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A Clinical Guide to Support the Implementation of Addiction Consult Services and the Value of Teaching and Technical Assistance

Fielman, Sarah; McNeely, Jennifer; Fitzpatrick, Amy; Kerensky, Todd; Tomanovich, Mary; Walley, Alexander Y; Kosakowski, Sarah; King, Carla; Appleton, Noa; Weinstein, Zoe M
People with substance use disorders (SUDs) are increasingly admitted to general hospitals; however, many hospital systems lack both formal structures and skilled staff to provide high-quality care for inpatients with SUDs. Inpatient addiction consult services (ACSs), which are increasingly being implemented around the country, are an evidence-based strategy to add focused care for people with SUDs into the general medical setting. In 2018, New York City Health + Hospitals (H + H) launched an ACS program called Consult for Addiction Care and Treatment in Hospitals in six hospitals, supported by a team of addiction consult experts to deliver teaching and technical assistance (TTA) for the Consult for Addiction Care and Treatment in Hospitals ACSs. This commentary describes the TTA, which included site visits, introductory educational lectures, case conferences, ad hoc support, implementation assistance, and the creation of an addiction care guide. Similar TTA services could be used in the future when hospitals or systems want to launch novel clinical programs.
PMID: 38498619
ISSN: 1935-3227
CID: 5640162

Strategies to improve delivery of equitable and evidence-informed care for pregnant and birthing people with a substance use disorder in acute care settings: A scoping review protocol

King, Carla; Laynor, Gregory; McNeely, Jennifer; Fawole, Adetayo; Lee, Matthew; Terplan, Mishka; Choi, Sugy
This protocol outlines a proposed scoping review to characterize evidence on implementation and quality improvement (QI) strategies that aim to improve equitable, evidence-informed care delivery for pregnant and birthing people with substance use disorder (SUD) in acute care. Untreated SUD during pregnancy is associated with an increased risk of overdose and severe maternal morbidity. Acute care settings are one important place to deliver equitable, evidence-informed clinical care. While clinical practice guidelines for substance use treatment and care of pregnant and birthing people with SUD exist, there are gaps in implementation. Our population of interest is pregnant and birthing people with SUD in an acute care setting. We will include US-based studies that describe or evaluate implementation or QI strategies, including experimental, observational, and descriptive studies published from 2016 to 2023. The proposed scoping review will be conducted in accordance with JBI methodology for scoping reviews and registered at OSF (registration number: BC4VZ). We will search MEDLINE (PubMed), CINAHL Complete (EBSCO), Scopus (Elsevier), and APA PsychInfo (Ovid) for published studies. Conference proceedings and Perinatal Quality Collaborative websites will be searched for grey literature. Two reviewers will independently screen then extract studies that meet inclusion criteria using a data extraction tool. The completion of this scoping review will help illuminate strengths and gaps in research and practice that aim to inform substance use treatment and care in acute care settings for pregnant and birthing people with SUD.
PMCID:10947689
PMID: 38498563
ISSN: 1932-6203
CID: 5640152

Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy

Mukhopadhyay, Suman; Huang, Hsin-Yi; Lin, Ziyan; Ranieri, Michela; Li, Shuai; Sahu, Soumyadip; Liu, Yingzhuo; Ban, Yi; Guidry, Kayla; Hu, Hai; Lopez, Alfonso; Sherman, Fiona; Tan, Yi Jer; Lee, Yeuan Ting; Armstrong, Amanda P; Dolgalev, Igor; Sahu, Priyanka; Zhang, Tinghu; Lu, Wenchao; Gray, Nathanael S; Christensen, James G; Tang, Tracy T; Velcheti, Vamsidhar; Khodadadi-Jamayran, Alireza; Wong, Kwok-Kin; Neel, Benjamin G
UNLABELLED:Non-small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines. Recurrent, potentially targetable, synthetic lethal (SL) genes were identified, including serine-threonine kinases, tRNA-modifying and proteoglycan synthesis enzymes, and YAP/TAZ/TEAD pathway components. Several SL genes were confirmed by siRNA/shRNA experiments, and the YAP/TAZ/TEAD pathway was extensively validated in vitro and in mice. Mechanistic studies showed that G12Ci treatment induced gene expression of RHO paralogs and activators, increased RHOA activation, and evoked ROCK-dependent nuclear translocation of YAP. Mice and patients with acquired G12Ci- or G12Ci/SHP2i-resistant tumors showed strong overlap with SL pathways, arguing for the relevance of the screen results. These findings provide a landscape of potential targets for future combination strategies, some of which can be tested rapidly in the clinic. SIGNIFICANCE/UNASSIGNED:Identification of synthetic lethal genes with KRASG12C using genome-wide CRISPR/Cas9 screening and credentialing of the ability of TEAD inhibition to enhance KRASG12C efficacy provides a roadmap for combination strategies. See related commentary by Johnson and Haigis, p. 4005.
PMID: 37729426
ISSN: 1538-7445
CID: 5606372

Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial [Comment]

