FC is not subject specific for five of the datasets. Subject specificity of SC-FC fit is achieved only for one of the six datasets, the multimodal Glasser Human Connectome Project (HCP) parcellated dataset. We show that subject specificity of SC-FC correspondence is limited across datasets due to relatively small variability between subjects in SC compared with the larger variability in FC.