Infrequent opioid overdose risk reduction behaviours among young adult heroin users in cities with wide coverage of HIV prevention programmes
Article Outline
Abstract
Background
Opioid overdose risk reduction behaviours include some preventive behaviours to avoid overdoses (PB) and others to avoid death after overdose, such as never using heroin while alone (NUA). Few studies have examined the prevalence and predictors of these behaviours.
Aim
To establish the prevalence and predictors of PBs and NUA among heroin users, both injectors and non-injectors, in three Spanish cities.
Methods
516 injecting and 475 non-injecting heroin users aged 18–30 were street-recruited in 2001–2003 and interviewed by face-to-face computer-assisted interview. PBs and NUA in the last 12 months were explored using open-ended and precoded questions, respectively. Specific predictors for three PB categories were investigated: control of route of drug administration, control of quantity or type of heroin used, and control of co-use of other drugs. Bivariate and logistic regression methods were used.
Results
Overall, the most prevalent PBs were: using a stable and not excessive amount of heroin (12.7%), injecting or using the whole heroin dose slowly or dividing it into smaller doses (12.4%), reducing or stopping heroin injection (8.3%), and not mixing heroin with tranquillisers (5.1%). Most PBs were significantly more prevalent among injectors than non-injectors. No one mentioned reducing the amount of heroin after an abstinence period. Some 36.2% had NUA. In multiple regression analysis, knowledge of risk factors for opioid overdose was a predictor of specific PBs, although this was not always the case. Use of syringe exchange programmes was a predictor of PB among injectors. However, attending methadone maintenance treatment (MMT) or other drug-dependence treatment was not a predictor of any opioid overdose reduction behaviour. Only ever having witnessed or experienced an overdose predicted PB in both injectors and non-injectors.
Conclusions
The proportion of heroin users with opioid overdose risk reduction behaviours is very low. Additional specific measures to prevent overdose are needed, as well as increased emphasis on reducing the risk of overdose in programmes to prevent HIV and other blood-borne infections in heroin injectors.
Keywords: Overdose prevention, Heroin injection, Harm reduction programmes
Introduction
Opioid overdose remains an important cause of death and emergency care among young people in many countries (Darke and Zador, 1996, EMCDDA, 2009, Green et al., 2009, Powis et al., 1999, Sporer, 2003). In Europe, an increase in overdose deaths was observed between 2003 and 2005 (Vicente, Giraudon, Matías, Hedrich, & Wiessing, 2009). In recent years Spain, England and Wales have reported the highest mortality rates from overdose in Europe (Morgan, Vicente, Griffiths, & Hickman, 2008). Studies have shown that non-fatal overdose is also very frequent among heroin users (annual prevalence 9–22%) (Brugal et al., 2002, Darke et al., 1996, Gossop et al., 1996).
In the field of opioid overdose prevention, there is solid evidence of the effectiveness of drug-dependence treatments (Darke et al., 2007) and especially methadone maintenance treatment (MMT) (Brugal et al., 2005, Darke and Hall, 2003, Langendam et al., 2001, Sporer, 2003, van Ameijden et al., 1999). Furthermore, some studies also suggest a beneficial effect of supervised injection facilities (SIFs) (Darke and Hall, 2003, Hedrich, 2004, MSIC Evaluation Committee, 2003) or resuscitation using naloxone by persons witnessing an opioid overdose (Darke and Hall, 2003, Doe-Simkins et al., 2009), and others describe how syringe exchange programmes (SEPs) have been used to implement specific programmes for overdose prevention (Doe-Simkins et al., 2009, Galea et al., 2005, Piper et al., 2008, Tobin et al., 2009).
Among the reasons that could explain the high rates of non-fatal opioid overdose are low prevalence of preventive behaviours to avoid opioid overdose (PB), which could be related with lack of knowledge of the main risk factors for opioid overdose (Dietze et al., 2006, Green et al., 2009, Neira-León et al., 2006), such as use of the injected route (Brugal et al., 2002, Darke and Hall, 2003), low tolerance after a period of abstinence (Darke and Hall, 2003, Farrell and Marsden, 2008) and concurrent consumption of other central nervous system depressors (Darke & Hall, 2003). However, the complexity of the mechanisms involved in the adoption of PBs can hinder the success of these educational interventions (Moore, 2004, Rhodes, 2009). This complexity would also help to explain some paradoxical findings, like the association found by Dietze et al. (2006) between knowledge of the dangers of mixing benzodiazepines and/or alcohol with heroin and an increased likelihood of such mixing prior to overdose.
Data on the number of patients in MMT and sterile syringe distribution by SEPs in the cities of Barcelona, Madrid and Seville in 2001–2003 suggest wide coverage of these programmes (AACM, 2004, Bravo et al., 2007, de la Fuente et al., 2006a, DGPNSD, 2006, Espelt et al., 2009, Secretaria del Plan Nacional sobre Sida, 2009). Other free drug-dependence treatment modalities were also easily accessible during that period (DGPNSD, 2006). However, even though harm reduction programmes generally included messages on overdose prevention, only Barcelona had a structured programme on naloxone distribution, albeit with limited coverage (AACM, 2002, AACM, 2003, AACM, 2004, Ilundain, 2009, Trujols, 2001). The Spanish national strategy on drugs does not explicitly mention overdose prevention as a priority (DGPNSD, 2005).
In 2009 the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) reported that 23 European Union member states addressed the prevention of infectious diseases among drug users as part of their national drug strategy, but only 12 countries included the reduction of drug-related deaths. The lack of awareness of the public health relevance of this issue could be a contributing factor to the sustained number of reported overdose deaths in Europe despite the downward trend in heroin injection and the expansion of treatment and harm reduction programmes in many countries.
Among the training needs identified by EMCDDA are the problems of reduced tolerance after abstinence periods and the consequences of taking multiple drugs (EMCDDA, 2008, EMCDDA, 2009). EMCDDA (2009) also emphasises that a large proportion of overdoses occur in the presence of witnesses, including drug users’ peers, family members, passers-by, police, or prison staff, a situation which could be used to advantage in avoiding deaths from overdose. In fact, quite a few countries have reported the existence of specific materials or interventions aimed at helping families, police officers or prison staff to recognise and manage drug overdoses (EMCDDA, 2009). To be most effective, these interventions should be promoted in conjunction with the message “Never use heroin while alone” (NUA).
Since many studies have focused on the prevalence of overdose and its predictors and very little work has been done on the preventive behaviours that could avoid overdose or death, we focused our study, first, on measuring the prevalence of PB and NUA in a sample of regular heroin users and second, on determining the factors that predict these risk reduction behaviours.
