[A severe, reversible encephalopathy after prolonged use of valproic acid]. / Ernstige, reversibele encefalopathie bij langdurig valproïnezuurgebruik.

Valproic acid is an effective mood stabilizer, registered for the treatment of bipolar disorder and epilepsy. Side effects of valproic acid are transient and generally well tolerated. A rare side effect is a valproic acid-induced encephalopathy. We saw a case of valproic acid-induced encephalopathy without hyperammonemia in a 71-year-old woman. She had used valproic acid as a mood stabilizer over the course of 16 years for a bipolar I disorder. The following clinical symptoms were observed: staring eye contact, somnolence, disorientation, hypotenacity, bradyfrenia, mutism and akathisia. Severe extrapyramidal symptoms were observed during neurological examination as well as hyperreflexia, a snoutreflex on both sides and a right-sided palmomental reflex. After cessation of the valproic acid, her symptoms disappeared completely. Based on this case report, we discuss the clinical aspects, pathophysiology, recognition and treatment of valproic acid-induced encephalopathy, both with and without hyperammonemia.

Negative content in auditory verbal hallucinations: a natural language processing approach.

INTRODUCTION: Negative content of auditory verbal hallucinations (AVH) is a strong predictor of distress and impairment. This paper quantifies emotional voice-content in order to explore both subjective (i.e. perceived) and objectively (i.e. linguistic sentiment) measured negativity and investigates associations with distress. METHODS: Clinical and non-clinical participants with frequent AVH (n = 40) repeated and recorded their AVH verbatim directly upon hearing. The AVH were analyzed for emotional valence using Pattern, a rule-based sentiment analyzer for Dutch. The AVH of the clinical individuals were compared to those of non-clinical voice-hearers on emotional valence and associated with experienced distress. RESULTS: The mean objective valence of AVH in patients was significantly more negative than those of non-clinical voice-hearers. In the clinical individuals a larger proportion of the voice-utterances was negative (34.7% versus 18.4%) in objective valence. The linguistic valence of the AVH showed a significant, strong association with the perceived negativity, amount of distress and disruption of life, but not with the intensity of distress. CONCLUSIONS: Our results indicate that AVH of patients have a more negative linguistic content than those of non-clinical voice-hearers, which is associated with the experienced distress. Thus, patients not only perceive their voices as more negative, objective analyses confirm this.

[Underexposed, potential lethal gastrointestinal adverse events associated with clozapine use]. / Onderbelichte, potentieel dodelijke gastro-intestinale bijwerkingen van clozapine.

Clozapine is an effective antipsychotic with antidopaminergic, anticholinergic and antiserotonergic effects. Due to potential adverse events, agranulocytosis being the most feared, patients using clozapine need to be closely monitored. A lesser known but equally common and potential lethal adverse effect is clozapine-induced gastrointestinal hypomotility (CIGH), which can cause a paralytic ileus, gut mucosal ischemia or aspiration pneumonia. We saw a male patient, aged 61 years, who used clozapine and suffered from CIGH, leading to frequent episodes of paralytic ileus requiring GE surgery. The case underlines the importance of timely recognition and treatment of clozapine-induced gastrointestinal hypomotility.

[Dutch medical disciplinary law cases concerning psychiatry, 2015-2019]. / Uitspraken van regionale tuchtcolleges in zaken betreffende de psychiatrie, 2015-2019.

BACKGROUND: The aim of medical disciplinary law (as part of the Dutch law 'Wet BIG') is to safeguard the quality of professional practice in the health services. Quantitative data about Dutch medical disciplinary law is sparse: little is known about the nature, quantity and the verdicts of disciplinary law complaints against psychiatrists and residents. AIM: Gaining insight in Dutch medical disciplinary law, in particular with regard to number and nature of disciplinary law complaints against psychiatrists(-psychotherapist) and psychiatry residents. METHOD: Descriptive retrospective study. We examined all medical disciplinary law cases against psychiatrists(-psychotherapist) and psychiatry residents in the period 2015-2019. RESULTS: In the study period the regional medical disciplinary courts handled 353 cases against psychiatrists(-psychotherapist) and residents psychiatry, on average 70.6 per year. 321 of these cases were against psychiatrists and 32 against residents. Complaint density was 1.74 for psychiatrists and 0.37 for residents. Subject of most cases was 'wrong diagnosis', followed by 'wrong therapeutic plan' and 'incorrect communication'. The number of cases resulting in a disciplinary measure was on average 31%: warning (49%), reprimand (30%), (conditional) suspension (15%). In 17 cases the professional was (partially) denied to practice. CONCLUSIONS Within Dutch psychiatry little attention is paid to disciplinary law, despite the fact that psychiatrists are relatively often confronted with disciplinary law complaints. The current explorative analysis underlines the need for further research, especially on the difference between male/female psychiatrists and an international comparison with respect to complaints about (sexual) misconduct.

[The effects of covid-19 on psychiatry training in the Netherlands]. / De invloed van COVID-19 op de opleiding psychiatrie in Nederland.

