IMPORTANCE: Opioid-dependent patients often use the emergency department (ED) for medical care. OBJECTIVE: To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to ...treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine). DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013. INTERVENTIONS: After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group. MAIN OUTCOMES AND MEASURES: Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes. RESULTS: Seventy-eight percent of patients in the buprenorphine group (89 of 114 95% CI, 70%-85%) vs 37% in the referral group (38 of 102 95% CI, 28%-47%) and 45% in the brief intervention group (50 of 111 95% CI, 36%-54%) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001). CONCLUSIONS AND RELEVANCE: Among opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00913770
Mitragyna speciosa, also known as kratom, has been reported to have a broad range of pharmacological properties. Freshly harvested leaves and their water extracts are consumed in Southeast Asia while ...preparations made from dried leaf material are consumed in Western countries. Our study evaluated the phytochemical composition of freshly harvested kratom leaves using LCMS/MS analysis of water and ethanol liquid extracts. Mitragynine and its congeners, including 7-hydroxymitragynine, speciocilliatine, speciogynine, paynantheine, as well as bioactive phenolics including chlorogenic acid, o-coumaric acid, quercitrin, and rutin were identified. However, 7-hydroxymitragynine was detected solely in the water-liquid extract. Currently, unknown compounds were also present in the chromatograms and mass spectra. The study results support that 7-hydroxymitragynine is a post-harvest oxidative derivative or metabolite of mitragynine. Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected ...scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West.
Our review of the Scopus database identified a total of 55 publications, including clinical case reports and case series reports, surveys, studies enrolling human participants, and publications based on large-scale national surveys or large-scale national or international health system database records.
Overall, there is dearth of reliable data on key epidemiological factors, including the prevalence rates, and on objective and reliable indices of the risk/safety profiles. Rigorous and systematic studies including improved epidemiological surveillance, human laboratory, and controlled clinical studies are urgently needed to advance our understanding of public health consequences of consuming kratom and kratom-derived products and to improve our understanding of their risk/safety profile and additional analytical studies to better inform development of needed regulatory oversight.
Mitragynine exerts its analgesic effect mainly via opioid receptors activation. Additionally, the effect may be mediated via mitragynine’s anti-inflammatory property and non-opioid receptor pain ...pathways, namely through the TRPV1 receptor. No studies identify hitherto, hence, the current study aimed to investigate the mitragynine’s analgesic effect via the anti-inflammatory property, non-opioid receptor (TRPV1) and the effective dose (ED) to alleviate pain. Male and female Sprague Dawley rats were pre-treated intraperitoneally with either mitragynine (1, 5, 10, 13, 15 or 30 mg/kg), vehicle, or indomethacin (1 mg/kg) 30 min before inducing inflammatory pain using acetic acid. The writhes and pain-related withdrawal behaviour occurrence were counted within a 1-h duration. Percentage of writhes inhibition, pain-related withdrawal behaviour aggregate, ED50 and ED95 were determined. The body temperature was recorded and TRPV1 expression in the rats' brains was measured. Mitragynine (except 1 mg/kg) significantly reduced the number of writhes compared with the vehicle administered group. Mitragynine (30 mg/kg) demonstrated 99.5% inhibition of writhing behaviour and low withdrawal behaviour score compared with vehicle and indomethacin and successfully blocked the hypothermia induced by acetic acid. The overall ED50 and ED95 values of mitragynine were 3.62 and 20.84 mg/kg, respectively. The percentage of writhing inhibition and withdrawal behaviour were similar in both genders. Mitragynine (15 and 30 mg/kg) significantly reduced the TRPV1 expression in the brain of the rats. Mitragynine alleviated pain-like behaviour and showed analgesic effects via anti-inflammatory and non-opioid receptor pathways. The findings also suggest that mitragynine might regulate some physiological functions of the rat.
•Mitragynine fully attenuated the writhing behaviour.•Mitragynine displayed a significantly lower cumulative withdrawal score.•Mitragynine maintain the normal body temperature even after the acetic acid injection.•Mitragynine-treated rats expressed lower TRPV1 expression in the brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
Background
Emergency department (ED)-initiated buprenorphine/naloxone with continuation in primary care was found to increase engagement in addiction treatment and reduce illicit opioid use ...at 30 days compared to referral only or a brief intervention with referral.
Objective
To evaluate the long-term outcomes at 2, 6 and 12 months following ED interventions.
Design
Evaluation of treatment engagement, drug use, and HIV risk among a cohort of patients from a randomized trial who completed at least one long-term follow-up assessment.
Participants
A total of 290/329 patients (88% of the randomized sample) were included. The followed cohort did not differ significantly from the randomized sample.
Interventions
ED-initiated buprenorphine with 10-week continuation in primary care, referral, or brief intervention were provided in the ED at study entry.
Main Measures
Self-reported engagement in formal addiction treatment, days of illicit opioid use, and HIV risk (2, 6, 12 months); urine toxicology (2, 6 months).