Since heroin injectors and non-injectors usually differ in overdose risk (Brugal et al., 2002, Darke and Hall, 2003, Darke et al., 1996), HIV prevalence (de la Fuente et al., 1999) or contact with health care services (Vallejo et al., 2007) all the analyses were stratified by injecting status. We hypothesised that prevalence of PB would be greater among heroin injectors and that different preventive factors would be identified for injectors and non-injectors. We especially focused on whether knowledge of the principal risk factors for opioid overdose and MMT or other drug-dependence treatment attendance are predictors of opioid overdose risk reduction behaviours among non-injectors or injectors, and whether SEP attendance is a predictor of risk reduction behaviours among drug injectors.
Materials and methods
We used data from the 991 subjects recruited at baseline in the Itinere cohort of young adult heroin users. The methodology used has been described in detail elsewhere (de la Fuente et al., 2005, Neira-León et al., 2006). Inclusion criteria were age 18–30 years, residence in the cities of Barcelona, Madrid or Seville, and having used heroin in the last 90 days, and on at least 12 days in the 12 months before the interview. The entire sample was recruited in 2001–2003 in outdoor settings by chain-referral procedures (Heckathorn, 1997). A questionnaire was administered in a computer-assisted interview (Des Jarlais et al., 1999, Newman et al., 2002). Questions were included on sociodemographic variables, patterns of drug use, perceived dependence, sexual and injection behaviour, self-reported HIV serological status, non-fatal opioid overdose (last time and last 12 months occurrence), attendance to courses or meetings related to overdose as well as on use of SEP, MMT, other drug-dependence treatment and other health and social services in the last 12 months. To measure the degree of subjective dependence on heroin we used the Severity of Dependence Scale (SDS). This scale contains five items that measure the main psychological components of dependence, particularly compulsive use (Gossop et al., 1995). A cut-off point of between 3 and 4 on this scale has been suggested for heroin dependence (Gonzalez-Saiz et al., 2008, Gossop et al., 1995).
Opioid overdose was defined as an episode occurring after opioid use characterised by extreme difficulty in breathing, loss of consciousness and problems waking up or recovering consciousness, and possibly bluish skin or lips. Open-ended questions were included on knowledge of the main risk factors for overdose (Neira-León et al., 2006).
As part of opioid overdose risk reduction behaviours we considered preventive behaviours to avoid opioid overdose (PBs) and measures to avoid death if overdose occurred, such as never using heroin while alone (NUA). To explore PBs, participants were asked the following open-ended question: “In the last 12 months have you ever engaged in any behaviour to avoid overdose from heroin, methadone or other opioids?” If they had, they were asked to make an open list of these PBs. By using open-ended questions we tried to minimise the effects of suggestion or influencing the responses, and to respect the importance that users spontaneously give to different behaviours, as an approximation to the free-listing technique (Bravo et al., 2003). Two precoded questions were also asked about heroin use while alone or accompanied in the last 12 months. Since drug use in the street or in open spaces means that witnesses may have been present, these occurrences were always classified as using while accompanied by someone else. Hereinafter, all references to “overdose” in this paper should be understood as opioid overdose.
Data analysis
The proportion of missing responses to the PB question was 0.5%. The spontaneous answers were transcribed verbatim. A coding procedure similar to that described elsewhere (Neira-León et al., 2006) was used. The literal responses were classified into three specific PB categories according to the same scheme as previously used to classify the reasons for overdose occurrence (Neira-León et al., 2006): (1) Control of the route of drug administration; (2) Control of the quantity or type of heroin used; (3) Control of the use of other drugs. The following indicators were also defined: having some PB (that is, at least one), two or more PBs and NUA. Almost all subsequent analyses were stratified by injecting status (injectors and non-injectors in the last 12 months). Within each stratum, bivariate analyses were made of the sociodemographic and drug-use variables (mainly referring to the last 12 months).
The statistical significance of differences was evaluated with the Chi-square test, rejecting the null hypothesis if p
<0.05. Based on various logistic regression models, we identified the main predictive factors for both PBs and NUA. All variables associated in the bivariate analysis (p<0.2) were introduced into the models. The final variables in the models were selected with a forward stepwise procedure. All the statistical analyses were made using SPSS version 15 for Windows.
Results
General characteristics of the sample
Overall, 52.1% of heroin users had injected in the last 12 months (injectors). Injectors generally had a sociodemographic profile of greater social and health vulnerability than non-injectors, with higher prevalences, for example, of obtaining income from marginal activities, of being homeless, of opioid overdose, HIV infection or use of emergency care. Half of the participants scored 9 or more on the Severity of Dependence Scale (SDS); the percentage in the top level of dependence was higher in injectors than in non-injectors (p<0.01) (Table 1). A more detailed description of the sample can be found elsewhere (de la Fuente et al., 2005).
Table 1. Characteristics of young adult heroin users by injecting status (%). Itinere project.
