Prevalence morbidity and mortality among heroin users and methadone patients

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Buster, M.C.A.

Publication date

2003

Link to publication

Citation for published version (APA):

Buster, M. C. A. (2003). Prevalence morbidity and mortality among heroin users and

methadone patients.

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G E N E R A L L

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P M A M A H U A M P P

G e n e r a ll I n t r o d u c t i o n

O V E R V I E W W

Heroinn use emerged in Amsterdam in the autumn of 1972. Thirty years laterr the chronic nature of heroin addiction is still visible on its streets.. In 1981 the municipality of Amsterdam adopted a pragmatic andd - for its time - revolutionary drug policy. In the absence of an effectivee cure for all heroin users the Municipal Health Service MHS aimedd to contact as many heroin users as possible to prevent social andd medical problems, or at least reduce them.

Thiss thesis reports on a number of studies being conducted at thee MHS. The first study involves estimating the size of the population off problematic opiate users in Amsterdam and thus the proportion in contactt with the health service. The second and third studies deal with pulmonaryy disease, Tuberculosis TB and Chronic Obstructive Pulmonaryy Disease COPD. At the beginning of the 1990s it was feared that,, along with the spread of the Human Immunodeficiency Virus HIV, aa TB epidemic would emerge among opiate users. Symptoms of COPD aree currently a cause of concern among opiate users and health care workers.. The other three studies are into mortality among opiate users.. The first describes overdose OD mortality in relation to time in methadonee treatment. Methadone treatment is known to prevent OD mortality.. Australian researchers, however, observed high OD morta-lityy rates during the first two weeks after the onset of treatment. The secondd compares four Northern European cities: Oslo, Frankfurt, Copenhagenn and Amsterdam. High and rising number of OD deaths are observedd in Oslo. They contacted the other three cities with lower numberss of OD cases and stable or decreasing levels to find an expla-nationn for the difference and clues to prevent OD mortality. The last studyy is taking place within the framework of a broader European pro-jectt initiated by the European Monitoring Centre of Drugs and Drug Addiction.. This project aims to improve comparability of mortality studiess of opiate users. The specific study presented here is con-cernedd with improving the outcome parameter in mortality studies of opiatee users.

Thee introduction situates these studies within a broader per-spective,, providing background information on heroin, cocaine and methadone,, the characteristic substances used by this population. Itt also explains the difference between drug use, abuse and depen-dencee and gives a brief history of the Amsterdam drug problem and thee steps being taken by the MHS. It concludes by introducing the indi-viduall studies and addresses their importance from a public health pointt of view.

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1 44 C e n t r a l i n t r o d u c t i o n

G E N E R A LL C O N T E X T

H e r o i n ,, c o c a i n e a n d m e t h a d o n e

Heroinn diacetytmorphine- is a semi-synthetic opiate derived from the chemicall manipulation of morphine, a process first described in 1874."" Morphine is one of the psycho-active components of opium, whichh is extracted from the opium poppy -Papaver Somniferum Cocainee is a stimulant extracted from the leaves of the Erythroxylon cocaa bush. The process of extracting cocaine has been known since

1855J22 The use of the raw materials of heroin and cocaine has a long

history.. Stories of the ancient Creeks and the native inhabitants of Latinn America refer to the use of opium and coca leaves

respec-tively.131** The history of methadone is much shorter. This synthetic

opioidd was developed for analgesia prior to world war II in Germany.,s

Nowadayss heroin and cocaine are predominantly used because off their euphoric effects. The nature of the effect, however, is differ-ent.. The desired psychotropic effect of cocaine is an energetic, active andd sociable one whereas the desired psychotropic effect of heroin is aa short period of feeling high 'kick' followed by a longer period of feel-ingg pleasant 'nothingness'.* Outside medical practice methadone is usedd predominantly to avert withdrawal symptoms, but it also gener-atess a euphoric effect if administered by injection.17

