Simultaneous use of alcohol with methamphetamine but not ecstasy linked with aggression among young adult stimulant users

IntroductionIllicit stimulants are often combined with alcohol in nightlife entertainment districts, an environment where aggressive behaviour commonly occurs. While alcohol and methamphetamine use are each associated with aggressive behaviour, relatively little is known about the impact of the combined use of alcohol and amphetamine-type stimulants (i.e., ecstasy [MDMA] and methamphetamine) on aggression.MethodAnalysis of longitudinal data from a population-based sample of Australian young adult amphetamine-type stimulant users (n = 248) to examine: (a) prevalence and timing of simultaneous alcohol and amphetamine-type stimulant use and (b) predictors of ecstasy- and methamphetamine-related aggression and hostility. Prediction models of ecstasy- and methamphetamine-related aggression and hostility were developed using multivariate logistic regression.ResultsSimultaneous alcohol consumption and amphetamine-type stimulant use was prevalent, with drinking generally occurring before consuming amphetamine-type stimulants and while ‘high’. Methamphetamine-related aggression and hostility was significantly associated with recurrent risky simultaneous methamphetamine and alcohol use (Adjusted Odds Ratio [AOR] 2.74, 95% CI 1.09–6.89), a high frequency and increasing use methamphetamine trajectory (AOR 7.23, 95% CI 1.27–41.03), and high trait aggression (AOR 5.78, 95% CI 2.53–13.20). In contrast, only trait aggression (moderate: AOR 3.01, 95% CI 1.55–5.84; high: AOR 5.02, 95% CI 2.38–10.61) was associated with ecstasy-related aggression and hostility.ConclusionsThese findings indicate a link between risky patterns of simultaneous alcohol and methamphetamine use and methamphetamine-related aggression and hostility, independent of separate use of alcohol, methamphetamine and cannabis, trait aggression, psychosis, and gender. The policy challenges of amphetamine-type stimulant and alcohol use require a targeted, multidisciplinary approach.     

Rewarding early abstinence in Veterans Health Administration addiction clinics

This study investigates the addition of a contingency management (CM) intervention to Veterans Health Administration substance use disorders treatment on during- and post-treatment outcomes for Veterans diagnosed with alcohol dependence only (n = 191) or stimulant dependence (n = 139). Participants were randomly assigned to 8 weeks of usual care or usual care plus CM. Follow-up assessments occurred at 2, 6 and 12 months. In the alcohol dependent subgroup, CM participants submitted significantly more negative samples (13 versus 11 samples, Cohen's d = 0.54), were retained significantly longer (7 versus 6 weeks, d = 0.47), achieved significantly longer median durations of abstinence (16 versus 9 consecutive visits; median difference = 7, 95% CI = 4–8), and submitted significantly more negative samples at follow-ups (unstandardized effect size = 0.669, se = 0.2483) compared to usual care participants. Intervention effects were non-significant for the stimulant dependent subgroup. The study provides support for the effectiveness of CM interventions for alcohol dependent patients.     

Treatment stabilization in children and adolescents with attention-deficit/hyperactivity disorder: data from the Netherlands

Abstract

Objective:

To evaluate the number of patients reaching stable treatment with a stimulant (methylphenidate or dexamphetamine) or non-stimulant (atomoxetine) attention-deficit/hyperactivity disorder (ADHD) medication approved for use in the Netherlands, and the time to treatment stabilization among children and adolescents aged 6–17 years.     

Criminal justice referral and incentives in outpatient substance abuse treatment

A substantial number of substance abusers entering outpatient psychosocial counseling treatment are referred from the criminal justice (CJ) system. This secondary analysis of previously published findings from a large (N = 415) multi-site trial of a prize-based abstinence incentive intervention ( Petry et al., 2005) examined the influence of CJ referral on usual care outcomes and response to the incentive procedure. CJ referrals (n = 138) were more likely than those not CJ referred (n = 277) to provide stimulant negative urine samples whether missing samples were counted as positive (50 versus 41%, p = .016) or as missing (96 versus 91%, p < .001). A significant interaction term was found only for percentage of treatment completers (p = .027). However, on that retention variable, and three additional drug use measures, significant incentive effects were confined to participants who entered treatment without referral from the criminal justice system. The study suggests that abstinence incentives should be offered as a first priority to stimulant users entering treatment without criminal justice referral. However, incentives can be considered for use with CJ-referred stimulant users based on the observation that best outcomes were obtained in CJ referrals who also received the abstinence incentive program.     

