Incidence of Drug-Induced Delirium During Treatment With Antidepressants or Antipsychotics: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2016.

OBJECTIVES: Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium. METHODS: This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics. RESULTS: A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID. CONCLUSIONS: With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

A Place to Live and to Die: A Qualitative Exploration of the Social Practices and Rituals of Death in Residential Aged Care.

In many countries, an increasing proportion of deaths occur in residential aged care (RAC) (nursing homes) meaning that these have become both a place to live - a home- and a place to die. This paper reports on death practices and rituals in 49 RAC facilities in Aotearoa/New Zealand narrated in semi-structured interviews with staff. Themes coalesced around 'good death'. Dying alone was not seen as a good death and the demands of trying to prevent this caused tension for staff. Meeting family wishes, post death decision-making, after death practices and rituals, including communicating and remembrance of the death, were explored as part of good death. Overall, death rituals in RAC were limited. Balancing the needs of the living, the dying and the dead created tension. The rituals and practices facilities are currently enacting in death/post-death require attention, since more people will die in RAC with increasingly diverse needs.

Repetitive enhancement of serum BDNF subsequent to continuation ECT.

INTRODUCTION: Continuation electroconvulsive therapy (c-ECT) is highly effective for the prevention of depressive symptom relapse. There is a lack of understanding, about how c-ECT works in humans, particularly with regard to its effects on brain derived neurotrophic factor (BDNF) concentrations. Here, we aimed to close a gap in the literature by evaluating BDNF levels in patients receiving c-ECT. METHODS: We included 13 patients with either unipolar or bipolar depression (mean age ± SD: 55.5 ± 17.1; f/m: 10/3; unipolar/bipolar: 10/3) who received between one and four c-ECT (average per patient: 2.8). Serum BDNF (sBDNF) levels were assessed before and after each c-ECT sessions. Clinical assessments were also administered both before and after treatment. RESULTS: Our analysis revealed a significant increase in sBDNF after each treatment (c-ECT 1-3: P < 0.001, c-ECT 4: P = 0.018). The application of multiple c-ECT treatments was not, however, associated with further sBDNF enhancements. Psychometric scores were not significantly altered following c-ECT. DISCUSSION: An increase in sBDNF concentrations subsequent to c-ECT parallel data from the animal literature, which has linked regularly applied electrical stimulation to neuroplastic processes. This finding suggests a relationship between ECT-induced sBDNF concentrations and (sustained) remission status, considering a stable clinical condition across c-ECT.

Vocal tract modelling in fallow deer: are male groans nasalized?

Males of several species of deer have a descended and mobile larynx, resulting in an unusually long vocal tract, which can be further extended by lowering the larynx during call production. Formant frequencies are lowered as the vocal tract is extended, as predicted when approximating the vocal tract as a uniform quarter wavelength resonator. However, formant frequencies in polygynous deer follow uneven distribution patterns, indicating that the vocal tract configuration may in fact be rather complex. We CT-scanned the head and neck region of two adult male fallow deer specimens with artificially extended vocal tracts and measured the cross-sectional areas of the supra-laryngeal vocal tract along the oral and nasal tracts. The CT data were then used to predict the resonances produced by three possible configurations, including the oral vocal tract only, the nasal vocal tract only, or combining the two. We found that the area functions from the combined oral and nasal vocal tracts produced resonances more closely matching the formant pattern and scaling observed in fallow deer groans than those predicted by the area functions of the oral vocal tract only or of the nasal vocal tract only. This indicates that the nasal and oral vocal tracts are both simultaneously involved in the production of a non-human mammal vocalization, and suggests that the potential for nasalization in putative oral loud calls should be carefully considered.

Psychosocial distress in haematological cancer survivors: An integrative review.

Haematological cancers are becoming more prevalent, however, survival is also increasing. Many survivors are faced with psychosocial issues after treatment ends, and they may not receive the support they need. This review aims to examine peer reviewed literature reporting psychosocial distress faced by haematological cancer survivors in the early post-treatment period. Database and hand searches were conducted between August and September 2015, with no year restriction. Eligible studies were those reporting on psychosocial sequelae in haematological cancer survivors up to 5 years post-treatment. The search yielded 512 studies, of these only seven (five quantitative and two qualitative) included data that addressed psychosocial distress in early post-treatment haematological cancer survivors. Data were thematically analysed to explore the presence and nature of distress. Most studies reported mild to moderate distress for survivors, with some evidence that younger age was an indicator of increased distress. However, predominately this review identified a gap in current literature regarding distress among this group of survivors. More research is needed to address the psychosocial issues facing this growing survivor group, to enable them to receive the support required to maintain good physical and psychological health in this period of the cancer trajectory and into the future.