Heroinn and cocaine can be swallowed, snorted, inhaled or inject-ed.. Among the drug users that are the focus of this study, however, bothh cocaine and heroin are either inhaled or injected. Compared to snorting,, these methods of administration result in a faster maximum concentration,, a higher peak, a shorter duration of effect and

proba-blyy higher addiction rates.18 The pharmacokinetic properties of the

substancess differ. When injected, the elimination half-life of cocaine is approximatelyy 40 minutes,19 that of heroin about 3 hours.110 Methadone iss a long-acting opiate with a median half-life of 3 3 - 4 6 hours in healthyy subjects but may vary considerably between individuals.I M"2

Heroinn and cocaine were introduced into official medical practice att the end of the nineteenth century. Elixirs containing heroin were consideredd to cure a wide variety of illnesses, including bronchitis, chronicc cough, asthma and tuberculosis. Cocaine also had medical applications,, for instance as a local anaesthetic for minor surgery

nose or throat- At the turn of the twentieth century the danger

off heroin and cocaine addiction was already recognised as a medical problem.. During the twentieth century international legislation and thee availability of alternative medication gradually reduced the medi-call use of heroin and cocaine.12 In Britain physicians have been allowed

too maintain addicts on heroin since the 1920s.|,J Only recently has the

prescriptionn of heroin to heroin users experienced an upsurge, follow-ingg experiments in Switzerland and the Netherlands which indicate

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C e n t r a ll I n t r o d u c t i o n I B

thatt this treatment is both feasible and beneficial for chronic treat-ment-resistantt heroin addicts.| U , I S

Methadonee is used predominantly as a substitute for heroin. Afterr the Second World War Isbetl & Vogel found that methadone could bee used effectively to take addicts off heroin. They replaced heroin withh methadone and gradually reduced the dosage. After reaching abstinencee from opiates, however, relapse rates of more than 90%

weree observed.1'6 A treatment in which methadone dosages were

main-tainedd was developed by Dole and Nyswander in the 1960s.1'7 Daily

highh dosages of methadone suppress the opioid abstinence syndrome, relievee the craving for narcotics, and block the effects of heroin. Methadonee maintenance treatment has been proved to reduce heroin

usee and criminal behaviour."8 It has become the main form of

treat-mentt for heroin addiction, in the year 2000 approximately 275 000 heroinn users were treated with methadone in the member states of the Europeann Union."9

U s e ,, a b u s e a n d d e p e n d e n c e

Thee 4th Diagnostical Statistical Manual of Mental Disorders DSM-IV dis-tinguishess between drug use, drug abuse and drug dependence. Drug abusee is characterised by a maladaptive pattern of drug use. one in whichh the use of drugs repeatedly results in failure to fulfil major role obligationss and consequently leads to social, Interpersonal or legal problemss or may put the person or others in danger e.g. driving

underunder influence' Drug dependence is described as a pattern of

repeatedd use that usually results in tolerance, withdrawal and com-pulsivee drug-taking behaviour. A great deal of time is spend On obtain-ingg drugs, using drugs or recovering from the use of drugs, and importantt social, occupational or recreational activities are given up becausee of drug use. Despite these significant substance-related

prob-lemss the drug use continues,1" The severity of dependence not only

dependss on the amount and frequency of the drug being taken but alsoo on the negative consequences of drug use. Tools to measure the severityy of dependence e.g. the Addiction Severity index- are designedd to assess the severity of the problem in areas commonly affectedd in alcohol and/or drug abusers: medical condition, employ-ment,, illegal activities, family relations and psychiatric condition.12'

