RISK OF OPIATE OVERDOSE DEATH DURING AND FOLLOWING SPECIALIST DRUG TREATMENT
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Slide 1 :
RISK OF OPIATE OVERDOSE DEATH DURING AND FOLLOWING SPECIALIST DRUG TREATMENT – RESULTS FROM VEDETTE STUDY AND IMPLICATIONS FOR SHORT TERM THERAPIES Marina Davoli(1), Anna Maria Bargagli(1), Carlo A Perucci (1) Matthew Hickman*(2), Salamina G (3), Decidue R (3), Vigna-Taglianti F (3), Faggiano F (3) (1) Social Medicine, Un(1)iversity of Bristol (2) Department of Epidemiology, Rome E Health Authority, Rome, Italy (for VEdeTTE Study Group) (3) University of Piemonte Orientale and Unit of Drug Dependence Piemonte
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Study questions How protective are a range of specialist drug treatments against overdose and drug related mortality? Not just methadone maintenance To what extent does the risk of overdose increase after ceasing treatment (drop-out or completion)? Is there an excess immediately following treatment – similar to increase risk observed after prison release – and what are implications What evidence is there for hypothesis that proportionally more deaths among drug users who complete detox/ rehabilitation than those who drop out? Proposed by small follow-up study of detox (Strang et al BMJ 2003)
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The VEdeTTE Study (National Multicenter Longitudinal Prospective Study) Designed to evaluate:- the effectviness of treatments offered in public treatment centers in preventing overdose mortality among heroin users Target population:- heroin users seeking for treatment, >18 yrs old, recruited from 115/554 statutory clinics Study population:- 10454 subjects enrolled October 1998 to March 2000 and followed-up until end 2001
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VEdeTTE Cohort Characteristics Total time in treatment: 10,208 p-yrs (78%) Total time out of treatment: 2,914 p-yrs (22%) Median length of follow-up: 547 days (99%) 86% males Average age: 31 yrs 80% IDU 41% had previous overdose episodes
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Vedette Cohort – Treatment modality
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Overall Mortality and Overdose Total number of deaths from all causes:- 100 deaths (37 in treatment and 63 out of treatment) Excess mortality risk for all causes (SMR, Standardised Mortality Ratio):- 3.9 (95% CI: 2.8-5.4) in treatment 21.4 (95% CI: 16.7-27.4) out of treatment Total number of overdose deaths* 41 (10 in treatment and 31 out of treatment) * ICD codes selected : 292; 304.0-.9; 305.2-.9; 965.0-.9; 969.0-.9; E850-E858; E980.0-.5-.9; E950.0-.5-.9; E962
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Treatment protective (OD rate 10* lower)Evidence that range of treatments protective during treatment * Adjusted for age, gender, psychiatric comorbidity, HIV status, previous non fatal overdose, route of administration, length of use
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HR: <=30 days since last treatment vs. > 30 days:- 3.6 (95%CI: 1.7-7.6) * Adjusted for age, gender, psychiatric comorbidity, HIV status, previous non fatal overdose, route of administration, length of use Overdose Death Rate by time since last treatment
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Risk of OD > 1% out of treatment compared to < 0.1% during treatment. BUT Risk of OD > 2% in first month (26 times higher after adjustment than overdose during treatment)
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30 days 90 days 60 days Scenario: Comparing OD mortality of short term treatment with no treatment
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2 months OUT of treatment Scenario: Comparing OD mortality of short term treatment with no treatment
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Treatment Drop-Out or Completion? Treatment drop-outs comprised 9/9 and 4/5 of the deaths in heroin addicts ceasing methadone maintenance and therapeutic communities respectively. In contrast, 6/7 patients that died after methadone detoxification had completed treatment Risk of mortality rate among completers of methadone detoxification treatment vs drop outs was 4.1 (95% CI 0.6 to 29.1)
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Strengths and Limitations – summary - revise Key strength Largest recent cohort of heroin addicts recruited from treatment sites to assess drug related mortality and overdose. Limitations Selection bias: patients selected at point of drug treatment may not be representative of all heroin users Unexplained confounding (adjusted for addiction severity, socioeconomic status, age and sex) Follow-up of participants out of treatment was substantially less than follow-up during treatment Lack of power to assess excess overdose risk following treatment by specific modality: Comparison of short term therapy versus no therapy was a secondary analysis – with wide CI - needs further testing and corroboration.
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Summary Heroin users have a substantially reduced risk of death during a range of treatments Strengthens evidence that MMT is protective Provides evidence that protective effect extends to range of other treatments Demonstrates that risk of death is higher in period immediately following treatment drop out or cessation. Adds evidence to hypothesis that overdose deaths may be more likely among completers of detoxification than treatment drop outs Raises hypothesis that short term therapies lasting one month or less may cause more deaths than they prevent
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Interpretation and Implications Heroin users have a substantial risk of death Drug treatment therapies protective thro’ reducing injecting Loss of tolerance increases risk of heroin OD if patient relapses. Most likely reason for elevated OD risk in period immediately following treatment Treatment retention should be a key priority for long-term/ maintenance therapies as part of overdose prevention Short term/ detoxification services reduce “tolerance” to opiates. Relapse is common. Should success of detoxification be considered against short term goals (Cochrane Rev 2006)? Recommend that risk of OD should be considered i.e potential harms and benefits should be weighed up Other large scale mortality studies required to test: Ho that short term therapies may increase OD deaths Effectiveness of relapse prevention
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