Wartko, Paige D; Bobb, Jennifer F; Boudreau, Denise M; Matthews, Abigail G; McCormack, Jennifer; Lee, Amy K; Qiu, Hongxiang; Yu, Onchee; Hyun, Noorie; Idu, Abisola E; Campbell, Cynthia I; Saxon, Andrew J; Liu, David S; Altschuler, Andrea; Samet, Jeffrey H; Labelle, Colleen T; Zare-Mehrjerdi, Mohammad; Stotts, Angela L; Braciszewski, Jordan M; Murphy, Mark T; Dryden, Douglas; Arnsten, Julia H; Cunningham, Chinazo O; Horigian, Viviana E; Szapocznik, José; Glass, Joseph E; Caldeiro, Ryan M; Phillips, Rebecca C; Shea, Mary; Bart, Gavin; Schwartz, Robert P; McNeely, Jennifer; Liebschutz, Jane M; Tsui, Judith I; Merrill, Joseph O; Lapham, Gwen T; Addis, Megan; Bradley, Katharine A; ,; Ghiroli, Megan M; Hamilton, Leah K; Hu, Yong; LaHue, Jennifer S; Loree, Amy M; Murphy, Sean M; Northrup, Thomas F; Shmueli-Blumberg, Dikla; Silva, Angela J; Weinstein, Zoe M; Wong, Mark TinFook; Burganowski, Rachael P
IMPORTANCE/UNASSIGNED:Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. OBJECTIVE/UNASSIGNED:To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. INTERVENTION/UNASSIGNED:The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. RESULTS/UNASSIGNED:During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03407638.
PMID: 37902748
ISSN: 2168-6114
CID: 5590292

Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods

Liebschutz, Jane M; Subramaniam, Geetha A; Stone, Rebecca; Appleton, Noa; Gelberg, Lillian; Lovejoy, Travis I; Bunting, Amanda M; Cleland, Charles M; Lasser, Karen E; Beers, Donna; Abrams, Catherine; McCormack, Jennifer; Potter, Gail E; Case, Ashley; Revoredo, Leslie; Jelstrom, Eve M; Kline, Margaret M; Wu, Li-Tzy; McNeely, Jennifer
BACKGROUND:Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS:The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population. DISCUSSION:Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population. TRIAL REGISTRATION:Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.
PMCID:10657560
PMID: 37980494
ISSN: 1940-0640
CID: 5608242

Strategies to support substance use disorder care transitions from acute-care to community-based settings: a scoping review and typology

Krawczyk, Noa; Rivera, Bianca D; Chang, Ji E; Grivel, Margaux; Chen, Yu-Heng; Nagappala, Suhas; Englander, Honora; McNeely, Jennifer
BACKGROUND:Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. METHODS:We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000 and 2021 that studied interventions linking patients with SUD from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. RESULTS:Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) or alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. CONCLUSIONS:Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.
PMID: 37919755
ISSN: 1940-0640
CID: 5609752

Implementation of substance use screening in rural federally-qualified health center clinics identified high rates of unhealthy alcohol and cannabis use among adult primary care patients

McNeely, Jennifer; McLeman, Bethany; Gardner, Trip; Nesin, Noah; Amarendran, Vijay; Farkas, Sarah; Wahle, Aimee; Pitts, Seth; Kline, Margaret; King, Jacquie; Rosa, Carmen; Marsch, Lisa; Rotrosen, John; Hamilton, Leah
BACKGROUND:Screening for substance use in rural primary care clinics faces unique challenges due to limited resources, high patient volumes, and multiple demands on providers. To explore the potential for electronic health record (EHR)-integrated screening in this context, we conducted an implementation feasibility study with a rural federally-qualified health center (FQHC) in Maine. This was an ancillary study to a NIDA Clinical Trials Network study of screening in urban primary care clinics (CTN-0062). METHODS:Researchers worked with stakeholders from three FQHC clinics to define and implement their optimal screening approach. Clinics used the Tobacco, Alcohol, Prescription Medication, and Other Substance (TAPS) Tool, completed on tablet computers in the waiting room, and results were immediately recorded in the EHR. Adult patients presenting for annual preventive care visits, but not those with other visit types, were eligible for screening. Data were analyzed for the first 12 months following implementation at each clinic to assess screening rates and prevalence of reported unhealthy substance use, and documentation of counseling using an EHR-integrated clinical decision support tool, for patients screening positive for moderate-high risk alcohol or drug use. RESULTS:Screening was completed by 3749 patients, representing 93.4% of those with screening-eligible annual preventive care visits, and 18.5% of adult patients presenting for any type of primary care visit. Screening was self-administered in 92.9% of cases. The prevalence of moderate-high risk substance use detected on screening was 14.6% for tobacco, 30.4% for alcohol, 10.8% for cannabis, 0.3% for illicit drugs, and 0.6% for non-medical use of prescription drugs. Brief substance use counseling was documented for 17.4% of patients with any moderate-high risk alcohol or drug use. CONCLUSIONS:Self-administered EHR-integrated screening was feasible to implement, and detected substantial alcohol, cannabis, and tobacco use in rural FQHC clinics. Counseling was documented for a minority of patients with moderate-high risk use, possibly indicating a need for better support of primary care providers in addressing substance use. There is potential to broaden the reach of screening by offering it at routine medical visits rather than restricting to annual preventive care visits, within these and other rural primary care clinics.
PMCID:10510292
PMID: 37726839
ISSN: 1940-0640
CID: 5610272

