Feasibility of implementing a screening tool for risk of opioid misuse in a trauma surgical population.

Background: As the opioid crisis continues to affect communities across the United States, new interventions for screening and prevention are needed to mitigate its impact. Mental health diagnoses have been identified as a risk factor for opioid misuse, and surgical populations and injury survivors are at high risk for prolonged opioid use and misuse. This study investigated the implementation of a novel opioid risk screening tool that incorporated putative risk factors from a recent study in four trauma units across Wisconsin. Method: The screening tool was implemented across a 6-month period at four sites. Data was collected via monthly meeting notes and "Plan, Do, Study, Act" (PDSA) forms. Following implementation, focus groups reflected on the facilitators and barriers to implementation. Meeting notes, PDSA forms, and focus group data were analyzed using the consolidated framework for implementation research, followed by thematic analyses, to generate themes surrounding the facilitators and barriers to implementing an opioid misuse screener. Results: Implementation facilitators included ensuring patient understanding of the screener, minimizing staff burden from screening, and educating staff to encourage engagement. Barriers included infrastructure limitations that prevented seamless administration of the screener within current workflows, overlap of the screener with existing measures, and lack of guidance surrounding treatment options corresponding to risk. Recommended solutions to address barriers include careful timing of screener administration, accommodating workflows, integration of the screening tool within the electronic health record, and evidence-based interventions guided by screener results. Conclusion: Four trauma centers across Wisconsin successfully implemented a pilot opioid misuse screening tool. Trauma providers and unit staff members believe that this tool would be a beneficial addition to their repertoire if their recommendations were adopted. Future research should refine opioid misuse risk factors and ensure screening items are well-validated with psychometric research supporting treatment responses to screener-indicated risk categories.

As the opioid crisis continues to affect communities across the United States, new interventions for early screening and prevention are needed to minimize the related harms. Prior research has identified risk factors associated with opioid misuse among a trauma surgical patient population, with the highest risk associated with distress-related posttraumatic stress disorder symptoms. A pilot screening tool was created based on this prior research, which was then administered at four trauma surgical units across the state of Wisconsin. Each of the four trauma units successfully implemented the pilot screening tool, and each identified a number of facilitators and barriers to the implementation process. Recommendations for improvement of the implementation process were also gathered. If their recommended changes were to be adopted, trauma providers and trauma unit staff members believed that such a screener for opioid misuse would be a beneficial addition to their current workflow among traumatic injury patients. Future research should refine opioid misuse risk factors and develop a psychometrically sound, validated screener to detect varying levels of risk and tailor treatment approaches based on a patient's risk score. Additionally, future research in the field of opioid misuse prevention should prioritize the recruitment of a more diverse population to support the translation of study findings across populations.

Pain management in trauma: the need for trauma-informed opioid prescribing guidelines.

Background/objectives: Surgical populations and particularly injury survivors often present with complex trauma that elevates their risk for prolonged opioid use and misuse. Changes in opioid prescribing guidelines during the past several years have yielded mixed results for pain management after trauma, with a limiting factor being the heterogeneity of clinical populations and treatment needs in individuals receiving opioids. The present analysis illuminates this gap between clinical guidelines and clinical practice through qualitative feedback from hospital trauma providers and unit staff members regarding current opioid prescribing guidelines and practices in the setting of traumatic injury. Methods: The parent study aimed to implement a pilot screening tool for opioid misuse in four level I and II trauma hospitals throughout Wisconsin. As part of the parent study, focus groups were conducted at each study site to explore the facilitators and barriers of implementing a novel screening tool, as well as to examine the current opioid prescribing guidelines, trainings, and resources available for trauma and acute care providers. Focus group transcripts were independently coded and analyzed using a modified grounded theory approach to identify themes related to the facilitators and barriers of opioid prescribing guidelines in trauma and acute care. Results: Three major themes were identified as impactful to opioid-related prescribing and care provided in the setting of traumatic injury; these include (1) acute treatment strategies; (2) patient interactions surrounding pain management; and (3) the multifactorial nature of trauma on pain management approaches. Conclusion: Providers and staff at four Wisconsin trauma centers called for trauma-specific opioid prescribing guidelines in the setting of trauma and acute care. The ubiquitous prescription of opioids and challenges in long-term pain management in these settings necessitate additional community-integrated research to inform development of federal guidelines. Level of evidence: Therapeutic/care management, level V.