Background The COVID-19 pandemic changes the training of residents and could offer new opportunities. Aim Gaining insight in the effects of the impact of the COVID-19-pandemic on psychiatry residents. Method A digital questionnaire was designed to evaluate the impact of the COVID-19 pandemic on educational activities. The experience of residents with regards to safety in the workplace, social cohesion with their peers and the involvement of supervisors were examined. Results We approached 34 training institutions. 24 chief residents of the resident group completed the questionnaire. The quality of regional education was considered unchanged by 20% and local education by 33%. Digital communication increased the participation of psychiatrists in the general report and education activities and ensured less travel time. Nevertheless, respondents missed contact with their peers, safety of residents was compromised at five institutions and half of all respondents indicated a lack of personal protective equipment. Conclusions A majority of the psychiatry residents are satisfied with their training during this historic pandemic, but the quality of local and regional education was considered changed, and not being beneficial. The challenge remains for stimulating contact with peers, monitoring the quality of education in general as in psychotherapy and providing personal protective equipment. Tijdschrift voor Psychiatrie 63(2021)1, 16-21.

Minimum spanning tree analysis of brain networks: A systematic review of network size effects, sensitivity for neuropsychiatric pathology, and disorder specificity.

Brain network characteristics' potential to serve as a neurological and psychiatric pathology biomarker has been hampered by the so-called thresholding problem. The minimum spanning tree (MST) is increasingly applied to overcome this problem. It is yet unknown whether this approach leads to more consistent findings across studies and converging outcomes of either disease-specific biomarkers or transdiagnostic effects. We performed a systematic review on MST analysis in neurophysiological and neuroimaging studies (N = 43) to study consistency of MST metrics between different network sizes and assessed disease specificity and transdiagnostic sensitivity of MST metrics for neurological and psychiatric conditions. Analysis of data from control groups (12 studies) showed that MST leaf fraction but not diameter decreased with increasing network size. Studies showed a broad range in metric values, suggesting that specific processing pipelines affect MST topology. Contradicting findings remain in the inconclusive literature of MST brain network studies, but some trends were seen: (1) a more linelike organization characterizes neurodegenerative disorders across pathologies, and is associated with symptom severity and disease progression; (2) neurophysiological studies in epilepsy show frequency band specific MST alterations that normalize after successful treatment; and (3) less efficient MST topology in alpha band is found across disorders associated with attention impairments.

The relevance of geriatric assessment for older patients receiving palliative chemotherapy.

OBJECTIVES: No tools accurately discriminate between older patients who are fit and those who are frail to tolerate systemic palliative treatment. This study evaluates whether domains of geriatric assessment (GA) are associated with increased risk of chemotherapy intolerance in patients who were considered fit to start palliative chemotherapy after clinical evaluation by their treating clinician. MATERIALS AND METHODS: This prospective multicenter study included patients ≥70 years who started first line palliative systemic treatment. Before treatment initiation, patients completed GA including Activities of Daily Life (ADL), Instrumental Activities of Daily Life (IADL), Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS-15) and the Timed Up and Go Test (TUGT). Primary endpoint was treatment modification, defined as inability to complete the first three sessions of systemic treatment as planned. Secondary endpoint was treatment related toxicity ≥ grade 3 (CTCAE Version 4). The association between GA and endpoints were assessed using univariable and multivariable logistic regression analysis. RESULTS: Ninety-nine patients with median age of 77 (+/- 8) years underwent GA. 48% of the patients required treatment modification and grade 3 toxicity occurred in 53% of patients. One or more geriatric impairments were present in 71% of patients and 32% of patients were frail in two or more domains. Only TUGT was associated with treatment modifications (OR 2.9 [95% CI 1.3-6.5]) and grade 3 toxicities (OR 2.8 [95% CI 1.2-6.3]). CONCLUSION: Frailty was common in older patients who were considered fit to receive palliative chemotherapy. Treatment modification was necessary in half of the patients. Only TUGT was significantly associated with treatment modifications and grade 3 chemotherapy toxicities.

Analysis of docetaxel therapy in elderly (≥70 years) castration resistant prostate cancer patients enrolled in the Netherlands Prostate Study.

BACKGROUND: Prostate cancer truly is an age-associated disease. Due to the increased life expectancy and more sensitive diagnostic techniques in the Western world, prostate cancer is diagnosed more frequently and with rapidly increasing incidence and prevalence rates. However, age above 65 or 70 years has been an exclusion criterion in clinical trials for decades and the knowledge about chemotherapy tolerance in elderly is limited. METHODS: We performed a retrospective analysis of data acquired from the recently published Netherlands Prostate Study (NePro) to evaluate the influence of advanced age on docetaxel therapy in elderly men (>70 years) with castration resistant prostate cancer (CRPC) and bone metastases. Statistical analyses were performed stratified for age into four categories: <70 (n=315), 70-74 (n=150), 75-79 (n=85), and ≥80 years old (n=18). RESULTS: We analysed 568 patients (median age 68.1 years, range 46-89 years, 44.5% aged ≥70 years). There was no relation between dosage and age (p=0.60). We found no significant differences between the number of dose reductions, time to progression (TTP), overall survival, chemotherapy tolerance and toxicity up to the age of 80 years. However, when compared to younger men, men aged 80 years or above more frequently experienced grade 3/4 toxicity and were five times less likely to complete the first three treatment cycles at the intended dose (Odds ratio (OR) 5.34, p=0.0052) and showed decreased overall survival (15.3 months versus 24.5 months in <80 years group, p=0.020). CONCLUSION: In CRPC patients up to the age of 80 years, docetaxel chemotherapy is well tolerated, with toxicity levels and TTP comparable to those of younger patients. For chemotherapeutic treatment of patients above the age of 80 years an individual assessment should be made.