The article examines various studies of ADHD and finds that individuals both with and without ADHD misuse stimulant medications, therefore suggesting careful monitoring of high-risk individuals.
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.
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).
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.
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.
There is a reciprocal relationship between the circadian and the reward systems. Polymorphisms in several circadian rhythm-related (clock) genes were associated with drug addiction. This study aims ...to search for associations between 895 variants in 39 circadian rhythm-related genes and opioid addiction (OUD). Genotyping was performed with the Smokescreen® array. Ancestry was verified by principal/MDS component analysis and the sample was limited to European Americans (EA) (OUD; n = 435, controls; n = 138). Nominally significant associations (p < 0.01) were detected for several variants in genes encoding vasoactive intestinal peptide receptor 2 (VIPR2), period circadian regulator 2 (PER2), casein kinase 1 epsilon (CSNK1E), and activator of transcription and developmental regulator (AUTS2), but no signal survived correction for multiple testing. There was intriguing association signal for the untranslated region (3' UTR) variant rs885863 in VIPR2, (p = .0065; OR = 0.51; 95% CI 0.31-0.51). The result was corroborated in an independent EA OUD sample (n = 398, p = 0.0036; for the combined samples). Notably, this SNP is an expression quantitative trait locus (cis-eQTL) for VIPR2 and a long intergenic non-coding RNA, lincRNA 689, in a tissue-specific manner, based on the Genotype-Tissue Expression (GTEx) project. Vasoactive intestinal peptide (VIP) is an important peptide of light-activated suprachiasmatic nucleus cells. It regulates diverse physiological processes including circadian rhythms, learning and memory, and stress response. This is the first report of an association of a VIPR2 variant and OUD. Additionally, analysis of combinations of single nucleotide polymorphisms (SNPs) genotypes revealed an association of PER2 SNP rs80136044, and SNP rs4128839, located 41.6 kb downstream of neuropeptide Y receptor type 1 gene, NPY1R (p = 3.4 × 10-6, OR = 11.4, 95% CI 2.7-48.2). The study provides preliminary insight into the relationship between genetic variants in circadian rhythm genes and long non-coding RNA (lncRNAs) in their vicinity, and opioid addiction.
Background Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of ...evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed “default-mode” network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. Methods Resting-state blood oxygen level–dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. Results Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions ( p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex ( p < 3 × 10−11 , corrected) and portions of posterior cingulate ( p < .02, corrected). Conclusions Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD.
Abstract Background Substance use screening is widely encouraged in health care settings, but the lack of a screening approach that fits easily into clinical workflows has restricted its broad ...implementation. The Substance Use Brief Screen (SUBS) was developed as a brief, self-administered instrument to identify unhealthy use of tobacco, alcohol, illicit drugs, and prescription drugs. We evaluated the validity and test-retest reliability of the SUBS in adult primary care patients. Methods Adults aged 18-65 years were enrolled from urban safety net primary care clinics to self-administer the SUBS using touch-screen tablet computers for a test-retest reliability study (n = 54) and a 2-site validation study (n = 586). In the test-retest reliability study, the SUBS was administered twice within a 2-week period. In the validation study, the SUBS was compared with reference standard measures, including self-reported measures and oral fluid drug tests. We measured test-retest reliability and diagnostic accuracy of the SUBS for detection of unhealthy use and substance use disorder for tobacco, alcohol, and drugs (illicit and prescription drug misuse). Results Test-retest reliability was good or excellent for each substance class. For detection of unhealthy use, the SUBS had sensitivity and specificity of 97.8% (95% confidence interval CI, 93.7-99.5) and 95.7% (95% CI, 92.4-97.8), respectively, for tobacco; and 85.2% (95% CI, 79.3-89.9) and 77.0% (95% CI, 72.6-81.1) for alcohol. For unhealthy use of illicit or prescription drugs, sensitivity was 82.5% (95% CI, 75.7-88.0) and specificity 91.1% (95% CI, 87.9-93.6). With respect to identifying a substance use disorder, the SUBS had sensitivity and specificity of 100.0% (95% CI, 92.7-100.0) and 72.1% (95% CI, 67.1-76.8) for tobacco; 93.5% (95% CI, 85.5-97.9) and 64.6% (95% CI, 60.2-68.7) for alcohol; and 85.7% (95% CI, 77.2-92.0) and 82.0% (95% CI, 78.2-85.3) for drugs. Analyses of area under the receiver operating curve (AUC) indicated good discrimination (AUC 0.74-0.97) for all substance classes. Assistance in completing the SUBS was requested by 11% of participants. Conclusions The SUBS was feasible for self-administration and generated valid results in a diverse primary care patient population. The 4-item SUBS can be recommended for primary care settings that are seeking to implement substance use screening.
Abstract Rationale Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found evidence of brain abnormalities in white matter. ...Objective Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. Methods Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. Results DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. Conclusions Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures.
Dysregulation of the stress response is implicated in drug addiction; therefore, polymorphisms in stress-related genes may be involved in this disease. An analysis was performed to identify ...associations between variants in 11 stress-related genes, selected a priori, and heroin addiction. Two discovery samples of American subjects of European descent (EA, n = 601) and of African Americans (AA, n = 400) were analyzed separately. Ancestry was verified by principal component analysis. Final sets of 414 (EA) and 562 (AA) variants were analyzed after filtering of 846 high-quality variants. The main result was an association of a non-coding SNP rs255105 in the CRH (CRF) receptor 2 gene (CRHR2), in the discovery EA sample (Pnominal = .00006; OR = 2.1; 95% CI 1.4-3.1). The association signal remained significant after permutation-based multiple testing correction. The result was corroborated by an independent EA case sample (n = 364). Bioinformatics analysis revealed that SNP rs255105 is associated with the expression of a downstream long intergenic non-coding RNA (lincRNA) gene AC005154.6. AC005154.6 is highly expressed in the pituitary but its functions are unknown. LincRNAs have been previously associated with adaptive behavior, PTSD, and alcohol addiction. Further studies are warranted to corroborate the association results and to assess the potential relevance of this lincRNA to addiction and other stress-related disorders.
Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain ...3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP.
Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale.
This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic.
ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.
Summary
Stress is a significant risk factor in the development of drug addictions and in addiction relapse susceptibility. This hypothesis‐driven study was designed to determine if specific SNPs in ...genes related to stress response are associated with heroin and/or cocaine addiction in African Americans. The analysis included 27 genes (124 SNPs) and was performed independently for each addiction. The sample consisted of former heroin addicts in methadone maintenance treatment (n = 314), cocaine addicts (n = 281), and controls (n = 208). Fourteen SNPs showed nominally significant association with heroin addiction (p < 0.05), including the African‐specific, missense SNP rs5376 (Asn334Ser) in the galanin receptor type 1 gene (GALR1) and the functional FKBP5 intronic SNP rs1360780. Thirteen SNPs showed association with cocaine addiction, including the synonymous SNPs rs237902, in the oxytocin receptor gene (OXTR), and rs5374 in GALR1. No signal remained significant after correction for multiple testing. Four additional SNPs (GALR1 rs2717162, AVP rs2282018, CRHBP rs1875999, and NR3C2 rs1040288) were associated with both addictions and may indicate common liability. The study provides preliminary evidence for novel association of variants in several stress‐related genes with heroin and/or cocaine addictions and may enhance the understanding of the interaction between stress and addictions.
Opioid use disorder continues to be a significant problem in the United States and worldwide. Three medications-methadone, buprenorphine, and extended-release injectable naltrexone,- are efficacious ...for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study "Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.
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