Increasing health care providers' knowledge of tracheostomy and laryngectomy.

BACKGROUND: The differences between tracheostomy and total laryngectomy are frequently misunderstood by healthcare professionals. Insufficient knowledge can potentially result in life-threatening consequences in the event of an emergent airway situation. METHODS: A seven-question assessment of providers' anatomical knowledge and airway management was completed prior to and following a standardized one-hour didactic lecture. RESULTS: Forty-six participants completed the pre- and post-assessment. There were 20 (43.5%) ENT ICU/IMC Staff (EBU), 20 (43.5%) Florida Surgical Center Staff (FSC), and 6 (13%) Anesthesia providers (Anes). Pre-lecture score average was 44.7% across all providers, significantly improving to 83.8% post-lecture (p < 0.001). Nursing staff from the Otolaryngology ICU, and OR staff, had significant improvement in knowledge base (p < 0.001). Anesthesia providers showed improvement, but the difference was not statistically significant (p = 0.052). CONCLUSIONS: Didactic lectures are a simple and low-cost option with significant potential in improving provider knowledge on these critical topics and improve patient care by non-otolaryngology providers.

A 40-YEAR (1980-2019) RETROSPECTIVE REVIEW OF MORBIDITY AND MORTALITY OF FENNEC FOXES (VULPES ZERDA) AT THE BRONX AND PROSPECT PARK ZOOS.

The Wildlife Conservation Society (WCS) has housed fennec foxes (Vulpes zerda) at its facilities since the early 1900s and currently has one of the largest populations managed by the fennec fox Species Survival Plan. Of the 83 foxes held by WCS institutions between 1980 and 2019, 52 medical records and 48 postmortem reports were available for review. Common causes of morbidity included trauma and dermatologic disease, especially atopic dermatitis. Average age at death for animals surviving past 10 wk was 9.76 yr. Common causes of death or euthanasia were neoplasia (15/48, 31%) and infectious disease (14/48, 29%), with neoplastic processes incidentally identified in an additional seven animals. Significant antemortem cardiac changes were identified in 22 animals. Hepatocellular carcinoma (HCC) was diagnosed in nine animals, consistent with previous documentation of HCC as one of the most common neoplasms in this species. Four animals were suspected to have succumbed to vaccine-induced canine distemper virus after receiving a modified live vaccine. No canine distemper infections have been documented after 1981 in this population and since the use of a canarypox-vectored recombinant vaccine. Recommendations for management of this species include routine screening for hepatic neoplasia in adult animals, regular cardiac evaluations including electrocardiogram, echocardiogram, and dermatologic examination as described by the current consensus statement on canine atopic dermatitis. This descriptive morbidity and mortality report is the first for the fennec fox.

Malpositioned nephrostomy tube with associated hemorrhagic pleural effusion.

Pleural effusion of extra-vascular origin has a large differential diagnosis. Ultrasonography can be utilized alongside pleural fluid analysis to determine a pleural effusion's complexity and size, thus helping aid in both diagnostic and therapeutic management. We describe the case of a 38-year-old male with a prior medical history of neurogenic bladder and nephrolithiasis with percutaneous nephrostomy tube placed one week prior to presentation. Using ultrasonography, the nephrostomy tube was determined to be positioned within the pleural cavity with a resultant hemorrhagic pleural effusion.

THE USE OF INTRADERMAL SKIN TESTING AND HYPOSENSITIZATION INJECTIONS TO CONTROL SEASONAL DERMATITIS IN GREATER ONE-HORNED RHINOCEROSES (RHINOCEROS UNICORNIS).

