The impact of badmouthing of medical specialties to medical students.

OBJECTIVES: This study aimed to evaluate the proportion of Irish medical students exposed to 'badmouthing' of different specialities and to ascertain: the degree of criticism of specialities based on the seniority of clinical or academic members of staff; if 'badmouthing' influenced student career choice in psychiatry; and attitudes of medical students towards psychiatry as a speciality and career choice. METHODS: Medical students in three Irish universities were invited to complete an online survey to determine the frequency and effect of non-constructive criticism on choice of medical specialty. The online questionnaire was distributed to Royal College of Surgeons in Ireland (RCSI), University of Galway (UoG) and University College Dublin (UCD) in the academic year 2020-2021. RESULTS: General practice (69%), surgery (65%) and psychiatry (50%) were the most criticised specialties. Criticism was most likely to be heard from medical students. 46% of students reported reconsidering a career in psychiatry due to criticism from junior doctors. There was a positive perception of psychiatry with 27% of respondents considering psychiatry as a first-choice specialty. CONCLUSIONS: Criticism of psychiatry by doctors, academics and student peers negatively influences students' career choice, which could be contributing to recruitment difficulties in psychiatry.

Changes in immunoglobulin levels during clozapine treatment in schizophrenia.

BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: ß = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: ß = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: ß = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: ß = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK.

BACKGROUND: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). OBJECTIVE: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. METHODS: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. RESULTS: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. CONCLUSIONS: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.

Severe Alprazolam Withdrawal With Delirium and Psychosis: A Case Report and Literature Review.

ABSTRACT: In our report, and review of the literature, we present an important clinical lesson for the recognition and treatment of alprazolam withdrawal with complicated delirium and psychosis, and present a strong case for future treatment algorithms. Our case is unique due to the severity of behavioral disturbance associated with acute psychosis secondary to alprazolam withdrawal and the significant quantity of alprazolam consumed. The use of high cumulative doses of longer-acting benzodiazepines resulted in rapid improvement in symptoms with full resolution of psychosis. Within 4 days of treatment in hospital, delirium and psychosis had fully resolved. Detoxification continued in the community and the patient was followed up in clinic for monitoring of mental state. There was no recurrence of psychotic symptoms.

High-dose olanzapine in treatment-resistant schizophrenia: a systematic review.

Background: Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed. Objectives: To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS. Design: This is a systematic review. Data Sources and Methods: We searched for eligible trials published prior to April 2022 in PubMed/MEDLINE, Scopus and Google Scholar. Ten studies met the inclusion criteria [five randomised controlled trials (RCTs), one randomised crossover trial and four open label studies]. Data were extracted for predefined primary outcomes (efficacy, tolerability). Results: Compared with standard treatment, high-dose olanzapine was non-inferior in four RCTs, three of which used clozapine as the comparator. Clozapine was superior to high-dose olanzapine in a double-blind crossover trial. Open-label studies demonstrated tentative evidence in support of high-dose olanzapine use. It was better tolerated than clozapine and chlorpromazine in two respective RCTs, and was generally well tolerated in open-label studies. Conclusion: This evidence suggests high-dose olanzapine is superior for TRS when compared with other commonly used first- and second-generation antipsychotics, including haloperidol and risperidone. In comparison with clozapine, the data are encouraging for the use of high-dose olanzapine where clozapine use is problematic, but larger, better designed trials are needed to assess the comparative efficacy of both treatments. There is insufficient evidence to consider high-dose olanzapine equivalent to clozapine when clozapine is not contraindicated. Overall, high-dose olanzapine was well tolerated, with no serious side effects. Registration: This systematic review was preregistered with PROSPERO [CRD42022312817].

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia.

The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity.

Mental disorders in Malaysia: an increase in lifetime prevalence.

There is an increasing prevalence of mental disorders in Malaysia, with a growing need to improve access to timely and efficient mental healthcare to address this burden. This review outlines the current legislative framework and the challenges of delivering mental healthcare and treating mental disorders in Malaysia.