| Injectorsa (n=516) | Non-injectorsa (n=475) | Total (n=991) | p | |
|---|---|---|---|---|
| City of residencea | *** | |||
| Barcelona | 53.5 | 18.5 | 36.7 | |
| Seville | 6.0 | 35.6 | 43.1 | |
| Madrid | 40.5 | 45.9 | 20.2 | |
| Age 25 years or less | 40.3 | 44.0 | 42.1 | NS |
| Women | 26.2 | 28.2 | 27.1 | NS |
| Primary education or lower | 40.8 | 50.9 | 45.7 | *** |
| Most income obtained from marginal or illegal activitiesa | 46.9 | 39.6 | 43.1 | * |
| Being homelessa | 14.5 | 5.7 | 10.3 | *** |
| Time in youth detention centre | * | |||
| Never or less than 1 month | 87.0 | 91.8 | 89.3 | |
| 1–12 months | 5.6 | 4.4 | 5.1 | |
| More than 12 months | 7.4 | 3.8 | 5.7 | |
| Level of heroin dependence (SDS score)a | ** | |||
| 0–4 | 11.1 | 19.1 | 14.9 | |
| 5–8 | 35.5 | 34.5 | 35.0 | |
| 9 or more | 53.4 | 46.4 | 50.1 | |
| <5 years history of heroin use | 18.6 | 26.1 | 22.2 | ** |
| Use of powder cocaine not mixed with heroina | 90.3 | 58.8 | 75.3 | *** |
| Use of other opioidsa,b | 62.1 | 53.3 | 57.9 | ** |
| Use of tranquillisersa | 86.8 | 75.8 | 81.5 | *** |
| Frequency of drug injectiona,c | *** | |||
| Daily | 28.7 | – | 14.3 | |
| Weekly | 40.6 | – | 20.2 | |
| Less than weekly | 30.6 | – | 15.2 | |
| Never | 0.0 | – | 50.3 | |
| Average consumption of pure alcohol/daya | NS | |||
| None | 18.3 | 17.7 | 18.0 | |
| <50ml/day | 54.4 | 55.3 | 54.8 | |
| ≥50ml/day | 27.3 | 27.0 | 27.2 | |
| Average tobacco consumptiona | NS | |||
| Non-smoker or <10cigarettes/day | 15.7 | 21.1 | 18.3 | |
| 10–19cigarettes/day | 58.1 | 51.8 | 55.1 | |
| 20 or more cigarettes/day | 26.2 | 27.2 | 26.3 | |
| HIV serological status (self-reported) | *** | |||
| Positive | 20.3 | 6.3 | 13.6 | |
| Negative | 66.5 | 66.9 | 66.7 | |
| Unknown | 13.2 | 26.7 | 19.7 | |
| Treatment for drug use or dependencea | ||||
| No treatment | 43.9 | 58.6 | 51.0 | *** |
| Methadone maintenance | 37.0 | 26.8 | 32.1 | |
| Other | 19.1 | 14.6 | 16.9 | |
| Received emergency medical carea | 61.8 | 44.2 | 53.3 | *** |
| Received non-emergency medical care outside of hospital or prisona | 63.3 | 55.0 | 59.3 | * |
| Received free syringes in SEPsa | 93.0 | – | 48.0 | – |
| Attended courses or meetings related with overdose preventiona | 9.3 | 1.3 | 5.5 | *** |
| Lifetime experience of overdose | *** | |||
| He/she overdosed | 41.3 | 6.5 | 24.6 | |
| He/she only witnessed | 45.0 | 49.4 | 47.1 | |
| He/she neither overdosed nor witnessed | 13.8 | 44.1 | 28.3 | |
| Last 12 months opioid overdose prevalence | 15.1 | 0.4 | 8.1 | *** |
| Perceived causes of opioid overdose (open-ended questions) | ||||
| Use of too much or too pure heroin | 77.6 | 82.3 | 79.8 | NS |
| Use of other drugs mixed with heroin | 48.1 | 27.2 | 38.3 | *** |
| Route of heroin administration | 3.5 | 12.9 | 7.9 | *** |
aRefers to last 12 months. |
bIncludes methadone illegally obtained and other opioids different from heroin or methadone. |
cFrequency of injection is unknown for 46 drug injectors. |
*p |
**p |
***p |
Many heroin users identified use of heroin in large amounts or that was too pure as a cause for overdose (79.8%), but very few identified the route of drug administration (7.9%), although the latter cause was more frequently identified by non-injectors than by injectors. The opposite occurred with the use of other drugs mixed with heroin, which was identified more frequently by injectors. Very few participants (5.5%) had ever attended specific courses or meetings related to opioid overdose prevention in the last 12 months despite the fact that almost half (49%) had received treatment for drug dependence. Almost all injectors (93%) had obtained some sterile injection material through SEPs in the same period (Table 1).
Prevalence of opioid overdose risk reduction behaviours
In addition to PBs, risk reduction also includes behaviours to prevent death when overdose occurs. Overall, 42.4% of the heroin users reported some PB during the last 12 months, with differences between cities: Barcelona (56.1%), Madrid (39.6%) and Seville (23.6%) (p<0.001). The PBs most frequently mentioned were, in decreasing order: using a stable and not excessive amount of heroin (12.7%, category 2), injecting or using the whole heroin dose slowly or dividing it into smaller doses (12.4%, category 1), reducing or stopping heroin injection (8.3%, category 1), and not mixing heroin with tranquillisers (5.1%, category 3) (Table 2). No one mentioned using a smaller than usual amount of heroin after a period of abstinence as a PB.
Table 2. Prevalence of preventive behaviours to avoid opioid overdose (PB) and never using heroin while alone in last 12 months (%). Itinere project.
| Injectorsa (n=516) | Non-injectorsa (n=475) | Total (n=991) | p | |
|---|---|---|---|---|
| PB Category 1b | ||||
| Controlling heroin administration route or drug effect | 25.8 | 15.9 | 21.1 | *** |
| Used the whole heroin dose slowly or divided it into various smaller doses | 21.4 | 2.5 | 12.4 | *** |
| Reduced or stopped heroin use by injection. Used heroin by non-injecting routes | 4.1 | 12.9 | 8.3 | *** |
| Was aware of the effects of heroin while injecting | 0.8 | – | 0.8 | |
| PB Category 2b | ||||
| Controlling quantity or type of heroin consumed | 25.6 | 11.4 | 18.8 | *** |
| Used a stable and not excessive quantity of heroin | 16.9 | 8.1 | 12.7 | *** |
| Reduced consumption | 4.7 | 3.0 | 3.9 | NS |
| Controlled heroin purity (always bought from the same dealer, tested dose before use, etc.) | 5.6 | 1.3 | 3.5 | *** |
| PB Category 3b | ||||
| Controlling use of other drugs | 19.4 | 4.2 | 12.2 | *** |
| Did not mix heroin with tranquillisers | 8.2 | 1.7 | 5.1 | *** |
| Did not use tranquillisers shortly before heroin or used smaller quantity of heroin if tranquillisers taken previously | 7.4 | 0.6 | 4.2 | *** |
| Stopped or reduced tranquilliser use | 2.7 | 1.5 | 2.1 | NS |
| Did not use heroin at the same time as other drugs | 1.6 | 1.1 | 1.3 | NS |
| Drank little or no alcohol | 0.4 | 0.0 | 0.2 | NS |
| Number of PBs | ||||
| Some | 55.5 | 28.1 | 42.4 | *** |
| One | 35.2 | 21.8 | 29.5 | *** |
| Two or more | 20.3 | 6.3 | 12.9 | *** |
| Never used heroin while alone | 38.0 | 34.3 | 36.2 | NS |
aRefers to injection in last 12 months. |
bRefers to % of participants who reported some PB in this category. |
***p |
Most of the specific PBs to avoid overdose, such as using the whole heroin dose slowly or dividing it into smaller doses, not using tranquillisers together with heroin, controlling the purity of heroin, and using a stable and not excessive amount of heroin, were adopted much more frequently by injectors than by non-injectors. In contrast, non-injectors more frequently mentioned that they had reduced or stopped the use of heroin by injection. The prevalence of some PB and of two or more PBs was much higher among injectors than among non-injectors.
