Florian Riese

European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium.

The purpose of this guideline is to present evidence-based and consensus-based recommendations for the prevention and treatment of postoperative delirium. The cornerstones of the guideline are the preoperative identification and handling of patients at risk, adequate intraoperative care, postoperative detection of delirium and management of delirious patients. The scope of this guideline is not to cover ICU delirium. Considering that many medical disciplines are involved in the treatment of surgical patients, a team-based approach should be implemented into daily practice. This guideline is aimed to promote knowledge and education in the preoperative, intraoperative and postoperative setting not only among anaesthesiologists but also among all other healthcare professionals involved in the care of surgical patients.

Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype

The biomarker potential of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimers disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound B-positive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid β deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimers disease.

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology.

Transition from psychiatric training to independent practice: a survey on the situation of early career psychiatrists in 35 countries

The transition from psychiatric training to independent practice is a crucial step in the professional development of every psychiatrist. For many psychiatrists, this phase also determines their choice of subspecialization and therefore has an important impact both on individual career paths as well as on the availability of psychiatrists in the various areas of our specialty. Despite its importance, this period of professional development is relatively understudied 1. In accordance with the WPA aim to “promote the professional development of early career psychiatrists worldwide” 2, the members of the WPA Early Career Psychiatrists Council (ECPC), Europe I area, conducted a survey to investigate this period in more detail 3. A 27-item online questionnaire was developed covering: a) factors influencing choice of psychiatric subspecialty and work setting, b) job availability, and c) availability of training and mentoring opportunities specific to this phase. All 60 Council members were asked to participate in the survey as experts of the situation in their countries. Forty Council members representing 35 countries from all five continents participated in the survey, resulting in a response rate of 66%. Career choice was more often reported to be strongly or very strongly influenced by personal variables, such as salary expectations (30/40), personal interests (29/40), and compatibility with private life (27/40), than by external factors such as societal expectations (13/40) and the political environment (10/40). Strikingly, gender inequalities were reported to have a strong influence on career choice in three countries. Furthermore, six of 40 respondents stated that in their countries the location of practice was decided “by somebody else” rather than the psychiatrists themselves. In 12 countries, higher salaries and access to subspecialty training are used as incentives to recruit psychiatrists into underserved regions. The risk for unemployment immediately after psychiatric specialization was judged either unlikely or very unlikely by almost all experts (37/40). However, more than half (21/40) stated it was difficult or very difficult to get the desired job. Positions in university hospitals and private psychiatric practices were most frequently cited as attractive career options. Of these, the availability of job opportunities in university hospitals was reported to be “quite bad” or “bad” in 21 of 40 countries. In addition, 14 of 40 representatives reported that it was not possible in their countries to immediately establish oneself as an independently practicing psychiatrist after completion of training. Limitations fixed by governments regarding the number of available positions and periods of mandatory service in the public sector — in one country up to nine years — were mentioned as restricting factors. Although the transition between psychiatric training and independent practice is associated with high levels of stress, anxiety, and difficulties with patient care amongst young psychiatrists 4, the survey highlighted a lack of specific support during this phase. Specific training opportunities to develop “real world” psychiatric skills, for example, in leadership or management, were reported to exist only by eight of 40 respondents. While 19 representatives stated that in their country a mentor was available during psychiatric training, that number dropped to 11 for the first years of working as a specialist. In our view, the transition from psychiatric training to independent practice should be recognized as a complex task and a crucial step toward mastery of our profession. It deserves both self-reflection by the young psychiatrist and support by psychiatric professional associations. Specific training opportunities for this transition period should be created. Furthermore, we believe that establishing incentives may be a more suitable approach than imposing restrictions in order to sustainably attract young psychiatrists to work in underserved regions of a country or neglected fields of psychiatry 5. While the latter approach may function in the short run, it can be a strain on the individual psychiatrist and a danger to recruitment in the long-term.