Increased rates of respiratory disease in schizophrenia: A systematic review and meta-analysis including 619,214 individuals with schizophrenia and 52,159,551 controls.

INTRODUCTION: Despite respiratory disease being a major cause of excess mortality in people with schizophrenia, the prevalence of respiratory conditions in this population is poorly defined. A systematic review and meta-analysis were conducted to establish the prevalence and association of respiratory diseases in people with schizophrenia. MATERIAL AND METHODS: Major electronic databases were searched from inception to 27 April 2020 for articles reporting respiratory disease (asthma, chronic obstructive pulmonary disease [COPD], pneumonia, and tuberculosis) in people with schizophrenia and, where possible, a control group. A random-effects meta-analysis was conducted. The study was registered with PROSPERO (CRD42018115137). RESULTS: Of 1569 citations, 21 studies consisting of 619,214 individuals with schizophrenia and 52,159,551 controls were included in the meta-analysis. Compared to the general population, people with schizophrenia had significantly higher rates of COPD (odds ratio [OR]: 1.82, 95% CI: 1.28-2.57), asthma (OR: 1.70, 95% CI: 1.02-2.83), and pneumonia (OR: 2.62, 95% CI: 1.10-6.23). In people with schizophrenia, the prevalence of COPD was 7.7% (95% CI: 4.0-14.4), asthma 7.5% (95% CI: 4.9-11.3), pneumonia 10.3% (95% CI 5.4-18.6), and tuberculosis 0.3% (95% CI 0.1 -0.8). After adjusting for publication bias, the prevalence of COPD increased to 19.9% (95% CI: 9.6-36.7). DISCUSSION: All respiratory diseases examined were significantly more prevalent in people with schizophrenia compared with the general population. Future studies should focus on improving the prevention and management of respiratory disease in this group to reduce associated excess mortality.

Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses.

Treatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject's contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges's g = 2.09, P < .001) and a reduced clustering coefficient (Hedges's g = 1.07, P < .001) with increased length (Hedges's g = -2.17, P < .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.

Employment and relationship outcomes in first-episode psychosis: A systematic review and meta-analysis of longitudinal studies.

As employment and relationship status are important long-term outcomes in individuals with a diagnosis of first episode psychosis (FEP) disorders, there is a need to elucidate more accurately the extent of these social deficits in people with FEP. This in turn can aid treatment planning and policy development ultimately ensuring more complete and sustainable recoveries. We carried out a systematic review and meta-analysis of longitudinal studies in FEP reporting on employment and relationship status during the illness course. Random effects meta-analyses and meta-regression analyses were employed. Seventy-four studies were included with a sample totalling 15,272 (range = 20-1724) FEP cases with an average follow-up duration of 8.3 years (SD = 7.2). 32.5% (95%CI = 28.5-36.9) of people with a diagnosis of FEP disorders were employed and 21.3% (95%CI = 16.5-27.1) were in a relationship at the end of follow-up. Studies from high-income countries and Europe had a higher proportion of people in employment at the end of follow-up compared to middle-income nations and non-European countries. The inverse was found for relationship status. The proportion of people with a diagnosis of FEP in employment decreased significantly with longer follow-up. Living with family, being in a relationship at first contact and Black and White ethnicities were identified as significant moderators of these outcomes. These findings highlight marked functional recovery deficits for people with FEP, although cultural factors need to be considered. They support the need for interventions to improve employment opportunities, and social functioning, both in early psychosis and during the longitudinal illness course.

Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

Neuroprotectin D1 Attenuates Blast Overpressure Induced Reactive Microglial Cells in the Cochlea.

