A Source Control Model for Treatment-Resistant Substance Use Disorder.

ABSTRACT: We propose applying the "source control" model of infectious disease treatment to the management of treatment-resistant substance use disorder (SUD). We believe that this conceptual framework complements other models for understanding SUD, fills a gap in our current understanding of treatment-resistant SUD, and advances the destigmatization of SUD by reinforcing SUD as a disease similar to other medical conditions. The model also harmonizes the need for multimodal treatment and novel interventions for both acute supportive care and long-term treatment of SUD. In this manuscript, we discuss the justification for, as well as the strengths and limitations of, the "source control" model for the management of treatment-resistant SUD. We also discuss the model's potential to direct innovative research questions and therapeutic interventions.

Compartment Syndrome Following Snake Envenomation in the United States: A Scoping Review of the Clinical Literature.

Introduction: Local tissue destruction following envenomation from North American snakes, particularly those within the Crotalinae subfamily, has the potential to progress to compartment syndrome. The pathophysiology of venom-induced compartment syndrome (VICS) is a debated topic and is distinct from trauma/reperfusion-induced compartment syndrome. Heterogeneity exists in the treatment practices of VICS, particularly regarding the decision to progress to fasciotomy. Associations with functional outcomes and evolution in clinical practice since the introduction of Crotalidae polyvalent immune Fab (FabAV) have not been well defined. Our goal was to identify the potential gaps in the literature regarding this phenomenon, as well as illuminate salient themes in the clinical characteristics and treatment practices of VICS. Methods: We conducted this systematic scoping-style review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Records were included if they contained data surrounding the envenomation and hospital course of one or more patients who were envenomated by a snake species native to North America and were diagnosed with compartment syndrome from 1980-2020. Results: We included 19 papers: 10 single- or two-patient case reports encompassing 12 patients, and nine chart reviews providing summary statistics of the included patients. In case reports, the median compartment pressure when reported was 60 millimeters of mercury (interquartile range 55-68), 66% underwent fasciotomy, and functional outcomes varied. Use of antivenom appeared to be more liberal with FabAV than the earlier antivenin Crotalidae polyvalent. Rapid progression of swelling was the most commonly reported symptom. Among the included retrospective chart reviews, important data such as compartment pressures, consistent laboratory values, and snake species was inconsistently reported. Conclusions: Venom-induced compartment syndrome is relatively rare. Existing papers generally describe good outcomes even in the absence of surgical management. Significant gaps in the literature regarding antivenom dosing practices, serial compartment pressure measurements, and functional outcomes highlight the need for prospective studies and consistent standardized reporting.

Effect of PTSD treatment on cardiovascular reactivity during trauma memory recall and correspondence with symptom improvement.

ABSTRACTBackground: Prior research has shown PTSD treatment leads to reductions in cardiovascular reactivity during trauma recall, but the extent to which such reductions are associated with changes in PTSD symptoms is less clear. Moreover, such relationships have not been investigated in a cognitively focused PTSD treatment.Objective: To examine changes in cardiovascular reactivity to the trauma memory in patients receiving cognitive processing therapy (CPT), CPT with a written trauma account, and a written account only condition. We also examined the association of such changes with symptom improvement.Method: 118 women with PTSD secondary to interpersonal violence completed pre- and post-treatment assessments of PTSD symptoms and cardiovascular reactivity during a script-driven imagery task.Results: Results indicated a significant but modest reduction in cardiovascular reactivity in CPT conditions. Changes in cardiovascular reactivity and reexperiencing symptoms were significantly associated among the whole sample. Among individuals with the greatest reactivity to the trauma memory at pretreatment, associations were also seen with changes in total PTSD, numbing, and trauma-related guilt.Conclusions: Results indicate that previous findings on the effect of PTSD treatment on cardiovascular reactivity during trauma recall extend to cognitively oriented treatment. Baseline cardiovascular reactivity may influence the extent to which reductions in PTSD symptoms and reactivity during trauma recall are related.