Oncee the drug is used, repeated use of heroin is more common thann repeated use of Other illicit drugs. A survey of Amsterdam house-holdss in 1997 revealed that, of people who reported ever having used heroinn -1.7% of the respondents-, 41% had used it more than 25 times. The percentagee of the 'ever' users who took the substances more than 25 timess was 10% among users of hallucinogens -LSD, magic

mush-rooms-rooms- , 18% among users of MDMA and 27% among cocaine users. The

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I BB G e n e r a l I n t r o d u c t i o n

ll and cigarettes both 88%; cannabis 44% "^ Also, compared to users of

otherr drugs, heroin users display more medical and social problems.123

Inn the ensuing chapters of this thesis the terms 'heroin user' and

'opiate'opiate user' are both applied. Everyone in the target population has a

historyy of heroin use but, as most studies are conducted in the frame-workk of methadone treatment, heroin may have been substituted for methadonee and therefore the term 'opiate user' is more appropriate. Althoughh the term 'opiate use' is utilised, the diagnosis of opioid dependencee will be applicable to the vast majority of the population examinedd in this thesis.

H i s t o r i c a ll c o n t e x t o f t h e h e r o i n p r o b l e m i nn A m s t e r d a m

Inn the history of the heroin problem in Amsterdam there are certain milestones:: the introduction of heroin In the autumn of 1972, the introductionn of the mobile methadone bus in 1979, the first diagnosis off Acquired Immunodeficiency Syndrome AIDS among heroin users in 1985,, the stabilisation of the heroin epidemic during the 1990s, and thee introduction of heroin prescriptions in 1998. The studies describedd in this thesis are taking place at the MHS, hence particular attentionn is paid to this organisation's drug-treatment services and studies.. The MHS, however, is not the only provider of services for drugg users in Amsterdam. In addition treatment is provided by the Jellinekk and the general practitioners in Amsterdam. Moreover there aree other low-threshold services such as the street-corner work foundation,, the Rainbow foundation, the AMOC and organisations for thee homeless such as the Salvation Army, the HVO and the Volksbond, whichh provide social help, daytime activities, accommodation and/or

refreshments,, and user rooms or needle exchange. The MDHC junky

union-union- and the Mainline foundation also offer health education and

informationn to this group.

Heroinn was introduced to Amsterdam in the autumn of 1972, whenn the withdrawal of US forces from Vietnam forced Southeast Asian

syndicatess to seek new markets for their heroin production.124 Before

19722 opium and amphetamines had been used on a small scale. Cohen describess this drug scene as part of a deviant youth culture: the vast majorityy 78% of the opium users he interviewed in 1968 were under

25.|2SS After 1972 the number of heroin users and the concomitant

problemss escalated rapidly. Heroin was mainly injected by the - origi-nallyy Dutch - users. A rapid upsurge in the number of heroin users was recordedd around 1975, when Surinam became independent and many Surinamesee migrated to The Netherlands. Single male Surinamese ado-lescentss came to play a major role in the heroin street trade, and many

becamee users themselves.17 As a result of initial contacts with Chinese

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GG a n r a I I n t r a d i t c t l o M 1 7

fromm heated aluminium foil 'Chasing the Dragon' instead of injecting.126

Nowadayss the vast majority of heroin users in Amsterdam and other

partss of the Netherlands administer the drug by Chasing the Dragon.117

Althoughh accurate data on the prevalence of heroin use in the 1970ss are not available, guestimates indicate an explosive rise. The steepp Increase in the number of heroin users brought an increase in publicc nuisance and criminality in its wake. To conquer these prob-lemss a large number of initiatives were taken by various competing organisations,, the majority of which were at least partial failures.'2*

Thee first mobile methadone bus on the streets of Amsterdam in 19799 was the precursor of the large-scale methadone maintenance programmee subsequently implemented by the MHS. The main goal of thee MHS programmes was, and stitl is, to contact and maintain contact withh heroin users, including those who are not witling or able to stop theirr heroin use. With this in mind, MHS programmes are

'low-thres-hold',hold', i.e. free of charge, without waiting lists, and the criteria

patientss have to meet are restricted to the ones necessary to run the programmee safely. Patients need to be registered, screened for

tuber-culosiss X-ray- and undergo periodical medical check-ups.