Effectiveness of a Maintenance and Reliever Digihaler System in Asthma: 24-Week Randomized Study (CONNECT2).

BACKGROUND: Digital health tools have been shown to help address challenges in asthma control, including inhaler technique, treatment adherence, and short-acting ß2-agonist overuse. The maintenance and reliever Digihaler System (DS) comprises 2 Digihaler inhalers (fluticasone propionate/salmeterol and albuterol) with an associated patient App and web-based Dashboard. Clinicians can review patients' inhaler use and Digihaler inhalation parameter data to support clinical decision-making. OBJECTIVE: CONNECT2 evaluated asthma control in participants using the DS versus standard-of-care (SoC) maintenance and reliever inhalers. METHODS: Participants (13 years or older) with uncontrolled asthma (Asthma Control Test [ACT] score <19) were randomized 4:3 (open-label) to the DS (n = 210) or SoC (n = 181) for 24 weeks. The primary endpoint was the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥20 or increase from baseline of ≥3 units at week 24). RESULTS: There was an 88.7% probability that participants using the DS would have greater odds of achieving improvement in asthma control compared with SoC after 24 weeks. The mean odds ratio (95% credible interval) for DS versus SoC was 1.35 (0.846-2.038), indicating a 35% higher odds of improved asthma control with the DS. The DS group had more clinician-participant interactions versus SoC, mainly addressing a poor inhaler technique. DS participants' maintenance treatment adherence was good (month 1: 79.2%; month 6: 68.6%); reliever use decreased by 38.2% versus baseline. App and Dashboard usability was rated "good." CONCLUSION: The positive results in asthma control in this study after 24 weeks demonstrate the effectiveness of the DS in asthma management.

Association of Fentanyl Test Strip Use, Perceived Overdose Risk, and Naloxone Possession among People Who Use Drugs.

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs (n = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p = 0.005), more often having multiple naloxone doses (OR: 2.98; p < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage.

Methamphetamine use and utilization of medications for opioid use disorder among rural people who use drugs.

BACKGROUND: Methamphetamine use is common among persons with opioid use disorder. This study evaluated associations between methamphetamine use and treatment with agonist medications for opioid use disorder (MOUD, specifically buprenorphine, and/or methadone) in U.S. rural communities. METHODS: The Rural Opioid Initiative (ROI) is a consortium spanning 10 states and 65 rural counties that included persons who reported past 30-day use of opioids and/or injection drug use between 1/2018 and 3/2020. Analyses were restricted to participants who had ever used opioids and had data on past 30-day methamphetamine use. Multivariable models examined the relationship between methamphetamine use and utilization of agonist MOUD. RESULTS: Among 2899 participants, 2179 (75.2%) also reported recent methamphetamine use. Persons with methamphetamine use compared to those without were younger, more likely to have injected drugs, be unhoused, criminal justice involved, and less likely to have health insurance. Adjusted for age, sex, race, and study site, recent methamphetamine use was associated with lower relative odds of past 30-day methadone treatment (aOR=0.66; 95% CI: 0.45-0.99) and fewer methadone treatment days (aIRR=0.76; 0.57-0.99), but not past 30-day buprenorphine receipt (aOR=0.90; 0.67-1.20), buprenorphine treatment days in past 6 months: aIRR=0.88; 0.69-1.12) or perceived inability to access buprenorphine (aOR=1.12; 0.87-1.44) or methadone (aOR=1.06; 0.76-1.48). CONCLUSION: Methamphetamine use is common among persons who use opioids in rural U.S. areas and negatively associated with current treatment and retention on methadone but not buprenorphine. Future studies should examine reasons for this disparity and reduce barriers to methadone for persons who use opioids and methamphetamine.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

Differences in drug use behaviors that impact overdose risk among individuals who do and do not use fentanyl test strips for drug checking.