Allergic dermatitis was diagnosed in a 25-yr-old female greater one-horned rhinoceros (Rhinoceros unicornis) and her 6-yr-old female offspring by skin biopsy, intradermal skin testing (IDST), and allergen-specific serum IgE testing. Dam and offspring presented with seasonal, erosive, and ulcerative dermatitis affecting the face, legs, and trunk starting at 6 and 2 yr of age, respectively. IDST was performed at the caudal pinnal base using 61 regionally specific allergens. Specific serum allergen responses were detected using Heska's Equine ALLERCEPT® Allergen Panel. Histopathology of the lesions was consistent with an allergic etiology. Injectable allergen-specific immunotherapy was initiated in both animals and within 6 to 18 mon after commencing hyposensitization clinical improvement was noted. This report documents a repeatable methodology for IDST and serological allergen testing for use in rhinoceroses. The hyposensitization protocol detailed here can help guide future treatment protocols.

Body structural representation in schizotypy.

A deficient sense of self, typically observed in schizophrenia spectrum disorders, is often accompanied by abnormalities in bodily perception and awareness. These abnormalities are seemingly among the most powerful predictive factors for the onset of schizophrenic illnesses. According to the hypothesis of the psychosis continuum, high schizotypal traits in the general population may be characterized by a progressive sense of detachment from one's lived body. Building upon previous research that found an abnormal Body Structural Representation (BSR) in individuals with schizophrenia, this study aims to extend these findings to schizotypy. To investigate this, we utilized the Finger Localization Task (FLT), in which participants must identify the finger touched by the experimenter, and the In Between Task (IBT), in which two fingers are touched and participants must specify the number of fingers in between the two stimulated fingers. We found that individuals with high schizotypy were significantly less accurate than individuals with low schizotypy in determining the spatial configuration of their own fingers relative to each other. Most significantly, performances on both tasks were negatively correlated with the score on the Dissociative Experiences Scale (DES). These findings support the hypothesis that the progressive loss of one's sense of self is associated with abnormal bodily experiences and dissociative symptomatology which may represent a potential marker for schizophrenia proneness.

Learning and Expertise in Mineral Exploration Decision-Making: An Ecological Dynamics Perspective.

The declining discovery rate of world-class ore deposits represents a significant obstacle to future global metal supply. To counter this trend, there is a requirement for mineral exploration to be conducted in increasingly challenging, uncertain, and remote environments. Faced with such increases in task and environmental complexity, an important concern in exploratory activities are the behavioural challenges of information perception, interpretation and decision-making by geoscientists tasked with discovering the next generation of deposits. Here, we outline the Dynamics model, as a diagnostic tool for situational analysis and a guiding framework for designing working and training environments to maximise exploration performance. The Dynamics model is based on an Ecological Dynamics framework, combining Newell's Constraints model, Self Determination Theory, and including feedback loops to define an autopoietic system. By implication of the Dynamics model, several areas are highlighted as being important for improving the quality of exploration. These include: (a) provision of needs-supportive working environments that promote appropriate degrees of effort, autonomy, creativity and technical risk-taking; (b) an understanding of the wider motivational context, particularly the influence of tradition, culture and other 'forms of life' that constrain behaviour; (c) relevant goal-setting in the design of corporate strategies to direct exploration activities; and (d) development of practical, representative scenario-based training interventions, providing effective learning environments, with digital media and technologies presenting decision-outcome feedback, to assist in the development of expertise in mineral exploration targeting.

Climate change modulates the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing from tropical eruptions.

Explosive volcanic eruptions affect climate, but how climate change affects the stratospheric volcanic sulfate aerosol lifecycle and radiative forcing remains unexplored. We combine an eruptive column model with an aerosol-climate model to show that the stratospheric aerosol optical depth perturbation from frequent moderate-magnitude tropical eruptions (e.g. Nabro 2011) will be reduced by 75% in a high-end warming scenario compared to today, a consequence of future tropopause height rise and unchanged eruptive column height. In contrast, global-mean radiative forcing, stratospheric warming and surface cooling from infrequent large-magnitude tropical eruptions (e.g. Mt. Pinatubo 1991) will be exacerbated by 30%, 52 and 15% in the future, respectively. These changes are driven by an aerosol size decrease, mainly caused by the acceleration of the Brewer-Dobson circulation, and an increase in eruptive column height. Quantifying changes in both eruptive column dynamics and aerosol lifecycle is therefore key to assessing the climate response to future eruptions.