Palliative psychiatry for severe persistent mental illness as a new approach to psychiatry? Definition, scope, benefits, and risks

BackgroundAs a significant proportion of patients receiving palliative care suffer from states of anxiety, depression, delirium, or other mental symptoms, psychiatry and palliative care already collaborate closely in the palliative care of medical conditions. Despite this well-established involvement of psychiatrists in palliative care, psychiatry does not currently explicitly provide palliative care for patients with mental illness outside the context of terminal medical illness.DiscussionBased on the WHO definition of palliative care, a, a working definition of palliative psychiatry is proposed. Palliative psychiatry focuses on mental health rather than medical/physical issues. We propose that the beneficiaries of palliative psychiatry are patients with severe persistent mental illness, who are at risk of therapeutic neglect and/or overly aggressive care within current paradigms. These include long-term residential care patients with severe chronic schizophrenia and insufficient quality of life, those with therapy-refractory depressions and repeated suicide attempts, and those with severe long-standing therapy-refractory anorexia nervosa. An explicitly palliative approach within psychiatry has the potential to improve quality of care, person-centredness, outcomes, and autonomy for patients with severe persistent mental illness.ConclusionsThe first step towards a palliative psychiatry is to acknowledge those palliative approaches that already exist implicitly in psychiatry. Basic skills for a palliative psychiatry include communication of diagnosis and prognosis, symptom assessment and management, support for advance (mental health) care planning, assessment of caregiver needs, and referral to specialized services. Some of these may already be considered core skills of psychiatrists, but for a truly palliative approach they should be exercised guided by an awareness of the limited functional prognosis and lifespan of patients with severe persistent mental illness.

Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer’s disease

Recent studies have shown that increased cognitive intraindividual variability (IIV) across accuracy scores from tests representing different cognitive domains (across-domain IIV) might indicate prodromal Alzheimer’s disease (AD). Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV) has not been examined in healthy controls subjects (HCS), mild cognitive impairment (MCI), and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI, and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p < 0.01). Only across-domain IIV was higher in AD vs. MCI (p = 0.001), and only within-domain IIV was higher in MCI vs. HCS (p = 0.05). Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage.

Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers

Changes in cerebral blood flow are an essential feature of Alzheimer’s disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E ɛ4-allele carriers (apolipoprotein E4+) than in apolipoprotein E4− across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiB+) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4+ versus apolipoprotein E4− compared with the contrasts PiB+ versus PiB− or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer’s disease.

Visualization and Quantification of APP Intracellular Domain-Mediated Nuclear Signaling by Bimolecular Fluorescence Complementation

Background The amyloid precursor protein (APP) intracellular domain (AICD) is released from full-length APP upon sequential cleavage by either α- or β-secretase followed by γ-secretase. Together with the adaptor protein Fe65 and the histone acetyltransferase Tip60, AICD forms nuclear multiprotein complexes (AFT complexes) that function in transcriptional regulation. Objective To develop a medium-throughput machine-based assay for visualization and quantification of AFT complex formation in cultured cells. Methods We used cotransfection of bimolecular fluorescence complementation (BiFC) fusion constructs of APP and Tip60 for analysis of subcellular localization by confocal microscopy and quantification by flow cytometry (FC). Results Our novel BiFC-constructs show a nuclear localization of AFT complexes that is identical to conventional fluorescence-tagged constructs. Production of the BiFC signal is dependent on the adaptor protein Fe65 resulting in fluorescence complementation only after Fe65-mediated nuclear translocation of AICD and interaction with Tip60. We applied the AFT-BiFC system to show that the Swedish APP familial Alzheimer’s disease mutation increases AFT complex formation, consistent with the notion that AICD mediated nuclear signaling mainly occurs following APP processing through the amyloidogenic β-secretase pathway. Next, we studied the impact of posttranslational modifications of AICD on AFT complex formation. Mutation of tyrosine 682 in the YENPTY motif of AICD to phenylalanine prevents phosphorylation resulting in increased nuclear AFT-BiFC signals. This is consistent with the negative impact of tyrosine phosphorylation on Fe65 binding to AICD. Finally, we studied the effect of oxidative stress. Our data shows that oxidative stress, at a level that also causes cell death, leads to a reduction in AFT-BiFC signals. Conclusion We established a new method for visualization and FC quantification of the interaction between AICD, Fe65 and Tip60 in the nucleus based on BiFC. It enables flow cytometric analysis of AICD nuclear signaling and is characterized by scalability and low background fluorescence.

Becoming a psychiatrist in Europe: the title is recognized across the European Union, but what are the differences in training, salary and working hours?

