The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

OBJECTIVE: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. METHODS: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. RESULTS: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. CONCLUSIONS: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Systematic review of the efficacy, effectiveness, and cost-effectiveness of stepped-care interventions for the prevention and treatment of problematic substance use.

BACKGROUND: Stepped-care is a commonly recommended and implemented care model across health care domains, including substance use. Despite their presumed efficient allocation of treatment resources, a current and robust evidence synthesis is needed on the efficacy, effectiveness and cost-effectiveness of stepped-care for substance use. METHODS: This systematic review analyzed articles describing evaluations of stepped-care models that measured the use of acutely psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in participants over 18 years old. The analysis investigated model and participant characteristics associated with treatment outcomes. RESULTS: The study team conducted a search of five databases of literature (PsychINFO, MEDLINE, Embase, Cochrane Library and Scopus) published between January 1, 2010, and November 1, 2020. The search yielded 1051 unique articles, 19 of which were included in the analysis. The studies had considerable variability in sample sizes (n = 18-2310), time to follow-up (4.5 months to 3 years), and retention rates (35.1-100 %). Studies examined outcomes for either alcohol alone (n = 9), alcohol and other drug use (n = 9), or drug use alone (n = 1). Most studies (n = 13;) were rated as good quality. Three (15.8 %) were rated as fair and three (15.8 %) were rated as poor quality. The evidence regarding the efficacy, effectiveness and cost-effectiveness of stepped-care approaches is limited, but four of seven studies found that adaptive-care interventions delivered in the context of other systemic interventions produced greater benefit than control conditions in relation to at least one alcohol-related outcome. We have insufficient evidence to determine whether the modes or intensity of interventions included in the models, or decision rules used to step people up or down to differing levels of care, have an impact on outcome. CONCLUSION: Heterogeneity between studies with regard to model and evaluation design limited the degree to which the analysis could draw robust conclusions. Sample recruitment and statistical power are particular challenges, and the field needs more innovative evaluation designs to assess the efficacy, effectiveness, and cost-effectiveness of stepped-care models.

A systematic review of the efficacy, effectiveness and cost-effectiveness of workplace-based interventions for the prevention and treatment of problematic substance use.

Employee alcohol and other drug use can negatively impact the workplace, resulting in absenteeism, reduced productivity, high turnover, and worksite safety issues. As the workplace can influence employee substance use through environmental and cultural factors, it also presents a key opportunity to deliver interventions, particularly to employees who may not otherwise seek help. This is a systematic review of workplace-based interventions for the prevention and treatment of problematic substance use. Five databases were searched for efficacy, effectiveness and/or cost-effectiveness studies and reviews published since 2010 that measured use of psychoactive substances (i.e., alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, and stimulants) as a primary or secondary outcome, in employees aged over 18. Thirty-nine articles were identified, 28 describing primary research and 11 reviews, most of which focused solely on alcohol use. Heterogeneity between studies with respect to intervention and evaluation design limited the degree to which findings could be synthesized, however, there is some promising evidence for workplace-based universal health promotion interventions, targeted brief interventions, and universal substance use screening. The few studies that examined implementation in the workplace revealed specific barriers including lack of engagement with e-health interventions, heavy use and reluctance to seek help amongst male employees, and confidentiality concerns. Tailoring interventions to each workplace, and ease of implementation and employee engagement emerged as facilitators. Further high-quality research is needed to examine the effectiveness of workplace substance use testing, Employee Assistance Programs, and strategies targeting the use of substances other than alcohol in the workplace. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227598, PROSPERO [CRD42021227598].

Climate vulnerability and resilience in the most valuable North American fishery.

Managing natural resources in an era of increasing climate impacts requires accounting for the synergistic effects of climate, ecosystem changes, and harvesting on resource productivity. Coincident with recent exceptional warming of the northwest Atlantic Ocean and removal of large predatory fish, the American lobster has become the most valuable fishery resource in North America. Using a model that links ocean temperature, predator density, and fishing to population productivity, we show that harvester-driven conservation efforts to protect large lobsters prepared the Gulf of Maine lobster fishery to capitalize on favorable ecosystem conditions, resulting in the record-breaking landings recently observed in the region. In contrast, in the warmer southern New England region, the absence of similar conservation efforts precipitated warming-induced recruitment failure that led to the collapse of the fishery. Population projections under expected warming suggest that the American lobster fishery is vulnerable to future temperature increases, but continued efforts to preserve the stock's reproductive potential can dampen the negative impacts of warming. This study demonstrates that, even though global climate change is severely impacting marine ecosystems, widely adopted, proactive conservation measures can increase the resilience of commercial fisheries to climate change.

A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation.