BACKGROUND: Opioid-involved overdose continues to rise, largely explained by fentanyl adulteration of the illicit opioid supply. Fentanyl test strips are a novel drug checking tool that can be used by people who use drugs to detect the presence of fentanyl in drug products. However, it is unclear whether fentanyl test strip use can prompt behavior changes that impact risk of overdose. METHODS: In this mixed-methods study involving a structured survey (n = 341) of syringe service program clients in southern Wisconsin, we examined the association between fentanyl test strip use and overdose risk behaviors in scenarios where the presence of fentanyl is confirmed and unknown. Individual items were transformed into summary scales representing the performance of riskier and safer behaviors. Linear regression examined the association of behaviors with FTS use. Models are adjusted for study site, race/ethnicity, age, gender, drug of choice, indicator of polysubstance use, times used per day, and lifetime overdose count. RESULTS: In response to survey questions before prompting about fentanyl risk, people who used fentanyl test strips reported an increased number of safer (p = 0.001) as well as riskier behaviors (p = 0.018) relative to people who did not use fentanyl test strips. The same held true in situations when fentanyl adulteration was suspected, though fentanyl test strip use lost significance in the fully adjusted model examining safer behaviors (safer: p = 0.143; riskier: p = 0.004). Among people who use fentanyl test strips, in unadjusted models, a positive test result was associated with more safer behaviors and fewer riskier behaviors, but these associations became nonsignificant in fully adjusted models (safer: p = 0.998; riskier: p = 0.171). Loss of significance was largely due to the addition of either polysubstance use or age to the model. CONCLUSIONS: Fentanyl test strip use is associated with behaviors that may impact overdose risk, including safer and riskier behaviors. Specifically, a positive test result may promote more risk reducing behaviors and fewer risk enhancing behaviors than a negative test result. Results suggest that while FTS may promote safer drug use behaviors, outreach and education should emphasize the need for multiple harm reduction techniques in all scenarios.

Discriminative Accuracy of the CAPTURE Tool for Identifying Chronic Obstructive Pulmonary Disease in US Primary Care Settings.

Importance: Chronic obstructive pulmonary disease (COPD) is underdiagnosed in primary care. Objective: To evaluate the operating characteristics of the CAPTURE (COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk) screening tool for identifying US primary care patients with undiagnosed, clinically significant COPD. Design, Setting, and Participants: In this cross-sectional study, 4679 primary care patients aged 45 years to 80 years without a prior COPD diagnosis were enrolled by 7 primary care practice-based research networks across the US between October 12, 2018, and April 1, 2022. The CAPTURE questionnaire responses, peak expiratory flow rate, COPD Assessment Test scores, history of acute respiratory illnesses, demographics, and spirometry results were collected. Exposure: Undiagnosed COPD. Main Outcomes and Measures: The primary outcome was the CAPTURE tool's sensitivity and specificity for identifying patients with undiagnosed, clinically significant COPD. The secondary outcomes included the analyses of varying thresholds for defining a positive screening result for clinically significant COPD. A positive screening result was defined as (1) a CAPTURE questionnaire score of 5 or 6 or (2) a questionnaire score of 2, 3, or 4 together with a peak expiratory flow rate of less than 250 L/min for females or less than 350 L/min for males. Clinically significant COPD was defined as spirometry-defined COPD (postbronchodilator ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity [FEV1:FVC] <0.70 or prebronchodilator FEV1:FVC <0.65 if postbronchodilator spirometry was not completed) combined with either an FEV1 less than 60% of the predicted value or a self-reported history of an acute respiratory illness within the past 12 months. Results: Of the 4325 patients who had adequate data for analysis (63.0% were women; the mean age was 61.6 years [SD, 9.1 years]), 44.6% had ever smoked cigarettes, 18.3% reported a prior asthma diagnosis or use of inhaled respiratory medications, 13.2% currently smoked cigarettes, and 10.0% reported at least 1 cardiovascular comorbidity. Among the 110 patients (2.5% of 4325) with undiagnosed, clinically significant COPD, 53 had a positive screening result with a sensitivity of 48.2% (95% CI, 38.6%-57.9%) and a specificity of 88.6% (95% CI, 87.6%-89.6%). The area under the receiver operating curve for varying positive screening thresholds was 0.81 (95% CI, 0.77-0.85). Conclusions and Relevance: Within this US primary care population, the CAPTURE screening tool had a low sensitivity but a high specificity for identifying clinically significant COPD defined by presence of airflow obstruction that is of moderate severity or accompanied by a history of acute respiratory illness. Further research is needed to optimize performance of the screening tool and to understand whether its use affects clinical outcomes.

