The Safety and Effectiveness of Orthobiologic Injections for Discogenic Chronic Low Back Pain: A Multicenter Prospective, Crossover, Randomized Controlled Trial with 12 Months Follow-up.

BACKGROUND: Chronic low back pain is one of the most common causes of disability, affecting more than 600 million people worldwide with major social and economic costs. Current treatment options include conservative, surgical, and minimally invasive interventional treatment approaches. Novel therapeutic treatment options continue to develop, targeting the biological cascades involved in the degenerative processes to prevent invasive spinal surgical procedures. Both intradiscal platelet-rich plasma (PRP) and bone marrow concentrate (BMC) applications have been introduced as promising regenerative treatment procedures. OBJECTIVES: The primary objective of this study is to assess the safety and effectiveness of an orthobiologic intradiscal injection, PRP or BMC, when compared to control patients. The secondary objectives are to measure: patient satisfaction and incidence of hospitalization, emergency room visit and spine surgery at predetermined follow-up intervals. STUDY DESIGN: A multicenter, prospective, crossover, randomized, controlled trial. SETTING: Comprehensive Spine and Sports Center and participating centers. METHODS: Forty patients were randomized into saline trigger point injection, intradiscal PRP, or BMC. Follow-up was 1, 3, 6, and 12 months posttreatment. Placebo patients were randomized to PRP and BMC injection if < 50% decrease in numeric rating scale (NRS) scores in 3 months, while PRP and BMC patients to the other active group if < 50% decrease in NRS scores in 6 months. RESULTS: Both PRP and BMC demonstrated statistically significant improvement in pain and function. All the placebo patients reported < 50% pain relief and crossed to the active arm. None of the patients had any adverse effects, hospitalization, or surgery up to 12 months posttreatment. LIMITATIONS: The limitations of our study were the small number of patients and open-label nature of the study. CONCLUSION: This is the only human lumbar disc study that evaluates both PRP and BMC in the same study and compares it to placebo. PRP and BMC were found to be superior to placebo in improving pain and function; however, larger randomized clinical trials are needed to answer further questions on the comparative effectiveness of various biologics as well as to identify outcome differences specific to disc pathology.

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

Comparison of Methods for Alcohol and Drug Screening in Primary Care Clinics.

Importance: Guidelines recommend that adult patients receive screening for alcohol and drug use during primary care visits, but the adoption of screening in routine practice remains low. Clinics frequently struggle to choose a screening approach that is best suited to their resources, workflows, and patient populations. Objective: To evaluate how to best implement electronic health record (EHR)-integrated screening for substance use by comparing commonly used screening methods and examining their association with implementation outcomes. Design, Setting, and Participants: This article presents the outcomes of phases 3 and 4 of a 4-phase quality improvement, implementation feasibility study in which researchers worked with stakeholders at 6 primary care clinics in 2 large urban academic health care systems to define and implement their optimal screening approach. Site A was located in New York City and comprised 2 clinics, and site B was located in Boston, Massachusetts, and comprised 4 clinics. Clinics initiated screening between January 2017 and October 2018, and 93 114 patients were eligible for screening for alcohol and drug use. Data used in the analysis were collected between January 2017 and October 2019, and analysis was performed from July 13, 2018, to March 23, 2021. Interventions: Clinics integrated validated screening questions and a brief counseling script into the EHR, with implementation supported by the use of clinical champions (ie, clinicians who advocate for change, motivate others, and use their expertise to facilitate the adoption of an intervention) and the training of clinic staff. Clinics varied in their screening approaches, including the type of visit targeted for screening (any visit vs annual examinations only), the mode of administration (staff-administered vs self-administered by the patient), and the extent to which they used practice facilitation and EHR usability testing. Main Outcomes and Measures: Data from the EHRs were extracted quarterly for 12 months to measure implementation outcomes. The primary outcome was screening rate for alcohol and drug use. Secondary outcomes were the prevalence of unhealthy alcohol and drug use detected via screening, and clinician adoption of a brief counseling script. Results: Patients of the 6 clinics had a mean (SD) age ranging from 48.9 (17.3) years at clinic B2 to 59.1 (16.7) years at clinic B3, were predominantly female (52.4% at clinic A1 to 64.6% at clinic A2), and were English speaking. Racial diversity varied by location. Of the 93,114 patients with primary care visits, 71.8% received screening for alcohol use, and 70.5% received screening for drug use. Screening at any visit (implemented at site A) in comparison with screening at annual examinations only (implemented at site B) was associated with higher screening rates for alcohol use (90.3%-94.7% vs 24.2%-72.0%, respectively) and drug use (89.6%-93.9% vs 24.6%-69.8%). The 5 clinics that used a self-administered screening approach had a higher detection rate for moderate- to high-risk alcohol use (14.7%-36.6%) compared with the 1 clinic that used a staff-administered screening approach (1.6%). The detection of moderate- to high-risk drug use was low across all clinics (0.5%-1.0%). Clinics with more robust practice facilitation and EHR usability testing had somewhat greater adoption of the counseling script for patients with moderate-high risk alcohol or drug use (1.4%-12.5% vs 0.1%-1.1%). Conclusions and Relevance: In this quality improvement study, EHR-integrated screening was feasible to implement in all clinics and unhealthy alcohol use was detected more frequently when self-administered screening was used at any primary care visit. The detection of drug use was low at all clinics, as was clinician adoption of counseling. These findings can be used to inform the decision-making of health care systems that are seeking to implement screening for substance use. Trial Registration: ClinicalTrials.gov Identifier: NCT02963948.