Cognitive Processing Therapy leads to reduced heart rate reactivity when recalling a trauma memory.Decreases in heart rate reactivity are associated with reduced reexperiencing symptoms.Changes in heart rate reactivity and PTSD symptoms are more closely related among patients with greater pretreatment reactivity.

Hospitalization is a missed opportunity for HIV screening, pre-exposure prophylaxis, and treatment.

BACKGROUND: Hospitalization is a "reachable moment" for people who inject drugs (PWID), but preventive care including HIV testing, prevention and treatment is rarely offered within inpatient settings. METHODS: We conducted a multisite, retrospective cohort study of patients with opioid use disorder with infectious complications of injection drug use hospitalized between 1/1/2018-12/31/2018. We evaluated HIV care continuum outcomes using descriptive statistics and hypothesis tests for intergroup differences. RESULTS: 322 patients were included. Of 300 patients without known HIV, only 2 had a documented discussion of PrEP, while only 1 was prescribed PrEP on discharge. Among the 22 people with HIV (PWH), only 13 (59%) had a viral load collected during admission of whom all were viremic and 10 (45%) were successfully linked to care post-discharge. Rates of readmission, Medicaid or uninsured status, and unstable housing were high in both groups. DISCUSSION: We observed poor provision of HIV testing, PrEP and other HIV services for hospitalized PWID across multiple U.S. medical centers. Future initiatives should focus on providing this group with comprehensive HIV testing and treatment services through a status neutral approach.

Heart rate reactivity during trauma recall as a predictor of treatment outcome in cognitive processing therapy for PTSD.

Emotional engagement when recollecting a trauma memory is considered a key element of effective trauma-focused therapy. Research has shown that reduced physiological reactivity during trauma recall is associated with worse treatment outcomes for posttraumatic stress disorder (PTSD), but this has yet to be examined in a cognitively oriented treatment. This study examined whether pretreatment heart rate (HR) reactivity during trauma recall predicts PTSD symptom improvement and treatment dropout during Cognitive Processing Therapy (CPT) for PTSD. Participants were 142 women with PTSD secondary to interpersonal violence enrolled in one of two clinicals trials. HR reactivity reflected the mean increase in HR after listening to two 30-s scripts of the trauma memory prior to treatment. Linear mixed-effects models showed the effect of HR reactivity on change in total PTSD symptoms was not significant, but lower HR reactivity predicted less improvement in reexperiencing and avoidance and was associated with increased dropout. Findings suggest pretreatment physiological reactivity to the trauma memory may be a prognostic indicator of some elements of treatment response in CPT. Results tentatively support the importance of emotional activation during trauma recall in cognitive treatment of PTSD, though more research is needed to clarify how low HR reactivity impacts treatment.

Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report.

BACKGROUND: Serotonin toxicity is a well-described phenomenon that is commonly attributed to a variety of drug-drug combinations. Some unregulated herbal supplements have been implicated in the onset of serotonin toxicity, however, there is currently minimal literature available on the potential for black cohosh to contribute to rhabdomyolysis and serotonin toxicity, in spite of its known serotonergic properties. CASE REPORT: A middle-aged woman presented to the emergency department with serotonin toxicity and rhabdomyolysis shortly after taking black cohosh supplements in the setting of long-term dual antidepressant use. The serotonin toxicity and rhabdomyolysis resolved with IV fluids, benzodiazepines, and discontinuation of the offending drugs. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients are sometimes not aware of how over-the-counter supplements might interact with their prescription medications. Female patients taking black cohosh to manage hot flashes and menopausal symptoms could be at risk for developing rhabdomyolysis and serotonin toxicity if they are also taking other serotonergic agents.

Oral potassium poisoning: a retrospective review of the National Poison Data System 2010-2021.

