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Objectives: Addressing the methamphetamine epidemic will require a more complete understanding of its effect on healthcare systems and of the populations at risk. The objective of the study was to assess the impact of methamphetamine use on psychiatric emergency services outcomes and on Asian American (AA) and Pacific Islander (PI) populations, a historically overlooked population in substance use research., Methods: A retrospective chart review was performed for all visits to a large level I trauma center in urban Hawaii from 2007 to 2019 that required psychiatric emergency services and in which urine drug screening was completed (N = 44,658). Demographic characteristics and emergency room courses were compared between amphetamine-positive and amphetamine-negative visits., Results: The proportion of amphetamine-positive visits approximately doubled from 13.3% in 2007 to 25.5% in 2019. Amphetamine-positive visits were more likely to involve arrival by law enforcement (38.3% vs 27.2.%, P < 0.001), require intramuscular psychotropic medications (17.3% vs 12.3%, P < 0.001), and have longer emergency department lengths of stay (median, 420 vs 372 minutes, P < 0.001). Visits by Native Hawaiian and Hispanic/Latino patients had the highest rate of amphetamine positivity, while visits by Chinese and Korean patients had the lowest., Conclusions: The findings reveal a concerning rise in amphetamine positivity that is associated with increased resource utilization. There was also significant variability in the rate of amphetamine positivity within the AA and PI population, a group of ethnicities often analyzed as a single entity in previous studies. Culturally sensitive interventions may curb the methamphetamine epidemic's effect on healthcare systems and vulnerable populations., Competing Interests: Conflicts of Interest and Source of Funding: For all authors, none were declared., (Copyright © 2024 American Society of Addiction Medicine.)

Background: We report a pediatric case where bilateral regional oxygen saturation (rSO 2 ) measurements were useful in determining the selective cerebral perfusion (SCP) flow rate., Case Presentation: A 9-year-old Japanese boy, 128 cm tall and weighing 25.6 kg, was scheduled for aortic arch reconstruction due to a 90-100 mmHg pressure gradient. Pediatric-sized oximetry sensors were attached to the bilateral forehead area. The rSO 2 levels were 70-80% on the right and 80-90% on the left during cardiopulmonary bypass. Immediately following deep hypothermic circulatory arrest with the body temperature cooled to 25 °C, SCP was initiated from the right brachiocephalic artery at 10 mL/kg/min. As the rSO 2 decreased steeply to 43-45% on the right and to 32-38% on the left, the SCP flow was increased to 15 mL/kg/min. The right rSO 2 increased promptly to 50-60%, but the left rSO 2 remained at 30-40%. After the SCP flow was increased to 20 mL/kg/min, bilateral rSO 2 levels of 50-60% were obtained, and the SCP flow rate was maintained. The patient was transferred to the ICU postoperatively and extubated on the second postoperative day with no neurological abnormalities., Conclusions: Bilateral rSO 2 measurements are essential even for a pediatric patient undergoing SCP, despite the limited forehead area., (© 2024. The Author(s).)

To facilitate the introduction of proteins, such as antibodies, into cells, a variety of delivery peptides have been engineered. These peptides are typically highly cationic and somewhat hydrophobic, enabling cytosolic protein delivery at the cost of causing cell damage by rupturing membranes. This balance between delivery effectiveness and cytotoxicity presents obstacles for their real-world use. To tackle this problem, we designed a new endosome-disruptive cytosolic delivery peptide, E3MPH16, inspired by mastoparan X (MP). E3MPH16 was engineered to incorporate three Glu (E3) and 16 His (H16) residues at the N- and C-termini of MP, respectively. The negative charges of E3 substantially mitigate the cell-surface damage induced by MP. The H16 segment is known to enhance cell-surface adsorption and endocytic uptake of the associated molecules. With these modifications, E3MPH16 was successfully trapped within endosomes. The acidification of endosomes is expected to protonate the side chains of E3 and H16, enabling E3MPH16 to rupture endosomal membranes. As a result, nearly 100% of cells achieved cytosolic delivery of a model biomacromolecule, Alexa Fluor 488-labeled dextran (10 kDa), via endosomal escape by co-incubation with E3MPH16. The delivery process also suggested the involvement of macropinocytosis and caveolae-mediated endocytosis. With the assistance of E3MPH16, Cre recombinase and anti-Ras-IgG delivered into HEK293 cells and HT1080 cells enabled gene recombination and inhibited cell proliferation, respectively. The potential for in vivo application of this intracellular delivery method was further validated by topically injecting the green fluorescent protein fused with a nuclear localization signal (NLS-GFP) along with E3MPH16 into Colon-26 tumor xenografts in mice., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Stiff-person syndrome (SPS) is a rare autoimmune disease characterized by fluctuating rigidity and stiffness of the axial muscles. There are no reports on the use of remimazolam in a patient with SPS. A 16-year-old Japanese woman with SPS was scheduled to undergo intrathecal baclofen pump exchange. General anesthesia was induced and maintained using remimazolam, remifentanil, and intermittent rocuronium bromide. No intraoperative mobility or significant autonomic symptoms were observed. Additionally, electroencephalographic