Study protocol for Ketamine as an adjunctive therapy for major depression (2): a randomised controlled trial (KARMA-Dep [2]).

BACKGROUND: Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common. One potential strategy for increasing ketamine's antidepressant efficacy and/or prolonging its therapeutic benefit may be serial infusions. There is limited evidence on the efficacy and safety of repeated ketamine infusions against an active comparator. METHODS: This protocol describes an ongoing pragmatic, randomised, controlled, parallel-group, patient- and rater-blind, superiority trial. Eligible adult inpatients with a confirmed DSM-5 diagnosis of a major depressive episode (unipolar or bipolar) are randomly allocated in a 1:1 ratio to a course of up to eight infusions of ketamine or midazolam twice-weekly over four weeks. The primary objective is to assess the efficacy of serial adjunctive ketamine infusions versus active comparator midazolam by measuring Montgomery-Åsberg Depression Rating Scale score difference between arms from before the first infusion to 24 h after the final infusion, supplemented by a 95% confidence interval. To facilitate generalisability of results, the trial takes place under "real world" conditions with both groups continuing to receive regular inpatient care including treatment-as-usual pharmacotherapy, nursing care, and psychological and other therapies during the randomised treatment phase and regular outpatient care thereafter. Participants are monitored for relapse during a 24-week follow-up after the end of the randomised phase. Secondary objectives of the trial are to assess: response and remission rates at the end of randomised phase; relapse status during the 24-week follow-up after the end of the randomised phase; the safety and tolerability of repeated ketamine infusions regarding psychotomimetic and other psychiatric side effects, cognitive side effects, as well as withdrawal symptoms, haemodynamic stability, neurological, urological, and other physical side effects; and quality of life and cost-effectiveness. DISCUSSION: There is an unmet clinical need for rapidly-acting novel antidepressants. This trial will provide efficacy, safety and health economic data on serial ketamine infusions and thus help inform clinical practice on the potential role of this treatment in the management of depression. TRIAL REGISTRATION: EudraCT 2019-003109-92. Registered 2 October 2019. CLINICALTRIALS: gov NCT04939649. Registered 25 June 2021.

Spinal epidural arteriovenous fistula in 3 cats.

Three young adult cats with intermittent spinal hyperesthesia and paraparesis and diagnosed with spinal epidural arteriovenous fistula are described. In all 3 cases, magnetic resonance imaging (MRI) showed focal dilatation of the veins in the epidural space of the thoracic spinal cord, whereas computed tomography angiography (CTA) showed dilatation and enhancement from the intercostal vein to the azygos vein at the same site in the arterial phase. Dorsal laminectomy and occlusion of the interarcuate branches running across the dorsal aspect of the spinal cord were performed in all 3 cats to decompress the spinal cord, which resulted in a remission of clinical signs and no recurrence during 14 to 40 months of follow-up after surgery in all cases.

Risk of adverse outcome of COVID-19 among patients in secure psychiatric services: observational cohort study.

BACKGROUND: Secure forensic mental health services treat patients with high rates of treatment-resistant psychoses. High rates of obesity and medical comorbidities are common. Population-based studies have identified high-risk groups in the event of SARS-CoV-2 infection, including those with problems such as obesity, lung disease and immune-compromising conditions. Structured assessment tools exist to ascertain the risk of adverse outcome in the event of SARS-CoV-2 infection. AIMS: To assess risk of adverse outcome in the event of SARS-CoV-2 infection in a complete population of forensic psychiatry patients using structured assessment tools. METHOD: All patients of a national forensic mental health service (n = 141) were rated for risk of adverse outcome in the event of SARS-CoV-2 infection, using two structured tools, the COVID-Age tool and the COVID-Risk tool. RESULTS: We found high rates of relevant physical comorbidities. Mean chronological age was 45.5 years (s.d. = 11.4, median 44.1), mean score on the COVID-Age tool was 59.1 years (s.d. = 19.4, median 58.0), mean difference was 13.6 years (s.d. = 15.6), paired t = 10.9, d.f. = 140, P < 0.001. Three patients (2.1%) were chronologically over 70 years of age, compared with 43 (30.5%) with a COVID-Age over 70 (χ2 = 6.99, d.f. = 1, P = 0.008, Fisher's exact test P = 0.027). CONCLUSIONS: Patients in secure forensic psychiatric services represent a high-risk group for adverse outcomes in the event of SARS-COV-2 infection. Population-based guidance on self-isolation and other precautions based on chronological age may not be sufficient. There is an urgent need for better physical health research and treatment in this group.

Molecular detection and genetic diversity of Babesia gibsoni in dogs in Bangladesh.

Babesia gibsoni is a tick-borne hemoprotozoan parasite of dogs that often causes fever and hemolytic illness. Detection of B. gibsoni has been predominantly reported in Asian countries, including Japan, Korea, Taiwan, Malaysia, Bangladesh and India. The present study shows the first molecular characterization of B. gibsoni detected from dogs in Bangladesh. Blood samples were collected on FTA® Elute cards from 50 stray dogs in Mymensingh District in Bangladesh. DNA eluted from the cards was subjected to nested PCR for the 18S rRNA gene of Babesia species. Approximately 800bp PCR products were detected in 15 of 50 dogs (30%). Based on restriction fragment length polymorphism (RFLP) and direct sequencing of the PCR products, all parasite isolates were identified as B. gibsoni. Furthermore, the BgTRAP (B. gibsoni thrombospondin-related adhesive protein) gene fragments were detected in 13 of 15 18S rRNA gene PCR positive blood samples. Phylogenetic analysis of the BgTRAP gene revealed that B. gibsoni parasites in Bangladesh formed a cluster, which was genetically different from other Asian B. gibsoni isolates. In addition, tandem repeat analysis of the BgTRAP gene clearly showed considerable genetic variation among Bangladeshi isolates. These results suggested that B. gibsoni parasites in a different genetic clade are endemic in dogs in Bangladesh. Further studies are required to elucidate the origin, distribution, vector and pathogenesis of B. gibsoni parasites circulating in dogs in Bangladesh.