Clinical Trial Design Challenges and Opportunities for Emerging Treatments for Opioid Use Disorder: A Review.

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous µ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, psychedelics, sedative-hypnotics, and immunotherapeutics, such as vaccines. Observations: Consensus recommendations are presented regarding the most critical elements of trial design for the evaluation of novel OUD treatments, such as: (1) stage of treatment that will be targeted (eg, seeking treatment, early abstinence/detoxification, long-term recovery); (2) role of treatment (adjunctive with or independent of existing OUD treatments); (3) primary outcomes informed by patient preferences that assess opioid use (including changes in patterns of use), treatment retention, and/or global functioning and quality of life; and (4) adverse events, including the potential for opioid-related relapse or overdose, especially if the patient is not simultaneously taking maintenance MOR agonist or antagonist medications. Conclusions and Relevance: Applying the recommendations provided here as well as considering input from people with lived experience in the design phase will accelerate the development, translation, and uptake of effective and safe therapeutics for individuals struggling with OUD.

2020 Rossi Award Lecture: The Evolving Art of Program Evaluation.

Evaluation of public programs has undergone many changes over the past four decades since Peter Rossi coined his "Iron Law" of program evaluation: "The expected value of any net impact assessment of any large-scale social program is zero." While that assessment may be somewhat overstated, the essence still holds. The failures far outnumber the successes, and the estimated favorable effects are rarely sizeable. Despite this grim assessment, much can be learned from "failed" experiments, and from ones that are successful in only some sites or subgroups. Advances in study design, statistical models, data, and how inferences are drawn from estimates have substantially improved our analyses and will continue to do so. However, the most actual learning about "what works" (and why, when, and where) is likely to come from gathering more detailed and comprehensive data on how the intervention was implemented and attempting to link that data to estimated impacts. Researchers need detailed data on the target population served, the content of the intervention, and the process by which it is delivered to participating service providers and individuals. Two examples presented here illustrate how researchers drew useful broader lessons from impact estimates for a set of related programs. Rossi posited three reasons most interventions fail-wrong question, wrong intervention, poor implementation. Speeding the accumulation of wisdom about how social programs can best help vulnerable populations will require that researchers work closely with program funders, developers, operators, and participants to gather and interpret these detailed data about program implementation.

Characteristics and context of fentanyl test strip use among syringe service clients in southern Wisconsin.

BACKGROUND: Fentanyl adulteration of illicit drugs is a major driver of opioid-involved overdose in the USA. Fentanyl test strips are increasingly used by people who use drugs to check for fentanyl. However, little is known about factors that influence test strip use in this population. METHODS: In this mixed-methods study employing semi-structured open-ended interviews (n = 29) and a structured survey (n = 341), we examined characteristics associated with test strip use, characteristics of test strip use, and situational, logistical and psychosocial factors influencing test strip use. Respondents were recruited from a syringe service program in southern Wisconsin. Bivariate tests of association and multivariable logistic regression examined the relationship between respondent characteristics and test strip use. Summary statistics were used to describe how situational, logistical and psychosocial factors impact test strip use. RESULTS: Most respondents were male (59.6%), non-Hispanic white (77.4%), young (mean 35.7 years), reported heroin as their primary drug (70.7%), injection as their primary route (87.9%), and use ≥ 3 times daily (78.6%). In multivariable models, site, race and ethnicity, drug of choice, and seeking fentanyl were associated with test strip use. Among test strip users, 36.5% use them most of the time or more and 80.6% get positive results half the time or more. Among individuals reporting heroin, fentanyl, methamphetamine, or cocaine or crack cocaine at least once per month, 99.1%, 56.8%, 42.2%, and 55.7% reported testing these drugs, respectively. Test strip use is supported by information from suppliers, regular transportation, diverse distribution locations, recommendations from harm reduction staff, and having a safe or private place to use. CONCLUSIONS: We found that individuals who use fentanyl test strips are more often non-Hispanic white, use heroin, and seek drugs with fentanyl relative to individuals without test strip use. Findings confirm high fentanyl penetration in the Wisconsin drug supply. Low rates of stimulant testing suggest inadequate awareness of fentanyl penetration. Findings support outreach to key populations, increased diversity of distributing locations, efforts to correct misperceptions about drug wasting, emphasis on pre-consumption testing, and the importance of adjunct behaviors to prevent overdose given high rates of intentional fentanyl use.