Healthcare resource use and cost associated with timing of pharmacological treatment for major depressive disorder in the United States: a real-world study

Abstract

Background: Guidelines recommend selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) as first-line treatments for major depressive disorder (MDD) and emphasize the importance of early pharmacological treatment as key factors to treatment success.

Objectives: To compare the MDD-related healthcare resource utilization (HCRU) and cost among patients (1) with early vs late pharmacological treatment initiation and (2) achieving minimum therapeutic dose (MTD) early vs late.

Methods: The MarketScan database (2010–2015) was used. Adults who were newly-treated with SSRI/SNRI within 12?months after the initial MDD diagnosis (index) were included. Patients who initiated SSRI/SNRI within 2?weeks of the index date were defined as early initiators; those who reached MTD within 4?weeks of index date were defined as early MTD achievers. MDD-related HCRU and costs per year after the index date were compared between early and late initiators and between early and late achievers using propensity score matching and generalized linear models.

Results: Of the 55,539 patients, 60% were early initiators and 61% were early MTD achievers. The mean number of MDD-related outpatient visits per year were significantly higher for late initiator (6.7 vs 4.2, p?<?.001) and late MTD achievers (6.5 vs 4.5, p?<?.001) vs their early counterparts. Mean annual MDD-related outpatient, drug, and total cost were significantly higher for late initiators and MTD achievers vs the early groups.

Conclusions: There is an opportunity to improve outcomes by treating MDD patients with SSRI/SNRI within 2?weeks and at or above the MTD within 4?weeks of diagnosis or less.     

Safety of stimulant treatment in attention deficit hyperactivity disorder: part II

Importance of the field: Attention deficit hyperactivity disorder (ADHD) is the most common childhood psychiatric disorder and in at least 50% of cases persists into adulthood. Treatment of ADHD with stimulants is one of the oldest and most effective pharmacological treatments in psychiatry. Yet, there continues to be controversy over the safety of stimulant medications in the treatment of ADHD.

Areas covered in this review: This paper is a continuation of an earlier paper that reviewed the safety profile of newer stimulant agents, especially in relation to special populations. This part II reviews, through essentially an organ-system approach, the various clinical concerns that have been raised over the safety of stimulant medications. This includes neuropsychiatric, cardiovascular effects on growth and development, and a number of other less common concerns.

What the reader will gain: A thorough review of safety concerns in stimulants that emphasizes clinical information, case reports, open series or controlled trials relating to stimulant use in the treatment of ADHD.

Take home message: While many safety concerns have been raised in the use of stimulants, the vast majority of treatment complications are either quickly reversible or easily manageable with appropriate clinical care. The negative consequences of untreated ADHD clearly outweigh the risks of the stimulant medicines when used in an appropriate and careful manner.     

Stimulant Medication for ADHD in Opioid Maintenance Treatment

Objective: The use of central stimulant medication in adults with attention deficit hyperactivity disorder (ADHD) who receive opioid maintenance treatment remains controversial and empirical evidence is limited. Because of the abuse potential of stimulant drugs, Norway has restrictions on prescribing central stimulants to individuals who have substance use disorders or who are on opioid maintenance treatment. In this naturalistic study, we describe experiences from a program through which central stimulant medication was administered to patients with ADHD receiving opioid maintenance treatment. Methods: This report is based on a program evaluation of a combined treatment project designed to provide stimulant medication to patients with adult ADHD who were receiving opioid maintenance treatment. As part of the clinical treatment, patients were monitored closely for any medical issues or adverse medication reactions and provided regular urine samples for analysis and information regarding demographics, treatment goals, legal involvement, diagnoses, substance abuse, and ADHD symptoms. Monitoring occurred at baseline, at 2 months (after patients being stabilized on the central stimulant), and again at 3, 6 and 24 months. Results: Among 42 patients initially offered the combined treatment, 24 were actually eligible, 20 started the combined treatment, and 10 stayed in the program. We were not able to identify a single major cause of treatment dropout. Patients reported significantly fewer symptoms of ADHD at the 6- to 8-week point, regardless of whether the data were analyzed using an intent-to-treat (all participants) or per-protocol (only those with complete data at all points) method. Even though self-assessed ADHD scores dropped significantly during treatment, the scores still remained fairly high, suggesting persistent functional impairment. Neither severe complications nor increase in substance abuse were observed during treatment with central stimulants. Conclusions: These findings show some promise with regard to the safety and utility of central stimulant medications for patients with ADHD who are receiving opioid maintenance treatment. Our study has methodological limitations, and systematic, well-designed clinical investigations are needed to increase the knowledge base.     