A RETROSPECTIVE ANALYSIS OF AMOEBIASIS IN REPTILES IN A ZOOLOGICAL INSTITUTION.

Amoebiasis is a significant protozoal disease of reptiles causing nonspecific clinical signs including diarrhea, anorexia, and lethargy. It frequently results in acute death. Investigation of the pathophysiology of amoebiasis in reptiles has been hampered by the inability to accurately identify amoeba to the species level using conventional techniques. This study reviewed reptile medical records from the Wildlife Conservation Society's archives from 1998 to 2017. Amoebae were identified histologically in 54 cases in 31 different species. Of these, amoebiasis was the cause of death in 32 (18 chelonians, 7 lizards, and 7 snakes), a significant co-morbidity in 14 (six chelonians, two lizards, and six snakes), and seen incidentally in eight cases (one chelonian, six lizards, and one snake). Relocation from one enclosure to another was also evaluated and 65% of cases had been moved within 180 days of death (median 46 days). Frozen tissue samples from 19 of these cases were tested via an Entamoeba (genus-specific) polymerase chain reaction (PCR) assay. PCR products were sequenced and Entamoeba species were identified. Six individuals were positive for Entamoeba invadens (three chelonians, two snakes, one lizard), two for Entamoeba ranarum (both snakes), and one for Entamoeba terrapinae (chelonian); the other 10 cases were negative via PCR. Entamoeba ranarum has typically been considered a disease of amphibians with only one report of disease in a snake. Entamoeba terrapinae has only been reported without associated disease in chelonians. These results suggest that amoebiasis is a complicated and nuanced disease of reptiles, and warrants additional study.

MYCOTIC PNEUMONIA AND ENCEPHALITIS IN SOUTHERN PUDU (PUDU PUDA).

This case series describes six confirmed cases of mycotic encephalitis and/or mycotic pneumonia in southern pudu (Pudu puda). One case involved a 10.5-yr-old intact female that presented with an inability to stand, eventually progressing to grand mal seizures. Magnetic resonance imaging showed a lesion within the cerebellar vermis with edema causing cerebellar herniation. The animal was euthanized based on a grave prognosis. Gross and histologic examination revealed primary central nervous system phaeohyphomycosis. Curvularia spicifera was sequenced from the cerebellar tissue. This is the first time this fungus has been reported as a primary central nervous system infection in an artiodactyl species. The remaining five cases occurred in neonates between 17 and 67 days old. Clinical signs varied widely, including facial swelling, weakness, posterior paresis, and sudden death. Antifungal therapy was initiated in three neonatal animals but was unsuccessful in each case. All neonates had active mycotic pneumonia caused by Aspergillus fumigatus or Mucor spp. at time of death; four of these animals also had disseminated disease that caused mycotic encephalitis. This case series indicates that fungal disease should be included in the differential diagnosis list of any pudu presenting for neurologic or respiratory clinical signs.