INTRODUCTION: Oral potassium poisoning can be life-threatening. The study aimed to describe patterns of oral potassium poisoning in adult and pediatric populations and characterize its clinical presentation and management as reported by United States poison centers. METHODS: This is a retrospective review of the National Poison Data System from 1 January 2010 through 30 June 2021. We descriptively analyzed cases involving single substance, oral potassium salts. In a second step, we requested a subset of case-specific narratives for cases that resulted in major outcome or death, as well as cases where patients received any of the following therapies: whole bowel irrigation, sodium bicarbonate, calcium, insulin or hemodialysis. We classified hyperkalemia by expected toxicity: mild (peak potassium concentration <6.5 mEq/L), moderate (peak potassium concentration 6.5 to <8 mEq/L) or severe (peak potassium concentration ≥ 8mEq/L). RESULTS: The National Poison Data System included 1,820 cases, 52.3 percent being adults. Among adult cases, 20% (n = 189) resulted in a moderate effect, major effect or death. Among pediatric cases aged <10 years, all exposures were unintentional. Analysis of 49 case narratives showed a median peak potassium concentration of 7.1 mEq/L (interquartile range 5.4-8.6) and a moderate correlation with the dose ingested (r = 0.66). Severe hyperkalemia was associated with QRS complex widening (P < 0.001), peaked T-waves (P = 0.001), and neurological symptoms (P = 0.04). Whole bowel irrigation was associated with mild hyperkalemia (P = 0.011), and hemodialysis was associated with severe hyperkalemia (P < 0.001). DISCUSSION: Analysis of data showed that therapy to promote intracellular shift of potassium is the mainstay of management of oral potassium poisoning, followed by hemodialysis. LIMITATIONS: Poison center data are susceptible to reporting bias. National Poison Data System data are affected by completeness and accuracy of reporting from health care providers and the lay public. CONCLUSIONS: Single substance, oral potassium poisoning, reported to United States poison centers, is mostly unintentional and rarely results in hyperkalemia.

Tobacco withdrawal-induced changes in sensorimotor filtering as a predictor of smoking lapse in trauma-exposed individuals.

Prepulse inhibition (PPI) is a measure of sensorimotor filtering thought to shield the processing of initial weaker auditory stimuli from interruption by a later startle response. Previous studies have shown smoking withdrawal to have a negative impact on sensorimotor filtering, particularly in individuals with psychopathology. Because tobacco use may alleviate sensory and sensorimotor filtering deficits, we examined whether smoking withdrawal-induced changes in PPI were associated with maintenance of smoking abstinence in trauma-exposed individuals with and without PTSD who were attempting to quit smoking. Thirty-eight individuals (n = 24 with current or past PTSD; 14 trauma-exposed healthy controls) made an acute biochemically-verified smoking cessation attempt supported by 8 days of contingency management (CM) and cognitive behavioral therapy (CBT) for smoking. Participants completed a PPI task at the pre-quit baseline, 2 days post-quit, and 5 days post-quit. Post-quit changes in PPI were compared between those who remained abstinent for the first 8-days of the quit attempt and those who lapsed back to smoking. PPI changes induced by biochemically-verified smoking abstinence were associated with maintenance of abstinence across the 8-day CM/CBT-supported quit attempt. As compared to those who maintained tobacco abstinence, participants who lapsed to smoking had significantly lower PPI at 2 and 5 days post-quit relative to baseline. Thus, among trauma-exposed individuals, decreases in PPI during acute smoking cessation supported by CM/CBT are associated with lapse back to smoking. Interventions that improve PPI during early smoking abstinence may facilitate smoking cessation among such individuals who are at high risk for chronic, refractory tobacco use.

Access to, Experience with, and Attitudes towards Take Home Naloxone: An Online Survey.

