Trends in suicidal ideation in an emergency department during COVID-19.

OBJECTIVE: This study aims to detail changes in presentations at a United States Emergency Department for suicidality before and after the outbreak of COVID-19. METHODS: A retrospective chart review was conducted of all adult patients who presented to an ED with suicidality and underwent psychiatric consultation during the study period. The cohorts consisted of patients who presented between December 2018 - May 2019 and December 2019 - May 2020. Information was collected on demographics, characteristics of suicidality, reasons for suicidality and disposition. The first wave from March - May 2020 was examined, using a difference-in-differences design to control for factors other than COVID-19 that may have influenced the outcomes' trend. RESULTS: Immediately following the pandemic outbreak there was a statistically significant increase in the proportion of undomiciled patients represented in visits for suicidality (40.7% vs. 57.4%; p-value <0.001). In addition, the proportion of patient visits attributed to social (18.0% vs. 29.2%; p-value 0.003) and structural (14.2% vs. 26.4%; p value <0.001) reasons for suicidality increased. Conversely, the proportion of visits due to psychiatric symptoms (70.5% vs 50.0%; p-value <0.001) decreased. Furthermore, patient visits were more likely to result in a medical admission (2.1% vs. 8.3%; p-value 0.002) and less likely to result in a psychiatric admission (68.4% vs 48.6%; p-value <0.001) during the initial phase of the pandemic. CONCLUSIONS: COVID-19 was associated with increased ED presentations for suicidality among undomiciled patients, as well as greater likelihood of social and structural reasons driving suicidality among all visits.

Functional Connectivity between Task-Positive Networks and the Left Precuneus as a Biomarker of Response to Lamotrigine in Bipolar Depression: A Pilot Study.

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10-12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10-12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Evaluating the association between COVID-19 and psychiatric presentations, suicidal ideation in an emergency department.

OBJECTIVE: To estimate the association between COVID-19 and Emergency Department (ED) psychiatric presentations, including suicidal ideation. METHODS: Using an interrupted time series design, we analyzed psychiatric presentations using electronic health record data in an academic medical center ED between 2018 and 2020. We used regression models to assess the association between the onset of the COVID-19 outbreak and certain psychiatric presentations. The period February 26-March 6, 2020 was used to define patterns in psychiatric presentations before and after the coronavirus outbreak. RESULTS: We found a 36.2% decrease (unadjusted) in ED psychiatric consults following the coronavirus outbreak, as compared to the previous year. After accounting for underlying trends, our results estimate significant differential change associated with suicidal ideation and substance use disorder (SUD) presentations following the outbreak. Specifically, we noted a significant differential increase in presentations with suicidal ideation six weeks after the outbreak (36.4 percentage points change; 95% CI: 5.3, 67.6). For presentations with SUD, we found a differential increase in the COVID-19 time series relative to the comparison time series at all post-outbreak time points and this differential increase was significant three weeks (32.8 percentage points; 95% CI: 4.0, 61.6) following the outbreak. Our results estimate no differential changes significant at the P value < 0.05 level associated with affective disorder or psychotic disorder presentations in the COVID-19 time series relative to the comparator time series. CONCLUSIONS: The COVID-19 outbreak in Boston was associated with significant differential increases in ED presentations with suicidal ideation and SUD.

Feasibility of a Ketamine Anesthesia Package in Support of Obstetric and Gynecologic Procedures in Kenya When No Anesthetist is Available.

The objective was to assess the feasibility and safety of the ̳Every Second Matters for Emergency and Essential Surgery - Ketamine' (ESM-Ketamine) package in support of obstetric and gynecologic emergency and essential surgery when no anesthetist is available. A consecutive case series was conducted in twelve hospitals across five severely resource-limited counties in Kenya. 530 women underwent obstetric or gynecological operative procedures supported by non-anesthetist clinicians using the ESM-Ketamine package between November 1, 2013 and September 30, 2017. Main outcomes included reasons for ESM-Ketamine activations and ketamine-related adverse events. There were two (0.4%) prolonged (>30 seconds) oxygen desaturations below 92%. Brief oxygen desaturations (<30 seconds) below 92% occurred in 15 (2.8%) cases and 113 (21.3%) were administered diazepam to treat hallucinations or agitation. There were no ketamine-related deaths or injuries. The ESM- Ketamine package appears feasible and safe for use in support of obstetric and gynecologic surgeries when no anesthetist is available.