signature showed sufficient anesthetic depth. The patient's emergence from general anesthesia was uneventful. In conclusion, remimazolam could be considered an effective anesthetic drug for patients with SPS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Kratom has been used for different reasons such as pain, opioid withdrawal, and relaxation. Kratom can cause dependence and overdose, and it's classified under 'drugs of concern' by the US Drug Enforcement Administration. Despite these concerns, kratom is legal in most of the United States and many countries around the world with easy accessibility. Literature searches reveal recommendations to use buprenorphine (or buprenorphine-naloxone), which are medications to treat opioid use disorder, in order to treat patients with kratom use disorder; however, there are no formal guidelines available. Buprenorphine (or buprenorphine-naloxone) induction is recommended to be conducted under observation (i.e. in the clinic) in the United States, but COVID-19 has resulted in shifts toward telehealth., Objectives: Describe case series of successful management of kratom use disorder using telehealth followed by unobserved buprenorphine-naloxone home induction and highlight implications for future management, including maintenance dosage and induction method., Methods: We present 2 very similar kratom use disorder patients who reported taking 35 g of kratom per day who underwent unobserved buprenorphine-naloxone home induction., Results: Both were seen via telehealth initially. They reported no adverse effects before, during, or after the unobserved home induction on buprenorphine-naloxone but stabilized on significantly different dosages., Conclusion: Telehealth followed by unobserved buprenorphine-naloxone induction at home may be an alternative to traditional buprenorphine-naloxone induction where treatment accessibility is limited. In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose/background: Phenibut (4-amino-3-phenyl-butyric acid) is a structural analog of GABA with central nervous system depressant and anxiolytic properties, developed in the former Soviet Union for anxiety, insomnia, and alcohol withdrawal. Its primary mechanism of action is believed to be a GABA-B receptor agonist-with high affinity at the α 2 δ subunit-containing voltage-dependent calcium channels and therefore gabapentinoid activity-as well as, to a lesser extent, GABA-A agonist activity. While not approved or regulated by the FDA, phenibut is easily obtainable online, where it is marketed as a nootropic, or cognitive enhancer. However, phenibut can lead to problems related to intoxication, dependency, and withdrawal, similar to other sedatives., Methods/procedures: We present a case of phenibut intoxication and withdrawal delirium that provided diagnostic and management challenges because of a patient that was initially not forthcoming about his phenibut use which resulted in five presentations to the hospital including two admissions., Findings/results: Initial differential including adrenergic, serotonergic or anticholinergic toxidrome based on clinical picture and history reported at that time, however phenibut use of 50 g daily was eventually revealed, an amount exceeding the highest reported cases in our review of the English literature., Implications/conclusions: High-dose phenibut intoxication and withdrawal can appear as dramatic and dangerous as high-dose sedative withdrawal, however given its specified receptor affinity and binding profile we found that a pharmacotherapeutic approach targeting GABA-B, GABA-A, and gabapentenoid receptors were effective in stabilizing this patient, eventually leading to the patient's full and sustained recovery., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Achieving fast coincidence timing resolution (CTR) is an important issue in clinical time-of-flight positron emission tomography (TOF-PET) to improve the reconstructed image quality. One of the major factors affecting the CTR is the crystal surface treatment, which is often parameterized as surface roughness. However, previous studies on the crystal surface treatment optimization had two limitations of crystal-by-crystal variation and worse CTR over 200 ps. Here, we report the effects of the crystal surface treatment on the performance of a 20 mm long fast-LGSO crystal based TOF detector by tracking the same crystals in the sub-180 ps CTR regime. The light collection efficiency (LCE), energy resolution (ER) and CTR of the TOF detector were evaluated with six different crystal surface treatments of chemically polished (C.P), C.P half side roughened (1/2S) treatment, and then the C.P one side roughened (1S) treatment, mechanically polished (M.P) treatment, M.P 1/2S treatment, and M.P 1S treatment. The four lateral surfaces of each crystal were wrapped by using enhanced specular reflector film while the top surface was covered by using Teflon tape. The bottom surface of the crystal was optically coupled to a silicon photomultiplier. The timing and energy signals were extracted by using a custom-made high-frequency readout circuit, and then digitized by using a waveform digitizer. All the experimental conditions were same except the crystal surface treatment. Among the six different crystal surface treatments, the M.P 1S would be the optimal crystal surface treatment which balanced enhancements in the CTR (165 ± 3 ps) and ER (10.5 ± 0.5%). Unlike the M.P 1S, the C.P 1S did not enhance the CTR and ER. Hence, the C.P without roughening would be the second-best optimal crystal surface treatment which balanced the CTR (169 ± 3 ps) and ER (10.5 ± 0.5%)., (© 2023 IOP Publishing Ltd.)

