Leveraging the Full Continuum of Care to Prevent Opioid Use Disorder.

Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.

Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Brief detection and co-occurrence of violence, depression and alcohol risk in prenatal care settings.

The purpose of the study was to examine the rates and inter-relationships among violence receipt, alcohol use problems, and depression in women seeking prenatal care. While waiting for their prenatal care appointment, women (n = 1054) completed measures of past year partner and non-partner violence receipt, alcohol misuse (TWEAK and quantity and frequency of alcohol use in past year), and depression (Center for Epidemiological Studies Depression Scale - CESD and prior history of depression). Over 30% of women reported either violence receipt, alcohol use problems or depression risk. Significant inter-relationships among all measured risk variables were found. Although violence receipt was significantly related to alcohol misuse, cigarette use, less education, and scoring above the cutoff on the CESD (>/= 16) was most strongly associated with violence. Practitioners should be well-equipped to provide assessment, interventions, or referrals as needed to the high numbers of women encountered in prenatal care settings experiencing psychosocial and behavioral problems that may affect their pregnancy.

Involvement of MAPK activation in bacterial endotoxin-inducible tissue factor upregulation in human monocytic THP-1 cells.

BACKGROUND: Monocytic tissue factor (mTF) hypercoagulation leading to thrombotic complications is commonly observed following sepsis. OBJECTIVE: We herein study the intracellular mechanism of mTF upregulation in human model monocytic THP-1 cells in response to bacterial endotoxin (lipopolysaccharide, LPS; Escherichia coli O111:B04), determining if mitogen-activated protein kinase (MAPK) activation is involved in the signaling. METHODS: We assessed mTF upregulation by its cell surface expression, protein synthesis, and functional activity based on flow cytometry, Western blotting analysis, and a single-stage clotting assay, respectively. RESULTS: A 3-h challenge with LPS (100 ng/ml) drastically induced mTF functional activity, accompanied by elevated surface mTF expression and synthesis. The suppression by genistein (G) of LPS-inducible mTF upregulation implied the involvement of protein tyrosine kinase activation in mTF upregulation. LPS activated MAPK, which was significantly depressed by G, SB 203580 (SB), and PD 98058 (PD). Interestingly, inclusion of SB and PD also markedly diminished LPS-inducible mTF upregulation. The parallelism between MAPK and mTF activities revealed the involvement of MAPK activation in such mTF upregulation. Based on the ability of SB and PD to respectively block LPS-inducible tyrosine phosphorylation of p38 MAPK and Erk1/2, it was evident that tyrosine phosphorylation of MAPKs is required for mediating LPS-inducible mTF synthesis and upregulation. Contrasting with the established prevention of mTF upregulation by these inhibitors, failure to offset the already LPS-induced mTF activity seemed to be consistent with the view that LPS readily activated MAPK responsible for mTF synthesis. CONCLUSION: Our data suggest that the tyrosine phosphorylation of MAPKs (p38 and Erk1/2) leading to their activation could be a prerequisite for LPS induction of mTF synthesis contributing to the upregulation of mTF-initiated extrinsic coagulation.

Diversity in relapse prevention needs: gender and race comparisons among substance abuse treatment patients.

Attempts to address high relapse rates following substance abuse treatment have focused on identifying relapse prevention needs and development of subsequent relapse prevention programs. Few studies have examined whether women and African-Americans have unique relapse prevention needs. Research in this area could provide an initial basis for the development of alternative relapse prevention approaches that could be more appropriate for this pop ulation. This study examined gender and race differences in psychosocial concerns among patients recruited from substance abuse treatment as potential indicators of relapse prevention needs. Participants (N = 331) completed several questionnaires during their first month of substance abuse treatment. Assessment packets included measures of coping, self-efficacy, resource needs, cravings, social influences, exposure, and leisure activities. Analyses focused on gender and race differences in these variables before and after controlling for background characteristics (i.e., age, marital status, income, polysubstance use, treatment type, and problem severity). Gender differences found were that men reported poorer coping skills and more negative social influences and exposure to substances than women; these differences remained significant when controlling for background characteristics. Significant race differences were found on all scales except negative social influences. After controlling for background characteristics, African-Americans reported significantly greater coping skills and self-efficacy than did Caucasians; however, African-Americans also reported greater resource needs in comparison to Caucasians. Results highlight the diversity in psychosocial issues among substance abusers in treatment, particularly between Caucasians and African-Americans. Implications for developing alternative relapse prevention approaches to address this diversity are discussed.