The professional qualification as a psychiatrist is automatically recognized across Europe if a national training program fulfils the minimum requirement of four years of training duration (1,2). This is applicable to all 28 European Union (EU) member states, as well as to other countries of the European Economic Area, such as Norway and Switzerland (2). However, what is equivalent on paper may be not in practice: patients and hospital staff increasingly encounter doctors with different educational backgrounds due to the open European labour market and the mobility of trainees and psychiatrists. In 2014/2015, the European Federation of Psychiatric Trainees surveyed training in psychiatry by a questionnaire directed at representatives of national psychiatric trainee associations. Except Cyprus, Czech Republic, Latvia, Luxembourg and Spain, all EU countries were covered. A medical practitioner who undergoes postgraduate training in psychiatry and qualifies as a specialist is called a psychiatrist. Only in the German speaking countries, i.e. Austria, Germany, Switzerland and Liechtenstein, the specialist holds the title of “psychiatrist and psychotherapist” (2), even though training in psychotherapy is a mandatory part of psychiatric training in most European countries (3). Although skills in psychotherapy are widely considered essential for psychiatrists, the number of patients to whom trainees are required to deliver psychotherapy varies and can be as little as zero, as in Estonia (4). In some countries, e.g. the Netherlands, child and adolescent psychiatry is a subspecialty of “adult” psychiatry. In other countries (25 out of 31) it is a separate specialty with up to 600 trainees (as reported from UK). However, only in Belgium the title specifies that a psychiatrist is specialized in adults (“psychiatrie de l’adulte”) (2). A title such as “general psychiatrist” (awarded in the UK) could help differentiate subspecialties and underline the balance of technical and non-technical elements of care (5). In order to match the EU minimum requirement, training duration needs to be four years or longer. The maximum required training durations are seven years in Ireland and six years in Austria, Finland, Switzerland and the UK. Training is not nationally standardized in four out of 31 countries (Belgium, Finland, France and Greece), underlining the challenge of establishing a single, unified European exam. In some countries it is required to rotate in a university hospital (six months in France) or a psychiatry ward in a general hospital (six months in Greece), or to spend twelve months in another hospital (Switzerland), pushing trainees to switch workplace. Outpatient care is strongly enforced in Finland, where half of the training has to take place in outpatient care. Overall, national curricula are still mainly defined by total duration and duration of rotations in (sub)specialties, despite the benefits of competency-based training (which may also facilitate a pan-European exam). Appropriate working conditions, including salary and working hours, are essential for high-quality clinical training. Trainees in EU countries work 35 (Bulgaria) to 65 hours (Malta, including on-call hours) per week. Non-EU countries are characterized by less working hours: 35 hours per week in Belarus, Russia, Serbia and Ukraine. Income varies from 90€ per month in Ukraine to >4,000€ in Switzerland, i.e. in some countries trainees earn 44 times more than in others. The top-five countries in terms of average monthly salaries, mostly including on-call hours, after tax deduction are Switzerland, Sweden and the UK (≥4,000€), Norway (3,400€) and Germany (2,900€), while the lowest monthly salaries are paid in Ukraine (90€), Bulgaria (140€), Belarus (150€), Russia (150-500€) and Romania (400€). In Portugal (1,200€) it is common for trainees to spend a period abroad, during which they continue to be paid by their institution. Trainees in Belgium are paid (1,900-2,400€ per month) by their supervisors, which may cause conflicts of interest. Notably, not all aspects of training (especially parts of the psychotherapy curricula) are free of charge for trainees (4), further reducing their spendable income. In most countries (17 out of 31), too few medical practitioners choose psychiatry as their specialty, yet initiatives to increase recruitment are lacking. As a consequence, in 16 countries, not all vacant positions are being filled, and only in very few countries (e.g., Greece) demand for training positions exceeds openings. Thus, the characteristics of psychiatric training vary widely across Europe, despite an open labour market where specialists frequently work in foreign countries. The fact that the qualification of psychiatrists is equivalent throughout Europe should stimulate international cooperation when re-designing training curricula. Guidance and support by international organizations such as the European Federation of Psychiatric Trainees (6), the European Psychiatric Association (7), the European Union of Medical Specialists (8), the World Health Organization and the WPA are crucial in order to facilitate harmonization of curricula. To improve local implementation, an international system of training programme inspections should be established.

Palliative psychiatry for severe and persistent mental illness

Despite all of psychiatrys efforts to prevent mental illness and to promote recovery, some patients will develop severe and persistent mental illness (SMI). These patients represent a particularly vulnerable population, at risk of either therapeutic neglect or overly aggressive care. We propose a complementary approach in the treatment of SMI; palliative psychiatry, as a means to improve quality of care, person-centeredness, and autonomy for SMI patients.