OBJECTIVE/HYPOTHESIS: We examined a neuroinflammatory response associated with glial activation in the cochlea exposed to blast overpressure and evaluated the potential therapeutic efficacy of specialized pro-resolving mediators such as neuroprotectin D1, NPD1; (10R, 17S-dihydroxy-4Z, 7Z, 11E, 13E, 15Z, 19Z-docosahexaenoic acid) in a rodent blast-induced auditory injury model. STUDY DESIGN: Animal Research. METHODS: A compressed-air driven shock tube was used to expose anesthetized adult male Long-Evan rats to shock waves simulating an open-field blast exposure. Approximately 30 minutes after blast exposure, rats were treated with NPD1 (100 ng/kg body wt.) or vehicle delivered intravenously via tail vein injection. Rats were then euthanized 48 hours after blast exposure. Unexposed rats were included as controls. Tissue sections containing both middle and inner ear were prepared with hematoxylin-eosin staining to elucidate histopathological changes associated with blast exposure. Cochlear tissues were evaluated for relative expression of ionized calcium-binding adaptor 1 (Iba1), as an indicator of microglial activation by immunohistochemistry and western blot analyses. RESULTS: Our animal model resulted in an acute injury mechanism manifested by damage to the tympanic membrane, hemorrhage, infiltration of inflammatory cells, and increased expression of Iba1 protein. Moreover, therapeutic intervention with NPD1 significantly reduced Iba1 expression in the cochlea, suggesting a reduction of a neuroinflammatory response caused by blast overpressure. CONCLUSIONS: Blast overpressure resulted in an increased expression of proteins involved in gliosis within the auditory system, which were reduced by NPD1. Treatment of NPD1 suggests an effective strategy to reduce or halt auditory microglial cell activation due to primary blast exposure. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2018-E2025, 2021.

Augmentation of clozapine with ECT: a retrospective case analysis.

OBJECTIVE: We sought to assess the effectiveness of clozapine augmentation with Electroconvulsive therapy (ECT) (C+ECT) in patients with clozapine-resistant schizophrenia. METHODS: We conducted a retrospective review of electronic health records to identify patients treated with C+ECT. We determined the response to C+ECT and the rate of rehospitalisation over the year following treatment with C+ECT. RESULTS: Forty-two patients were treated with C+ECT over a 10-year period. The mean age of the patients at initiation of ECT was 46.3 (SD = 8.2) years (range 27-62 years). The mean number of ECTs given was 10.6 (SD = 5.3) (range 3-25) with the majority receiving twice weekly ECT. Seventy-six per cent of patients (n = 32) showed a Clinical Global Impression-Improvement (CGI-I) score of ≤3 (at least minimally improved) following C+ECT. The mean number of ECT treatments was 10.6 (SD = 5.3) (range 3-25) with the majority receiving twice weekly ECT. Sixty-four per cent of patients experienced no adverse events. Response to C+ECT was not associated with gender, age, duration of illness or duration of clozapine treatment. Seventy-five per cent of responders remained out of hospital over the course of 1-year follow-up, while 70% of those with no response to C+ECT were not admitted to hospital. Three patients received maintenance ECT, one of whom was rehospitalised. CONCLUSION: This study lends support to emerging evidence for the effectiveness of C+ECT in clozapine-resistant schizophrenia. These results are consistent with the results of a meta-analysis and the only randomised controlled trial (RCT) of this intervention. Further RCTs are required before this treatment can be confidently recommended.

Takotsubo syndrome in bipolar affective disorder with alcohol withdrawal syndrome.

A 40-year-old woman presented to the emergency department with epigastric pain and agitation. She recently separated from her husband and was consuming 30 units of alcohol daily for 5 days. She had a history of bipolar affective disorder, borderline personality disorder and alcohol dependence syndrome. Investigations revealed the following: elevated troponin I levels, ST elevation, early Q waves and prolonged QTc. Emergency angiogram confirmed Takotsubo's appearance. Medications with QTc prolongation propensity were held. A multidisciplinary apporach was required. She was discharged 10 days later when medically stabilised. It was later discovered that she died unexpectedly the following month. Takotsubo syndrome is a rare but unique cause of cardiac failure. This case highlights the need to consider the differential of Takotsubo syndrome in people presenting with possible acute ischaemic events, particularly in those with a history of combined emotional and physical stressors and a background history of mood disorder.

