A Quality Framework for Emergency Department Treatment of Opioid Use Disorder.

Emergency clinicians are on the front lines of responding to the opioid epidemic and are leading innovations to reduce opioid overdose deaths through safer prescribing, harm reduction, and improved linkage to outpatient treatment. Currently, there are no nationally recognized quality measures or best practices to guide emergency department quality improvement efforts, implementation science researchers, or policymakers seeking to reduce opioid-associated morbidity and mortality. To address this gap, in May 2017, the National Institute on Drug Abuse's Center for the Clinical Trials Network convened experts in quality measurement from the American College of Emergency Physicians' (ACEP's) Clinical Emergency Data Registry, researchers in emergency and addiction medicine, and representatives from federal agencies, including the National Institute on Drug Abuse and the Centers for Medicare & Medicaid Services. Drawing from discussions at this meeting and with experts in opioid use disorder treatment and quality measure development, we developed a multistakeholder quality improvement framework with specific structural, process, and outcome measures to guide an emergency medicine agenda for opioid use disorder policy, research, and clinical quality improvement.

Tools to implement measurement-based care (MBC) in the treatment of opioid use disorder (OUD): toward a consensus.

BACKGROUND: The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fail. In other fields such as depression, brief measures to address these tasks combined with an action plan-so-called measurement-based care (MBC)-have been associated with better outcomes. This workgroup aimed to determine whether brief measures can be identified for using MBC for optimizing dosing or informing treatment decisions in OUD. METHODS: The National Institute on Drug Abuse Center for the Clinical Trials Network (NIDA CCTN) in 2022 convened a small workgroup to develop consensus about clinically usable measures to improve the quality of treatment delivery with MBC methods for OUD. Two clinical tasks were addressed: (1) to identify the optimal dose of medications for OUD for each patient and (2) to estimate the effectiveness of a treatment for a particular patient once implemented, in a more granular fashion than the binary categories of early or sustained remission or no remission found in The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). DISCUSSION: Five parameters were recommended to personalize medication dose adjustment: withdrawal symptoms, opioid use, magnitude (severity and duration) of the subjective effects when opioids are used, craving, and side effects. A brief rating of each OUD-specific parameter to adjust dosing and a global assessment or verbal question for side-effects was viewed as sufficient. Whether these ratings produce better outcomes (e.g., treatment engagement and retention) in practice deserves study. There was consensus that core signs and symptoms of OUD based on some of the 5 DSM-5 domains (e.g., craving, withdrawal) should be the basis for assessing treatment outcome. No existing brief measure was found to meet all the consensus recommendations. Next steps would be to select, adapt or develop de novo items/brief scales to inform clinical decision-making about dose and treatment effectiveness. Psychometric testing, assessment of acceptability and whether the use of such scales produces better symptom control, quality of life (QoL), daily function or better prognosis as compared to treatment as usual deserves investigation.

Sex differences in weight gain during medication-based treatment for opioid use disorder: A meta-analysis and retrospective analysis of clinical trial data.

BACKGROUND: Side effects of medications for opioid use disorder (MOUD) such as weight gain contribute to their stigma. Substantial evidence suggests that women have a more severe side effect profile to MOUD than men, and concerns about weight gain during treatment are prevalent. However, the few studies reporting sex differences in weight gain during treatment show conflicting results and are restricted to methadone. In addition, little is known about possible sex differences in weight gain to buprenorphine, which is the most commonly prescribed MOUD in the United States. METHODS: To address these issues, we performed a systematic review and meta-analysis on the few studies reporting longitudinal data on sex differences in body mass index (BMI) gain during methadone treatment (Study 1). In a separate study, we also re-analyzed data from trial CTN-0030 of the National Institute on Drug Abuse Clinical Trial Network (NIDA CTN), which involved a 12-week buprenorphine treatment regimen (Study 2; n = 360; 209 Male, 151 Female). RESULTS: For Study 1, across all papers reporting longitudinal data (k = 4, n = 362 OUD patients), there were BMI increases that ranged from 2.2 to 5.4 BMI after at least one year of methadone treatment, but there were no significant sex differences in BMI increases (Standardized Mean Difference, Female > Male = 0.352, SE =0.270; 95 % CI = [-0.18 0.88]; p = .193). Study 2 showed no significant differences in weight before and after 12 weeks of buprenorphine treatment nor did it show sex differences in weight change with treatment (ß = 2.34, p = .511). CONCLUSION: These analyses corroborate evidence of weight gain with methadone treatment but did not observe a sex-based disparity in weight gain with methadone or buprenorphine treatment for OUD.