With regard to behaviours to avoid death after opioid overdose, 36.2% of the overall sample had NUA, with no significant differences between injectors and non-injectors.
Predictive factors for preventive behaviours to avoid opioid overdose
In the overall sample, the bivariate analysis showed that the factors most strongly associated with some PB were previous experience of overdose (prevalence of some PB was 59.7% among those who had ever overdosed, 46.1% among those who had only witnessed an overdose, and 21.0% among those who had never overdosed or witnessed an overdose, p<0.001), and frequency of injection in the last 12 months (prevalence of some PB was 62.2%, 58.4%, 52.4% and 28.1% among daily, weekly, less than weekly, and never injectors, respectively, p<0.001). The factors most strongly associated with some PB in the logistic regression analysis were having ever suffered an overdose (OR=3.3; 95% CI: 2.1–5.3), having only witnessed an overdose (OR=2.6; 95% CI: 1.8–3.7) and having injected drugs daily (OR vs. not injecting=3.0; 95% CI: 1.9–4.8), weekly (OR=2.5; 95% CI: 1.6–3.7), or less than weekly (OR=2.3; 95% CI: 1.5–3.6) in the last 12 months. MMT or other drug-dependence treatment attendance in the last 12 months was not retained as a predictive factor for PBs.
As shown in Table 3, only ever having overdosed and ever having witnessed an overdose were associated with having some PB in both injectors and non-injectors. Moreover, being a non-smoker or smoking less than 10cigarettes/day was significantly associated with having some PB among non-injectors. Among injectors, other predictive factors were: having received some free syringes at SEPs (the strongest predictor), living in Barcelona, male gender, never having been in youth detention centres or having been there for less than a month, negative HIV serology, and abstaining from or consuming less than 50ml of pure alcohol daily. Frequency of injection was not retained in the model as a predictive factor for having some PB among injectors.
Table 3. Predictive factors for having some preventive behaviour to avoid opioid overdose (PB) in the last 12 months. Itinere project.
| Injectorsa | Non-injectorsa | |||||||
|---|---|---|---|---|---|---|---|---|
| % Who reported PB | pb | aOR | 95% CI | % Who reported PB | pb | aOR | 95% CI | |
| City of residencea | ** | NS | – | – | ||||
| Barcelona | 53.4 | 1.8 | 1.2–2.7 | 33.3 | ||||
| Seville | 40.6 | 0.4 | 0.1–1.0 | 29.4 | ||||
| Madrid | 6.0 | 1 | 23.8 | |||||
| Gender | * | NS | – | – | ||||
| Male | 58.8 | 1.9 | 1.2–2.9 | 29.7 | ||||
| Female | 46.3 | 1 | 24.1 | |||||
| Time in youth detention centre | NS | NS | – | – | ||||
| Never or less than 1 month | 56.3 | 2.3 | 1.1–4.9 | 28.6 | ||||
| 1–12 months | 62.1 | 2.0 | 0.7–5.8 | 19.0 | ||||
| More than 12 months | 40.5 | 1 | 27.8 | |||||
| Average consumption of pure alcohol/daya | ** | NS | – | – | ||||
| None | 64.1 | 2.3 | 1.3–4.2 | 34.5 | ||||
| <50ml/day | 59.2 | 1.8 | 1.1–2.8 | 24.9 | ||||
| ≥50ml/day | 43.9 | 1 | 30.7 | |||||
| Average tobacco consumptiona | NS | – | – | * | ||||
| Non-smoker or <10cigarettes/day | 63.0 | 38.0 | 2.2 | 1.2–4.0 | ||||
| 10–19cigarettes/day | 52.8 | 25.2 | 1.1 | 0.7–1.9 | ||||
| 20 or more cigarettes/day | 56.7 | 26.0 | 1 | |||||
| HIV serological status | ** | NS | – | – | ||||
| Positive | 48.1 | 1.8 | 0.9–3.6 | 30.0 | ||||
| Negative | 60.6 | 2.2 | 1.2–4.0 | 30.3 | ||||
| Unknown | 41.2 | 1 | 22.2 | |||||
| Received free syringe in SEPsa | *** | – | – | – | ||||
| Yes | 57.6 | 3.7 | 1.2–11.2 | |||||
| No | 20.0 | 1 | ||||||
| Lifetime experience of overdose | *** | *** | ||||||
| He/she overdosed | 54.9 | 3.5 | 1.8–6.7 | 61.3 | 8.4 | 3.7–19.4 | ||
| He/she only witnessed | 60.8 | 3.5 | 1.8–6.5 | 31.6 | 2.0 | 1.3–3.2 | ||
| He/she neither overdosed nor witnessed | 26.8 | 1 | 19.2 | 1 | ||||
aRefers to last 12 months. |
bLevel of significance for the difference in prevalence of PBs in the bivariate analysis. |
*p |
**p |
***p |
The predictive factors for having engaged in two or more PBs were quite similar in nature, strength and direction to those described for some PB.
Predictive factors were identified for each PB category. In summary, several factors stand out (Table 4): First, for having a PB aimed at controlling the route of heroin administration or drug effect (category 1), a positive association was found among both injectors and non-injectors with having suffered or witnessed an overdose. No other predictive factors were identified in this category among non-injectors; however, in injectors this dependent variable was also positively associated with use of powder cocaine not mixed with heroin, use of less than 50ml/day of pure alcohol, and identification of route of administration as a cause of overdose. Second, for having a PB aimed at controlling the quantity and type of heroin (category 2), being a non-smoker or smoking less than 10cigarettes/day was shown to be a predictive factor in both injectors and non-injectors. Furthermore, being HIV negative was a predictive factor for this PB among injectors, as was having an intermediate level of heroin dependence among non-injectors. Third, having a PB aimed at controlling the use of other drugs (category 3) was strongly and positively associated with identifying the concurrent use of heroin and other drugs as a cause of overdose in both injectors and non-injectors. In non-injectors it was also associated with being HIV positive, whereas in injectors this dependent variable was also positively associated with living in Barcelona and with having ever overdosed or only witnessed an overdose; a negative association was found with identifying the use of too much or too pure heroin as a cause of overdose.