Diagnosis and Evaluation of Thyroid Nodules-the Clinician's Perspective.

Thyroid nodules are a common clinical problem encountered in an endocrine practice. More and more thyroid nodules are now being detected on unrelated imaging studies, leading to an increased diagnosis of low-risk thyroid cancers. There is therefore a greater emphasis on risk assessment based on clinical and sonographic features to avoid morbidity secondary to unnecessary therapy. Molecular diagnostics are also being widely used to further characterize indeterminate nodules. The American Thyroid Association and American College of Radiology-Thyroid Imaging Reporting and Data System guidelines are the most commonly used in clinical practice for risk assessment.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

BACKGROUND: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). METHODS: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. RESULTS: The GE-XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications. CONCLUSIONS: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.

Barriers and facilitators affecting the implementation of substance use screening in primary care clinics: a qualitative study of patients, providers, and staff.

BACKGROUND: Alcohol and drug use are leading causes of morbidity and mortality that frequently go unidentified in medical settings. As part of a multi-phase study to implement electronic health record-integrated substance use screening in primary care clinics, we interviewed key clinical stakeholders to identify current substance use screening practices, barriers to screening, and recommendations for its implementation. METHODS: Focus groups and individual interviews were conducted with 67 stakeholders, including patients, primary care providers (faculty and resident physicians), nurses, and medical assistants, in two urban academic health systems. Themes were identified using an inductive approach, revised through an iterative process, and mapped to the Knowledge to Action (KTA) framework, which guides the implementation of new clinical practices (Graham et al. in J Contin Educ Health Prof 26(1):13-24, 2006). RESULTS: Factors affecting implementation based on KTA elements were identified from participant narratives. Identifying the problem: Participants consistently agreed that having knowledge of a patient's substance use is important because of its impacts on health and medical care, that substance use is not properly identified in medical settings currently, and that universal screening is the best approach. Assessing barriers: Patients expressed concerns about consequences of disclosing substance use, confidentiality, and the individual's own reluctance to acknowledge a substance use problem. Barriers identified by providers included individual-level factors such as lack of clinical knowledge and training, as well as systems-level factors including time pressure, resources, lack of space, and difficulty accessing addiction treatment. Adapting to the local context: Most patients and providers stated that the primary care provider should play a key role in substance use screening and interventions. Opinions diverged regarding the optimal approach to delivering screening, although most preferred a patient self-administered approach. Many providers reported that taking effective action once unhealthy substance use is identified is crucial. CONCLUSIONS: Participants expressed support for substance use screening as a valuable part of medical care, and identified individual-level as well as systems-level barriers to its implementation. These findings suggest that screening programs should clearly communicate the goals of screening to patients and proactively counteract stigma, address staff concerns regarding time and workflow, and provide education as well as treatment resources to primary care providers.

Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia.

Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F (2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F (2,738) = 3.17, p = 0.04, F (2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and treatment targets for reducing an important modifiable cause of general morbidity and mortality in patients with schizophrenia.

Implications of epidemiological data for identifying persons with substance use and other mental disorders.

The authors conducted systematic searches in standard databases using key search terms related to epidemiology, prevalence, and co-occurring substance use and other mental disorders (COD), as well as specific combinations of drug and mental disorders. The authors targeted high-quality, large sample epidemiological surveys so as to utilize studies of high methodological rigor in the construction of recommendations for clinical identification. Further refined searches to identify these studies revealed common themes and related research gaps. Findings suggest that clinicians should have increased expectation that a patient with a substance use disorder (SUD) has a co-occurring mental disorder if the SUD is relatively severe, if the patient began using substances (including tobacco) at an early age, is female, is dependent on nicotine, or has a drug use disorder. Patients identified as having at least one SUD and one co-occurring mental disorder should be assessed to identify other likely CODs, because disorders are not normally distributed and tend to cluster in relatively few individuals.

Problem and pathological gambling in a sample of casino patrons.

Relatively few studies have examined gambling problems among individuals in a casino setting. The current study sought to examine the prevalence of gambling problems among a sample of casino patrons and examine alcohol and tobacco use, health status, and quality of life by gambling problem status. To these ends, 176 casino patrons were recruited by going to a Southern California casino and requesting that they complete an anonymous survey. Results indicated the following lifetime rates for at-risk, problem, and pathological gambling: 29.2, 10.7, and 29.8%. Differences were found with regards to gambling behavior, and results indicated higher rates of smoking among individuals with gambling problems, but not higher rates of alcohol use. Self-rated quality of life was lower among pathological gamblers relative to non-problem gamblers, but did not differ from at-risk or problem gamblers. Although subject to some limitations, our data support the notion of higher frequency of gambling problems among casino patrons and may suggest the need for increased interventions for gambling problems on-site at casinos.

Psicoterapia psicodinâmica e o tratamento do jogo patológico / Psychodynamic psychotherapy and the treatment of pathological gambling

OBJETIVO: A busca por tratamentos com base empírica para o jogo patológico está em sua infância, havendo relativamente poucos ensaios clínicos e uma ausência de estudos naturalísticos. A adesão dos jogadores ao tratamento tem sido um problema, sendo que o tratamento cognitivo-comportamental e os estudos farmacoterápicos relatam índices particularmente altos de abandono. As abordagens psicodinâmicas, com sua ênfase na relação terapêutica e no significado dos comportamentos autodestrutivos e aparentemente irracionais, e nos obstáculos à capacidade de se perdoar, poderiam melhorar o desfecho. MÉTODO: Após uma descrição da psicoterapia psicodinâmica, foi feita uma revisão da literatura que investigou a eficácia de tratamentos psicoterápicos de curto e longo prazo para uma série de transtornos. Com relação ao jogo patológico, foi feito um resumo da literatura psicanalítica inicial (1914-1970) e a seguir foi revisada a literatura mais recente sobre a utilização da psicoterapia psicodinâmica no jogo patológico. RESULTADOS: A pesquisa da literatura recente sobre psicoterapia psicodinâmica não revelou nenhum estudo controlado aleatorizado sobre a eficácia ou efetividade desse tratamento. No entanto, há oito estudos com desfechos positivos descritos como ecléticos multimodais; a metade destes parece utilizar abordagens psicodinâmicas. São descritos dois programas entre os que obtiveram maior êxito. CONCLUSÕES: Uma observação sobre os desfechos mais gerais da psicoterapia psicodinâmica na literatura demonstra eficácia suficiente para uma variedade de transtornos que justificam um ensaio clínico sobre o jogo patológico. A psicoterapia psicodinâmica de curto prazo, com seu foco em questões nucleares, pode ser particularmente aplicável à necessidade dos jogadores patológicos de evitar ou escapar de efeitos e problemas intoleráveis. Terapias de mais longo prazo podem ser necessárias para modificar um padrão evitativo de comportamento e defesas psicodinâmicas.