The opioid public health crisis continues to burden individuals, communities, and economies. Public health opinion has emphasized the need for increased access to harm reduction services, but there is a dearth of information on the views and experiences of people who use opioids. Our study aimed to investigate the prevalence of naloxone use, attitudes, and experiences with naloxone among an online community of people who use drugs. We performed a cross-sectional survey looking at experiences with and attitudes towards take-home naloxone. Data is presented descriptively, with analysis of the differences between people who do and do not use opioids using the χ2 and Fisher's exact tests. There were 1,143 respondents, of whom 70% were from the United States. Only 38% of participants who use opioids had received naloxone training, but 56% of these individuals said that they felt comfortable using a naloxone kit. Nearly all respondents (95%) said they would be willing to use naloxone on someone who had overdosed and approximately 90% would want naloxone used on them in case of an overdose. Regarding harm reduction, 24% of respondents said they had access to safe use programs, and 33% said they had access to clean needle exchange programs. A majority of the participants who use opioids were in favor of having naloxone with them when using drugs and believed naloxone should be freely available. This study demonstrates the receptiveness of take-home naloxone and highlights the need for better implementation of naloxone within communities that use opioids.

Hydrofluoric acid ingestions: Retrospective evaluations from cases reported to the National Poison Data System 2007-2017.

Background: Hydrofluoric acid (HF) is associated with systemic toxicity, particularly with high-concentration formulations. However, most existing data describe dermal exposures; there is a paucity of data related to outcomes after ingestions. Objective: To determine the morbidity and mortality associated with HF ingestions as reported to the National Poison Data System (NPDS). A secondary objective is to assess for clinical criteria that are associated with serious outcomes after HF ingestion. Methods: We performed a retrospective review of HF ingestions reported to the NPDS from 2007 to 2017. Data including patient demographics, exposure and caller sites, electrolyte abnormalities, treatments, and serious (moderate or major effect or death as documented in NPDS) and non-serious outcomes were abstracted from case narratives. Cases meeting the criteria for a qualifiable HF ingestion were included in the study. Results: During the study period, there were 653 HF ingestions reported to NPDS, of which 142 were included in the final data analysis. Most HF exposures occurred in men (68.3%), and the most common exposure site was at the exposed individual's own residence (78.2%). Nearly half of all exposures (46.5%) were due to transfer into a non-labeled secondary storage container. Total of 45.8% of the cases resulted in a serious outcome. Electrolyte disturbances were associated with an increased risk of a serious outcome. Hypocalcemia was the most frequently reported electrolyte abnormality, occurring in 24.6% of cases. Nine (6.3%) individuals died. Conclusions: Mortality after HF ingestion is low. However, a large cohort of exposures occurred after the transfer of HF to secondary containers. Targeted interventions to reduce this practice are necessary to decrease hazardous chemical exposures.

Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT.

BACKGROUND: Over a decade and a half of research has resulted in inconsistent evidence for the efficacy of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, for augmenting exposure-based cognitive behavioral therapy (CBT) for anxiety- and fear-based disorders. These variable findings have motivated the search for moderators of DCS augmentation efficacy. METHODS: In this secondary analysis of a previous randomized clinical trial, we evaluated the value of de novo threat conditioning outcomes-degree of threat acquisition, extinction, and extinction retention-for predicting treatment response to exposure-based CBT for social anxiety disorder, applied with and without DCS augmentation in a sample of 59 outpatients. RESULTS: We found that average differential skin conductance response (SCR) during extinction and extinction retention significantly moderated the prediction of clinical response to DCS: participants with poorer extinction and extinction retention showed relatively improved treatment response with DCS. No such effects were found for expectancy ratings, consistent with accounts of DCS selectively aiding lower-order but not higher-order extinction learning. CONCLUSIONS: These findings provide support for extinction and extinction retention outcomes from threat conditioning as potential pre-treatment biomarkers for DCS augmentation benefits. Independent of DCS augmentation, the current study did not support threat conditioning outcomes as useful for predicting response to exposure-based CBT.

Undertreatment of opioid use disorder in patients hospitalized with injection drug use-associated infections.