Predicting onset of early- and late-treatment resistance in first-episode schizophrenia patients using advanced shrinkage statistical methods in a small sample.

Evidence suggests there are two treatment-resistant schizophrenia subtypes (i.e. early treatment resistant (E-TR) and late-treatment resistant (L-TR)). We aimed to develop prediction models for estimating individual risk for these outcomes by employing advanced statistical shrinkage methods. 239 first-episode schizophrenia (FES) patients were followed-up for approximately 5 years after first presentation to psychiatric services; of these, n=56 (25.2%) were defined as E-TR and n=24 (12.6%) were defined as L-TR. Using known risk factors for poor schizophrenia outcomes, we developed prediction models for E-TR and L-TR using LASSO and RIDGE logistic regression models. Models' internal validation was performed employing Harrell's optimism-correction with repeated cross-validation; their predictive accuracy was assessed through discrimination and calibration. Both LASSO and RIDGE models had high discrimination, good calibration. While LASSO had moderate sensitivity for estimating an individual risk for E-TR and L-TR, sensitivity estimated for RIDGE model for these outcomes was extremely low, which was due to having a very large estimated optimism. Although it was possible to discriminate with sufficient accuracy who would meet criteria for E-TR and L-TR during the 5-year follow-up after first contact with mental health services for schizophrenia, further work is necessary to improve sensitivity for these models.

Pathogenesis and management of Brugada syndrome in schizophrenia: A scoping review.

CONTEXT: Excess cardiovascular morbidity and an increased prevalence of sudden cardiac death (SCD) contributes to premature mortality in schizophrenia. Brugada syndrome (BrS) is an important but underrecognized cause of SCD. It is more commonly seen in schizophrenia than in general population controls. METHODS: We conducted a scoping review to describe the pathogenesis of BrS in schizophrenia and to identify the psychotropic medications that increase the risk of unmasking BrS and associated ventricular arrhythmias resulting in SCD. FINDINGS: Schizophrenia and BrS share similar calcium channel abnormalities, which may result in aberrant myocardial conductivity. It remains uncertain if there is a genetic pre-disposition for BrS in a subset of patients with schizophrenia. However, the unmasking of Brugada ECG patterns with the use of certain antipsychotics and antidepressants increases the risk of precipitating SCD, independent of QT prolongation. CONCLUSIONS AND FUTURE DIRECTIONS: Specific cardiology assessment and interventions may be required for the congenital or unmasked Brugada ECG pattern in schizophrenia. The current long-term standard of care for BrS is an implantable cardioverter defibrillator (ICD), but post-implantation psychological effects must be considered. Careful use of antipsychotic and other psychotropic medications is necessary to minimize proarrhythmic effects due to impact on cardiac sodium and calcium ion channels. When prescribing such drugs to patients with schizophrenia, clinicians should be mindful of the potentially fatal unmasking of Brugada ECG patterns and how to manage it. We present recommendations for psychiatrists managing this patient population.

Complications Following Orbital Floor Repair: Impact of Intraoperative Computed Tomography Scan and Implant Material.

