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Buprenorphine is increasingly used to treat pain in patients with sickle cell disease but optimal timing and approach for transitioning patients from full agonist opioids to buprenorphine is unknown. We present the case of a 22-year-old woman with sickle cell disease and acute on chronic pain who transitioned from high-dose oxycodone to buprenorphine/naloxone during a hospital stay for vaso-occlusive episode. Utilizing a microdosing approach to minimize pain and withdrawal, buprenorphine/naloxone was gradually uptitrated while she received full agonist opioids. During the transition, she experienced some withdrawal in the setting of swallowed buprenorphine/naloxone tablets, which were intended to be dosed sublingually. Nevertheless, the transition was tolerable to the patient and her pain and function significantly improved with buprenorphine treatment. This case also highlights the challenges and unique considerations that arise when providing care for the hospitalized patient who is also incarcerated.

Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals, very little is known about how the azoles are imported into pathogenic fungal cells. Here the in-vitro accumulation and import of Fluconazole (FLC) was examined in the pathogenic fungus, Candida albicans. In energized cells, FLC accumulation correlates inversely with expression of ATP-dependent efflux pumps. In de-energized cells, all strains accumulate FLC, suggesting that FLC import is not ATP-dependent. The kinetics of import in de-energized cells displays saturation kinetics with a K(m) of 0.64 μM and V(max) of 0.0056 pmol/min/10⁸ cells, demonstrating that FLC import proceeds via facilitated diffusion through a transporter rather than passive diffusion. Other azoles inhibit FLC import on a mole/mole basis, suggesting that all azoles utilize the same facilitated diffusion mechanism. An analysis of related compounds indicates that competition for azole import depends on an aromatic ring and an imidazole or triazole ring together in one molecule. Import of FLC by facilitated diffusion is observed in other fungi, including Cryptococcus neoformans, Saccharomyces cerevisiae, and Candida krusei, indicating that the mechanism of transport is conserved among fungal species. FLC import was shown to vary among Candida albicans resistant clinical isolates, suggesting that altered facilitated diffusion may be a previously uncharacterized mechanism of resistance to azole drugs.

Introduction: Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient’s perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches. Methods: This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semistructured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation. Results: Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment. Conclusion: Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.

Background There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain. Methods A cross-sectional study examined baseline data from participants ( N  = 303) enrolled in a randomized controlled trial of a mind–body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression. Results Participants were self-identified as women ( n  = 157), men ( n  = 144), and non-binary ( n  = 2). Fifty-seven percent ( n  = 172) self-reported chronic pain, and 41% ( n  = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%). Conclusion The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment. Trial registration NCT04082637.

With opioid overdoses rising, practices should consider stocking this safe rescue drug alongside other emergency devices and medications.

A recent clinical trial of people with near-daily methamphetamine use achieved >75% study-drug adherence via financial incentives and close follow-up.5 Bubble packs are useful, as is preferentially choosing once per day dosing options (eg, metoprolol succinate over carvedilol). A recently established inpatient consultation addiction care team at our hospital provides services such as motivational interviewing, discussion of safer use strategies, behavioural and pharmacological SUD treatment, and linkage to ongoing care in the community.6 To address social determinants of health, we established a multidisciplinary team (cardiology, primary care, palliative care, addiction medicine, social work, case management and street medicine), which meets monthly to discuss patients with HF, SUDs and frequent admissions. Directly observed therapy and reward-based incentives have been shown to be effective in chronic disease management in patients with SUDs and infectious diseases, but these strategies remain underexplored in HF.7 We developed a novel two times-per-week cardiology–addiction comanagement clinic for patients with co-occurring HF and stimulant use disorder which incorporates contingency management (figure 1). A systematic review of community-based interventions to improve oral chronic disease medication regimen adherence among individuals with substance use disorder.