OBJECTIVE: The search for empirically based treatments for pathological gambling is in its infancy, with relatively few clinical trials and an absence of naturalistic studies. Treatment retention of gamblers has been a problem; cognitive-behavioral treatment and pharmacotherapy studies report especially high dropout rates. Psychodynamic approaches, with their emphasis on the therapeutic relationship, and the meaning of the patient's self-destructive and seemingly irrational behaviors, and on obstacles to self-forgiveness, might improve outcome. METHOD: After a description of psychodynamic psychotherapy, the literature on both short-term and longer therapies is reviewed regarding their efficacy for a variety of disorders. With regard to pathological gambling, the author summarizes the early (1914-1970) psychoanalytic literature then reviews the more recent psychodynamic psychotherapy literature on pathological gambling. RESULTS: A review of the recent psychodynamic psychotherapy literature on pathological gambling failed to disclose a single randomized controlled study of treatment efficacy or effectiveness. However, there are eight positive outcome studies described as multi-modal eclectic; half of those seem to utilize psychodynamic approaches. Two of the more successful programs are described. CONCLUSIONS: A review of the outcomes literature for psychodynamic psychotherapy demonstrates efficacy for a variety of disorders sufficient to justify a clinical trial for pathological gambling. Short-term psychodynamic psychotherapy, with its focus on core issues, may be particularly applicable to the pathological gambler's need to avoid or escape intolerable affects and problems. Longer therapies may be needed to modify an avoidant coping style and defenses.

Improving the care of individuals with schizophrenia and substance use disorders: consensus recommendations.

National attention continues to focus on the need to improve care for individuals with co-occurring mental illnesses and substance use disorders, as emphasized in the 2003 President's New Freedom Commission Report on Mental Health and recent publications from the Substance Abuse and Mental Health Services Administration (SAMHSA). These reports document the need for best practice recommendations that can be translated into routine clinical care. Although efforts are underway to synthesize literature in this area, few focused recommendations are available that include expert opinion and evidence-based findings on the management of specific co-occurring disorders, such as schizophrenia and addiction. In response to the need for user-friendly recommendations on the treatment of schizophrenia and addiction, a consensus conference of experts from academic institutions and state mental health systems was organized to 1) frame the problem from clinical and systems-level perspectives; 2) identify effective and problematic psychosocial, pharmacological, and systems practices; and 3) develop a summary publication with recommendations for improving current practice. The results of the consensus meeting served as the foundation for this publication, which presents a broad set of recommendations for clinicians who treat individuals with schizophrenia. "Integrated treatment" is the new standard for evidence-based treatment for this population and recommendations are given to help clinicians implement such integrated treatment. Specific recommendations are provided concerning screening for substance use disorders in patients with schizophrenia, assessing motivation for change, managing medical conditions that commonly occur in patients with dual diagnoses (e.g., cardiovascular disease, liver complications, lung cancer, HIV, and hepatitis B or C infections) and selecting the most appropriate medications for such patients to maximize safety and minimize drug interactions, use of evidence-based psychosocial interventions for patients with dual diagnoses (e.g., Dual Recovery Therapy, modified cognitive-behavioral therapy, modified motivational enhancement therapy, and the Substance Abuse Management Module), and key pharmacotherapy principles for treating schizophrenia, substance use disorders, and comorbid anxiety, depression, and sleep problems in this population. Finally the article reviews programmatic and systemic changes needed to overcome treatment barriers and promote the best outcomes for this patient population. An algorithm summarizing the consensus recommendations is provided in an appendix.