The NIDA clinical trials network: evolving, expanding, and addressing the opioid epidemic.

Over the past two decades, the National Drug Abuse Treatment Clinical Trials Network (CTN), a program of the National Institute on Drug Abuse (NIDA), has expanded from the initial six Nodes to 16 Nodes, as a nationwide consortium of research scientists and treatment providers working together to improve care for substance use in the nation's communities. Encompassing both specialty care programs and general medical settings, the Network has become a unique resource for expertise on clinically focused research, bridging the gap between research and treatment delivery. Over 22 years, the CTN has completed 101 studies, resulting in 650 publications. In response to the opioid epidemic, a CTN task force generated a comprehensive list of research priorities in the areas of prevention, treatment, knowledge dissemination, and workforce training, to form the basis of the Network's opioid portfolio. The Network's opioid portfolio currently includes five main categories of studies: (1) large multi-site studies; (2) studies aimed at closing the treatment gap; (3) expansion of ongoing studies to improve service delivery and implementation; (4) studies to explore the use of substance use data in electronic health record systems; (5) training and dissemination projects to expand the research/health care provider workforce. With funding from the Helping to End Addiction Long-Term InitiativeSM (HEAL), the CTN established five new Nodes, which, along with the pre-existing Nodes, are distributed in every region of the nation and engage researchers and clinicians in areas that have been among the hardest hit by the opioid epidemic. Through this expanded network and its commitment to developing personalized, evidence-based treatments, the CTN is poised to address and provide solutions for the ongoing epidemic of opioid use and addiction.

Prevalence of obesity among U.S. population with substance dependence.

AIM: To investigate associations between substance dependence and obesity. METHODS: Obesity (body mass index ≥ 30 kg/m2) status and the status of dependence on heroin, stimulant, marijuana, nicotine and alcohol (past-month status for nicotine and past-year status for all others) were identified from the U.S. National Survey on Drug Use and Health (NSDUH, 2015-2017) datasets. SAS Surveylogistic regression was used to estimate adjusted odds ratio (AOR) for the association between each substance dependence and obesity, adjusting for potentially confounding effects of sociodemographic factors and health condition. RESULTS: It was estimated that 10.6 % of noninstitutional U.S. residents aged 12 years or older were nicotine-dependent, 3.0 % alcohol-dependent, 1.0 % marijuana-dependent, 0.6 % stimulant-dependent, and 0.2 % heroin-dependent. Heroin-dependent individuals had 59 % lower odds of obesity relative to their non-dependent counterparts (AOR = 0.41; 95 % CI: 0.28-0.60; p < 0.0001). Lower odds of obesity were also noted for marijuana-dependent (AOR = 0.64; 95 % CI: 0.56-0.73; p < 0.0001), nicotine-dependent (AOR = 0.68; 95 % CI: 0.64-0.72; p < 0.0001) and alcohol-dependent (AOR = 0.77, 95 % CI: 0.69-0.84; p < 0.0001) individuals, but not statistically significant for stimulant-dependent individuals (AOR = 0.84; 95 % CI: 0.68-1.02; p = 0.0825). CONCLUSIONS: Heroin, marijuana, nicotine and alcohol dependence were associated with lower odds of obesity than their non-dependence counterparts. Main findings based on 2015-2017 NSDUH are consistent with findings from our prior report based on clinical trials data from National Institute on Drug Abuse Clinical Trials Network, and other epidemiological evidence in the literature. These findings can alert substance abuse treatment professionals to monitor weight change, especially among weight-concerned substance abusers.

Measurement-based care using DSM-5 for opioid use disorder: can we make opioid medication treatment more effective?