Table 4. Predictive factors for having some preventive behaviour to avoid opioid overdose (PB) in each PB category in the last 12 months. Itinere project.
| Injectorsa | Non-injectorsa | |||||||
|---|---|---|---|---|---|---|---|---|
| % Who reported PB | pb | aOR | 95% CI | % Who reported PB | pb | aOR | 95% CI | |
| PB category 1: controlling heroin administration route or drug effect | ||||||||
| Consumption of powder cocaine not mixed with heroina | * | NS | ||||||
| Yes | 27.3 | 4.4 | 1.5–12.8 | 14.5 | – | – | ||
| No | 12.0 | 1 | 17.5 | |||||
| Consumption of pure alcohol/daya | * | NS | ||||||
| None | 29.3 | 2.3 | 1.2–4.5 | 19.0 | – | – | ||
| <50ml/day | 28.5 | 1.9 | 1.1–3.3 | 13.4 | ||||
| 50ml/day or more | 18.0 | 1 | 18.9 | |||||
| Identification of route of administration as cause of overdose | * | NS | ||||||
| Yes | 52.9 | 3.5 | 1.2–10.1 | 15.9 | – | – | ||
| No | 24.7 | 1 | 19.6 | |||||
| Lifetime experience of overdose | * | *** | ||||||
| He/she overdosed | 26.9 | 2.2 | 1.0–5.3 | 48.4 | 13.0 | 5.3–31.6 | ||
| He/she only witnessed | 28.9 | 2.6 | 1.2–6.0 | 19.7 | 3.4 | 1.8–6.4 | ||
| He/she neither overdosed nor witnessed | 12.7 | 1 | 6.7 | 1 | ||||
| PB category 2: Controlling the quantity and type of heroin consumed | ||||||||
| Level of heroin dependence (SDS score)a | NS | – | – | *** | ||||
| 0–4 | 24.6 | 12.2 | 2.0 | 0.9–4.9 | ||||
| From 5 to 8 | 31.5 | 18.5 | 3.6 | 1.8–7.4 | ||||
| 9 or more | 22.3 | 5.5 | 1 | |||||
| Tobacco consumptiona | ** | ** | ||||||
| Non-smoker or <10cigarettes/day | 39.5 | 3.1 | 1.7–5.9 | 21.1 | 2.9 | 1.2–6.8 | ||
| 10–19cigarettes/day | 25.4 | 1.6 | 0.9–2.7 | 9.8 | 1.3 | 0.6–2.9 | ||
| 20 or more cigarettes/day | 17.9 | 1 | 7.1 | 1 | ||||
| HIV serological status | NS | NS | ||||||
| Positive | 23.1 | 2.1 | 0.9–5.0 | 6.7 | – | – | ||
| Negative | 28.0 | 2.6 | 1.2–5.2 | 11.7 | ||||
| Unknown | 17.6 | 1 | 11.9 | |||||
| PB category 3: Controlling the consumption of other drugs | ||||||||
| City of residencea | *** | NS | – | – | ||||
| Barcelona | 29.1 | 3.1 | 1.7–5.6 | 4.6 | ||||
| Seville | 9.7 | 2.1 | 0.5–8.8 | 4.6 | ||||
| Madrid | 8.1 | 1 | 3.6 | |||||
| HIV serological status (self-reported) | NS | – | – | *** | ||||
| Positive | 13.5 | 23.3 | 6.2 | 1.4–28.1 | ||||
| Negative | 19.8 | 3.2 | 0.8 | 0.2–3.1 | ||||
| Unknown | 26.5 | 2.4 | 1 | |||||
| Identification of use of other drugs mixed with heroin as cause of overdose | *** | *** | ||||||
| Yes | 34.6 | 5.4 | 2.9–10.2 | 12.8 | 7.0 | 2.4–20.6 | ||
| No | 6.0 | 1 | 1.6 | 1 | ||||
| Identification of using too much or too pure heroin as cause of overdose | *** | NS | – | – | ||||
| Yes | 14.1 | 0.5 | 0.3–0.8 | 3.7 | ||||
| No | 34.9 | 1 | 9.1 | |||||
| Lifetime experience of overdose | NS | – | – | |||||
| He/she overdosed | 23.1 | *** | 7.3 | 1.6–32.8 | 9.7 | |||
| He/she only witnessed | 20.7 | 7.5 | 1.7–33.9 | 5.1 | ||||
| He/she neither overdosed nor witnessed | 4.2 | 1 | 2.4 | |||||
aRefers to last 12 months. |
bLevel of significance of the difference in PBs prevalence in the bivariate analysis. |
*p |
**p |
***p |
Predictive factors for never using heroin while alone
In the logistic analysis, the factors positively associated with NUA in both injectors and non-injectors were low level of heroin dependence and having used heroin for less than 5 years. Among injectors, this dependent variable was also positively associated with having received emergency medical care, and having attended courses or meetings related with overdose prevention. Among non-injectors it was positively associated with female gender (Table 5).
Table 5. Predictive factors for never using heroin while alone (NUA) in last 12 months. Itinere project.
| Associated factors | Injectorsa | Non-injectorsa | ||||||
|---|---|---|---|---|---|---|---|---|
| % Who NUAa | pb | aOR | 95% CI | % Who NUAa | pb | aOR | 95% CI | |
| City of residencea | ** | ** | ||||||
| Barcelona | 44.9 | 1.4 | 1.0–2.2 | 49.4 | – | – | ||
| Seville | 22.6 | 0.6 | 0.2–1.6 | 33.5 | – | – | ||
| Madrid | 31.3 | 1 | 27.5 | – | – | |||
| Gender | NS | *** | ||||||
| Female | 43.3 | – | – | 48.9 | 3.0 | 1.9–4.7 | ||
| Male | 36.1 | – | – | 28.6 | 1 | |||
| History of heroin use | ** | *** | ||||||
| <5 years | 52.1 | 1.9 | 1.2–3.0 | 48.4 | 1.9 | 1.2–3.1 | ||
| 5 or more years | 34.8 | 1 | 29.3 | 1 | ||||
| Level of heroin dependence (SDS score)a | ** | *** | ||||||
| 0–4 | 56.1 | 2.3 | 1.2–4.3 | 51.1 | 2.3 | 1.3–4.1 | ||
| 5–8 | 42.2 | 1.6 | 1.2–2.7 | 35.8 | 1.5 | 0.9–2.4 | ||
| 9 or more | 31.1 | 1 | 26.7 | 1 | ||||
| Tobacco consumptiona | NS | NS | ||||||
| Non-smoker or <10cigarettes/day | 37.0 | – | – | 38.0 | 0.8 | 0.5–1.5 | ||
| 10–19cigarettes/day | 39.9 | – | – | 31.3 | 0.5 | 0.3–0.9 | ||
| 20 or more cigarettes/day | 34.6 | – | – | 37.3 | 1 | |||
| Received non-emergency medical care outside of hospital or prisona | * | NS | ||||||
| No | 44.9 | 1.5 | 1.0–2.2 | 29.9 | – | – | ||
| Yes | 34.4 | 1 | 37.8 | – | – | |||
| Received emergency medical carea | ** | NS | ||||||
| No | 46.9 | 1.8 | 1.2–2.7 | 32.2 | – | – | ||
| Yes | 33.1 | 1 | 36.8 | – | – | |||
| Attended courses/meetings on overdose preventiona | ** | NS | ||||||
| Yes | 57.4 | 1.8 | 1.2–2.6 | 33.3 | – | – | ||
| No | 36.9 | 1 | 34.6 | – | – | |||
aRefers to 12 months before the interview. |
bLevel of significance of the difference in prevalence of NUA in the bivariate analysis. |
*p |
**p |
***p |
Discussion
Our study yielded several main findings: (1) The prevalence of opioid overdose risk reduction behaviours was low in this Spanish sample. (2) The prevalence of PBs was higher among injectors than among non-injectors, while the prevalence of NUA was similar in both groups. (3) Knowledge of the main risk factors for opioid overdose tends to be associated with the practice of the corresponding PB, although this is not always the case. (4) Having received treatment for drug dependence, including MMT, was not associated with a higher prevalence of PBs or NUA, whereas the use of other harm reduction programmes like SEPs or overdose prevention workshops was associated with having some PB among injectors. (5) Overdose experience (having suffered or only witnessed an overdose) tends to be associated with a higher prevalence of PBs, but not of NUA. Each of these findings is discussed below.