Importance: Orbital floor fracture repair is complex and postoperative complications are common. A variety of applicable surgical techniques and technologies are available to surgeons, so data about which of these may decrease postoperative complication rates can help better guide clinical decision making. Objectives: To characterize the patient demographics and surgical techniques utilized in orbital floor fracture repairs at San Antonio Military Medical Center and their relationship with rates of postoperative complications. Design, Setting, and Participants: Retrospective chart review of patients who underwent orbital floor fracture repairs from March 2014 to March 2019 with a mean follow-up time of 1.86 months at a tertiary care academic military hospital and level 1 trauma center. Main Outcomes and Measures: Demographic data, indication for surgical repair, fracture severity, orbital floor approach, implant material, and use of intraoperative computed tomography (CT) scan were recorded. Chi-square analysis was performed to determine the relationship between these factors and postoperative diplopia, hypoglobus, enophthalmos, and infection. Results: A total of 124 procedures were performed during the study period: 71.8% of patients were male and 74% were civilian. Mean age was 39 years (range 19-81). Thirty-one patients were lost to follow-up. The most common approach was transconjunctival (83%), which was most frequently used exclusively (68.5%), but was also combined with cantholysis, transcaruncular, or transantral approach. Postoperative diplopia at follow-up was common (53.8%), resolved after an average of 36.3 days, and was significantly associated with surgical indication of entrapment or revision (p = 0.01) and nonutilization of intraoperative CT (p = 0.04). From 2014 to 2016, intraoperative CT was utilized in 21% of cases and revision rate was 10.5%. From 2017 to 2019, 50% of cases utilized intraoperative CT and revision rate was 2% (p = 0.15). Three cases were revisions performed for abnormal plate position noted on postoperative CT scan. Conclusions and Relevance: A statistically significant association was found between postoperative diplopia, surgical indication of entrapment or revision, and nonutilization of intraoperative CT. Revision rates decreased when use of intraoperative CT increased. Three revision cases may have been prevented by use of an intraoperative CT scan. Patients with entrapment should be counseled regarding the increased risk of postoperative diplopia.

Hospitalisation and length of hospital stay following first-episode psychosis: systematic review and meta-analysis of longitudinal studies.

BACKGROUND: Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up. METHODS: Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted. RESULTS: 81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3-60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1-138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS. CONCLUSION: One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.

Mechanical Energy Dissipation Through the Ossicular Chain and Inner Ear Using Laser Doppler Vibrometer Measurement of Round Window Velocity.

HYPOTHESIS: Round window velocity measurements should correlate closely with vibration measurements taken at proximal points along an intact chain over a set frequency range. These round window vibration measurements should be similar to the vibration measurements taken of the ossicles if mechanical energy is conserved through the vestibular organ. BACKGROUND: To date there has not been a study which compares vibratory velocity measurements through an intact ossicular chain to the level of the round window. This study attempted to quantify the degree of mechanical energy transmission and suspected dissipation through the ossicular chain and vestibular organ through incus, stapes, and round window velocity measurements in response to sound stimulus. METHODS: Five thawed human temporal bones with intact ossicular chain and tympanic membrane underwent complete mastoidectomy and a facial recess approach. A laser Doppler vibrometer (LDV) was mounted on the operating microscope to measure vibration of incus, stapes, and round window in response to a sound stimulus within the external auditory canal. Sound stimulus frequencies ranged from 0.5 to 4 kHz at 90 dB SPL. RESULTS: Vibration velocity was measured across the frequency range for each incus, stapes, and round window. Vibration velocity curves obtained over the frequency range were similar for each of the bones with a notable resonant frequency around 2 kHz. The incus and stapes curve amplitudes were nearly identical with similar maximum velocity and frequency at which this maximal velocity was noted. Round window vibration velocity demonstrated a unique peak velocity. Transfer function measurements of the stapes and round window demonstrated markedly similar curves. The variation in velocity between temporal bones in response to the standardized stimulus was more dramatic in the round window measurements when compared with the incus and stapes. CONCLUSIONS: This study supports the concept that round window transfer function is equivalent to stapes footplate transfer function when subjected to the same acoustic stimuli. This study also demonstrates that the round window is a much more difficult target to measure when using LDV technology and improvements in experimental design are required to better understand round window physiology in relation to transfer of acoustic vibratory stimulus transferred throughout the middle ear. A complete and thorough understanding of the biophysical properties of the middle and inner ear are critical for optimal ossiculoplasty outcomes and the development of future ossicular prosthetics.