Drug overdose (OD) is a public health challenge and an important cause of out-of-hospital cardiac arrest (OHCA). Existing studies evaluating OD-related OHCA (OD-OHCA) either aggregate all drugs or focus on opioids. The epidemiology, presentation, and outcomes of drug-specific OHCA are largely unknown. To evaluate the temporal pattern, clinical presentation, care, and outcomes of adult patients with OHCA overall and according to the drug-specific profile. This cohort study of adults with OHCA in King County Washington was conducted between January 1, 2015, and December 31, 2021. Etiology of OHCA was determined using emergency medical service, hospital, and medical examiner records. Etiology was classified as non-OD OHCA or OD-OHCA, with drug-specific profiles categorized as (1) opioid without stimulant, (2) stimulant without opioid, (3) opioid and stimulant, or (4) all other nonstimulant, nonopioid drugs. Statistical analysis was performed on July 1, 2023. Out-of-hospital cardiac arrest. The primary outcome was survival to hospital discharge. The secondary outcome was survival with favorable functional status defined by Cerebral Performance Category 1 or 2 based on review of the hospital record. In this cohort study, there were 6790 adult patients with emergency medical services-treated OHCA from a US metropolitan system. During the 7-year study period, there were 702 patients with OD-OHCA (median age, 41 years [IQR, 29-53 years]; 64% male [n = 450] and 36% female [n = 252]) and 6088 patients with non-OD OHCA (median age, 66 years [IQR, 56-77 years]; 65% male [n = 3944] and 35% female [n = 2144]). The incidence of OD-OHCA increased from 5.2 (95% CI, 3.8-6.6) per 100 000 person-years in 2015 to 13.0 (95% CI, 10.9-15.1) per 100 000 person-years in 2021 (P < .001 for trend), whereas there was no significant temporal change in the incidence of non-OD OHCA (P = .30). OD-OHCA were more likely to be unwitnessed (66% [460 of 702] vs 41% [2515 of 6088]) and less likely to be shockable (8% [56 of 702] vs 25% [1529 of 6088]) compared with non-OD OHCA. Unadjusted survival was not different (20% [138 of 702] for OD vs 18% [1095 of 6088] for non-OD). When stratified by drug profile, combined opioid-stimulant OHCA demonstrated the greatest relative increase in incidence. Presentation and outcomes differed by drug profile. Patients with stimulant-only OHCA were more likely to have a shockable rhythm (24% [31 of 129]) compared with patients with opioid-only OHCA (4% [11 of 295]) or patients with combined stimulant-opioid OHCA 5% [10 of 205]), and they were more likely to have a witnessed arrest (50% [64 of 129]) compared with patients with OHCA due to other drugs (19% [14 of 73]) or patients with combined stimulant-opioid OHCA (23% [48 of 205]). Patients with a combined opioid-stimulant OHCA had the lowest survival to hospital discharge (10% [21 of 205]) compared with patients with stimulant-only OHCA (22% [29 of 129]) or patients with OHCA due to other drugs (26% [19 of 73]), a difference that persisted after multivariable adjustment. In a population-based cohort study, the incidence of OD-OHCA increased significantly from 2015 to 2021, with the greatest increase observed among patients with a combined stimulant-opioid OHCA. Presentation and outcome differed according to the drug-specific profile. The combination of increasing incidence and lower survival among among patients with a opioid-stimulant OHCA supports prevention and treatment initiatives that consider the drug-specific profile.

Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals, very little is known about how the azoles are imported into pathogenic fungal cells. Here the in-vitro accumulation and import of Fluconazole (FLC) was examined in the pathogenic fungus, Candida albicans. In energized cells, FLC accumulation correlates inversely with expression of ATP-dependent efflux pumps. In de-energized cells, all strains accumulate FLC, suggesting that FLC import is not ATP-dependent. The kinetics of import in de-energized cells displays saturation kinetics with a Km of 0.64 uM and Vmax of 0.0056 pmol/min/108 cells, demonstrating that FLC import proceeds via facilitated diffusion through a transporter rather than passive diffusion. Other azoles inhibit FLC import on a mole/mole basis, suggesting that all azoles utilize the same facilitated diffusion mechanism. An analysis of related compounds indicates that competition for azole import depends on an aromatic ring and an imidazole or triazole ring together in one molecule. Import of FLC by facilitated diffusion is observed in other fungi, including Cryptococcus neoformans, Saccharomyces cerevisiae, and Candida krusei, indicating that the mechanism of transport is conserved among fungal species. FLC import was shown to vary among Candida albicans resistant clinical isolates, suggesting that altered facilitated diffusion may be a previously uncharacterized mechanism of resistance to azole drugs.