Young adult heroin users in three large Spanish cities were shown to have few PBs, and only slightly more than one-third always followed the risk reduction strategy of NUA. Overall, 42.4% of participants had at least one PB in the last year and 12.9% had two or more. The prevalence of some specific PBs which the evidence has shown to be very important (Brugal et al., 2002, Darke et al., 1996, Sporer, 1999, Sporer, 2003) was very low, such as not mixing heroin with tranquillisers (5.1%) or alcohol (0.2%), or reducing/stopping the use of heroin by injection (8.3%). Using a smaller than usual amount of heroin after a period of abstinence was not mentioned as a PB by anybody. According to Farrell and Marsden (2008), the risk of death from overdose or “problems related with substance use” (coroners cited the involvement of opioids in 95% of cases) during the period immediately following prison release is very high. Another study also found that the risk of overdose was 27 times higher in the first month out of treatment (Davoli et al., 2007). The low prevalence of PBs to avoid overdose and NUA among heroin users in Barcelona, Madrid and Seville despite extensive harm reduction programmes (SEPs, SIFs, MMT) (Bravo et al., 2007, Bravo et al., 2009, de la Fuente et al., 2006a) suggests that these programmes may have prioritised HIV prevention over overdose prevention; in fact, reduction of overdose mortality is not mentioned in the Spanish National Strategy on Drugs (DGPNSD, 2005). It also helps explain the slow decline in overdose mortality in Spain in recent years (de la Fuente et al., 2006b, DGPNSD, 2008). After including attendance to courses/meetings in the models, living in Barcelona was a predictor of both more PBs aimed at controlling the use of other drugs to avoid opioid overdose and more NUA among injectors. These results may also reflect a higher level of awareness of overdose risk among Barcelona drug injectors who did not attend educational activities; this in turn could be related with the naloxone distribution programme in Barcelona between 2001 and 2003, a subject not explicitly addressed in the questionnaire (Ilundain, 2009, Trujols, 2001). In the international context, England and Wales also have high overdose death rates (Morgan et al., 2008) despite wide availability of MMT or SEPs.
A considerable proportion (36.2%) had NUA in the last 12 months, however, this figure is lower than that observed by McGregor, Darke, Ali, and Christie (1998) based on a reference period of 6 months. In our study we do not know to what extent this was a conscious risk reduction strategy to avoid the fatal consequences of overdose or a social practice due to other reasons. Promotion of this risk reduction strategy among users should be accompanied by interventions aimed at encouraging persons who witness an overdose to provide appropriate assistance (Dietze et al., 2006, EMCDDA, 2009, Seal et al., 2005, Tobin et al., 2005). In fact, the effectiveness of educational programmes in techniques of cardiorespiratory resuscitation or naloxone use (Baca & Grant, 2005) would be expected to improve if the proportion of those who inject alone is reduced. Moore (2004) makes some interesting points about the superficial social relations existing among injectors, who often interact in a context of trust/distrust with family members, peers or acquaintances, and which is marked by the daily need to alleviate the abstinence syndrome. These aspects can be expected to condition their choice of company which, in case of overdose, could act by contacting the emergency services or police, or by administering an antagonist which would put them in a position where they again needed a new dose. In addition, having a low score (between 0 and 4) on heroin dependence was a predictor of more NUA among both injectors and non-injectors, probably because people who are not compulsive heroin users tend to use the drug more as a social activity.
PBs were much more frequent among injectors than non-injectors, and being an injector was a predictive factor for these behaviours in the logistic regression analysis of the overall sample. This is consistent with the higher risk of overdose in injectors than in non-injectors (15–30 times higher) (Brugal et al., 2002). However, the relative difference in the prevalence of PBs between the two groups would not compensate for the important difference in the risk of opioid overdose. Thus, overdose prevention programs should primarily target drug injectors, especially considering that in our study no differences were found between injectors and non-injectors in the prevalence of NUA.
We also found that increased frequency of injection was not accompanied by an important increase in the probability of practising PBs; a similar relationship was previously found between frequency of injection and the probability of suffering an opioid overdose (Brugal et al., 2002).
Knowledge of the main risk factors for overdose was associated with the practice of the corresponding preventive actions, although this was not always so. The identification of both the route of administration and the use of other drugs as causes of opioid overdose was positively associated with PBs aimed at avoiding these risk factors. This suggests that knowledge of the causes of overdose is important in the development of preventive initiatives at the individual level and would support educational programmes (Darke & Hall, 2003); our finding of a higher prevalence of NUA among those who attended courses or meetings related with overdose prevention would also support such initiatives. However, we found a negative relation between identification of the use of too much or too pure heroin as a risk factor for opioid overdose and the adoption of PBs. Other authors have also reported paradoxical findings in this regard (Dietze et al., 2006) and have emphasised (Moore, 2004, Rhodes, 2009) that the interrelation between knowledge and risk behaviour, which is the basis of educational programmes for prevention, assumes “rational” decision-making, whereas this interrelation is undermined by the lifestyle associated with illegal drug use and the need to alleviate the withdrawal syndrome. As Moore (2004) mentions, messages about overdose prevention are added to a long list of “possible risks” encountered during the course of a day. The findings of Dietze et al., together with our results, would support a move towards a policy of action in research and responses that considers the social conditions and interrelations involved in risk behaviour for overdose.