A Predictive Machine Learning Tool for Asthma Exacerbations: Results from a 12-Week, Open-Label Study Using an Electronic Multi-Dose Dry Powder Inhaler with Integrated Sensors.

Purpose: Machine learning models informed by sensor data inputs have the potential to provide individualized predictions of asthma deterioration. This study aimed to determine if data from an integrated digital inhaler could be used to develop a machine learning model capable of predicting impending exacerbations. Patients and Methods: Adult patients with poorly controlled asthma were enrolled in a 12-week, open-label study using ProAir® Digihaler®, an electronic multi-dose dry powder inhaler (eMDPI) with integrated sensors, as reliever medication (albuterol, 90 µg/dose; 1-2 inhalations every 4 hours, as needed). Throughout the study, the eMDPI recorded inhaler use, peak inspiratory flow (PIF), inhalation volume, inhalation duration, and time to PIF. A model predictive of impending exacerbations was generated by applying machine learning techniques to data downloaded from the inhalers, together with clinical and demographic information. The generated model was evaluated by receiver operating characteristic area under curve (ROC AUC) analysis. Results: Of 360 patients included in the predictive analysis, 64 experienced a total of 78 exacerbations. Increased albuterol use preceded exacerbations; the mean number of inhalations in the 24-hours preceding an exacerbation was 7.3 (standard deviation 17.3). The machine learning model, using gradient-boosting trees with data from the eMDPI and baseline patient characteristics, predicted an impending exacerbation over the following 5 days with an ROC AUC of 0.83 (95% confidence interval: 0.77-0.90). The feature of the model with the highest weight was the mean number of daily inhalations during the 4 days prior to the day the prediction was made. Conclusion: A machine learning model to predict impending asthma exacerbations using data from the eMDPI was successfully developed. This approach may support a shift from reactive care to proactive, preventative, and personalized management of chronic respiratory diseases.

Association between spine injury and opioid misuse in a prospective cohort of Level I trauma patients.

Objective: To explore patient and treatment factors explaining the association between spine injury and opioid misuse. Design: Prospective cohort study. Setting: Level I trauma center in a Midwestern city. Participants: English speaking patients aged 18 to 75 on Trauma and Orthopedic Surgical Services receiving opioids during hospitalization and prescribed at discharge. Exposure: Spine injury on the Abbreviated Injury Scale. Main outcome measures: Opioid misuse was defined by using opioids: in a larger dose, more often, or longer than prescribed; via a non-prescribed route; from someone other than a prescriber; and/or use of heroin or opium. Exploratory factor groups included demographic, psychiatric, pain, and treatment factors. Multivariable logistic regression estimated the association between spine injury and opioid misuse when adjusting for each factor group. Results: Two hundred eighty-five eligible participants consented of which 258 had baseline injury location data and 224 had follow up opioid misuse data. Most participants were male (67.8%), white (85.3%) and on average 43.1 years old. One-quarter had a spine injury (25.2%). Of those completing follow-up measures, 14 (6.3%) developed misuse. Treatment factors (injury severity, intubation, and hospital length of stay) were significantly associated with spine injury. Spine injury significantly predicted opioid misuse [odds ratio [OR] 3.20, 95% confidence interval [CI] (1.05, 9.78)]. In multivariable models, adjusting for treatment factors attenuated the association between spine injury and opioid misuse, primarily explained by length of stay. Conclusion: Spine injury exhibits a complex association with opioid misuse that predominantly operates through treatment factors. Spine injury patients may represent a subpopulation requiring early intervention to prevent opioid misuse.

Association of Methamphetamine and Opioid Use With Nonfatal Overdose in Rural Communities.