SARS-COV-2 INFECTION AND LONGITUDINAL FECAL SCREENING IN MALAYAN TIGERS (PANTHERA TIGRIS JACKSONI), AMUR TIGERS (PANTHERA TIGRIS ALTAICA ), AND AFRICAN LIONS (PANTHERA LEO KRUGERI) AT THE BRONX ZOO, NEW YORK, USA.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged as the cause of a global pandemic in 2019-2020. In March 2020, New York City became the epicenter in the United States for the pandemic. On 27 March 2020, a Malayan tiger (Panthera tigris jacksoni) at the Bronx Zoo in New York City developed a cough and wheezing with subsequent inappetence. Over the next week, an additional Malayan tiger and two Amur tigers (Panthera tigris altaica) in the same building and three lions (Panthera leo krugeri) in a separate building also became ill. The index case was anesthetized for diagnostic workup. Physical examination and bloodwork results were unremarkable. Thoracic radiography and ultrasonography revealed a bronchial pattern with peribronchial cuffing and mild lung consolidation with alveolar-interstitial syndrome, respectively. SARS-CoV-2 RNA was identified by real-time, reverse transcriptase PCR (rRT-PCR) on oropharyngeal and nasal swabs and tracheal wash fluid. Cytologic examination of tracheal wash fluid revealed necrosis, and viral RNA was detected in necrotic cells by in situ hybridization, confirming virus-associated tissue damage. SARS-CoV-2 was isolated from the tracheal wash fluid of the index case, as well as the feces from one Amur tiger and one lion. Fecal viral RNA shedding was confirmed in all seven clinical cases and an asymptomatic Amur tiger. Respiratory signs abated within 1-5 days for most animals, although they persisted intermittently for 16 days in the index case. Fecal RNA shedding persisted for as long as 35 days beyond cessation of respiratory signs. This case series describes the clinical presentation, diagnostic evaluation, and management of tigers and lions infected with SARS-CoV-2 and describes the duration of viral RNA fecal shedding in these cases. This report documents the first known natural transmission of SARS-CoV-2 from humans to nondomestic felids.

CEFOVECIN PROTEIN BINDING AS A PREDICTOR FOR EXTENDED DURATION OF ACTION: A REVIEW OF CURRENT LITERATURE AND IN VITRO ANALYSIS IN MULTIPLE ZOOLOGICAL SPECIES.

Cefovecin is a third-generation cephalosporin antibiotic with an efficacy of 2 wk following a single injection in domestic dogs and cats. A high degree of plasma protein binding to cefovecin has been proposed as one of the mechanisms responsible for the long elimination half-life, but protein binding has not been evaluated extensively in nondomestic species. In this study, a review of the current literature was conducted, and pharmacokinetic data were compiled for species in which cefovecin has been evaluated thus far. Additionally, in vitro cefovecin protein binding was evaluated in plasma from 22 nondomestic species representing a broad range of taxa. Animals of the order Carnivora demonstrated protein-binding levels of >98%, which is supportive of the long elimination half-life seen in related species. Protein binding was highly variable in Artiodactyl and Perissodactyl species, with dolphins (Tursiops truncatus) and barasingha (Rucervus duvaucelii) displaying high protein binding (99.12% to >99%), but not gazelles (Eudorcas thomsonii) or equids (91.76-92.70%). Cefovecin was not highly bound in any reptiles or birds, corresponding to short half-lives reported for these taxa. These results suggest that a high percentage of plasma protein binding in vitro may predict in which species cefovecin may exhibit a long half-life and duration of action in vivo. These findings may aid in selecting species for cefovecin pharmacokinetic research and for empirical treatment of infections caused by susceptible bacteria.

Minimal Climate Impacts From Short-Lived Climate Forcers Following Emission Reductions Related to the COVID-19 Pandemic.

We present an assessment of the impacts on atmospheric composition and radiative forcing of short-lived pollutants following a worldwide decrease in anthropogenic activity and emissions comparable to what has occurred in response to the COVID-19 pandemic, using the global composition-climate model United Kingdom Chemistry and Aerosols Model (UKCA). Emission changes reduce tropospheric hydroxyl radical and ozone burdens, increasing methane lifetime. Reduced SO2 emissions and oxidizing capacity lead to a decrease in sulfate aerosol and increase in aerosol size, with accompanying reductions to cloud droplet concentration. However, large reductions in black carbon emissions increase aerosol albedo. Overall, the changes in ozone and aerosol direct effects (neglecting aerosol-cloud interactions which were statistically insignificant but whose response warrants future investigation) yield a radiative forcing of -33 to -78 mWm-2. Upon cessation of emission reductions, the short-lived climate forcers rapidly return to pre-COVID levels; meaning, these changes are unlikely to have lasting impacts on climate assuming emissions return to pre-intervention levels.

From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo.