Particularlyy important is the fact that there are no sanctions if urine testss reveal illegal substance use. The use of high dosages of methadonee 1s encouraged, since this is more successful in reducing heroinn use."8 , i* Lower dosages can be given, however, if patients so request.. In such cases regular contact and the use of ancillary services aree considered to be important.

Thee MHS targets the most problematic heroin users. More stable userss should be treated by their general practitioners. Some GPs were alreadyy doing this in the 1970s, and currently half of Amsterdam GPs

providee methadone treatment.130 In order to prevent multiple

prescrip-tionss of methadone being supplied to the same person at different locationss Jeltinek, pharmacy or MHS> a Central Methadone Register

CMRCMR has been set up.

Inn addition to the methadone treatment programmes, medical doctorss from the MHS started providing methadone at police stations too prevent withdrawal symptoms among arrested heroin users. A hos-pitall project was also established: nurses from the MHS assist with hospitall admissions of heroin users and advise the physicians in charge.. Again the use of methadone is recommended to prevent with-drawall and subsequent premature discharge.

Afterr the introduction of these programmes there was no imme-diatee reduction in the heroin problem in Amsterdam, owing mainly to foreignn heroin users, predominantly Germans, who frequented

Amsterdamm in the first half of the 1980s.13' The majority of the German

userss took their heroin intravenously and Were vulnerable to overdose

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I SS G * n r a I I n t r o d u c t i o n

overdosee deaths. To discourage this migration, foreign drug users weree given only limited access to the Amsterdam methadone treat-mentt programmes. They could only receive methadone treatment in thee case of severe health problems or prostitution -i.e. humanitarian

assistanceassistance and prevention of sexually transmitted diseases- This

pol-icyy of discouragement led to the MHS setting up a Foreigners and Prostitutionn Outpatients Clinic. The large numbers of injecting drug userss visiting the city for shorter or longer periods of time probably formedd the breeding ground for the next period, one dominated by the threatt of HIV.

Inn Amsterdam, the first AIDS case among heroin users was diag-nosedd in 1985.'" That year, the MHS began a prospective cohort study off predominantly injecting heroin users to study this disease. Subsequentt research revealed that 30% of injecting drug users were

alreadyy infected with the virus by then.114 Annual mortality of

HIV-positivee drug users reached its peak in 1993 N = 57-, since when it has decreased.135 5

Amongg injecting drug users needle sharing using one another's

needlesneedles - is an important route for the transmission of blood-borne

viruses.. A needle exchange programme was introduced by the MDHC ass early as 1984 to reduce the spread of the Hepatitis B Virus HBV. A feww years later the needle exchange programmes were expanded to preventt further spread of HIV. The infrastructure of methadone pro-grammess facilitated the provision of clean needles, condoms and healthh education. Researchers reported a decline in risk behaviour amongg injecting drug u s e r s .1" ' " They observed a decline in the HIV

andd H8V incidence rates.138139,4 but a stable high incidence rate of

infectionn with Hepatitis C Virus HCV.**1 The behavioural change

observedd among injecting drug users could reduce the likelihood of becomingg infected with HIV but seemed to be insufficient to lower the incidencee of HCV Infections.142

Duringg the nineties there was a decline in the prevalence of injectingg drug use, attributed to selective migration and mortality, moree people ceasing to inject and fewer people initiating or relapsing

intoo injecting heroin use.'43 A qualitative study of drug users who

stoppedd injecting suggests that the main factor in cessation was healthh reasons i.e. poor condition of superficial veins-|44 The increas-ingg methadone dosages in treatment programmes may have facilitated thee reduction in risk behaviour, injecting and consequently HIV infec-tion.145'461477 Also, the increasing popularity of non-injecting use of base cocainee may have contributed to the decline in injecting use. For those opiatee users who were already infected with HIV the treatment oppor-tunitiess increased w i t h the introduction of Highly Active Anti-Retrovirall Therapy HAART in 1996. Evidently the main threat of an HIV epidemicc among opiate users has passed.