Acoustic structure of alarm calls in Indian sambar (Rusa unicolor) and Indian muntjac (Muntiacus vaginalis) in South Vietnam.

The alarm call acoustic structure and nonlinear vocal phenomena of the Indian sambar (Rusa unicolor) and northern Indian muntjac (Muntiacus vaginalis) have been analyzed in detail as well as their vocal behavior in response to mobbing humans under natural conditions of southern Vietnam. The alarm calls of sambars, tonal barks separated by large intervals, were produced by animals standing on the place and gazing at a potentially dangerous object. Muntjacs flee off in danger and produced a series of dull barks interrupted with short intervals from a distance. The alarm call frequencies were characterized for sambars and muntjacs. The results of our study have been compared with the published data on alarm calls of other Cervidae species.

Evidence of biphonation and source-filter interactions in the bugles of male North American wapiti (Cervus canadensis).

With an average male body mass of 320 kg, the wapiti, ITALIC! Cervus canadensis, is the largest extant species of Old World deer (Cervinae). Despite this large body size, male wapiti produce whistle-like sexual calls called bugles characterised by an extremely high fundamental frequency. Investigations of the biometry and physiology of the male wapiti's relatively large larynx have so far failed to account for the production of such a high fundamental frequency. Our examination of spectrograms of male bugles suggested that the complex harmonic structure is best explained by a dual-source model (biphonation), with one source oscillating at a mean of 145 Hz (F0) and the other oscillating independently at an average of 1426 Hz (G0). A combination of anatomical investigations and acoustical modelling indicated that the F0 of male bugles is consistent with the vocal fold dimensions reported in this species, whereas the secondary, much higher source at G0 is more consistent with an aerodynamic whistle produced as air flows rapidly through a narrow supraglottic constriction. We also report a possible interaction between the higher frequency G0 and vocal tract resonances, as G0 transiently locks onto individual formants as the vocal tract is extended. We speculate that male wapiti have evolved such a dual-source phonation to advertise body size at close range (with a relatively low-frequency F0 providing a dense spectrum to highlight size-related information contained in formants) while simultaneously advertising their presence over greater distances using the very high-amplitude G0 whistle component.

Psychiatric patients' perception of physical restraint.

OBJECTIVE: To investigate psychiatric patients' subjective perception during and after belt fixation. METHOD: All patients who were involuntarily admitted and physically restrained at a psychiatric intensive care unit within an 18-month study period were analysed. Ratings were obtained at four visits when questioning was possible. RESULTS: Within a heterogeneous diagnostic sample of 47 patients, only 12 patients were eligible to participate during belt fixation. After cessation of fixation, eight patients lacked any memory of restraint, while 36 could be questioned. Visual analogue scale median scores indicated powerlessness and depressiveness rather than anxiety and aggression. Patients' acceptance of the coercive measure was significantly higher (P = 0.003), while patients' memory was significantly lower than expected (P < 0.001). About 50% of the patients documented high perceived coercion, and post-traumatic stress disorder (PTSD) could be supposed in a quarter of the restrained individuals. Subjective perceptions concerning fixation showed no significant changes over time. Results showed high interindividual variability. CONCLUSION: Visual analogue scale revealed that belt fixation seemed to be forgotten or accepted in the majority of patients, probably due to psychiatric intensive care, psychopharmacological treatment and clinical improvements. The responses of a quarter of the patients assessed before discharge may be in accordance with symptoms of PTSD.

Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET.

Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT(1A)) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT(1A) function and density by antidepressants. Further, alterations of the 5-HT(1A) receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT(1A) receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-(11)C]WAY100635, twice before (test-retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (~83%) were responders to ECT. The voxel-wise comparison of the 5-HT(1A) receptor binding (BP(ND)) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (-27.5%), the orbitofrontal cortex (-30.1%), the amygdala (-31.8%), the hippocampus (-30.6%) and the insula (-28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT(1A) receptor binding in the effect of ECT.

Psychosis in neurosyphilis -- clinical aspects and implications.