CONTEXT AND PURPOSE: Measurement-based care (MBC) is an evidence-based health-care practice in which indicators of disease are tracked to inform clinical actions, provide feedback to patients and improve outcomes. The current opioid crisis in multiple countries provides a pressing rationale for adopting a basic MBC approach for opioid use disorder (OUD) using DSM-5 to increase treatment retention and effectiveness. PROPOSAL: To stimulate debate, we propose a basic MBC approach using the 11 symptoms of OUD (DSM-5) to inform the delivery of medications for opioid use disorder (MOUD; including methadone, buprenorphine and naltrexone) and their evaluation in office-based primary care and specialist clinics. Key features of a basic MBC approach for OUD using DSM-5 are described, with an illustration of how clinical actions are guided and outcomes communicated. For core treatment tasks, we propose that craving and drug use response to MOUD should be assessed after 2 weeks, and OUD remission status should be evaluated at 3, 6 and 12 months (and exit from MOUD treatment) and beyond. Each of the 11 DSM-5 symptoms of OUD should be discussed with the patient to develop a case formulation and guide selection of adjunctive psychological interventions, supplemented with information on substance use, and optionally extended with information from other clinical instruments. A patient-reported outcome measure should be recorded and discussed at each remission assessment. CONCLUSIONS: MBC can be used to tailor and adapt MOUD treatment to increase engagement, retention and effectiveness. MBC practice principles can help promote patient-centred care in OUD, personalized addiction therapeutics and facilitate communication of outcomes.

Prevalence of obesity for opioid- and stimulant-dependent participants in substance use treatment clinical trials.

AIMS: To estimate obesity prevalence among drug-dependent individuals and to compare prevalence across different types of drug dependence. METHODS: 1596 opioid- and/or stimulant-dependent participants were extracted from six clinical trials within the National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse (NIDA CTN) to estimate obesity prevalence among drug-dependent users. Age-, sex-, and race-matched National Health and Nutrition Examination Survey (NHANES) samples were used as a general population reference. Standardized prevalence ratios (SPRs) were calculated to compare the CTN sample to NHANES as well as to compare within the CTN sample. Logistic regression estimated associations between the type of drug dependence and obesity. RESULTS: The standardized obesity prevalence among the drug-dependent CTN trial participants was 67% of expected for age-, sex- and race-matched NIHANES participants (SPR = 0.67, 95% CI: 0.60-0.74). Obesity was least prevalent among opioid-dependent-only participants (SPR = 0.36, 95% CI: 0.27-0.46 compared to the NHANES, and SPR = 0.33, 95% CI: 0.23-0.46 compared to the stimulant-dependent-only participants). Compared to stimulant-dependent-only users (p < 0.0001), the odds of obesity were 67% lower among opioid-dependent-only users (adjusted odds ratio [AOR] = 0.33, 95% CI: 0.23-0.46) and 33% lower among opioid and stimulant-co-dependent users (AOR = 0.67, 95%CI: 0.49-0.90) after controlling for age, sex, race, education and employment pattern. CONCLUSIONS: The prevalence of obesity among drug-dependent clinical trial participants was lower than the general population, and lowest among opioid-dependent-only users, suggesting an inverse relationship between obesity prevalence and drug dependence, most notable among opioid-dependent-only users.

The 2017 CALDAR Summer Institute and International Conference Promoting Global Health-Precision Research in Substance Abuse, HIV, and Care.

The 2017 CALDAR Summer Institute on Longituidnal Research and International Conference Series to Promote Global Health will take place in Los Angeles Universal City, CA, USA from August 15 to August 17, 2017. The conference will present a selection of the lastest and most current reseach in the areas of addiction, HIV, and related treatment.

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies.

Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies.

Pediatric Hodgkin lymphoma: biomarkers, drugs, and clinical trials for translational science and medicine.

Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging. Targeted HL therapy with the antibody-drug conjugate Brentuximab vedotin (Bv) has proven to be superior to conventional salvage chemotherapy and clinical trials are being conducted to incorporate Bv into frontline therapy that substitutes Bv for alkylating agents to minimize secondary malignancies. The appearance of secondary malignancies has been a concern in pediatric HL, as these patients are at highest risk among all childhood cancer survivors. The risk of developing secondary leukemia following childhood HL treatment is 10.4 to 174.8 times greater than the risk in the general pediatric population and the prognosis is significantly poorer than the other hematological malignancies with a mortality rate of nearly 100%. Therefore, identifying clinically valuable biomarkers is of utmost importance to stratify and select patients who may or may not need intensive regimens to maintain optimal balance between maximal survival rates and averting late effects. Here we discuss epidemiology, risk factors, staging, molecular and genetic prognostic biomarkers, treatment for low and high-risk patients, and the late occurrence of secondary malignancies in pediatric HL.

Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine.

Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for maintaining cell morphology and interaction with the surrounding microenvironment. Deregulation of SDC1 contributes to cancer progression by promoting cell proliferation, metastasis, invasion and angiogenesis, and is associated with relapse through chemoresistance. SDC1 expression level is also associated with responses to chemotherapy and with prognosis in multiple solid and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At the tissue level, the expression levels of SDC1 and the released extracellular domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic potential for both solid and hematological tumors in a tissue-specific manner. The SDC1 expression profile varies among cancer types, but the differential expression signatures between normal and cancer cells in epithelial and stromal compartments are directly associated with aggressiveness of tumors and patient's clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling may be useful for selecting patients that would most likely respond to a particular therapy at the time of diagnosis or perhaps for predicting relapse. In addition, the reciprocal expression signature of SDC between tumor epithelial and stromal compartments may have synergistic value for patient selection and the prediction of clinical outcome.

Challenges and opportunities for integrating preventive substance-use-care services in primary care through the Affordable Care Act.

Undertreated or untreated substance use disorders (SUD) remain a pervasive, medically-harmful public health problem in the United States, particularly in medically underserved and low-income populations lacking access to appropriate treatment. The need for greater access to SUD treatment was expressed as policy in the Final Rule on standards related to essential health benefits, required to be covered through the 2010 Affordable Care Act (ACA) health insurance exchanges. SUD treatment services have been included as an essential health benefit, in a manner that complies with the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008. Consequently, with the ACA, a vast expansion of SUD-care services in primary care is looming. This commentary discusses challenges and opportunities under the ACA for equipping health care professionals with appropriate workforce training, infrastructure, and resources to support and guide science-based Screening, Brief Intervention, and Referral to Treatment (SBIRT) for SUD in primary care.

Expanding the National Drug Abuse Treatment Clinical Trials Network to address the management of substance use disorders in general medical settings.

The Patient Protection and Affordable Care Act (2010) and the Mental Health Parity and Addiction Equity Act (2008) expand substance use disorder (SUD) care services in the USA into general medical settings. Care offered in these settings will engage substance-using patients in an integrated and patient-centered environment that addresses physical and mental health comorbidities and follows a chronic care model. This expansion of SUD services presents a great need for evidence-based practices useful in general medical settings, and reveals several research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse can serve an important role in this endeavor. High-priority research gaps are highlighted in this commentary. A discussion follows on how the National Drug Abuse Treatment Clinical Trials Network can transform to address changing patterns in SUD care to efficiently generate evidence to guide SUD treatment practice within the context of recent US health care legislation.

Patient registries for substance use disorders.

This commentary discusses the need for developing patient registries of substance use disorders (SUD) in general medical settings. A patient registry is a tool that documents the natural history of target diseases. Clinicians and researchers use registries to monitor patient comorbidities, care procedures and processes, and treatment effectiveness for the purpose of improving care quality. Enactments of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity Act 2008 open opportunities for many substance users to receive treatment services in general medical settings. An increased number of patients with a wide spectrum of SUD will initially receive services with a chronic disease management approach in primary care. The establishment of computer-based SUD patient registries can be assisted by wide adoption of electronic health record systems. The linkage of SUD patient registries with electronic health record systems can facilitate the advancement of SUD treatment research efforts and improve patient care.

Can Substance Use Disorders be Managed Using the Chronic Care Model? Review and Recommendations from a NIDA Consensus Group.

Brain imaging and genetic studies over the past two decades suggest that substance use disorders are best considered chronic illnesses. The passing of the Affordable Care Act in the United States has set the occasion for integrating treatment of substance use disorders into mainstream healthcare; and for using the proactive, team-oriented Chronic Care Model (CCM). This paper systematically examines and compares whether and how well the CCM could be applied to the treatment of substance use disorders, using type 2 diabetes as a comparator. The chronic illness management approach is still new in the field of addiction and research is limited. However comparative findings suggest that most proactive, team treatment-oriented clinical management practices now used in diabetes management are applicable to the substance use disorders; capable of being implemented by primary care teams; and should offer comparable potential benefits in the treatment of substance use disorders. Such care should also improve the quality of care for many illnesses now negatively affected by unaddressed substance abuse.