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G e n e r a ll I n t r o d u c t i o n _{1 9 9}

NumberNumber of methadone treatment patients

<< 50 5050 - 99 100100 - 249 250250 - 499 500-749500-749 750-999 1000-1249 1250 1499 >I500 5 55 + 5 0 0 5 4 4 4 5 5 -- 4 9 4 0 0 -- 4 4 3 5 5 -- 3 9 3 0 0 -- 3 4 2 5 5 -- 2 9 << 2 5 00 0 cn n

Y ' e « «

fNI I 0 0 0 Cn n rr, rr, CO O 0 1 1 0 0 0 cn n LA A 0 0 0 « 5 5 CO O cn n r-. . 00 0 cn n CO O CO O cn n cn n CO O cn n o o cn n cn n 199 1 1 199 2 2 199 3 3 11 99 4 199 5 5 199 6 6 199 7 7 199 8 8 cn n cn n cn n o o o o o o ( M M _ _ O O o o r s j j

FigureFigure I Age t r e n d : annual n u m b e r ss of m e t h a d o n e patients by agee category, 1981 - 2 0 0 1

D u r i n gg the 1990s there was a g r o w i n g n o t i o n that the h e r o i n e p i d e m i cc was s t a b i l i s i n g . The annual n u m b e r of heroin users p a r t i c i -p a t i n gg in methadone t r e a t m e n t decreased f r o m 3 9 4 0 in 1989 to 2 9 1 2 inn 2 0 0 0 . M e a n w h i l e , t r e a t m e n t c o m p l i a n c e of those in t r e a t m e n t increasedd and, as a result, a stable n u m b e r of a p p r o x i m a t e l y 2 0 0 0 patientss p a r t i c i p a t e d in the v a r i o u s p r o g r a m m e s each week. The m e d i a nn age of these patients rose f r o m 3 1 . 7 in 1989 to 41.2 in 2000.1488 Particularly i m p o r t a n t is the decreasing number of y o u n g peo-plee a m o n g p a r t i c i p a n t s in m e t h a d o n e p r o g r a m m e s and a m o n g those w h oo are arrested and receive m e t h a d o n e at a police s t a t i o n . The n u m -berr of patients in m e t h a d o n e t r e a t m e n t aged under 25 decreased f r o m 4 9 88 in 1989 to 44 in 2 0 0 0 , the n u m b e r of y o u n g under-25 h e r o i n userss receiving methadone at police s t a t i o n s decreased f r o m 2 9 0 in 19899 to 63 in 2 0 0 0 . Figure 1 shows the t r e n d in the epidemic based onn the annual numbers of clients p a r t i c i p a t i n g in the A m s t e r d a m m e t h a d o n ee t r e a t m e n t p r o g r a m m e s by age category. It shows the i n i t i a l increasee and later decrease a m o n g the y o u n g e r age categories and the i n c r e a s i n gg number of older p a t i e n t s .

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S II G e n e r a l I n t r o d u c t i o n

Otherr studies, as well as the data from the Central Methadone Register,, confirm that heroin has lost its attraction for youngsters.1"1*9 Wee are, however, observing increasing consumption of MDMA, amphetaminee and cocaine - administered orally or by snorting. Within thee general population, the prevalence of use of these drugs is much higherr than prevalence of heroin use. The demand for treatment, how-ever,, is relatively low: only 1% and 2% of the demand for outpatient drugg treatment is related primarily to the use of MDMA and amphetaminee respectively. Twenty-three percent of the demand was relatedd to the use of cocaine. One-third of the demand involved snort-ingg and two-thirds inhaling cocaine.1"