Key Results
A greater number of patients in the buprenorphine group were engaged in addiction treatment at 2 months 68/92 (74%), 95% CI 65–83 compared with referral 42/79 (53%), 95% CI 42–64 and brief intervention 39/83 (47%), 95% CI 37–58;
p
< 0.001. The differences were not significant at 6 months 51/92 (55%), 95% CI 45–65; 46/70 (66%) 95% CI 54–76; 43/76 (57%) 95% CI 45–67;
p
= 0.37 or 12 months 42/86 (49%) 95% CI 39–59; 37/73 (51%) 95% CI 39–62; 49/78 (63%) 95% CI 52–73;
p
= 0.16. At 2 months, the buprenorphine group reported fewer days of illicit opioid use 1.1 (95% CI 0.6–1.6) versus referral 1.8 (95% CI 1.2–2.3) and brief intervention 2.0 (95% CI 1.5–2.6),
p
= 0.04. No significant differences in illicit opioid use were observed at 6 or 12 months. There were no significant differences in HIV risk or rates of opioid-negative urine results at any time.
Conclusions
ED-initiated buprenorphine was associated with increased engagement in addiction treatment and reduced illicit opioid use during the 2-month interval when buprenorphine was continued in primary care. Outcomes at 6 and 12 months were comparable across all groups.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and aim
To address the widespread severe problems with opioid use disorder, buprenorphine–naloxone treatment provided by primary care physicians has greatly expanded treatment access; ...however, treatment is often provided with minimal or no behavioral interventions. Whether or which behavioral interventions are feasible to implement in various settings and improve treatment outcomes has not been established. This study aimed to evaluate two behavioral interventions to improve buprenorphine–naloxone treatment.
Design
A 2 × 2 factorial, repeated‐measures, open‐label, randomized clinical trial.
Settings
General medical practice offices in Muar, Malaysia.
Participants
Opioid‐dependent individuals (n = 234).
Interventions
Participants were randomly assigned to one of four treatment conditions and received study interventions for 24 weeks: (1) physician management with or without behavioral counseling and (2) physician management with or without abstinence‐contingent buprenorphine–naloxone (ACB) take‐home doses.
Measurements
The primary outcomes were proportions of opioid‐negative urine tests and HIV risk behaviors assessed by audio computer‐assisted AIDS risk inventory (ACASI‐ARI).
Findings
The rates of opioid‐negative urine tests over 24 weeks of treatment were significantly higher with 68.2%, 95% confidence interval (CI) = 65–71 than without behavioral counseling (59.2%, 95% CI = 56–62, P < 0.001) and with (71.0%, 95% CI = 68–74) than without ACB (56.4%, 95% CI = 53–59, P < 0.001); interaction effects between and among behavioral interventions and time were not statistically significant. Scores on ACASI‐ARI decreased significantly from baseline across all treatment groups (P < 0.001) and did not differ significantly with or without behavioral counseling (P = 0.099) or with or without ACB (P = 0.339).
Conclusions
Providing opioid‐dependent patients in Muar, Malaysia with buprenorphine–naloxone and physician management plus behavioral counseling or abstinence‐contingent buprenorphine–naloxone (ACB) resulted in greater reductions of opioid use compared with providing buprenorphine–naloxone and physician management without behavioral counseling or ACB.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Study objective Brief interventions have been shown to reduce alcohol use and improve outcomes in hazardous and harmful drinkers, but evidence to support their use in emergency department (ED) ...patients is limited. The use of research assessments in studies of brief interventions may contribute to uncertainty about their effectiveness. Therefore we seek to determine (1) if an emergency practitioner-performed Brief Negotiation Interview or a Brief Negotiation Interview with a booster reduces alcohol consumption compared with standard care; and (2) the impact of research assessments on drinking outcomes using a standard care-no-assessment group. Methods We randomized 889 adult ED patients with hazardous and harmful drinking. A total of 740 received an emergency practitioner–performed Brief Negotiation Interview (n=297), a Brief Negotiation Interview with a 1-month follow-up telephone booster (Brief Negotiation Interview with booster) (n=295), or standard care (n=148). We also included a standard care with no assessments (n=149) group to examine the effect of assessments on drinking outcomes. Primary outcomes analyzed with mixed-models procedures included past 7-day alcohol consumption and 28-day binge episodes at 6 and 12 months, collected by interactive voice response. Secondary outcomes included negative health behaviors and consequences collected by telephone surveys. Results The reduction in mean number of drinks in the past 7 days from baseline to 6 and 12 months was significantly greater in the Brief Negotiation Interview with booster (from 20.4 95% confidence interval {CI} 18.8 to 22.0 to 11.6 95% CI 9.7 to 13.5 to 13.0 95% CI 10.5 to 15.5) and Brief Negotiation Interview (from 19.8 95% CI 18.3 to 21.4 to 12.7 95% CI 10.8 to 14.6 to 14.3 95% CI 11.9 to 16.8) than in standard care (from 20.9 95% CI 18.7 to 23.2 to 14.2 95% CI 11.2 to 17.1 to 17.6 95% CI 14.1 to 21.2). The reduction in 28-day