OBJECTIVE: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids. METHOD: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018. Three hundred and twenty-two patients were included and their individual patient records were manually reviewed to identify inpatient receipt of medication for opioid use disorder (MOUD), initiation of MOUD, and addiction consultation. The main outcomes of interest were premature discharge, MOUD on discharge, linkage to outpatient MOUD, one-year readmission and death. RESULTS: Three hundred and twenty-two patients were predominately male (59%), white (66%), and median age 38 years, with 36% unstably housed, and 30% uninsured. One hundred and forty-five (45%) patients received MOUD during hospitalization, including only 65 (28%) patients not on baseline MOUD. Discharge was premature for 64 (20%) patients. In the year following discharge, 27 (9%) patients were linked to MOUD, and 159 (50%) patients had at least one readmission. Being on MOUD during hospitalization was significantly associated with higher odds of planned discharge [odds ratio (OR) 3.87, P  < 0.0001], MOUD on discharge (OR 129.7, P  < 0.0001), and linkage to outpatient MOUD (OR 1.25, P  < 0.0001), however, was not associated with readmission. Study limitations were the retrospective nature of the study, so post-discharge data are likely underestimated. CONCLUSION: There was dramatic undertreatment with MOUD from inpatient admission to outpatient linkage, and high rates of premature discharge and readmission. Engagement in addiction care during hospitalization is a critical first step in improving the care continuum for individuals with opioid use disorder; however, additional interventions may be needed to impact long-term outcomes like readmission.

Use of nonstigmatizing language is associated with improved outcomes in hospitalized people who inject drugs.

BACKGROUND: Stigma surrounding opioid use disorder (OUD) is a barrier to treatment. The use of stigmatizing language may be evidence of negative views toward patients. OBJECTIVE: We aimed to identify associations between language and clinical outcomes in patients admitted for infectious complications of OUD. DESIGNS: We performed a retrospective medical record review. SETTINGS AND PARTICIPANTS: Four U.S. academic health systems. Participants were patients with OUD admitted for infectious complications of injection opioid use from January 1, 2018, to December 31, 2018, identified through international classification of diseases, 10th revision codes consistent with OUD and acute bacterial/fungal infection. MAIN OUTCOME AND MEASURES: Discharge summaries were reviewed for language, specifically: abuse, addiction, dependence, misuse, use disorder, intravenous drug use, and others. Binary outcomes including medication for OUD, planned discharge, naloxone provision, and an OUD treatment plan were evaluated using logistic regressions and admission duration was evaluated using Gamma regression. RESULTS: A total of 1285 records were reviewed and 328 met inclusion criteria. Of those, 191 (58%) were male, with a median age of 38 years. The most common term was "abuse" (219, 67%), whereas "use disorder" was recorded in 75 (23%) records. Having "use disorder" in the discharge summary was associated with increased odds of having a documented plan for ongoing OUD treatment (adjusted odds ratio [AOR]: 4.11, 95% confidence interval [CI]: 1.89-8.93) and having a documented plan for addiction-specific follow-up care (AOR: 2.31, 95% CI: 1.30-4.09). CONCLUSIONS: Stigmatizing language was common in this study of patients hospitalized for infectious complications of OUD. Best-practice language was uncommon, but when used was associated with increased odds of addiction treatment and specialty care referrals.

Leveraging observational data to identify in-session patient and therapist predictors of cognitive processing therapy response and completion.

Cognitive processing therapy (CPT) is an evidence-based treatment for posttraumatic stress disorder (PTSD), but little is known about in-session process variables that predict symptom reduction and treatment completion during CPT. Examining potentially malleable factors that may promote or impede recovery can inform care delivery and enhance outcomes. The current study used observational ratings of CPT session recordings to examine in-session patient and therapist factors in cognitive, affective, and interpersonal domains to identify their relative contributions to predicting symptom outcomes and treatment completion. Participants were 70 adult survivors of interpersonal violence who received CPT. Predictors of better posttreatment PTSD outcomes included less patient fear, ß = .32, and less patient avoidance of engaging with the therapist, ß = .35. When using the last available PTSD score, less fear, ß = .23, and avoidance, ß = .28, continued to predict better outcomes, and more patient cognitive flexibility emerged as a stronger predictor of outcome, ß = -.33. Predictors of a higher likelihood of treatment completion included more therapist use of Socratic dialogue, OR = 6.75, and less therapist encouragement of patient affect, OR = 0.11. Patient sadness and anger and therapist expression of empathy did not predict symptom outcomes or treatment completion versus dropout. The results highlight the importance of patients' cognitions, emotions, and engagement with their therapist in CPT as well as the role of therapist behaviors in patient completion of treatment.