Inhalingg of base cocaine is causing increasing concern. Base

cocainee became popular in Amsterdam in 1981|51 and its popularity

increasedd in the course of the decade.151 At that time users themselves

preparedd base coke from cocaine hydrochloride. During the 1990s, however,, ready-to-use base coke was increasingly available on the streets.. Besides the pharmacokinetic properties of the drug, the ease off administration, availability of ready-to-use substance and relatively loww cost per dose may make smoked cocaine 'crack' more likely to be abusedd and to contribute to the proces of marginalisatlon.1""

Thee population of base cocaine users largely coincides with the populationn of heroin users. Among base cocaine users of the street drugg scene in the Bijlmer district of Amsterdam, 71% reported to use

heroinn on a daily basis and only 10% never used it.1" Among the

heroinn users selected for experimental heroin co-prescription it is the

otherr way around: 90% used cocaine during the previous month.115

Amongg young drug users recruited for a cross sectional study at the MHS,, almost all respondents reported a history of base-coke use -90%-Herotnn or methadone was used less o f t e n . ' " Key informants confirm thee preference for cocaine base among marginalized groups, but they alsoo report cocaine users slipping into heroin use.149 Despite efforts to findd a pharmacological treatment that specifically targets cocaine addiction,, none has yet been found.1"

Inn The Netherlands, the heroin epidemic now seems to be in its finall phase, and the chronic nature of heroin use among those who are stilll using it is increasingly accepted as a fact. This does not mean, however,, that the ongoing problems it brings with it are also accept-able.. Social marginalization remains a major problem for both heroin userss and society at large. Many heroin users remain stuck in poverty, drugg use and deviant behaviour. Also, some methadone treatment clientss continue using heroin compulsively despite sufficiently high dosagess of methadone.

Methadonee is not a panacea, and additional forms of substitu-tionn treatment have been introduced for those heroin users who have nott responded satisfactorily to methadone treatment. A group of 1100

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CC i i i r i I I n t r o d a c t l o n 2 1

heroinn users who were frequently arrested by the police were selected forr heroin prescriptions as early as 1982. The prescription programme neverr got under way, however. A small-scale pilot scheme -N = 26- was launchedd in 1983 using morphine as a substitute for heroin. The

patientss evaluated showed moderately positive results.1" The

mor-phinee substitution programme was not extended, but those subjects in whomm morphine substitution led to positive results were permitted to continuee with the treatment. In 1990, the MHS started a palliative treatmentt with prescribing intravenous methadone to severely

addict-edd AIDS patients who were in very poor health.158 In 1996 a selected

groupp of methadone clients with ongoing heroin use were treated with

dextromoramidee Palfium9 Again the results appeared to be

moder-atelyy positive, but as in the morphine study there was no comparable controll group.1*9 Finally the first randomised controlled trial in which methadonee was compared with methadone plus heroin cö-prescription wass started in 1998. The initial results show a statistically significant improvementt in physical, mental and social health among heroin users."** In addition to heroin co-prescription an involuntary pro-grammee has been introduced, the Penal Care Facility for Addicts SOV. Thiss treatment targets chronic heroin users who are frequently arrest-edd and is based on detoxification and rehabilitation within the correc-tionall system. No results are available from this project yet.*0

T H EE C O N T E N T O F T H I S T H E S I S

Thiss thesis contains six epidemiological studies describing the preva-lencee of problematic opiate use in the city of Amsterdam, focusing on twoo important forms of morbidity among opiate users -tuberculosis

andand chronic obstructive pulmonary disease- Three of the studies deal

withh mortality among opiate users. Apart from the study on pulmonary functionn they are based on data already available at the MHS. Data fromm other European cities, regions or countries are used in the last twoo studies in addition to the Amsterdam data.