Effect of a smartphone intervention as a secondary prevention for use among university students with unhealthy alcohol use: randomised controlled trial

Bertholet, Nicolas; Schmutz, Elodie; Studer, Joseph; Adam, Angéline; Gmel, Gerhard; Cunningham, John A; McNeely, Jennifer; Daeppen, Jean-Bernard
OBJECTIVE:To estimate the effects of providing access to an alcohol intervention based on a smartphone. DESIGN:Randomised controlled trial.. SETTING:Four higher education institutions in Switzerland. PARTICIPANTS:1770 students (≥18 years) who screened positive for unhealthy alcohol use (ie, a score on the alcohol use disorders identification test-consumption (AUDIT-C) of ≥4 for men and ≥3 for women) were randomly assigned by 1:1 allocation ratio in blocks of 10. INTERVENTION:Providing access to a brief, smartphone based alcohol intervention. OUTCOME MEASURES:six months), and baseline outcome values as fixed effects. RESULTS:Between 26 April 26 2021 and 30 May 2022, 1770 participants (intervention group (n=884); control group (n=886)) were included. Mean age was 22.4 years (standard deviation 3.07); 958 (54.1%) were women; and 1169 (66.0%) were undergraduate students, 533 (30.1%) were studying for a master's degree, 43 (2.4%) were studying for a doctorate, and 25 (1.4%) were students of other higher education programme. The baseline mean number of standard drinks per week was 8.59 (standard deviation 8.18); the baseline number of heavy drinking days was 3.53 (4.02). Of 1770 participants, follow-up rates were 1706 (96.4%) at three months, 1697 (95.9%) at six months, and 1660 (93.8%) at 12 months. Of 884 students randomly assigned to the intervention group, 738 (83.5%) downloaded the smartphone application. The intervention had a significant overall effect on the number of standard drinks per week (incidence rate ratio 0.90 (95% confidence interval 0.85 to 0.96)), heavy drinking days (0.89 (0.83 to 0.96)), and the maximum number of drinks consumed on one occasion (0.96 (0.93 to 1.00), P=0.029), indicating significantly lower drinking outcomes in the intervention group than in the control group during the follow-up period. The intervention did not affect alcohol related consequences or academic performance. CONCLUSIONS:Providing access to the smartphone application throughout the 12 month follow-up was effective at limiting the average drinking volume of university students who had self-reported unhealthy alcohol use at baseline. TRIAL REGISTRATION:ISRCTN 10007691.
PMCID:10428135
PMID: 37586742
ISSN: 1756-1833
CID: 5595772

Strategies to support substance use disorder care transitions from acute-care to community-based settings: A Scoping review and typology

Krawczyk, Noa; Rivera, Bianca D; Chang, Ji E; Grivel, Margaux; Chen, Yu-Heng; Nagappala, Suhas; Englander, Honora; McNeely, Jennifer
BACKGROUND/UNASSIGNED:Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. METHODS/UNASSIGNED:We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000-2021 that studied interventions linking SUD patients from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. RESULTS/UNASSIGNED:Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) followed by alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. CONCLUSIONS/UNASSIGNED:Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.
PMID: 37162840
CID: 5599082

Proteomic Dynamics of Breast Cancer Cell Lines Identifies Potential Therapeutic Protein Targets

Sun, Rui; Ge, Weigang; Zhu, Yi; Sayad, Azin; Luna, Augustin; Lyu, Mengge; Liang, Shuang; Tobalina, Luis; Rajapakse, Vinodh N; Yu, Chenhuan; Zhang, Huanhuan; Fang, Jie; Wu, Fang; Xie, Hui; Saez-Rodriguez, Julio; Ying, Huazhong; Reinhold, William C; Sander, Chris; Pommier, Yves; Neel, Benjamin G; Aebersold, Ruedi; Guo, Tiannan
Treatment and relevant targets for breast cancer (BC) remain limited, especially for triple-negative BC (TNBC). We identified 6091 proteins of 76 human BC cell lines using data-independent acquisition (DIA). Integrating our proteomic findings with prior multi-omics datasets, we found that including proteomics data improved drug sensitivity predictions and provided insights into the mechanisms of action. We subsequently profiled the proteomic changes in nine cell lines (five TNBC and four non-TNBC) treated with EGFR/AKT/mTOR inhibitors. In TNBC, metabolism pathways were dysregulated after EGFR/mTOR inhibitor treatment, while RNA modification and cell cycle pathways were affected by AKT inhibitor. This systematic multi-omics and in-depth analysis of the proteome of BC cells can help prioritize potential therapeutic targets and provide insights into adaptive resistance in TNBC.
PMID: 37343696
ISSN: 1535-9484
CID: 5542772