Enhanced Mental Reinstatement of Exposure to Improve Extinction Generalization: A Study on Claustrophobia and MRI Fear.

Fear of enclosed spaces prevents many people from receiving magnetic resonance imaging (MRI) scans. Although exposure therapy can effectively treat such fears, reductions in fear during exposure often do not generalize beyond the context in which they took place. This study tested a strategy designed to increase generalization, which involved revisiting the memory of a prior exposure to enhance retrieval of extinction learning. Forty-five participants with claustrophobia that included fear of MRI scans underwent a series of exposures lying inside a narrow cabinet. One week later, participants were randomly assigned to enhanced mental reinstatement (EMR) or control procedures. Prior to entering a mock MRI scanner, EMR participants recalled the memory of exposure training and listened to an audio recording of themselves describing what they learned, whereas control participants recalled a neutral memory. Compared to the control condition, EMR led to significantly reduced heart rate reactivity in the mock MRI scanner, but not self-reported fear or avoidance. There were no differences between conditions in claustrophobia symptoms or MRI fear at 1-month follow-up. Results suggest some benefits of mental reinstatement for improving generalization of gains following exposure training for claustrophobia, with measures of subjective fear and physiological arousal showing discordant outcomes.

Efficacy of Cognitive Behavioral Therapy for Anxiety-Related Disorders: A Meta-Analysis of Recent Literature.

PURPOSE OF REVIEW: Effective treatment of anxiety-related disorders is crucial, considering the prevalence of such disorders and their association with poor psychosocial functioning. To evaluate the most recent evidence on the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders in adults, we conducted a meta-analysis of randomized placebo-controlled trials published since 2017. RECENT FINDINGS: Ten studies with a total of 1250 participants met the inclusion criteria. Seven of these studies examined PTSD. The findings demonstrated small placebo-controlled effects of CBT on target disorder symptoms (Hedges' g = 0.24, p < 0.05) and depression (Hedges' g = 0.15, p = n.s). When examining only PTSD studies, effects were reduced (Hedges' g = 0.14, p < 0.05). Heterogeneity in most analyses was very low, and no publication bias was found. Effect sizes from placebo-controlled trials from the past 5 years appear to be smaller than those in prior meta-analyses. The findings are largely driven by research on PTSD, with few placebo-controlled trials of other anxiety-related disorders published since 2017.

Electronic Advisories Increase Naloxone Prescribing Across Health Care Settings.

BACKGROUND: Naloxone is a life-saving, yet underprescribed, medication that is recommended to be provided to patients at high risk of opioid overdose. OBJECTIVE: We set out to evaluate the changes in prescriber practices due to the use of an electronic health record (EHR) advisory that prompted opioid prescribers to co-prescribe naloxone when prescribing a high-dose opioid. It also provided prescribers with guidance on decreasing opioid doses for safety. DESIGN: This was a retrospective chart abstraction study looking at all opioid prescriptions and all naloxone prescriptions written as emergency department (ED) discharge, inpatient hospital discharge, or outpatient medications, between July 1, 2018, and February 1, 2020. The EHR advisory went live on June 1, 2019. SUBJECTS: Included in the analysis were all adult patients seen in the abovementioned settings at a large county hospital and associated outpatient clinics. MAIN MEASURES: We performed an interrupted time series analysis looking at naloxone prescriptions and daily opioid dosing in morphine milligram equivalents (MMEs), before and after initiation of the EHR advisory. KEY RESULTS: The EHR advisory was associated with changes in prescribers' behavior, leading to increased naloxone prescriptions and decreased prescribed opioid doses. CONCLUSIONS: EHR advisories are an effective systems-level intervention to enhance the safety of prescribed opioids and increase rates of naloxone prescribing.