Chapterr 2 describes an estimation of the prevalence of problem-aticc opiate users in the city of Amsterdam. This chapter focuses on the method,, a three-sample capture-recapture, and emphasises the impor-tancee of case definition. As described earlier, one of the main goals of thee Amsterdam treatment programmes is regular contact with the tar-gett population: the potential impact of preventive measures increases

withh the proportion of the target population reached.'1" In order to

knoww what this proportion is, the prevalence needs to be estimated. Prevalencee estimations are also anchor points in the description of the heroinn problem, enabling us to interpret the prevalence of heroin-relatedd health problems -e.g. heroin overdose mortality or TB among

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F M A M A H U A M P P

2 22 G « n e r a I I n t r o d u c t i o n

heroinheroin users- in terms of risk. A prevalence estimation also permits a

quantitativee comparison of the Amsterdam heroin problem with those off other cities, either in absolute terms or in relation to population size,, if prevalence estimations are performed periodically, trends over timee become visible.

Sectionn 3.1 describes the incidence rate of TB among methadone clientss in Amsterdam, At the start of the 1990s it was feared that the HiVV epidemic among opiate users would be accompanied by a TB epi-demic.. TB remains a threat: opiate users suffering from TB can trans-mitt the TB bacillus to other drug users, health care workers and the populationn at large.

TBB is a disease of the disadvantaged and marginalized popula-tions.16'' Drug dependence was first suggested as a risk factor in TB by

Reichmannn et al. in 1979.165 Among drug users infected with HIV, TB

oftenn appears as the first manifestation of AIDS.164 Selwyn et al.

describee the increased risk of TB among HIV positive drug users.164 The

riskk of the infection being transmitted is considered to be high, espe-ciallyy at the treatment centres. Heroin users participating in methadonee programmes at the MHS are periodically screened, unlike methadonee patients who attend their GPs. This study describes the incidencee of TB in various treatment programmes.

Sectionn 3.2 describes the situation as regards pulmonary func-tionn in methadone clients, focusing on chronic obstructive pulmonary disease.. COPD is a cause for concern among health care providers and heroinn users. It is characterised by airflow limitation that is not fully reversible.. COPD has been associated with an abnormal response of thee lungs to noxious particles and gases and occurs in approximately

15%% of chronic cigarette smokers.'66 The airflow limitation is usually

progressive,, and functional impairment presents only after 2 0 - 3 0

yearss of exposure.167 Chronic cigarette smoking is much more common

amongg opiate users than in the general population.168

Ass stated before, nowadays, the majority of the heroin users in Thee Netherlands inhale the substance. The influence of inhalation of heroinn on pulmonary problems has not been described in the scien-tificc literature, apart from a few case studies which report asthma attackss after inhalation of heroin. The degree of exposure to heroin by inhalationn among methadone clients varies widely: some have never inhaled,, others have inhaled daily for over twenty years. Based on thesee contrasts we attempt to find a best estimate for the effect of heroinn inhalation on pulmonary function.

Sectionn 4.1 describes overdose mortality in relation to the periodd during methadone treatment and after methadone treatment. Severall studies indicate that methadone treatment reduces overdose

mortalityy among heroin users.|S9|70t7t In New South Wales -Australia-,

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mortal-P M A M A H U A M mortal-P mortal-P

G e n e r a ll I n t r o d u c t i o n 2 3

ityy rates during the first two weeks of methadone treatment 70.4/1000 py- Rates during other periods of treatment and rates with-outt treatment were estimated at 0.7 and 10.5 respectively.'" In Amsterdamm methadone maintenance is the main treatment for heroin users.. Treatment-related deaths are of particular importance because theyy may be preventable by modifying procedures within the methadonee treatment programme.

Sectionn 4 . 2 describes the differences and similarities between thee situations regarding overdose mortality in four European cities

Copenhagen, Frankfurt and Amsterdam- This study was

initiat-edd by the city of Oslo, which experienced a rising number of overdose deathss during the nineties. Although the number of opiate users in the otherr three cities is comparable, the number of OD deaths is lower and decreasingg or stable trends are observed. A working group containing representativess from each city visited the cities, studied the available informationn and conducted interviews with local opiate users, police officers,, social workers, paramedics, politicians and policy-makers.

