UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)
UvA-DARE (Digital Academic Repository)
Prevalence morbidity and mortality among heroin users and methadone patients
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.
General rights
It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.
© ©
G E N E R A L L
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n 1 3 7
InIn this final chapter we elaborate on the topics discussed in
thethe previous chapters. Here we discuss how the prevalence
estimatesestimates relate to other Indicators of problematic drug use
inin Amsterdam and we describe the prevalence trends. We
discussdiscuss the concept of health services coverage and we
brieflybriefly discuss the chapters concerning TB and COPD. In
addition,addition, we express our view on the policy measures In
placeplace to prevent overdose mortality and we discuss the
increasedincreased risk of mortality among of opiate users.
Furthermore,Furthermore, we propose future research directions for
thesethese areas.
P R E V A L E N C EE E S T I M A T I O N A N D C O V E R A G E
B e t t e rr m e t h o d , b e t t e r r e s u l t ?
Inn 19£7 the prevalence of problematic opiate users in Amsterdam was estimatedd to be 4130 -95% CI:3753-4566- The sampling method used is ann improvement on the method which was used traditionally, a 3-samplee capture-recapture analysis C/RC with a three month sam-plingg period, as opposed to a 2-sample C/RC with a one year sampling period.. The 3-sample C/RC with sampling periods longer than three monthss resulted in statistically unstable models, inflated estimates andd inflated confidence intervals. This is an indication that the results aree biased, and this is most probably caused by the violation of the closedd population assumption. In this section we do not present any neww information, but the estimates already made are presented graph-icallyy and discussed more extensively.
Figuree 1 shows the probability curves of the 2-sample and the 3-samplee estimates using data samples provided by the police, hospi-talss and two different treatment samples. These two different treat-mentt samples reflect the different methadone programmes in Amsterdam.. Problematic opiate users are treated via low-threshold treatmentt i.e. MHS-, less problematic opiate users via high-threshold treatmentt i.e. Jetlinek or CP- Probability distributions of 2-sample C/RCC estimates are normal distributions. The 3-sample C/RC estimates resultt in normal distributions on a log-normal scale. The peak of the probabilityy curve represents the point estimate. As the total area underr each probability curve is 1.0, smaller variances result in higher peaks. .
1 3 1 1
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n
HT:HT: High-treshold LT:LT: Low-treshold
22 sample treatment LT/hospital 22 sample police/treatment LT 22 sample hospital/police 22 sample treatment HT/hospital 22 sample treatment HT/police
33 sample treatment LI'/hospital/police
adjustedadjusted for positive dependence treatment LT/hospital
33 sample treatment HI'/hospital/police
adjustedadjusted for negative dependence treatment HT/police
0 , 0 2 0 0 0 , 0 1 8 8 0 . 0 1 6 6 0 , 0 1 4 4 0 , 0 1 2 2 0 , 0 1 0 0 0 , 0 0 8 8 0 , 0 0 6 6 0 , 0 0 4 4 0 , 0 0 2 2 0 , 0 0 0 0 o o o o ~ ~ o o o o o o o o ro o o o r"i i O O o o V V o o TT T O O o o " " o o m m O O O O I D D o o KO O o o o o N N O O N N O O o o X X o o co o o o O O O O 01 1 o o o o O ! ! o o o o o o o o o o o o o o o o o o o o o o o o = = o o o o o o r g g o o o o IN N o o o o o o o o o o --o --o o o o o f f o o o o ï ï o o o o o o o o o o o o o o o o I O O o o o o I D D o o o o o o o o o o o o o o o o o o o o o o o o o o oo < OO C i n n --FigureFigure 1 P r o b a b i l i t y d i s t r i b u t i o n s o f t h e
v a r i o u ss 2 sample and 3-sample C/RC e s t i m a t e s ;
h i g h - t h r e s h o l dd t r e a t m e n t and l o w - t h r e s h o l d t r e a t m e n tt p a t i e n t s .