BACKGROUND: The World Health Organization estimates that 10-12 million new syphilis infections occur each year. Without treatment, years to decades after initial infection, 30% of affected individuals may develop tertiary syphilis, which can manifest as neurosyphilis. The aim of this review is to evaluate the research literature examining the psychopathological manifestations of psychosis in association with neurosyphilis. METHOD: The authors performed a systematic electronic search for published studies (1995-2012). The following databases were used: Medline, Embase and the Cochrane Library as well as the search engines Scopus and Google Scholar. RESULTS: 61 articles were used for detailed analysis. Psychotic symptoms due to neurosyphilis are numerous and can inform differential diagnosis for many psychotic manifestations according to ICD-10 or DSM-IV. CONCLUSION: Due to our results, current epidemiological data, and the difficulties in differential diagnosis of neurosyphilis, routine screening tests are still recommended in the psychiatric field. Long-term psychiatric input, with periodic syphilis titre controls, seems indicated in individuals affected by neurosyphilis with psychiatric symptoms. Furthermore, individuals with mental health problems may be at higher risk of acquiring syphilis.

Comparison of etomidate and methohexital as anesthetic agents for continuation and maintenance electroconvulsive therapy: A retrospective analysis of seizure quality and safety.

BACKGROUND: The ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes. METHODS: All subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis. Data for each ECT session were obtained from the electronic health records. Anesthesia was performed with either methohexital/succinylcholine or etomidate/succinylcholine. Standard seizure quality parameters, anesthesiological monitoring data, pharmacological interventions and side-effects were recorded. RESULTS: 573 mECT treatments in 88 patients were included (methohexital n = 458, etomidate n = 115). Seizures lasted significantly longer after using etomidate (electroencephalography: +12.80 s [95 %-CI:8.64-16.95]; electromyogram +6.59 s [95 %-CI:4.14-9.04]). Time to maximum coherence was significantly longer with etomidate (+7.34 s [95 %-CI:3.97-10.71]. Use of etomidate was associated with longer procedure duration (+6.51 min [95 %-CI:4.84-8.17]) and higher maximum postictal systolic blood pressure (+13.64 mmHg [95 %-CI:9.33-17.94]). Postictal systolic blood pressure > 180 mmHg, the use of antihypertensives, benzodiazepines and clonidine (for postictal agitation), as well as the occurrence of myoclonus was significantly more common under etomidate. CONCLUSIONS: Due to longer procedure duration and an unfavorable side effect profile, etomidate appears inferior to methohexital as an anesthetic agent in mECT despite longer seizure durations.

Dystocia and fetotomy associated with cerebral aplasia in a greater one-horned rhinoceros (Rhinoceros unicornis).

The captive greater one-horned rhinoceros population consists of 176 animals. Since 1971, a total of 226 calves were born into this captive population. However, 24% of the offspring born were either stillborn or did not survive the first 3 months. The causes for this high rate of stillbirth and neonate mortality have not yet been documented. Here, we report on the veterinary management of a dystocia and foetotomy resulting from a malpositioned greater one-horned rhinoceros foetus. The dead foetus presented with a forelimb flexed at the shoulder joint, with all other joints extended. The foetus was dissected into five parts and extracted during two anaesthesias on two consecutive days. The dam recovered fully and came into oestrous 31 days after surgery. Post-mortem and CT examination of the malformed foetal head revealed cranioschisis with cerebral aplasia and cerebellar hypoplasia. The cerebral aplasia presented here and in other recent cases suggests that neural tube defects and cranial malformations may be associated with more captive rhinoceros stillbirths than previously considered. Epidemiologic studies of these phenomena and possible nutritional deficiencies or hereditary defects are warranted.

Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.

INTRODUCTION: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment. METHODS: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals. RESULTS: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period. DISCUSSION: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

INTRODUCTION: The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. METHODS: Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. RESULTS: VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. DISCUSSION: Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary.

Esophagopericardial Fistula Causing Pyopneumopericardium.

An esophagopericardial fistula is a rare complication of esophageal malignancy, trauma, or surgery. Imaging is a cornerstone of diagnosis, with detection of pneumopericardium or hydropneumopericardium at imaging raising suspicion for pyopneumopericardium and prompting immediate search for the causative pathologic process. Given the high associated mortality rate of over 50% for patients with esophagopericardial fistulas, early diagnosis and intervention are vital. Supplemental material is available for this article. © RSNA, 2020.

First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension.

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease). The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability. Riociguat had a favourable safety profile at single doses < or =2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg. The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.

Enhancement of nonlinear effects at the degenerate band edge of two-dimensional photonic crystals.