Att first sight the mechanism and treatment of a heroin OD do not seemm to be very complicated. The main causal mechanism of a fatal heroinn OD is the effect of heroin on the respiratory centre of the brain, causingg respiratory depression and consequently a lack of oxygen.

Thee vast majority of fatal ODs do not occur instantaneously,17517* and

deathh can be avoided by administering oxygen and an opioid antago-nistt Naloxone -,7S

inn practice, however, comparing different cities is a complicated business.. They may apply different procedures and definitions when it comess to recording OD mortality. Also, the breakdown of their popula-tionss of opiate users may vary, with higher or lower proportions of specificc risk groups such as intravenous heroin users,17*'77 those

con-currentlyy using alcohol and/or benzodiazepine/7 8 1" homeless heroin

users,1711 HIV-positive heroin users.'73 Different proportions of opiate userss may experience periods of higher risk such as periods following detoxification,'^^ incarceration'" or start of methadone treatment'82 or lowerr risk for example during stable methadone maintenance. On top off this the way people act if they witness an overdose may differ. Bennett & Higgins reported that although most witnesses to an over-dosee thought that emergency help should be sought -7i%>, only 44%

actuallyy contacted thé emergency services.'83

Thee main question the study examined is whether drug policy influencess OD mortality figures. Oslo's drug policy relies predominant-lyy on abstinence and rehabilitation. Amsterdam's policy focuses on preventingg and solving medical and social problems among heroin userss referred to as a 'harm reduction policy*. Frankfurt developed a drugg policy modelled on the Amsterdam policy at the beginning of the nineties.. Copenhagen gradually moved from an abstinence and

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reha-P M A M A H U A M reha-P reha-P

1 44 G n r a I I n t r o d u c t i o n

bflitation-orientedd approach to one focusing on harm reduction. Sectionn 4 . 3 describes the last study, which aims to improve com-parabilityy of the outcome measure between mortality studies. This studyy is part of a project initiated by the European Monitoring Centre forr Drugs and Drug Addiction, an organisation which aims to provide objective,, reliable and comparable information at European level on drugss and drug addiction and their consequences. The project on mor-talityy among opiate users involves multiple European countries, regionss or cities and aims to improve comparability of the results by usingg similar enrolment criteria for drug users, follow-up procedures

andd methods of data analysis.184 The specific study presented in

sec-tionn 4.3 aims to improve the comparability of outcome parameters. Thee main outcome parameters in general use are crude mor-talityy rates and Standardised Mortality Ratios. The SMR corrects for dif-ferencess in age and gender distribution between the study population andd the reference population. Unfortunately, this does not result in fulll comparability between different study populations. Firstly, the SMR generallyy takes the population of a particular country or city at the timee of the study as a reference population, so variations in mortality ratess between reference populations can produce proportional varia-tionss in the SMR. Secondly, several studies suggest that rate ratios of heroinn users to the general population are heterogeneous.1"1"1 8 7 Rate ratioss are lower among the older age categories than the younger ones,, and lower among males than females. The study describes this heterogeneityy based on the nine European cohorts of opiate users. It alsoo presents stratum-specific mortality rates, which can be used as a referencee for calculating valid and comparable SMRs in single-group mortalityy studies of opiate users.

Thee final chapter chapter - of this thesis elaborates on the

findingss of the individual studies. It discusses the concept of

'cover-ageage by drug-related services' and 'drug-related deaths' and provides

additionall information on trends in prevalence of drug use. It enunci-atess the concept of the 'sick heroin user effect', which, similarly to the

'healthy'healthy worker effect', complicates mortality studies of opiate users.

Itt concludes by presenting the main conclusions of the studies and outliningg directions for future studies on related topics.

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