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

ANALYSIS OF PLASMODIUM LINEAGES IDENTIFIED IN CAPTIVE PENGUINS (SPHENISCIFORMES SPP.), EIDERS (SOMATERIA SPP.), AND INCA TERNS (LAROSTERNA INCA) IN A NORTH AMERICAN ZOOLOGICAL COLLECTION.

Vector-borne Plasmodium spp. infect a wide range of bird species. Although infections may be asymptomatic, certain genera, especially those that evolved in regions without endemic malaria, appear particularly susceptible to symptomatic disease, leading to morbidity and mortality. High mortalities associated with malaria infections have been documented in captive species of Sphenisciformes, Somateria, and Larosterna, all genera that evolved in climates with low mosquito exposure. To better characterize trends in Plasmodium-related mortality in a zoological collection in New York, necropsy reports for birds of all three genera that died between 1998 and February 2018 were analyzed; comparisons were made between birds that died with or without evidence of malaria infection. A seasonal peak in deaths was observed in birds regardless of their malaria status. There was no significant difference in the age of birds at death between malaria-positive and malaria-negative animals. These results suggest that age and season of death were not associated with malaria status. To investigate an association between parasite lineage and clinical outcome, polymerase chain reaction was used to identify parasite lineage in necropsied birds as well as healthy birds sampled as part of surveillance studies. Twelve different Plasmodium lineages were identified. The relative prevalence of parasite lineages was compared between necropsy and surveillance samples. A single parasite lineage, SGS1 (species: Plasmodium relictum), was significantly more likely to be found in surveillance samples; it was detected in a plurality of surveillance data but found in only one necropsy case. Other parasite lineages were more likely to be found in necropsies than in surveillance samples, most notably SEIAUR01 (species: Plasmodium cathemerium). These data may be consistent with a difference in virulence between parasite lineages. This investigation has implications for the monitoring and care of vulnerable avian species.

REVIEW OF CANINE DISTEMPER VACCINATION USE AND SAFETY IN NORTH AMERICAN CAPTIVE LARGE FELIDS (PANTHERA SPP.) FROM 2000 TO 2017.

Data on canine distemper virus (CDV) vaccination were collected on 812 large felids (351 tigers, Panthera tigris; 220 lions, Panthera leo; 143 snow leopards, Panthera uncia; 50 leopards, Panthera pardus; and 48 jaguars, Panthera onca) from 48 institutions to assess vaccine use and safety. The documented individual vaccination events with multiple products numbered 2,846. Canarypox-vectored CDV vaccines were the most commonly used vaccines (96.3% of all vaccinations) and the Purevax® Ferret Distemper (PFD) vaccine was the most commonly used canarypox-vectored vaccine (91.0% of all vaccinations). Modified live virus (MLV) CDV vaccines were used for 3.7% of all vaccinations, and only in tigers, lions, and snow leopards. Adverse effects were reported after 0.5% (13 of 2,740) of the canarypox-vectored vaccinations and after 2.9% (3 of 104) of the MLV CDV vaccinations. This low complication rate suggests large felids may not be as sensitive to adverse effects of MLV CDV vaccines as other exotic carnivores. Serological data were available from 159 individuals (69 tigers, 31 lions, 31 snow leopards, 22 jaguars, and 6 Amur leopards, Panthera pardus orientalis) vaccinated with the PFD vaccine, and 66.0% of vaccinates seroconverted (defined as acquiring a titer ≥1: 24) at some point postvaccination: 24.3% after one vaccination, 55.8% after two vaccinations, 54.3% after three vaccinations, and 79.2% after four or more vaccinations. Among animals exhibiting seroconversion after the initial PFD vaccinations, 88.9% still had titers ≥12 mo and ≥24 mo after the last vaccination, and 87.5% had titers ≥1: 24 at ≥36 mo after the last vaccination. The study was unable to assess fully the safety of vaccination with either canarypox-vectored or MLV CDV vaccines during gestation because of the small number of animals vaccinated while pregnant (n = 6, all vaccinated with PFD).

Advances in Therapeutics and Delayed Drug Release.