Importance: Overdoses continue to increase in the US, but the contribution of methamphetamine use is understudied in rural communities. Objective: To estimate the prevalence of methamphetamine use and its correlates among people who use drugs (PWUD) in rural US communities and to determine whether methamphetamine use is associated with increased nonfatal overdoses. Design, Setting, and Participants: From January 2018 through March 2020, the National Rural Opioid Initiative conducted cross-sectional surveys of PWUD in rural communities in 10 states (Illinois, Kentucky, New Hampshire, Massachusetts, North Carolina, Ohio, Oregon, Vermont, West Virginia, and Wisconsin). Participants included rural PWUD who reported any past-30-day injection drug use or noninjection opioid use to get high. A modified chain-referral sampling strategy identified seeds who referred others using drugs. Data analysis was performed from May 2021 to January 2022. Exposures: Use of methamphetamine alone, opioids alone, or both. Main Outcomes and Measures: Unweighted and weighted prevalence of methamphetamine use, any past-180-day nonfatal overdose, and number of lifetime nonfatal overdoses. Results: Among the 3048 participants, 1737 (57%) were male, 2576 (85%) were White, and 225 (7.4%) were American Indian; the mean (SD) age was 36 (10) years. Most participants (1878 of 2970 participants with any opioid or methamphetamine use [63%]) reported co-use of methamphetamine and opioids, followed by opioids alone (702 participants [24%]), and methamphetamine alone (390 participants [13%]). The estimated unweighted prevalence of methamphetamine use was 80% (95% CI, 64%-90%), and the estimated weighted prevalence was 79% (95% CI, 57%-91%). Nonfatal overdose was greatest in people using both methamphetamine and opioids (395 of 2854 participants with nonmissing overdose data [22%]) vs opioids alone (99 participants [14%]) or methamphetamine alone (23 participants [6%]). Co-use of methamphetamine and opioids was associated with greater nonfatal overdose compared with opioid use alone (adjusted odds ratio, 1.45; 95% CI, 1.08-1.94; P = .01) and methamphetamine use alone (adjusted odds ratio, 3.26; 95% CI, 2.06-5.14; P < .001). Those with co-use had a mean (SD) of 2.4 (4.2) (median [IQR], 1 [0-3]) lifetime overdoses compared with 1.7 (3.5) (median [IQR], 0 [0-2]) among those using opioids alone (adjusted rate ratio, 1.20; 95% CI, 1.01-1.43; P = .04), and 1.1 (2.9) (median [IQR], 0 [0-1]) among those using methamphetamine alone (adjusted rate ratio, 1.81; 95% CI, 1.45-2.27; P < .001). Participants with co-use most often reported having tried and failed to access substance use treatment: 827 participants (44%) for both, 117 participants (30%) for methamphetamine alone, and 252 participants (36%) for opioids alone (χ22 = 33.8; P < .001). Only 66 participants (17%) using methamphetamine alone had naloxone. Conclusions and Relevance: These findings suggest that harm reduction and substance use disorder treatment interventions must address both methamphetamine and opioids to decrease overdose in rural communities.

Assessment of Real-World Escalation to Biologics in US Patients With Asthma.

BACKGROUND: Previous studies indicate that suboptimal medication adherence may contribute to uncontrolled asthma. Global Initiative for Asthma (GINA) guidelines recommend treatment escalation to biologics for patients with uncontrolled asthma despite adherence to high-dose maintenance medication and who have eosinophilic/allergic biomarkers or require maintenance oral corticosteroids. OBJECTIVE: This study aimed to describe the clinical status of patients with asthma escalated to biologic therapy. METHODS: This retrospective claims database analysis enrolled US patients with asthma who were escalated to biologics between January 2016 and June 2020. Exacerbations, control status, GINA step, and maintenance medication adherence during the 12 months before biologic therapy initiation were analyzed. Asthma control was assessed using both the European Respiratory Society/American Thoracic Society (ERS/ATS) and Stempel criteria. Adherence was defined as the proportion of days covered (PDC) by maintenance medication claims. RESULTS: Of 1786 patients escalated to biologics, 506 were included for analysis. During the 12 months before escalation, 346 patients had confirmed exacerbations. Uncontrolled asthma status was estimated in 55% and 70% of patients (ERS/ATS and Stempel criteria, respectively). GINA step was inferred for 395 patients: 154 were at step 2, 11 at step 3, 104 at step 4, and 126 at step 5. Of 403 patients with maintenance medication claims, 63% had suboptimal maintenance medication adherence (PDC <80%). CONCLUSION: In this study, most patients initiating biologic therapy had mild-to-moderate asthma or suboptimal maintenance medication adherence, possibly indicating inappropriate escalation. Incorporating objective medication adherence monitoring into existing guidelines may reduce inappropriate escalation to biologics.