The ability of two-dimensional (2D) photonic crystals (PC) for high enhancements of nonlinear processes is analyzed in the case of a degenerate band edge when two symmetrical diffracted beams are generated by Bragg diffraction in the 2D-PC. Calculations are performed using the very simple Bragg-coupled wave theory which only involves three coupled waves (the incident wave and the two diffracted waves) for the linear interaction. The validity of the approximation is proved for wavelengths lying at the neighborhood of the band edges of 2D-PC. Very large local-field intensities are predicted around the band-edge wavelengths, in particular for the upper band edge. Nonlinear propagation is studied through the analysis of degenerate four-wave mixing. For counterpropagating pump beams orthogonally sent onto the 2D-PC huge improvement of the phase conjugate reflectivity are predicted at least for small incidence angles of the signal beam. These results represent an improvement by a factor of 20 when compared to the case of a one-dimensional PC of the same thickness made of the same materials. As three intense phase conjugate beams are generated in the four-wave mixing interaction, the 2D-PC could be very interesting for the purpose of dense parallel optical signal processing. Moreover, the simple theoretical analysis developed in the paper can be used for any kind of 2D-PC.

Report of the 3rd Havemeyer workshop on allergic diseases of the Horse, Hólar, Iceland, June 2007.

Allergic diseases occur in most mammals, although some species such as humans, dogs and horses seem to be more prone to develop allergies than others. In horses, insect bite hypersensitivity (IBH), an allergic dermatitis caused by bites of midges, and recurrent airway obstruction (RAO), a hyperreactivity to stable born dust and allergens, are the two most prevalent allergic diseases. Allergic diseases involve the interaction of three major factors: (i) genetic constitution, (ii) exposure to allergens, and (iii) a dysregulation of the immune response determined by (i) and (ii). However, other environmental factors such as infectious diseases, contact with endotoxin and degree of infestation with endoparasites have been shown to influence the prevalence of allergic diseases in humans. How these factors may impact upon allergic disease in the horse is unknown at this time. The 3rd workshop on Allergic Diseases of the Horse, with major sponsorship from the Havemeyer Foundation, was held in Hólar, Iceland, in June 2007 and focussed on immunological and genetic aspects of IBH and RAO. This particular venue was chosen because of the prevalence of IBH in exported Icelandic horses. The incidence of IBH is significantly different between Icelandic horses born in Europe or North America and those born in Iceland and exported as adults. Although the genetic factors and allergens are the same, exported adult horses show a greater incidence of IBH. This suggests that environmental or epigenetic factors may contribute to this response. This report summarizes the present state of knowledge and summarizes important issues discussed at the workshop.

Metabolic changes in the normal ageing brain: consistent findings from short and long echo time proton spectroscopy.

OBJECTIVES: Sixty three healthy subjects were measured to assess dependence of brain metabolites on age using short- and long echo time spectroscopy in different brain regions. MATERIAL AND METHODS: Younger and elderly humans were measured with long echo time (TE=135ms) 3D-MR-spectroscopic imaging (MRSI) (10 subjects) and with ultra-short echo (TE=11ms) time 2D-MRSI (7 subjects). In addition, results from single voxel (1)H-spectroscopy (TE=20ms) of two cohorts of 46 healthy subjects were retrospectively correlated with age. RESULTS: 3D-MR SI revealed reduced NAA/Cr in the older group in the frontal lobe (-22%; p<0.01), parietal lobe (-28%; p<0.01) and semiovale (-9%; p<0.01) compared to the younger group. Cho/Cr was elevated in the semiovale (+35%; p<0.01) and in the n. lentiformis (+42%; p<0.01) in the older group. NAA/Cho was reduced in all regions measured, except the thalamus, in the older group compared to the younger group (from -21 to -49%; p<0.01). 2D-MRSI revealed decreased total NAA (-3.1% per decade; p<0.01) and NAA/Cr (-3.8% per decade; p<0.01), increased total Cho (+3.6% per decade; p<0.01) and Cho/Cr (+4.6% per decade; p<0.01) and increased total myo-Inositol (mI, +4.7% per decade; p<0.01) and mI/Cr (+5.4% per decade; p<0.01) and decreased NAA/Cho (-8% per decade; p<0.01) in semiovale WM. Results from single voxel spectroscopy revealed a significantly negative correlation of NAA/Cho in frontal (-13% per decade; p<0.01) and in temporal lobe (-7.4% per decade; p<0.01) as well as increased total Cr (10% per decade; p<0.01) in frontal lobe. Other results from single voxel measurements were not significant, but trends were comparable to that from multivoxel spectroscopy. CONCLUSION: Age-related changes measured with long echo time and short echo time 1H-MRS were comparable and cannot, therefore, be caused by different T2 relaxation times in young and old subjects, as suggested previously.