An ounce of prevention: A pre-randomization protocol to improve retention in substance use disorder clinical trials

BackgroundMissing data in substance use disorder (SUD) research pose a significant threat to internal validity. Participants terminate involvement or become less likely to attend intervention and research visits for many reasons, which should be addressed prior to becoming problematic. During a 9-month study targeting stimulant abuse, early dropouts and participant reported attendance barriers led to implementing a structured, pre-randomization protocol with participants about retention and solution-focused strategies (the “Fireside Chat”). Our aim is to outline this approach and present data on intervention participation and research visit attendance after implementation.Methods/designSTimulant Reduction using Dosed Exercise (STRIDE) was a two-arm, multisite randomized clinical trial testing treatment-as-usual for stimulant abuse/dependence augmented by Exercise or Health Education. For both groups, study intervention visits at the site were scheduled 3/week for 12 weeks followed by 1/week for 24 weeks. During The Chat, research staff thoroughly reviewed participants' expectations, and barriers and solutions to retention. Fifteen participants were randomized (to Exercise or Health Education) prior to and fourteen were randomized after Chat implementation. Intervention and monthly follow-up attendance (before and after implementation) were compared at the site (N = 29) that developed and rigorously implemented The Chat.ResultsIndividuals who participated in The Chat (n = 14) attended significantly more intervention visits during weeks 1–12 (p < 0.001) and weeks 13–36 (p < 0.05) and attended more research visits (p < 0.001).DiscussionProactive discussion of expectations and barriers prior to randomization was associated with greater study attendance. SUD researchers should consider tailoring this approach to suit their needs. Further investigation is warranted.     

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy

Objective: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D?+?T; oral) and those initiated on 1?L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous).

Methods: Patients with melanoma initiated on D?+?T or N/P from Q1/2014 to Q2/2016 (defined as 1?L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D?+?T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1?L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates).

Results: Of the 445 patients included, 202 and 243 were initiated on D?+?T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1?L therapy than those initiated on D?+?T (difference?=?18.6 visits PPY [95% CI?=?16.0–21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference?=?8.1 visits PPY [95% CI?=?1.9–13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1?L therapy).

Conclusions: HRU during 1?L therapy was generally similar between patients initiated on D?+?T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.     

尿沉渣分析仪和镜检法在尿沉渣检测中的相关性研究

目的探讨尿沉渣分析仪和镜检法在尿沉渣检测中的相关性。方法2010年1月—2010年5月门诊和住院送验检查标本,部分样本选自肾内科及泌尿科患者共328例,观察两种检测方法符合情况,统计UF2100全自动尿沉渣分析仪检测与镜检法符合率。结果328例患者经光学显微镜检查阳性228例,阳性率69．51％;阴性100例,阴性率30．48％;经UF2100全自动尿沉渣分析仪检查阳性222例,阳性率67．68％;阴性106例,阴性率32．31％。结论尿沉渣分析仪有一定局限性,还不能完全取代传统显微镜检,可用于过筛和治疗监控,有很高的临床使用价值,使用过程中应结合显微镜检查,排除其误、漏诊因素,提高尿沉渣检验的准确性。     

Changing trends in osteoporosis care from specialty to primary care physicians

Abstract

Background:

Inadequate treatment by non-specialty primary care physicians (PCPs) has been a concern in improving osteoporosis care. An increase in outpatient visits by older patients seeking osteoporosis care has been reported. But what percentages of these visits are made to PCPs are unknown. We investigated recent trends of outpatient visits and treatment for osteoporosis in older adults (>50 years) by physician type (PCPs vs. specialty care non-PCPs).     

Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult

Abstract

Background: The use of the natural product, kratom, has increased significantly in recent years. The active compounds in kratom have been shown to produce both opioid and stimulant-like effects. While kratom is marketed as a safe, non-addictive method to treat pain and opioid withdrawal, there have been reports demonstrating that kratom is physiologically addictive and linked to overdose deaths. A limited number of case-reports are available describing treatment of kratom use disorder in middle-aged adults, generally in the context of chronic pain and in inpatient settings. Our case is unique in that we describe outpatient treatment of kratom use disorder in a young adult with comorbid attention deficit hyperactivity disorder (ADHD) and in the absence of chronic pain. Case: A 20-year-old college student with ADHD presented to an office-based opioid agonist treatment clinic (OBOT) for treatment of kratom use disorder. He was unable to attend inpatient or residential substance use treatment due to work and school obligations. Additionally, he had stopped taking his prescribed stimulant due to cardiac side effects. The OBOT team successfully initiated buprenorphine-naloxone (BUP/NAL) sublingual films via home induction to treat his kratom use disorder. The patient is being monitored monthly with plans to slowly taper his BUP/NAL dose as tolerated. Discussion: We present a case of a young adult male with kratom use disorder, complicated by a diagnosis of ADHD, successfully treated with BUP/NAL via home induction. The patient is currently kratom-free, reports improved mood and sleep patterns since initiating BUP/NAL, and is able to once again tolerate his ADHD stimulant medication. Healthcare providers should be aware of the use of kratom and consider utilizing BUP/NAL to treat dependence to this botanical drug.     

Validity of the Self-Reported Drug Use Section of the Addiction Severity Index and Associated Factors Used under Naturalistic Conditions

The study examined the validity of 1848 self-reported uses of drugs determined within an Addiction Severity Index interview in comparison with urinalysis results among drug-dependent subjects undergoing treatment in outpatient clinics (Aquitaine area, southwest France, 1994–2005). Agreement and kappa statistics were calculated for each substance. Factors associated with agreement were defined using a multivariate analysis. The conditional kappa coefficients were excellent for all substances assessed. The accuracy between self-reports and urinalysis results was influenced by factors that only slightly affected conditional kappa coefficients. Clients did not underreport their substance use in naturalistic clinical assessment conditions.     

Methadone maintenance and the cost and utilization of health care among individuals dependent on opioids in a commercial health plan

Background

Few health plans provide maintenance medication for opioid dependence. This study assessed the cost of treating opioid-dependent members in a commercial health plan and the impacts of methadone maintenance on costs of care.

Methods

Individuals with diagnoses of opioid dependence (two or more diagnoses per year) and at least 9 months of health plan eligibility each year were extracted from electronic health records for the years 2000 through 2004 (1,518 individuals and 2,523 observations across the study period—some individuals were in multiple years). Analyses examined the patterns and costs of health care for three groups of patients: (1) one or more methadone visits during the year (n = 1,298; 51%); (2) no methadone visits and 0 or 1 visits in the Addiction Medicine Department (n = 370; 15%); (3) no methadone visits and 2 or more visits in addiction medicine (n = 855; 34%).

Results

Primary care (86%), emergency department (48%) and inpatient (24%) visits were common. Mean total annual costs to the health plan were $11,200 (2004 dollars) per member per year. The health plan's costs for members receiving methadone maintenance were 50% lower ($7,163) when compared to those with two or more outpatient addiction treatment visits but no methadone ($14,157) and 62% lower than those with one or zero outpatient addiction treatment visits and no methadone treatment ($18,694).

Conclusions

Use of opioid maintenance services was associated with lower total costs of care for opioid-dependent members in a commercial health plan.     

基于人工智能的药物-靶标相互作用预测

目的 建立一个高效的药物-靶标相互作用预测分类模型，为生物实验提供有力的补充工具。方法 研究开发一种基于深度学习的方法来预测药物-靶标相互作用：通过引入高维分子指纹和蛋白质描述符，并应用概率矩阵分解算法生成负样本集，构建一个高效的药物-靶标相互作用预测分类模型。结果 与其他已报道的方法相比，本方法具有可比性或优越性，预测准确性、特异性、敏感性以及AUC值均>90%，提示该方法在药物靶标预测方面具有良好的应用前景。结论 人工智能深度学习模型以及概率矩阵分解算法的结合有助于解决药物-靶标相互作用预测精度低、负样本选择不合理等问题。     

