What to Expect With Pregnant or Postpartum Prescribing of Extended-Release Buprenorphine (CAM2038).

Weekly and monthly CAM2038 (Brixadi®) extended-release subcutaneous buprenorphine (XR bup) has been available in Europe and Australia for several years and was approved by the Food and Drug Administration in May 2023. Little is known about the clinical experience of patients and providers using this new medication during prenatal care. Two cases of pregnant persons with opioid use disorder receiving weekly XR bup in an ongoing randomized multi-site outpatient clinical trial are presented along with a brief review of the pharmacology and literature on XR bup formulations. The cases in pregnancy illustrate how treatment with the weekly formulation is initiated including how to make dose adjustments, which may be necessary given the longer half-life; it takes 1 month to achieve steady state. Injection site pain with medication administration was time limited and managed readily. Other injection site reactions experienced included subcutaneous erythema and induration that was delayed in onset and typically mild, resolving with minimal intervention. Delivery management and breastfeeding recommendations while on weekly XR bup were not different compared to sublingual buprenorphine (SL bup). Weekly XR bup is a new treatment for opioid use disorder that may be used in the obstetric population. Obstetric and addiction medicine clinicians should be aware of this new formulation as its use is expected to increase.

An Innovative Curriculum For Teaching Transesophageal Echocardiography (TEE) to Emergency Medicine Residents.

BACKGROUND: Focused transesophageal echocardiogram (TEE) can be a valuable tool for emergency physicians (EP) during cardiac arrest. OBJECTIVES: We sought to demonstrate the ability of emergency medicine (EM) residents without prior TEE experience to perform a simulated four-view TEE following a short, flipped conference curriculum. METHODS: This was a prospective, simulation-based study where EM residents participated in the following four-view TEE curriculum: 1 h of online content reviewed prior to a 20-min in-person lecture and 30-min hands-on practice using a TEE trainer. Each resident attended four testing sessions over an 8-week period and performed a total of 25 TEE scans. Each TEE scan was graded in real time using a 10-point checklist by a TEE-credentialed EP. Interrater reliability of the checklist was calculated using the kappa coefficient (κ). A random sample of 10% of the TEE scans were reviewed by a TEE expert using a standard ultrasound 1-5 scale for image acquisition quality, with a "3" considered to be satisfactory. Residents completed an online pretest and posttest. RESULTS: Twenty-four residents participated. Mean pre- and posttest scores were 52% (SD 16) and 92% (SD 12), respectively. Mean TEE scores using the 10-point checklist after sessions one and four were 9.4 (SD 0.4) and 9.7 (SD 0.3), respectively. Mean time to complete each TEE scan after sessions one and four were 118.1 (SD 28.3) and 57.1 (SD 17.0) s, respectively. The κ for the checklist was 1. The median score for the image acquisition review was 3 (interquartile range 3-4). CONCLUSIONS: This simplified flipped conference curriculum can train EM residents to competently perform TEE in a simulated environment.

Expansion of Preexposure Prophylaxis Capacity in Response to an HIV Outbreak Among People Who Inject Drugs-Cabell County, West Virginia, 2019.

From January 1, 2018, through October 9, 2019, 82 HIV diagnoses occurred among people who inject drugs (PWID) in Cabell County, West Virginia. Increasing the use of HIV preexposure prophylaxis (PrEP) among PWID was one of the goals of a joint federal, state, and local response to this HIV outbreak. Through partnerships with the local health department, a federally qualified health center, and an academic medical system, we integrated PrEP into medication-assisted treatment, syringe services program, and primary health care settings. During the initial PrEP implementation period (April 18-May 17, 2019), 110 health care providers and administrators received PrEP training, the number of clinics offering PrEP increased from 2 to 15, and PrEP referrals were integrated with partner services, outreach, and testing activities. The number of people on PrEP increased from 15 in the 6 months before PrEP expansion to 127 in the 6 months after PrEP implementation. Lessons learned included the importance of implementing PrEP within existing health care services, integrating PrEP with other HIV prevention response activities, adapting training and material to fit the local context, and customizing care to meet the needs of PWID. The delivery of PrEP to PWID is challenging but complements other HIV prevention interventions. The expansion of PrEP in response to this HIV outbreak in Cabell County provides a framework for expanding PrEP in other outbreak and non-outbreak settings.