Reducing the frequency of drug administration in the treatment of exotic pets is advantageous because it may decrease handling frequency and thus potential stress and injury risk for the animal, increase owner compliance with the prescribed treatment, and decrease need for general anesthesia in patients that cannot be handled safely. Increasing efficient drug plasma concentration using sustained-released delivery systems is an appealing solution. Potential candidates that could provide a promising solution have been investigated in exotic pets. In this article, the technologies that are the closest to being integrated in exotic pet medicine are reviewed: osmotic pumps, nanoparticles, and hydrogels.

Husbandry, morbidity, and mortality of slender-tailed cloud rats (Phleomys pallidus).

The Wildlife Conservation Society's Bronx Zoo has been housing and breeding slender-tailed cloud rats (Phleomys pallidus) since 1985. Records of 82 animals from 1985 to 2013 were reviewed for this study. The animals were kept successfully in small family groups with a single adult male, multiple adult females, and their offspring. Sexual maturity was noted at approximately 2 years of age and gestation length ranged from 52 to 55 days. Animals were fed a diet including a complete commercial pelleted feed, mixed greens, carrot or yam, mixed hard nuts, and locally sourced browse. Medical conditions requiring treatment in neonates were often fatal whereas most medical conditions in adults were survivable. The most common cause of morbidity and mortality in neonates was maternal neglect or trauma (42%, 5/12 antemortem problems; cause of death in 32%, 8/25). The most significant problems in adults were cryptococcal pneumonia and trauma. Cryptococcus sp. was the cause of death in 11 cases (34%, 11/32) and significant comorbidity in an additional three cases. Treatment with antifungal medications was attempted but was unsuccessful in four cases. Many cases of trauma were treated successfully with conservative management or limited intervention. In four cases, treatment was complicated by extensive self-mutilation after surgical repair of traumatic lesions, which resulted in death or euthanasia. Lymphoplasmacytic thyroiditis was a common postmortem finding in adults (95%, 21/22 for which the thyroid gland was examined histologically). It is unclear if thyroiditis resulted in functional hypothyroidism so the significance of this finding is undetermined.

Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT.

BACKGROUND: Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. OBJECTIVES: The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. DESIGN: Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. SETTING: Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. PARTICIPANTS: Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). INTERVENTION: Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. MAIN OUTCOME MEASURES: Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson-Angus Scale, quality of life measured with the World Health Organization's quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. RESULTS: A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI -£8923 to -£122) and societal costs (95% CI -£8985 to -£153) for those continuing with amisulpride. LIMITATIONS: The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. CONCLUSIONS: Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. FUTURE WORK: Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.

Antipsychotic treatment of very late-onset schizophrenia-like psychosis (ATLAS): a randomised, controlled, double-blind trial.