Neither MMT nor other drug-dependence treatment in the last 12 months was a predictor of PBs in either injectors or non-injectors, whereas use of a SEP was a predictor for some PB in injectors. This finding is consistent with low involvement of treatment services in overdose prevention. While some countries like Australia (Ministerial Council on Drug Strategy, 2001) have launched intensive overdose prevention initiatives, others, like Spain, have not–despite the existence of an extensive infrastructure of public centres for drug treatment and harm reduction. EMCDDA (2009) notes that very few countries have interventions targeting prisoners or those in drug treatment, despite evidence showing an important increase in the risk of death after prison release (Farrell & Marsden, 2008) or ending treatment (Davoli et al., 2007). Our study, like others recently published (Doe-Simkins et al., 2009, Galea et al., 2005, Piper et al., 2008, Tobin et al., 2009) supports the idea of SEPs as a suitable place for overdose prevention initiatives. It is essential to take advantage of important treatment resources implemented partly as a result of the epidemic of HIV and HCV in injectors. It may also be useful to monitor opioid overdose risk reduction behaviours, as already done with risk behaviours for infections, by introducing some basic indicators in drug information systems.
The factor most strongly associated with having some PB in the overall sample, in both injectors and non-injectors, was overdose experience—ever having overdosed or witnessed an overdose. Overdose experience was also a predictor of some specific preventive behaviours such as controlling the route of heroin administration (among injectors and non-injectors) or controlling the use of other drugs (among injectors). This finding is consistent with the higher risk of overdose among those who have already suffered an overdose (Darke et al., 2007, Powis et al., 1999). The fact that persons who have experienced an overdose also have more PBs should be considered when implementing regular screening for overdose in treatment and harm reduction programs, as Darke et al. (2007) have proposed. Moreover, drug treatment services should monitor which of their clients’ PBs are most effective in avoiding opioid overdose according to existing scientific evidence (Darke & Hall, 2003).
Use of little or no alcohol and tobacco, as well as having experienced an overdose, were associated with a higher prevalence of PBs, but not of NUA. Given the synergism between alcohol and opioids (Darke and Hall, 2003, Ruttenber et al., 1990), those in our study in the highest category of alcohol consumption had a very high risk since they also had the fewest PBs. However, it is not easy to explain the positive relation between having PBs and being a non-smoker or a less intense smoker, although it is consistent with maintaining a lifestyle with less risk to health.
Male gender was a predictor of more PBs, however the strategy of NUA was associated with being female. This could be related with the commonly observed cross-cultural phenomenon of males influencing the drug use and practices of their female sexual partners (Evans et al., 2003, Bravo et al., 2003). It is also likely that heroin consumption among men takes place in more varied social contexts than women, including injecting alone, with a partner, or in a group.
In interpreting our results, several caveats must be borne in mind. First, its cross-sectional design does not allow causal inference. Although we made a rigorous attempt to make the sample as representative as possible by using different recruitment strategies in different places, and by including some types of less accessible users (those who are integrated in the community, very young or recent drug users, etc.), the degree of representativeness is unknown since we lack a reference sampling framework. It was not possible to evaluate the effect of SIF use because the corresponding question was introduced in the questionnaire after 2001–2003 (Bravo et al., 2009). To reduce socially undesirable responses, the interviews were not conducted at sites of SEPs, SIFs or drug-dependency treatment.
In conclusion, our findings suggest that in Spain, and probably in some other countries with a similar drug scene and policy responses, far more efforts should be made to promote preventive behaviours to protect against opioid overdose. Clearly, harm reduction programmes and treatment services need to focus strongly on overdose prevention, especially among drug injectors. In addition, drug information systems should consider monitoring basic behavioural indicators for overdose prevention.
Acknowledgements
Study design, collection and analysis of data were funded by the Foundation for AIDS Prevention and Research in Spain (Fipse 3035/99). A supplemental grant by RTA (RD06/0001/1018) made it possible to write the paper. We also thank Kathryn M. Fitch for translation and suggestions.
The authors have no conflict of interest to declare.
References
- . Memoria 2001 [Annual Report 2001]. Madrid: Agencia Antidroga de la Comunidad de Madrid (AACM); 2002;
- . Memoria 2002 [Annual Report 2002]. Madrid: Agencia Antidroga de la Comunidad de Madrid (AACM); 2003;
- . Memoria 2003 [Annual Report 2003]. Madrid: Agencia Antidroga de la Comunidad de Madrid (AACM); 2004;
- . Take-home naloxone to reduce heroin death. Addiction. 2005;100:1823–1831
- . Reasons for selecting an initial route of heroin administration and for subsequent transitions during a severe HIV epidemic. Addiction. 2003;98:749–760
- . More free syringes, fewer drug injectors in the case of Spain. Social Science & Medicine. 2007;65:1773–1778
- Use of supervised injection facilities and injection risk behaviors among young drug injectors. Addiction. 2009;104:614–619
- . Factors associated with non-fatal heroin overdose: Assessing the effect of frequency and route of heroin administration. Addiction. 2002;97:319–327
- . Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain. Addiction. 2005;100:981–989
- . Heroin overdose: Research and evidence-based intervention. Journal of Urban Health. 2003;80:189–200
- . Fatal heroin ‘overdose’: A review. Addiction. 1996;91:1765–1772
- . Overdose among heroin users in Sydney, Australia: I. Prevalence and correlates of non-fatal overdose. Addiction. 1996;91:405–411
- . Patterns of nonfatal heroin overdose over a 3-year period: Findings from the Australian treatment outcome study. Journal of Urban Health. 2007;84:283–291
- Risk of fatal overdose during and after specialist drug treatment: The VEdeTTE study, a national multi-site prospective cohort study. Addiction. 2007;102:1954–1959
- . Prevalencia de infección por el virus de la inmunodeficiencia humana y de conductas de riesgo entre los consumidores de heroína de Barcelona, Madrid y Sevilla: un ejemplo de las ventajas de centrar los estudios en los consumidores y no sólo en los usuarios por vía intravenosa [The prevalence of human immunodeficiency virus infection and the risk behaviors in the heroin addicts of Barcelona Madrid and Seville: An example of the advantages of centering studies on addicts and not just on intravenous users]. Medicina Clinica. 1999;113:646–651