Correlates of expressed and received violence across relationship types among men and women substance abusers.

This study examined expressed and received violence among men and women in substance abuse treatment. Rates of past-year partner violence (PV) did not differ by gender, although men reported markedly higher rates of nonpartner violence (NPV). Compared with PV, NPV was associated with more demographic and background factors (e.g., childhood aggression and conduct problems, family history of violence). The most consistent correlates of violence across relationship types were age, minority status, drug-related consequences, psychiatric distress, and frequency of childhood aggression. Only a few gender-specific correlates were identified; most notably, witnessing father-to-mother violence was related to received PV only for women. Identification of correlates of expressed and received violence in partner and nonpartner relationships is essential for the assessment and treatment of individuals in substance abuse treatment settings.

Cocaine and methamphetamine: differential addiction rates.

Clients admitted to treatment centers for stimulant addiction were categorized as either regular users of cocaine or of methamphetamine based on an algorithm involving 5 specific criteria. A subsample consisting of 90 regular users of cocaine and nonusers of methamphetamine, and 39 regular users of methamphetamine and nonusers of cocaine, was selected for comparison. Analyses showed that, when compared with cocaine users, the methamphetamine users exhibited a shorter period of time from 1st use to regular use (period of initial use) and from 1st use to treatment entry (period of pretreatment use). Relative to cocaine use, the use of methamphetamine appears to induce a faster rate of progression toward regular use and subsequent need for treatment.

A comparison of substance abuse patients' and counselors' perceptions of relapse risk: relationship to actual relapse.

This study compared substance abuse patients' and their counselors' perceptions of relapse risk during treatment and evaluated whether these perceptions predict actual relapse 2 years later. Participants (N = 240) completed the Relapse Risk Index (RRI), which assesses confidence in abilities and need for services across four domains: coping skills, social support, resources, and leisure activities. Participants reported greater confidence and greater needs than counselors reported. Determinants of counselors' relapse risk perceptions included income, whereas participants' perceptions were related to polysubstance use. Counselors' ratings of coping skills predicted alcohol relapse; counselors' ratings did not predict drug relapse. Participants' ratings of coping skills and leisure activities predicted alcohol relapse; social support predicted drug relapse. When including background characteristics, counselors' ratings did not predict alcohol or drug relapse; participants' ratings predicted alcohol relapse but not drug relapse. Findings suggest the potential utility of considering patient perceptions to understand and possibly prevent relapse.

The relationship between alcohol problems and health functioning of older adults in primary care settings.

OBJECTIVE: The purpose of this study was to determine the relationship between alcohol use and health functioning in a sample of older adults screened in primary care settings. DESIGN: A cross-sectional study. SETTING: Thirty-seven primary care clinics. PARTICIPANTS: Older adults (n = 8,578; aged 55-97) with regularly scheduled appointments in primary care clinics were screened. MEASUREMENTS: Participants were categorized based on alcohol consumption levels as abstainers, low-risk drinkers, and at-risk drinkers (women: 9 or more drinks/week; men: 12 or more drinks/week). Dependent variables were eight SF-36 health functioning scales. RESULTS: Sixty-one percent of participants were abstainers, 31% were low-risk drinkers, and 7% were at-risk drinkers. ANCOVAs found significant effects of drinking status on General Health, Physical Functioning, Physical Role Functioning, Bodily Pain, Vitality, Mental Health, Emotional Role, and Social Functioning, controlling for age and gender, with low-risk drinkers scoring significantly better than abstainers. At-risk drinkers had significantly poorer mental health functioning than low-risk drinkers. Few significant gender differences were found on SF-36 scales. CONCLUSIONS: Older adults who are at-risk drinkers may not present with poor physical health functioning. Future studies are needed to determine the relationship between drinking limits for older adults and other areas of physical and psychosocial health.