Purpose: To reveal the recurrence rate of Graves ophthalmopathy (GO) presenting as diplopia in the primary position for 1 year after varied doses of intravenous methylprednisolone (IVMP) followed by oral prednisolone, with dosing based on the magnetic resonance imaging (MRI) findings., Study Design: Retrospective study., Methods: We analyzed the medical charts of 25 patients who were diagnosed with new-onset GO and who received treatment for diplopia in the primary position at our hospital. Treatment consisted of MRI-determined varied doses of IVMP followed by oral prednisolone. If the MRI findings showed deterioration or were unchanged after 6 g of IVMP, 3 g of IVMP was added for further treatment. Simple and multiple linear regression analyses were performed to reveal the associations between the independent variables and the dependent variable, defined as recurrence., Results: The mean patient age (± standard deviation) was 61.3 ± 11.3 years. The female to male ratio was 15:10. Twenty-one of the 25 patients received a total of 6 g of IVMP, whilst the remaining 4 patients received a total of 9 g of IVMP. In 5 patients (20%), the GO recurred within 1 year of IVMP administration. Simple and multiple linear regression analyses showed that the MRI findings after 6 g of IVMP affected recurrence (P < .05)., Conclusion: This study showed that in 20% of patients, GO recurred within 1 year of administration of varied doses of IVMP, with the dosing based on the MRI findings. Furthermore, assessment of inflammation by use of MRI after 6 g of IVMP has a potential role in predicting recurrence., (© 2022. Japanese Ophthalmological Society.)

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is one of the most common fatty acid oxidation disorders. The choice of anesthetics and blood glucose management are crucial to prevent metabolic decompensation. A 5-year-old Japanese boy with MCAD deficiency was scheduled to undergo surgery for an inguinal hernia. Glucose was continuously infused perioperatively, and his glucose concentrations were within the normal range. Anesthesia was induced and maintained with remimazolam, remifentanil, and intermittent rocuronium. No metabolic decompensation was observed. This case indicates the importance of a continuous intravenous glucose infusion, and that remimazolam can be the first-line anesthetic for a patient with MCAD deficiency., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Primary care physicians (PCPs) in Hawai'i face many challenges in treating patients with substance use disorders (SUD) who tend to have higher medical complexity and thus require more resources. PCPs play a vital role in identifying early misuse, integrating and coordinating care for patients with SUD including office-based interventions like medication-assisted treatment, and connecting patients to community treatment programs. In addition to enormous burdens to care for and increasingly complex patient panels, the challenges include lack of education on addiction medicine, insufficient resources and SUD treatment programs in the office and community, low reimbursement for the complexity of care provided, and an overall physician shortage which drives higher patient volume and less time for any given physician. This article suggests responses to address these challenges such as providing more training and continuing education in SUD for PCPs and trainees, enhancing team-based care to better support PCPs, and funding more SUD treatment programs. More funding should widen accessibility to treatment and reduce the overall burden on the health care system by preventing or treating the disease early, which is a core principle of primary care. Additionally, incentives to practice in Hawai'i in primary care, and especially to treat patients with SUD, need to be improved. Such steps must be taken to address the overall physician shortage that limits patients' access to SUD treatment. A collaborative care model between PCPs, care managers, and addiction specialists is an example of an integrated care system that may address many of these challenges in the short term. To truly improve care for all in Hawai'i, however, system wide interventions are essential to increase the incentive for PCPs to remain and practice in Hawai'i to take care of its unique population, including those dealing with SUD., (©Copyright 2022 by University Health Partners of Hawai‘i (UHP Hawai‘i).)