- Metodología del estudio de cohortes del Proyecto Itinere sobre consumidores de heroína en tres ciudades españolas y características básicas de los participantes [Cohort study methodology of the Itinere Project on heroin users in three Spanish cities and main characteristics of the participants]. Revista Española de Salud Pública. 2005;79:475–491
- Injecting and HIV prevalence among young heroin users in three Spanish cities and their association with the delayed implementation of harm reduction programmes. Journal of Epidemiology and Community Health. 2006;60:537–542
- . Más de treinta años de drogas ilegales en España: una amarga historia con algunos consejos para el futuro. Revista Española de Salud Pública. 2006;80:505–520
- Audio-computer interviewing to measure risk behaviour for HIV among injecting drug users: A quasi-randomised trial. The Lancet. 1999;353:1657–1661
- . Estrategia Nacional sobre Drogas. Plan de Acción 2005–2008 [National strategy on drugs. Action plan 2005–2008]. Madrid: Delegación del Gobierno para el Plan Nacional sobre Drogas (DGPNSD). Ministrerio de Sanidad y Consumo; 2005;
- . Memoria 2004 [Annual Report 2004]. Madrid: Delegación del Gobierno para el Plan Nacional sobre Drogas (DGPNSD). Ministerio de Sanidad y Consumo; 2006;
- . Observatorio Español sobre Drogas (OED). Informe 2005–2006. Madrid: Delegación del Gobierno para el Plan Nacional sobre Drogas (DGPNSD). Ministerio de Sanidad y Consumo; 2008;
- . When is a little knowledge dangerous? Circumstances of recent heroin overdose and links to knowledge of overdose risk factors. Drug and Alcohol Dependence. 2006;84:223–230
- . Saved by the nose: Bystander-administered intranasal naloxone hydrochloride for opioid overdose. American Journal of Public Health. 2009;99:788–791
- . The state of the drugs problem in Europe. Annual Report 2008. Luxembourg: European Monitoring Center for Drugs and Drug Addiction (EMCDDA); 2008;
- . The state of the drugs problem in Europe. Annual Report 2009. Luxembourg: European Monitoring Center for Drugs and Drug Addiction (EMCDDA); 2009;
- . Actualització dels Indicadors de Drogues. 4 Trimestre 2008 [Update of Drug Indicators. 4th Quarter 2008]. Barcelona: Agència de Salud Pública; 2009;
- . Gender differences in Sexual and Injection Risk Behavior Among Active Young Injection Drug Users in San Francisco (the UFO study). Journal of Urban Health. 2003;80:137–146
- . Acute risk of drug-related death among newly released prisoners in England and Wales. Addiction. 2008;103:251–255
- . Provision of naloxone to injection drug users as an overdose prevention strategy: Early evidence from a pilot study in New York City. Addictive Behaviors. 2005;31:907–912
- Validity of the Severity of Dependence Scale (SDS) construct applying the item response theory to a non-clinical sample of heroin users. Substance Use & Misuse. 2008;43:919–935
- The severity of dependence scale (SDS): Psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction. 1995;90:607–614
- . Frequency of non-fatal heroin overdose: Survey of heroin users recruited in non-clinical settings. British Medical Journal. 1996;313:402
- Social and structural aspects of the overdose risk environment in St. Petersburg, Russia. International Journal of Drug Policy. 2009;20:270–276
- . Respondent-driven sampling: A new approach to the study of hidden populations. Social Problems. 1997;44:174–179
- . European report on drug consumption rooms. Lisbon: European Monitoring Centre for Drugs and Drug Addiction; 2004;
- . Drogas, enfermedad y exclusión ¿Can Tunis (Barcelona) como paradigma? [Drugs, illness and exclusion ¿Can Tunis (Barcelona) as paradigm?]. Barcelona: Fundación Medicina y Humanidades Médicas; 2009;
- . The impact of harm-reduction-based methadone treatment on mortality among heroin users. American Journal of Public Health. 2001;91:774–780
- . Experience of non-fatal overdose among heroin users in Adelaide, Australia: Circumstances and risk perceptions. Addiction. 1998;93:701–711
- . National heroin overdose strategy. Camberra: Commonwealth of Australia; 2001;
- . Governing street-based injecting drug users: A critique of heroin overdose prevention in Australia. Social Science & Medicine. 2004;59:1547–1557
- . Trends in overdose deaths from drug misuse in Europe: What do the data tell us?. Addiction. 2008;103:699–700
- . Final report on the evaluation of the Sydney medically supervised injecting centre. Sydney: Authors; 2003;
- Do young heroin users in Madrid, Barcelona and Seville have sufficient knowledge of the risk factors for unintentional opioid overdose?. Journal of Urban Health. 2006;83:477–496
- . The differential effects of face-to-face and computer interview modes. American Journal of Public Health. 2002;92:294–297
- Evaluation of a naloxone distribution and administration program in New York City. Substance Use & Misuse. 2008;43:858–870
- Self-reported overdose among injecting drug users in London: Extent and nature of the problem. Addiction. 1999;94:471–478
- . Risk environments and drug harms: A social science for harm reduction approach. International Journal of Drug Policy. 2009;20:193–201
- . The role of ethanol abuse in the etiology of heroin-related death. Journal of Forensic Sciences. 1990;35:891–900
- Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: A pilot intervention study. Journal of Urban Health. 2005;82:303–311
- . ICAP Informe del cuestionario de actividades de prevención del VIH en las Comunidades Autónomas [ICAP. Report from the HIV prevention activities questionnaire in the Authonomous Communities]. 2009;Retrieved 3 October 2009 from http://www.msc.es/gl/ciudadanos/enfLesiones/enfTransmisibles/sida/docs/ICAP2007/ICAP2007.pdf
- . Acute heroin overdose. Annals of Internal Medicine. 1999;130:584–590
- . Strategies for preventing heroin overdose. British Medical Journal. 2003;326:442–444
- . Calling emergency medical services during drug overdose: An examination of individual, social and setting correlates. Addiction. 2005;100:397–404
- . Evaluation of the Staying Alive programme: Training injection drug users to properly administer naloxone and save lives. International Journal of Drug Policy. 2009;20:131–136
- . Take home naloxone: Life-saving intervention, medico-legal concern and heroin users’ competence. British Medical Journal. 2001;322:895–896
- Hepatitis B vaccination: An unmet challenge in the era of harm reduction programs. Journal of Substance Abuse Treatment. 2007;34:398–406
- . Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programs. Addictive Behaviors. 1999;24:559–563
- . Rebound of overdose mortality in the European Union 2003–2005: Findings from the 2008 EMCDDA Annual Report. Eurosurveillance. 2009;14:
PII: S0955-3959(10)00098-8
doi:10.1016/j.drugpo.2010.06.003
© 2010 Elsevier B.V. All rights reserved.