Older adult treatment outcome following elder-specific inpatient alcoholism treatment.

This study examined multidimensional 6-month outcomes of elder-specific inpatient alcoholism treatment for 90 participants over the age of 55. At baseline, physical health functioning was similar to that reported by seriously medically ill inpatients in other studies while psychosocial functioning was worse, and nearly one third of the sample had comorbid psychiatric disorders. Based on 6-month outcomes, participants were classified into the following groups: Abstainers, Non-Binge Drinkers, and Binge Drinkers. The groups did not differ on any baseline measures (demographics, drinking history, alcohol symptoms and age of onset, comorbidity, or length of treatment). General health improved between baseline and follow-up for all groups. Psychological distress decreased for Abstainers and Non-Binge Drinkers, but did not change for Binge Drinkers. Results suggest that a large percentage of older adults who receive elder-specific treatment attain positive outcomes across a range of outcome measures.

Stability in the drinking habits of older problem-drinkers recruited from nontreatment settings.

Few prospective studies have examined older problem-drinkers not currently in treatment to determine the stability in alcohol problems over time. Seventy-eight currently drinking, older adults meeting a diagnosis of alcohol abuse or dependence were recruited via advertising to complete a health interview; 48 were reinterviewed approximately 3 years later. Participants were categorized based on alcohol consumption (risk) and alcohol-related diagnostic symptoms (problem) at baseline and follow-up. At follow-up, few older adults (11.4%) were resolved using both risk and problem criteria. Alcohol risk/problem groups were not significantly stable between baseline and follow-up. Health problems was the most common reason for changing drinking habits. Average and maximum consumption at baseline and follow-up were significant markers of follow-up risk group and follow-up alcohol-related consequences, respectively, with maximum consumption being more robust. The course of alcohol problems among older adults fluctuates over time, and heavy drinking appears to be the best indicator of problem continuation.

Blockade by polyunsaturated n-3 fatty acids of endotoxin-induced monocytic tissue factor activation is mediated by the depressed receptor expression in THP-1 cells.

BACKGROUND: Monocytic hypercoagulation often occurs in inflammatory conditions. We have previously reported that polyunsaturated n-3 fatty acids (n-3 FA) including eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) prevent the activation of monocytic tissue factor (TF) induced by bacterial endotoxin [lipopolysaccharide (LPS)] in cell cultures and animals. HYPOTHESIS: We herein explore the mode of inhibitory action of n-3 FA to determine if LPS transmembrane signaling is blocked, exerting such antagonism. RESULTS: Exposure of human leukemia monocytic THP-1 cells to bacterial endotoxin (Escherichia coli 0111:B04, 1.5 microg/ml) for 6 h significantly activated TF activity and the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-1beta in conditioned medium. Pretreatment with n-3 FA, 20:5 and 22:6 at 10 microM, resulted in time-dependent suppression of not only TF activation but also the elicitation of NO, TNF-alpha, and IL-1beta. These LPS responses were substantially depressed by more than 50% after a 72-h pretreatment. FACScan analysis showed that n-3 FA readily prevented fluorescein isothiocyanate (FITC)-conjugated LPS from binding to THP-1 cells by approximately 70%. The observation that anti-CD14 mAb diminished FITC-LPS binding in a dose-dependent fashion has revealed CD14 dependency in LPS recognition. LPS upregulated CD14 expression, which was significantly arrested by n-3 FA. Similarly, the upregulation of the expression of CD11b, another proposed LPS receptor, was also minimally but significantly depressed by n-3 FA. CONCLUSION: The present study demonstrates that n-3 FA are able to block LPS transmembrane signaling via suppression of the receptor upregulation, mediating a variety of significant antagonisms against LPS action.

I. Suppression by compound 48/80 of bacterial endotoxin-inducible monocytic tissue factor activity: direct blockade of factor VII binding to THP-1 monocytes.