History of postpartum depression as a contributor to the severity of NAS.

Currently, there are no clinical tools available to accurately predict the severity of neonatal withdrawal. Studies of non-exposed neonates suggest that maternal depression and anxiety are predictive of negative short and long-term neonatal outcomes, but research is lacking in the addicted population. We studied of 109 pregnant women in medication-assisted treatment (MAT) and their neonates to determine if psychiatric conditions co-occurring with Substance Use Disorder (SUD) contributed to the severity of neonatal withdrawal. The need for pharmacological intervention, Finnegan scores, length of methadone treatment, and length of hospital stay were used to assess withdrawal severity. Categorical variables were analyzed in Stata14 using Chi Square and continuous variables were analyzed using Wilcoxon Rank Sum. Among the 110 neonates whose outcomes were reviewed, a maternal history of Postpartum Depression (PPD) was found to be correlated with increased severity of withdrawal. The neonates born to mothers with past diagnoses of PPD had more consecutive days of high Finnegan scores (95% confidence interval [CI], P = 0.003), longer length of treatment (95% CI, P = 0.006), and length of hospital stay (95% CI, P = 0.014). There was no apparent relationship between NAS severity and other psychiatric disorders. In a study of pregnant women with SUD and their neonates, we uncovered a relationship between the severity of NAS and maternal history of PPD. Our findings demonstrate that further research into these deleterious outcomes is warranted. Until then, we suggest collection of maternal history of PPD and careful screening for new cases in the SUD population.

Novel Withdrawal Symptoms of a Neonate Prenatally Exposed to a Fentanyl Analog.

Neonatal abstinence syndrome (NAS) is a withdrawal syndrome observed in neonates exposed to drugs in utero, typically opioids, which is associated with symptoms affecting the central and autonomic nervous systems and the gastrointestinal system. West Virginia, particularly the southeastern region of the state, has remarkably higher rates of NAS than similar communities. Our facility is increasingly faced with complex cases of NAS caused by in utero exposure to multiple substances. We present a case report of a neonate born to a 25-year-old mother enrolled in a medication-assisted treatment program for substance use disorder who was noncompliant in prenatal care, using multiple substances throughout the pregnancy, including gabapentin and fentanyl. After birth, the neonate began to exhibit unusual withdrawal symptoms including arching, tongue thrusting, and irregular eye movements, which are typically associated with in utero gabapentin exposure. The parents denied consent to treat with gabapentin, the suggested management for these symptoms; thus, a treatment protocol for methadone and clonidine were followed. This case exemplifies the medical and social complexities involved in treating polysubstance exposure-associated NAS.

Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease.

The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an ¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as well as the peptide's absorption, distribution, and excretion. Analysis of these data support a model wherein ShK-186 is absorbed slowly from the injection site, resulting in blood concentrations above the Kv1.3 channel-blocking IC50 value for up to 7 days in monkeys. Pharmacodynamic studies on human peripheral blood mononuclear cells showed that brief exposure to ShK-186 resulted in sustained suppression of cytokine responses and may contribute to prolonged drug effects. In delayed-type hypersensitivity, chronic relapsing-remitting experimental autoimmune encephalomyelitis, and pristane-induced arthritis rat models, a single dose of ShK-186 every 2 to 5 days was as effective as daily administration. ShK-186's slow distribution from the injection site and its long residence time on the Kv1.3 channel contribute to the prolonged therapeutic effect of ShK-186 in animal models of autoimmune disease.