Changes in brain Glx in depressed bipolar patients treated with lamotrigine: A proton MRS study.

BACKGROUND: Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response. METHODS: We studied 21 bipolar patients who received lamotrigine treatment for a current episode of depression. Before starting lamotrigine and after 10-12 weeks treatment, patients underwent proton magnetic resonance spectroscopy (MRS) scanning at 3 Tesla where levels of glutamate (measured as Glx) were determined in anterior cingulate cortex (ACC). RESULTS: Overall, lamotrigine treatment had no significant effect on Glx levels in ACC. However, in patients who responded clinically to lamotrigine treatment Glx concentrations were significantly increased. Baseline levels of Glx did not predict response to lamotrigine. LIMITATIONS: The main limitation of the study was the modest sample size. Most patients were medicated which may have modified the effect of lamotrigine on glutamate activity. MRS at 3T cannot give a reliable estimate of glutamate separate from its main metabolite, glutamine, and thus changes in Glx may not give a precise estimate of effects of lamotrigine on glutamate itself. CONCLUSION: Lamotrigine does not appear to have a direct effect on glutamate levels in ACC in bipolar patients. However, therapeutic improvement during lamotrigine was associated with increased Glx, suggesting that alterations in glutamatergic activity might be related to recovery from bipolar depression.

Feasibility of a ketamine anesthesia package in support of obstetric and gynecologic procedures in Kenya when no anesthetist is available

The objective was to assess the feasibility and safety of the _Every Second Matters for Emergency and Essential Surgery ­ Ketamine' (ESM-Ketamine) package in support of obstetric and gynecologic emergency and essential surgery when no anesthetist is available. A consecutive case series was conducted in twelve hospitals across five severely resource-limited counties in Kenya. 530 women underwent obstetric or gynecological operative procedures supported by non-anesthetist clinicians using the ESM-Ketamine package between November 1, 2013 and September 30, 2017. Main outcomes included reasons for ESM-Ketamine activations and ketamine-related adverse events. There were two (0.4%) prolonged (>30 seconds) oxygen desaturations below 92%. Brief oxygen desaturations (<30 seconds) below 92% occurred in 15 (2.8%) cases and 113 (21.3%) were administered diazepam to treat hallucinations or agitation. There were no ketamine-related deaths or injuries. The ESM-Ketamine package appears feasible and safe for use in support of obstetric and gynecologic surgeries when no anesthetist is available

Brain glutamate in medication-free depressed patients: a proton MRS study at 7 Tesla.

BACKGROUND: The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine. METHOD: We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference. RESULTS: Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001). CONCLUSIONS: The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Correction to: Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

The corrected order of the authors is as reflected in this erratum. Sebastian Suarez and Ayla Senay are co-second authors.

Safety and Feasibility of a Ketamine Package to Support Emergency and Essential Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216 Consecutive Operative Procedures.

BACKGROUND: Lack of access to emergency and essential surgery is widespread in low- and middle-income countries. Scarce anesthesia services contribute to this unmet need. The aim of this study was to evaluate the safety and feasibility of the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM-Ketamine) package for emergency and essential procedures when no anesthetist was available. METHODS: From November 2013 to September 2017, the ESM-Ketamine package was used for patients requiring emergency or life-improving surgeries in fifteen selected facilities across Kenya when no anesthetist was available. A mixed-methods approach was used to assess safety and feasibility of the ESM-Ketamine package, including demand, acceptability, and practicality. The primary outcome was ketamine-related adverse events. Key-informant interviews captured perceptions of providers, hospital administrators, and surgeons/proceduralists. RESULTS: Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical procedures across the fifteen study facilities. The median ketamine dose was 2.1 mg/kg. Brief (<30 s) oxygen desaturations occurred in 39 patients (3%), and prolonged (>30 s) oxygen desaturations occurred in seven patients (0.6%). There were 157 (13%) reported cases of hallucinations and agitation which were treated with diazepam. All patients recovered uneventfully, and no ketamine-related deaths were reported. Twenty-seven key-informant interviews showed strong support for the program with four main themes: financial considerations, provision of services, staff impact, and scaling considerations. CONCLUSIONS: The ESM-Ketamine package appears safe and feasible and is capable of expanding access to emergency and essential surgeries in rural Kenya when no anesthetist is available.

Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing.

RATIONALE: Lithium remains the most effective treatment for bipolar disorder and also has important effects to lower suicidal behaviour, a property that may be linked to its ability to diminish impulsive, aggressive behaviour. The antioxidant drug, ebselen, has been proposed as a possible lithium-mimetic based on its ability in animals to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. OBJECTIVES: The aim of the study was to determine whether treatment with ebselen altered emotional processing and diminished measures of risk-taking behaviour. METHODS: We studied 20 healthy participants who were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, randomized, cross-over design. Three hours after the final dose of ebselen/placebo, participants completed the Cambridge Gambling Task (CGT) and a task that required the detection of emotional facial expressions (facial emotion recognition task (FERT)). RESULTS: On the CGT, relative to placebo, ebselen reduced delay aversion while on the FERT, it increased the recognition of positive vs negative facial expressions. CONCLUSIONS: The study suggests that at the dosage used, ebselen can decrease impulsivity and produce a positive bias in emotional processing. These findings have implications for the possible use of ebselen in the disorders characterized by impulsive behaviour and dysphoric mood.

Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla.

RATIONALE: Lithium is an effective treatment for bipolar disorder, but safety issues complicate its clinical use. The antioxidant drug, ebselen, may be a possible lithium-mimetic based on its ability to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. OBJECTIVES: Our primary aim was to determine whether ebselen lowered levels of inositol in the human brain. We also assessed the effect of ebselen on other brain neurometabolites, including glutathione, glutamate, glutamine, and glutamate + glutamine (Glx) METHODS: Twenty healthy volunteers were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, random-order, crossover design. Two hours after the final dose of ebselen/placebo, participants underwent proton magnetic resonance spectroscopy ((1)H MRS) at 7 tesla (T) with voxels placed in the anterior cingulate and occipital cortex. Neurometabolite levels were calculated using an unsuppressed water signal as a reference and corrected for individual cerebrospinal fluid content in the voxel. RESULTS: Ebselen produced no effect on neurometabolite levels in the occipital cortex. In the anterior cingulate cortex, ebselen lowered concentrations of inositol (p = 0.028, Cohen's d = 0.60) as well as those of glutathione (p = 0.033, d = 0.58), glutamine (p = 0.024, d = 0.62), glutamate (p = 0.01, d = 0.73), and Glx (p = 0.001, d = 1.0). CONCLUSIONS: The study suggests that ebselen produces a functional inhibition of IMPase in the human brain. The effect of ebselen to lower glutamate is consistent with its reported ability to inhibit the enzyme, glutaminase. Ebselen may have potential as a repurposed treatment for bipolar disorder.

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans.

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials.

Variant anatomy of renal arteries in a Kenyan population.

BACKGROUND: Variant anatomy of renal arteries is important in renal transplant, vascular reconstruction, and uroradiological procedures. The variations show ethnic and population differences. Data from Africans are scarce and altogether absent for Kenyans. OBJECTIVE: To describe patterns of origin, trajectories and branching of renal arteries in a Kenyan population. STUDY DESIGN AND SETTING: Descriptive cross-sectional study conducted in the Department of Human Anatomy, University of Nairobi. MATERIAL/METHODS: Three hundred and fifty six kidneys from 178 cadavers and postmortem specimens were used in the study. Aorta, renal arteries and kidneys were exposed by dissection. Number, trajectories, level of branching, number of branches and point of entry into the kidney were recorded. Data was analyzed using SPSS version 16.0, and presented using macrographs, tables, and bar charts. RESULTS: Additional arteries occurred in 14.3% of the cases. In 82.4% of these, there was one additional artery. Fifty nine point five per cent of the double renal arteries were parallel and 7.1% crossed. Of the 305 single arteries, 76.4% showed hilar, 21.6% prehilar and 2% intraparenchymal branching. In the hilar branching, ladder type was present in 65% and fork type in 35%. Bifurcation and trifurcation were present in 59.6% and 33.1% respectively. Polar arteries were present in 16.9% cases. CONCLUSIONS: Over 14% of the Kenyan population may have additional renal arteries while more than 20% show early branching. Several trajectories and hilar branching patterns exist which renal transplant surgeons and radiologists should be aware of to avoid inadvertent vascular injury.