Hypercoagulation with upregulated monocytic tissue factor (TF) activity often occurs under a variety of inflammatory conditions including endotoxemia. The antagonism to bacterial endotoxin (LPS) signaling often results in the depression in TF upregulation. We herein report that compound 48/80 (48/80) significantly depressed LPS-induced TF activity in human and cebus monkey peripheral blood monocytes. Employing a model monocyte-like cell line (THP-1), we explored the regulatory mechanism to identify the inhibitory site(s) of 48/80. We determine whether the inhibition results from the blockade of LPS signaling. 48/80 dose-dependently inhibited LPS-induced TF activity. Chase of LPS-challenged cells with 48/80 also significantly offset TF upregulation. In immunofluorescent approaches, FACScan analysis revealed that 48/80 had no effect on either LPS recognition or the expression of its receptors (CD14 and CD11b). Moreover, LPS-induced TF expression as well as synthesis remained unaffected in the presence of 48/80. Consistent with the independence of LPS action, 48/80 was also able to inhibit TF activity induced by A23187, ionomycin, or Quin-2 AM. Interestingly, 48/80 significantly decreased the FVII binding to either resting or LPS-challenged cells. In conclusion, our results elucidate that the inhibitory action of 48/80 was independent of LPS signaling including recognition, receptor expression, and the induced TF expression/ synthesis. However, 48/80 was able to directly block FVII binding to monocytic TF, thereby resulting in such antagonism to LPS-induced TF-initiated extrinsic coagulation.

Methods of ensuring high follow-up rates: lessons from a longitudinal study of dual diagnosed participants.

Despite growing research interest in co-occurring psychiatric and substance misuse disorders, relatively few longitudinal studies have been conducted with dual diagnosis populations. Many of the longitudinal studies that have been done have experienced excessive attrition. Thus, investigators have noted that one of the primary difficulties of conducting longitudinal studies with this population is successfully minimizing attrition during follow-up. This study, conducted in 1991 1993, describes retention and tracking methods employed in a longitudinal study of 485 dual diagnosis participants. Follow-up interview completion rates at the 2-, 6-, 10-, 14-, and 18-month interviews were 86.7, 85.6, 85.1, 84.5, and 88.4%, respectively. Several case studies are provided that document some of the challenges facing project staff and successful strategies for handling them. A notable finding from this study was that participants reported that the relationship established with the interviewer was more important than material incentives in preventing study attrition.

Tracking substance abusers in longitudinal research: understanding follow-up contact difficulty.

Studies examining follow-up contact difficulty provide useful information for planning longitudinal studies and for assessing the validity of follow-up data. Contact difficulty was examined among 96 substance abusers following substance abuse treatment. Interview completion rates at the 3-month and 6-month follow-ups were 93 and 97%, respectively. The extent of contact efforts required to complete follow-up interviews varied substantially but tended to be greater at the 3-month follow-up than at the 6-month follow-up. Contact difficulty was related to reuse of substances at the 3-month and at the 6-month follow-ups with reusers requiring greater contact efforts than abstainers. None of the baseline individual and contextual variables examined significantly predicted level of contact effort at follow-ups. Attrition-related validity implications are discussed along with practical suggestions for planning tracking efforts.

The use of aztreonam as an alternate therapy for multi-resistant Pseudomonas aeruginosa.

The emergence of multi-resistant Gram-negative bacteria has created a most alarming clinical situation. The armamentarium of antibiotics used against this group of organisms is rapidly being depleted. Our routine therapeutic approach to control and prevent these Gram-negative bacteria from gaining a foothold was the empirical use of an aminoglycoside combined with piperacillin. However, aminoglycoside resistance is now routine rather than unusual. We evaluated the role of the monobactam aztreonam in burn wound infections and compared it to the aminoglycosides amikacin and gentamicin as well as piperacillin for the Enterobacteriacae and Pseudomonas aeruginosa. A total of 1274 Gram-negative isolates including P. aeruginosa were evaluated for susceptibility to the above-mentioned antibiotics from January 1995 to August 1995 (Table I). Among the Enterobacteriacae, aztreonam was more effective than amikacin and piperacillin (58.4 per cent vs. 45.8 per cent, respectively). However, it still fluctuated among the Enterobacteriacae as did the aminoglycosides. One major significant finding was that while susceptibility to aztreonam was variable for the Enterobacteriacae, P. aeruginosa remained 90 per cent susceptible to aztreonam and 90 per cent susceptible to piperacillin, whereas it was 79 per cent resistant to the aminoglycosides. Consequently, when choosing an antimicrobial in a suspected P. aeruginosa burn wound infection, aztreonam and piperacillin should be considered as the first line of defense.

