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.

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.

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.

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.

Bright-light amaurosis fugax: an unusual symptom of retinal hypoperfusion corrected by external carotid revascularization.

The eye often serves as an important monitor of carotid artery disease by manifesting visual disturbances before cerebral events. The most typical ocular symptom complex is amaurosis fugax characterized by loss of vision in one eye that occurs suddenly and clears within seconds to minutes. This symptom is a hallmark of carotid artery disease and is usually caused by an embolic event. Although monocular visual disturbance on a hemodynamic basis is a more unusual manifestation of carotid artery disease, significant stenosis in combination with a low-flow state can cause transient, unilateral telescoping of vision. This report describes another visual disturbance associated with carotid artery disease in which unilateral visual loss occurred upon exposure to bright light. We term this syndrome bright-light amaurosis fugax and document successful treatment by external carotid artery revascularization in two patients.

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.

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.

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.

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.

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.

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.

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.

The efficacy of Polysporin First Aid Antibiotic Spray (polymyxin B sulfate and bacitracin zinc) against clinical burn wound isolates.

Polysporin First Aid Antibiotic Spray (Burroughs Wellcome Co., Research Triangle Park, N.C.) is a dry spray containing 200,000 units Aerosporin (polymyxin B sulfate) and 10,000 units bacitracin zinc, along with a propellant. Each 1-second spray delivers approximately 2300 units of polymyxin B sulfate and 115 units of bacitracin zinc. This study was designed to evaluate the efficacy of Polysporin Spray against various clinical isolates. Blood agar plates were inoculated with a pure culture of each isolate. Polysporin was then sprayed in an area approximately 30 mm in diameter. The area of inhibition was measured and recorded after 18 to 24 hours of incubation. A clear zone at least 20 mm in diameter with surrounding edges of growth indicated sensitivity. A zone less than 20 mm in diameter or growth over the whole plate indicated resistance. Three hundred fifty-three clinical isolates (202 gram positive and 151 gram negative) were tested. The results show that Polysporin inhibits the growth of all the gram-positive organisms, including methicillin-resistant strains of Staphylococcus. The gram-negative organisms were also sensitive to Polysporin Spray, with the exception of Serratia marcescens, Morganella morganii, and Proteus mirabilis. This study suggests that Polysporin First Aid Antibiotic Spray may be effective for wounds contaminated with gram-positive and some gram-negative organisms.

Influence of burn size on the incidence of contamination of burn wounds by fecal organisms.

Ischemia and reperfusion injury of the gut mucosa after severe injury have been shown to allow endogenous gastrointestinal tract microorganisms to pass into systemic areas (bacterial translocation); this has been hypothesized as a source of burn-wound contamination. To study this phenomenon, 53 pediatric patients with burns underwent routine fecal culture at the time of admission. These cultures were compared with wound cultures that were obtained at the time of admission and throughout their hospitalization. Patients were grouped according to burn size: Small (1% to 20% total body surface area burned), Moderate (21% to 50%), and Severe (greater than 50%). The incidence of corresponding isolates was determined for each group and compared by analysis of variance. No difference in the frequency of corresponding isolates could be demonstrated between the Small (4.0%) and Moderate (7.7%) groups, whereas the Severe group (53.3%) demonstrated a significantly larger incidence of corresponding isolates (p less than 0.0001). Translocation of gut flora after severe burn injury may account for some instances of burn-wound contamination.

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.

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.

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.

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.

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.