Effectiveness of a Digital Inhaler System for Patients With Asthma: A 12-Week, Open-Label, Randomized Study (CONNECT1).

BACKGROUND: The albuterol Digihaler (albuterol 90 µg/dose) transmits data wirelessly to a smart device application, which synchronizes with a Digital Health Platform to store and transfer data to a web-based Dashboard. The Reliever Digihaler System (RDS) comprises the albuterol Digihaler, application, Digital Health Platform and Dashboard. This allows patients and health care professionals to review reliever inhaler usage and inhalation quality to aid clinical decision making. OBJECTIVE: To demonstrate the effectiveness, as measured by change in asthma control, of the RDS compared with standard of care. METHODS: In this 12-week study, participants aged 13 years or older with suboptimal asthma control (Asthma Control Test [ACT] score < 19) were randomized to use either RDS or standard of care albuterol reliever inhalers. The health care professionals were recommended at study start to check each participant's inhalation data (including inhalation quantity and quality parameters) 1 or more times per week. Primary outcome was the proportion of participants achieving clinically meaningful improvement in asthma control (ACT score ≥ 20 at week 12 and/or increase ≥ 3 units from baseline). Bayesian statistical analysis provided a posterior probability distribution for odds ratios with corresponding credible intervals. RESULTS: Participants using the RDS (n = 167) had an 85.3% probability of greater odds of clinically meaningful asthma control improvements than those using SoC (n = 166) after 3 months (mean odds ratio 1.33; 95% credible interval 0.813-2.050). CONCLUSIONS: In this study, participants using the RDS had greater odds of clinically meaningful improvements in asthma control versus SoC after 3 months. Further investigation of the potential of the RDS to help improve asthma management is warranted.

Development and multimodal validation of a substance misuse algorithm for referral to treatment using artificial intelligence (SMART-AI): a retrospective deep learning study.

BACKGROUND: Substance misuse is a heterogeneous and complex set of behavioural conditions that are highly prevalent in hospital settings and frequently co-occur. Few hospital-wide solutions exist to comprehensively and reliably identify these conditions to prioritise care and guide treatment. The aim of this study was to apply natural language processing (NLP) to clinical notes collected in the electronic health record (EHR) to accurately screen for substance misuse. METHODS: The model was trained and developed on a reference dataset derived from a hospital-wide programme at Rush University Medical Center (RUMC), Chicago, IL, USA, that used structured diagnostic interviews to manually screen admitted patients over 27 months (between Oct 1, 2017, and Dec 31, 2019; n=54 915). The Alcohol Use Disorder Identification Test and Drug Abuse Screening Tool served as reference standards. The first 24 h of notes in the EHR were mapped to standardised medical vocabulary and fed into single-label, multilabel, and multilabel with auxillary-task neural network models. Temporal validation of the model was done using data from the subsequent 12 months on a subset of RUMC patients (n=16 917). External validation was done using data from Loyola University Medical Center, Chicago, IL, USA between Jan 1, 2007, and Sept 30, 2017 (n=1991 adult patients). The primary outcome was discrimination for alcohol misuse, opioid misuse, or non-opioid drug misuse. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Calibration slope and intercept were measured with the unreliability index. Bias assessments were performed across demographic subgroups. FINDINGS: The model was trained on a cohort that had 3·5% misuse (n=1 921) with any type of substance. 220 (11%) of 1921 patients with substance misuse had more than one type of misuse. The multilabel convolutional neural network classifier had a mean AUROC of 0·97 (95% CI 0·96-0·98) during temporal validation for all types of substance misuse. The model was well calibrated and showed good face validity with model features containing explicit mentions of aberrant drug-taking behaviour. A false-negative rate of 0·18-0·19 and a false-positive rate of 0·03 between non-Hispanic Black and non-Hispanic White groups occurred. In external validation, the AUROCs for alcohol and opioid misuse were 0·88 (95% CI 0·86-0·90) and 0·94 (0·92-0·95), respectively. INTERPRETATION: We developed a novel and accurate approach to leveraging the first 24 h of EHR notes for screening multiple types of substance misuse. FUNDING: National Institute On Drug Abuse, National Institutes of Health.