Treatment for substance use disorder: opportunities and challenges under the affordable care act.

Addiction is a chronic brain disease with consequences that remain problematic years after discontinuation of use. Despite this, treatment models focus on acute interventions and are carved out from the main health care system. The Patient Protection and Affordable Care Act (2010) brings the opportunity to change the way substance use disorder (SUD) is treated in the United States. The treatment of SUD must adapt to a chronic care model offered in an integrated care system that screens for at-risk patients and includes services needed to prevent relapses. The partnering of the health care system with substance abuse treatment programs could dramatically expand the benefits of prevention and treatment of SUD. Expanding roles of health information technology and nonphysician workforces, such as social workers, are essential to the success of a chronic care model.

Medication-assisted therapy for opioid addiction.

The "Medication-Assisted Therapy for Opioid Addiction" session was chaired by Dr. Betty Tai and had three presenters. The presenters (and their topics) were: Dr. Andrew J. Saxon (Methadone and Buprenorphine for Treatment of Opioid Addiction and HIV Risk Reduction), Dr. Walter Ling (Opioid Antagonist Treatment for Opioid Addiction), and Dr. Betty Tai (Chronic Care Model for Substance Use Disorder).

Integrating substance abuse care with community diabetes care: implications for research and clinical practice.

Cigarette smoking and alcohol use are prevalent among individuals with diabetes in the US, but little is known about screening and treatment for substance use disorders in the diabetic population. This commentary discusses the scope and clinical implications of the public health problem of coexisting substance use and diabetes, including suggestions for future research. Diabetes is the seventh leading cause of death in the US, and is associated with many severe health complications like cardiovascular disease, stroke, kidney damage, and limb amputations. There are an estimated 24 million adults in the US with type 2 diabetes. Approximately 20% of adults aged 18 years or older with diabetes report current cigarette smoking. The prevalence of current alcohol use in the diabetic population is estimated to be around 50%-60% in epidemiological surveys and treatment-seeking populations. Cigarette smoking is associated with an increased risk of type 2 diabetes in a dose-dependent manner and is an independent modifiable risk factor for development of type 2 diabetes. Diabetic patients with an alcohol or other drug use disorder show a higher rate of adverse health outcomes. For example, these patients experience more frequent and severe health complications as well as an increased risk of hospitalization, and require longer hospital stays. They are also less likely to seek routine care for diabetes or adhere to diabetes treatment than those without an alcohol or other drug use disorder. The Affordable Care Act of 2010 and the Mental Health Parity Act and Addiction Equity Act of 2008 provide opportunities for facilitating integration of preventive services and evidence-based treatments for substance use disorders with diabetes care in community-based medical settings. These laws also offer emerging areas for research.

Preventing deaths from rising opioid overdose in the US - the promise of naloxone antidote in community-based naloxone take-home programs.

The opioid overdose epidemic is an alarming and serious public health problem in the United States (US) that has been escalating for 11 years. The 2011 National Survey on Drug Use and Health (NSDUH) demonstrated that 1 in 20 persons in the US aged 12 or older reported nonmedical use of prescription painkillers in the past year. Prescription drug overdose is now the leading cause of accidental death in the United States - surpassing motor vehicle accidents. Great efforts have been initiated to curb the overdose crisis. Notable examples of these efforts are (1) the Drug Enforcement Administration's (DEA) National Take-Back Initiative instituted in 2010; (2) the Prescription Drug Monitoring Programs (PDMPs) implemented in most US states to provide practitioners with point-of-care information regarding a patient's controlled substance use; (3) the naloxone rescue programs initiated in the community to avert mortality resulting from overdose. The use of naloxone rescue strategies has gained traction as an effective measure to prevent fatal opioid overdose. Many US federal-government agencies are working to make these strategies more accessible to first responders and community participants. This new approach faces many challenges, such as accessibility to naloxone and the equipment and training needed to administer it, but none is more challenging than the fear of legal repercussions. US federal-government agencies, local governments, health care institutions, and community-based organizations have begun to tackle these barriers, and naloxone take-home programs have gained recognition as a feasible and sensible preventive strategy to avoid a fatal result from opioid overdose. Although many challenges still need to be overcome, it is important for federal government research agencies to initiate and support independent and rigorous evaluation of these programs to inform policymakers how effective these programs can be to save lives and curb the opioid overdose public health crisis.