UNLABELLED: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, is implicated as a possible therapy for airway inflammation via induction of the transcription factor NF-E2-related factor 2 (NRF2). In this proof-of-concept clinical study, we show that supplementation of SFN with broccoli sprout homogenate in healthy human subjects did not induce expression of antioxidant genes or protect against neutrophilic airway inflammation in an ozone-exposure model. Therefore, dietary sulforaphane supplementation is not a promising candidate for larger scale clinical trials targeting airway inflammation. TRIAL REGISTRATION: NCT01625130 . Registered 19 June, 2012.

Blood pressure responses to dietary sodium and potassium interventions and the cold pressor test: the GenSalt replication study in rural North China.

BACKGROUND: In the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, we observed that blood pressure (BP) responses to dietary sodium and potassium interventions and the cold pressor test (CPT) varied greatly among individuals. We conducted a replication study to confirm our previous findings among 695 study participants. METHODS: The dietary intervention included a 7-day low sodium (51.3 mmol/day), a 7-day high sodium (307.8 mmol/day), and a 7-day high sodium with potassium supplementation (307.8 mmol sodium and 60 mmol potassium/day). BP measurements were obtained during the baseline and each intervention phase. During the CPT, BP was measured before and at 0, 1, 2, and 4 minutes after the participants immersed their right hand in ice water for 1 minute. RESULTS: Systolic and diastolic BP responses (mean ± SD (range), mm Hg) were 8.1±8.4 (-39.1 to 18.2) and -3.5±5.1 (-25.1 to 11.1) to low sodium, 9.1±8.4 (-13.3 to 33.1) and 4.0±5.4 (-16.0 to 20.7) to high sodium, and -4.6±5.8 (-31.8 to 11.6) and -1.9±4.3 (-16.9 to 14.2) to potassium supplementation, respectively (all P < 0.0001 for comparison with each former phase). The mean maximum systolic and diastolic BP responses to the CPT were 16.5±10.5 (-15.3 to 63.3) and 7.6±6.1 (-8.7 to 39.3), respectively (all P < 0.0001). CONCLUSIONS: Our study indicates that there are large variations in BP responses to dietary sodium and potassium interventions and to the CPT among individuals.

Reproducibility of blood pressure responses to dietary sodium and potassium interventions: the GenSalt study.

Blood pressure responses to dietary sodium and potassium interventions vary among individuals. We studied the long-term reproducibility of blood pressure responses to dietary sodium and potassium intake. We repeated the dietary sodium and potassium interventions among 487 Chinese adults 4.5 years after the original dietary intervention. The identical dietary intervention protocol, which included a 7-day low-sodium feeding (51.3 mmol/d), a 7-day high-sodium feeding (307.8 mmol/d), and a 7-day high-sodium feeding with oral potassium supplementation (60.0 mmol/d), was applied in both the initial and repeated studies. Three blood pressure measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. The results from the 24-hour urinary excretion of sodium and potassium showed excellent compliance with the study diet. Blood pressure responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients (95% confidence interval) for systolic blood pressure levels were 0.77 (0.73-0.80) at baseline, 0.79 (0.75-0.82) during low sodium, 0.80 (0.77-0.83) during high sodium, and 0.82 (0.79-0.85) during high sodium and potassium supplementation interventions (all P<0.0001). The correlation coefficients for systolic blood pressure changes were 0.37 (0.29-0.44) from baseline to low sodium, 0.37 (0.29-0.44) from low to high sodium, and 0.28 (0.20-0.36) from high sodium to high sodium plus potassium supplementation (all P<0.0001). These data indicate that blood pressure responses to dietary sodium and potassium interventions have long-term reproducibility and stable characteristics in the general population.

Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20µg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations.

Patterns and costs of treatment for heroin dependence over 12 months: findings from the Australian Treatment Outcome Study.

OBJECTIVE: To determine patterns and costs of treatment for heroin dependence over a 12-month period among a cohort of heroin users seeking treatment. METHODS: The design was a longitudinal cohort study of heroin users seeking treatment who participated in the Australian Treatment Outcome Study (ATOS), which was conducted in Sydney, Melbourne and Adelaide, Australia. Treatment for heroin dependence, for those who were followed up at 12 months, was recorded and costed. Unit costs, obtained from secondary sources, were used to estimate the cost of treatment. This study does not include wide societal costs and only includes personal costs as they pertain to treatment. RESULTS: A follow-up rate of 81% at 12 months was achieved, resulting in data for 596 participants. Participants spent an average of 188 days in treatment over 2.7 episodes. Sixty-nine per cent of the sample reported at least one episode of treatment following their index treatment. There was a noticeable trend for subjects who received maintenance or residential rehabilitation as their index treatment to return to the same form of treatment for subsequent episodes. In contrast, those who received detoxification as index treatment accessed a wider variety of treatment types over the follow-up period. The cost of treatment over the 12-month follow-up totalled dollar 3,901,416, with a mean of dollar 6,517 per person. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that individuals seeking treatment have multiple treatment episodes throughout a 12-month period, with a tendency to return to the same form of treatment. This study also demonstrates that it is feasible and affordable to provide ongoing treatment for a group of heroin users seeking treatment.