BACKGROUND: Very late (aged ≥60 years) onset schizophrenia-like psychosis occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy and risks of antipsychotic treatment. We investigated whether low-dose amisulpride (100 mg daily) is superior to placebo in reducing psychosis symptoms over 12 weeks and whether any benefit is maintained by continuing treatment after 12 weeks. METHODS: The ATLAS double-blind controlled trial enrolled participants from 25 old age psychiatry services in the UK. Eligible participants (ie, those with a diagnosis of very late-onset schizophrenia-like psychosis and a Brief Psychiatric Rating Scale [BPRS] score of ≥30, without cognitive impairment) were randomly assigned (1:1:1) to one of three groups in a two-stage trial: amisulpride in stage 1 and 2 (group A), amisulpride then placebo (group B), or placebo then amisulpride (group C). Treatment (100 mg oral amisulpride daily vs placebo) was given for 12 weeks in stage 1 and, initially, 24 weeks then reduced to 12 weeks in stage 2. Participants, investigators, and outcome assessors were masked to treatment allocation. Primary outcomes were psychosis symptoms assessed by the BPRS at 4, 12, and 24, or 36 weeks, and trial treatment discontinuation for non-efficacy. The primary, secondary, and safety endpoints were all analysed in participants given at least one dose of study treatment in modified intention-to-treat analyses. This study is registered with EudraCT, number 2010-022184-35, and ISRCTN, number ISRCTN45593573. FINDINGS: Between Sept 27, 2012, and June 28, 2016, we recruited 101 participants. 92 (91%) of 101 participants took trial medication, of whom 59 (64%) completed stage 1 and 34 (58%) of these 59 participants completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7·7 points (95% CI 3·8-11·5, p=0·0002) greater with amisulpride (mean 11·9 points [SE 1·3]) than with placebo (4·2 points [1·0]). In stage 2, BPRS scores improved by a mean of 1·1 points (1·6) from 12 weeks to the final assessment in those who continued amisulpride but deteriorated by 5·2 points (2·0) in those who switched from amisulpride to placebo (difference 6·3 points [95% CI 0·9-11·7], p=0·024). Fewer participants who were allocated amisulpride than placebo stopped treatment because of non-efficacy in stage 1 (p=0·010) and stage 2 (p=0·031). Serious adverse events were reported more frequently in the amisulpride group than in the placebo group in stage 1 (p=0·057) and stage 2 (p=0·19). The most common serious adverse events were infection (five patients in the amisulpride group, three in the placebo group) and extrapyramidal side-effects (three patients in the amisulpride group, none in the placebo group). Five patients died during the study, one from a gastric ulcer bleed before treatment started (group B), two while taking stage 2 treatment (one in group A and one in group C), and two who stopped trial treatment in stage 1 and died many weeks later (one in group B and one in group C). No deaths were related to treatment. INTERPRETATION: Low-dose amisulpride is effective and well tolerated as a treatment for very late-onset schizophrenia-like psychosis, with benefits maintained by prolonging treatment. FUNDING: UK National Institute for Health Research.

PHARMACOKINETICS, EFFICACY, AND SAFETY OF VORICONAZOLE AND ITRACONAZOLE IN HEALTHY COTTONMOUTHS (AGKISTRODON PISCIVORUS) AND MASSASAUGA RATTLESNAKES (SISTRURUS CATENATUS) WITH SNAKE FUNGAL DISEASE.

Snake fungal disease (SFD; Ophidiomyces ophiodiicola) is posing a significant threat to several free-ranging populations of pitvipers. Triazole antifungals have been proposed for the treatment of mycoses in reptiles; however, data are lacking about their safety and efficacy in snakes with SFD. Study 1 investigated in vitro susceptibility, and identified that plasma concentrations >250 ng/ml (voriconazole) and >1,000 ng/ml (itraconazole) may be effective in vivo for SFD. In Study 2, the pharmacokinetics after a single subcutaneous voriconazole injection were assessed in apparently healthy free-ranging cottonmouths (Agkistrodon piscivorus). Based on pilot-study results, four snakes were administered a single injection of voriconazole (5 mg/kg). One pilot snake and three full-study snakes died within 12 hr of voriconazole administration. All surviving snakes maintained plasma concentrations >250 ng/ml for 12-24 hr. In Study 3, two Eastern massasaugas (Sistrurus catenatus) and a timber rattlesnake (Crotalus horridus horridus) diagnosed with SFD were treated with voriconazole delivered by subcutaneous osmotic pumps. The timber rattlesnake (12.1-17.5 mg/kg/hr) reached therapeutic concentrations, whereas the massasaugas (1.02-1.6 mg/kg/hr) did not. In Study 4, the pharmacokinetics of a single 10-mg/kg per-cloaca dose of itraconazole (Sporanox®) was evaluated in seven apparently healthy free-ranging cottonmouths. Similarly, the plasma and tissue concentrations did not meet therapeutic concentrations based on in vitro data. The data presented in this report serve as an initial step toward understanding the pharmacokinetics, efficacy, and safety of triazole antifungals in pitviper species with SFD. Further study is needed to determine the appropriate dose and route of administration of triazole antifungals in pitviper species.