Efecto del seguimiento farmacoterapéutico en pacientes con hiperparatiroidismo secundario tratados con cinacalcet

ObjectivesTo assess the effect of pharmaceutical intervention in the identification of drug-related problems, to improve desired clinical outcomes, and to evaluate the effectiveness of cinacalcet in achieving clinical outcomes recommended by the KDOQI Clinical Guidelines.MethodQuasi-experimental pre-post intervention study. Patients with Secondary Hyperparathyroidism due to Chronic Kidney Disease, aged ≥18 years and under treatment with cinacalcet were recruited at the hospital outpatient pharmacy between 2007 and 2009. Dáder follow-up method and SMAQ and Moriski questionnaires were used to verify adherence at the first interview. Then, the pharmacist analyzed each case and designed an adequate intervention. Clinical parameters were consulted in the hospital laboratory data base.ResultsThirty four patients were included, 29 drug-related problems were found before pharmacist intervention, and among these, non-adherence was the most common (15). After the intervention, 9 drug-related problems remained, which means that 68.9% of them were resolved (P<0.001), reaching an adherence of 80%. Parathyroid hormone, calcium and calcium-phosphorus product serum levels decreased significantly after 3 months of treatment (P<0.001, <0.001 and 0.045, respectively), achieving the KDOQI Clinical Guideline recommendations.ConclusionThese results suggest that this simple and easy-to-apply intervention was effective in preventing and resolving drug-related problems in these patients. Moreover, it improved patient adherence and confirmed that cinacalcet treatment is effective for achieving the clinical outcomes recommended by KDOQI clinical guidelines.     

Diagnosis and treatment of adult attention-deficit/hyperactivity disorder at US ambulatory care visits from 1996 to 2003

ABSTRACT

Objective: To determine national-estimates and characteristics of United States (US) ambulatory care visits made by adults, aged 18 years or older, with attention-deficit hyperactivity disorder (ADHD) diagnosis, treatment patterns, and significant factors associated with adult-ADHD treatment.

Methods: Retrospective analyses were conducted of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey over a combined 8‐year period (1996–2003). Mental-health disorder (including ADHD) visits were identified using International Classification of Diseases, 9th revision, Clinical Modification (ICD‐9‐CM) diagnostic codes. Significant factors of adult-ADHD treatment were determined in multivariable logistic regression analyses.

Results: An estimated total 10.5 million ambulatory-ADHD visits accounted for 3.5% of 301 million adult mental-health disorder visits. The census-adjusted visit rate was 0.3–0.4%. Increasing in numbers from the year 2000, ADHD visits were most often to psychiatrists, by Caucasian men, aged 18 to 40 years. Significantly fewer ADHD visits without, versus with, psychiatric comorbidity (mainly depression) received various treat-ments – behavioral (46% vs. 83%), antidepressant (18% vs. 66%), or combined behavioral and ADHD-specific (stimulant or atomoxetine) pharmacotherapy (36% vs. 57%) respectively. However, more ADHD visits without than with psychiatric comorbidity received ADHD-specific pharmacotherapy alone (76% vs. 68%) or no treatment (14% vs. 6.5%). At ADHD visits, adjusting for gender, age, and US census geographic-region, psychiatric comorbidity (odds ratio [OR], 6.5, 95% confidence interval [Cl], 3.5–12.4, p < 0.05) and self-pay reimbursement-source (OR, 2.7, 95% Cl, 1.3–5.7, p < 0.05) significantly increased the likelihood of behavioral treatment. Insurance reimbursement-sources other than private and self-pay significantly decreased the likelihood of an ADHD-specific pharmacotherapy (OR, 0.4, 95% Cl, 0.2–0.7, p < 0.05) or any ADHD-treatment (OR, 0.2, 95% Cl, 0.1–0.5, p < 0.05).

Conclusions: Adult-ADHD visits have increased in recent years, with a census-adjusted visit rate of 0.3–0.4%. Psychiatric comorbidity and reimbursement-source were associated with ADHD-treatment. Limited treatment may be a significant problem in US-ambulatory care. It is important to continue validation studies, educate providers, examine the efficacy of multimodal-treatments, and study insurance-related barriers to adult ADHD-treatment.