Social settings and addiction relapse.

Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

The role of attributions in abstinence, lapse, and relapse following substance abuse treatment.

This study examined the role of attributions in the lapse and relapse process following substance abuse treatment. According to Marlatt and Gordon's theoretical framework, attributions made after a lapse (e.g., the Abstinence Violation Effect [AVE]) determine whether it progresses to a relapse. Also examined were the attributions of recovering drug users who were tempted but remained abstinent (never lapsed). Ninety-seven participants were recruited from an inpatient treatment center for substance abuse and completed an interview 6 months after leaving treatment. Findings partially confirmed predictions made by the AVE. Predictions made by the AVE were not supported in that lapsers and relapsers were similar regarding their internal/external attributions following a return to drug use; predictions were supported as relapsers made more stable and global attributions as compared to lapsers. Also as predicted, abstainers made more internal, stable, and global attributions regarding their abstinence (as compared to lapsers following their slip). Abstainers' attributions for their success in remaining abstinent tended to be similar to the attributions made by relapsers for their failure to remain abstinent (i.e., for their relapse). Combined, these findings highlight the complexity of the attributional process in early recovery from substance abuse. Clinical and research implications of the findings are discussed in relation to substance abuse relapse prevention.

Determinants of early alcohol and drug use among young women in alcoholism treatment.

Substance abuse experimentation may be one of several types of problem behaviors. Data from 99 Caucasian women interviewed in alcoholism treatment (19-29 years old) were used to test a developmental model of substance experimentation. Respondents were classified into three groups based on their use prior to age 15: nonusers, users of alcohol only, and users of alcohol and other drugs. Family history of alcoholism was not related to childhood anxiety and impulse control problems. Childhood anxiety and impulse control problems predicted adolescent emotional and impulse control problems but did not differentiate early experimenters. Whereas adolescent emotional problems were not related to early experimentation, early drug and alcohol users were significantly more likely to have engaged in other impulsive behaviors (e.g., running away from home, trouble with school authorities) than were nonusers or users of alcohol only. Alcoholism prevention programs, therefore, would do well to target youth who exhibit acting-out behaviors as a high-risk group for early alcohol and drug use.

Selective tolerance to discriminative stimulus effects of morphine or d-amphetamine.

Pharmacological selectivity of tolerance to the discriminative stimulus effects of morphine or d amphetamine was examined in pigeons trained to discriminate among 3.2mg/kg morphine, saline, and 1.8mg/kg d-amphetamine under a 3-key fixed-ratio 30 schedule of food delivery. Cumulative doses of morphine (0.32-10mg/kg) or d-amphetamine (0.10-3.2mg/kg) evoked morphine-or d-amphetamine-key responding, respectively, in a dose-dependent manner. Suspending training and administering repeated doses of morphine (32mg/kg b.i.d.) for 1 week increased the dose of morphine required for morphine-key responding approximately 5-fold, without altering sensitivity to d-amphetamine. Conversely, repeated treatment with d-amphetamine (5.6mg/kg b.i.d.) increased the dose of d-amphetamine required for d-amphetamine-key responding approximately 7-fold, without decreasing sensitivity to morphine. Repeated treatment with saline (1ml/kg b.i.d.) for 1 or 2 weeks did not alter sensitivity to stimulus effects of either morphine or d-amphetamine. Sensitivity to stimulus effects of morphine recovered fully within 1 week after morphine treatment ended; sensitivity to stimulus effects of d-amphetamine recovered partially within 3 days after d-amphetamine treatment ended. For morphine, but not for d-amphetamine, increases in the dose required for stimulus effects were accompanied by increases in the dose required for rate-reducing effects. These results demonstrate that tolerance to discriminative stimulus effects of morphine and d-amphetamine is pharmacologically selective and suggest that pharmacotherapies targeted to one drug of abuse may produce little change in sensitivity to subjective effects of drugs from a different pharmacological class.