binge episodes was also greater in the Brief Negotiation Interview with booster (from 7.5 95% CI 6.8 to 8.2 to 4.4 95% CI 3.6 to 5.2 to 4.7 95% CI 3.9 to 5.6) and Brief Negotiation Interview (from 7.2 95% CI 6.5 to 7.9 to 4.8 95% CI 4.0 to 5.6 to 5.1 95% CI 4.2 to 5.9) than in standard care (from 7.2 95% CI 6.2 to 8.2 to 5.7 95% CI 4.5 to 6.9 to 5.8 95% CI 4.6 to 7.0). The Brief Negotiation Interview with booster offered no significant benefit over the Brief Negotiation Interview alone. There were no differences in drinking outcomes between the standard care and standard care–no assessment groups. The reductions in rates of driving after drinking more than 3 drinks from baseline to 12 months were greater in the Brief Negotiation Interview (38% to 29%) and Brief Negotiation Interview with booster (39% to 31%) groups than in the standard care group (43% to 42%). Conclusion Emergency practitioner–performed brief interventions can reduce alcohol consumption and episodes of driving after drinking in hazardous and harmful drinkers. These results support the use of brief interventions in ED settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background and Aims
In a recent randomized trial, patients with opioid dependence receiving brief intervention, emergency department (ED)‐initiated buprenorphine and ongoing follow‐up in primary care ...with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community‐based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost‐effectiveness of these three methods of intervening on opioid dependence in the ED.
Design
Measured health‐care use was converted to dollar values. We considered a health‐care system perspective and constructed cost‐effectiveness acceptability curves that indicate the probability each treatment is cost‐effective under different thresholds of willingness‐to‐pay for outcomes studied.
Setting
An urban ED in the United States.
Participants
Opioid‐dependent patients aged 18 years or older.
Measurements
Self‐reported 30‐day assessment data were used to construct cost‐effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit opioid‐free in the past week.
Findings
Considering only health‐care system costs, cost‐effectiveness acceptability curves indicate that at all positive willingness‐to‐pay values, ED‐initiated buprenorphine treatment was more cost‐effective than brief intervention or referral. For example, at a willingness‐to‐pay threshold of $1000 for 30‐day treatment engagement, we are 79% certain ED‐initiated buprenorphine is most cost‐effective compared with other studied treatments. Similar results were found for days illicit opioid‐free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates.
Conclusion
In the United States, emergency department‐initiated buprenorphine intervention for patients with opioid dependence provides high value compared with referral to community‐based treatment or combined brief intervention and referral.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Aims
With the broad goals of developing a clinical research and training program and disseminating effective opioid use disorder treatments in Iran, this pilot clinical trial compared the ...effectiveness of oral naltrexone (NTX) and sublingual buprenorphine/naloxone (BNX).
Design
Twelve‐week single‐site, two‐group parallel randomized double‐blind clinical trial.
Setting
An out‐patient clinical research program in Tehran, Iran.
Participants
Following medically assisted withdrawal, participants with opioid use disorder were assigned randomly to NTX (n = 51) or BNX (n = 51).
Intervention
Medications were administered three times per week, double‐blind, double‐dummy for 12 weeks. All participants received weekly group drug counseling.
Measurements
The primary outcome was initial duration of opioid abstinence verified by urine toxicology tests. Secondary outcomes included the number of opioid‐negative urine tests, treatment retention and proportions with sustained, verified opioid‐abstinence for 12 weeks.
Findings
Mean 95% confidence interval (CI) number of days of initial duration of verified abstinence was 28.8 (20.0–37.5) with BNX and 21.6 (14.4–28.7) with NTX (P = 0.205). The mean (95% CI) number of opioid‐negative urine tests was 19.7 (17.7–21.6) with BNX and 15.4 (13.1–17.8) with NTX (P = 0.049). The mean (95% CI) number of days in treatment was 70.6 (63.6–77.7) with BNX versus 56.5 (47.8–65.3) with NTX (P = 0.013). The rate of sustained, 12‐week opioid abstinence was 16% (8/51) in the BNX group and 8% (4/51) in the NTX group (P = 0.219).
Conclusions
Among patients with opioid use disorder in Iran, sublingual buprenorphine/naloxone was associated with a greater number of opioid‐negative urine tests and treatment retention than oral naltrexone, but not significantly greater initial abstinence duration or proportions with sustained abstinence.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Highlights • The study evaluated the real-world implementation of a large methadone maintenance treatment (MMT) system in China. • Electronic medical records on 8811 patients were used to compute ...process and outcome measures. • Methadone dosing protocols and daily attendance are identified as priority areas for improving treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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