Iff the l o w - t h r e s h o l d t r e a t m e n t sample is used, the 2-sample e s t i m a t ee based on t h e t r e a t m e n t / h o s p i t a l sample results in a l o w e r e s t i m a t e ,, 3072 users, than the 2-sample estimate based on t h e treat-m e n t / p o l i c ee satreat-mple 4 0 6 9 users, a n d the p o l i c e / h o s p i t a l s a treat-m p l e , 4 7 2 1 users.. The best f i t t i n g model is the m o d e l w h i c h is a d j u s t e d f o r a p o s i t i v ee d e p e n d e n c y between the t r e a t m e n t / h o s p i t a l sample. The p r o b a b i l i t yy curve f o r the 3-sample C/RC analysis reaches its peak at an e s t i m a t e dd n u m b e r o f 4 1 3 0 p r o b l e m a t i c opiate users -point estimate-andd 95% o f its surface area lies b e t w e e n 3753 and 4 5 6 6 95% Confidence
CI-P M A M A H U A M CI-P CI-P
GG it r a I D i s c u s c l a n 1 3 8
Iff the high-threshold treatment sample Is used, the 2-sample estimatee together with the hospital sample leads to a higher estimate, 75077 opiate users, whereas the estimate with the police sample resultss in the extremely high estimate of 16 637 opiate users. The best fittingg model for the 3-sample C/RC analysis with the high-threshold treatment,, police/hospital sample is the model which adjusts for the negativee dependency between the police and treatment sample. The probabilityy curve for this analysis reaches its peak at an estimated numberr of 6226 opiate users and 95% of its surface area lies between 46477 and 8688.
Thee statistical parameters indicating the fit of the model which includee the likelihood ratio and Akaike's and Bayesian information cri-teria,, suggest that estimates using the high or low-threshold are equallyy valid. However, in chapter 2 we argue that estimates with the high-thresholdd treatment sample do not lead to valid results. The majorityy of high-threshold patients do not belong to the population of interest"" i.e. the group of problematic opiate users. Neither does the estimatedd number of 6226 opiate users reflect the size of a larger population,, i.e. the total number opiate users; the hidden population off non-problematic heroin users can not be estimated by including sta-bilizedd methadone patients in one of the samples. Although both groupss are opiate users, their characteristics differ tremendously.
itt is important to notice that a statistically sound analysis derivedd from the 3-sample C/RC does not necessarily lead to a valid estimatee of the number of drug users. Therefore, C/RC estimates shouldd be treated with caution.
O t h e rr i n d i c a t o r s o f p r e v a l e n c e
I nn order to check the validity of our estimate of the number of opiate userss in Amsterdam -4130; 95% Gl 3753-4566- we compared our results to otherr indicators of the prevalence of 'problematic heroin use. Several otherr indicators have been used:
** results of a population survey conducted by the University of Amsterdam12 2
number of needles exchanged in relation to the number of needless that are used per injecting drug user13'4
** number of Dutch and Surinam OD deaths among opiate users andd the estimated Op mortality incidence rate1516
** number of TB cases among opiate users related to the estimated TBB incidence rate.17
Inn a population survey the problematic heroin users are likely to bee underrepresented. So, if the prevalence estimate derived from a populationn survey is higher than the C/RC estimate, this would either suggestt that our estimate of the user numbers is a serious underesti-mationn or that a high proportion of the Amsterdam heroin users are
P M A M A H U A M P P
CC e n r « I D i s c u s s i o n
non-problematicc heroin users. The results of the population survey suggestt that the prevalence of current heroin users is 2 per 1000 inhabitantss in the age range 1 5 - 6 4 years.12 In 1997, the official Amsterdamm population in the age range 1 5 to 64 years was 509 562. Therefore,, our prevalence estimate of between 3753 and 4566 users leadss to a maximum city prevalence rate of 7.4 to 9.0 per thousand inhabitantss in this age category. This is a maximum estimate, because non-registeredd residents are counted in the numerator but not in the denominatorr of officially registered inhabitants. So, we may conclude thatt this comparison does not invalidate the C/ftC estimate. Furthermore,, it should be noted that our prevalence estimate is no higherr than recently published prevalence estimates for other Western Europeann cities. | 8 t 9 t ,
Wee will also provide an indication of the population size of activee injecting drug users. Injecting drug users are considered to be aa minority of the problematic opiate users. Assuming that the number off syringes which are used in Amsterdam is equal to the number of syringess exchanged, we are able to estimate the number of injecting drugg users. Recent data concerning injectors in the AIDS study cohort indicatess that the average number of different syringes which are cur-rentlyy used by injectors in one month is 58.5. The median number of syringess was 22.5 -inter quartiie range within 2.6-90-1" The total
numberr of syringes exchanged in 2000 totals 334 345 which is an averagee of 28 695 syringes per month. If these two figures are com-binedd the estimated number of drug users currently injecting is
28 695/58.5=- 490. Taking into account the confidence intervals of our prevalencee estimate this would imply that 10 to 14% of users are injectingg opiate users; a range which is consistent with other esti-mates."** This estimate depends on the assumption that the observa-tionss among injecting drug users within the AlDS-study cohort can be extrapolatedd to the total number in injecting drug users of Amsterdam. .
Inn addition, we also used the number of OD deaths as an indica-torr of the prevalence of drug usage. We related this number to the mortalityy rate among low-threshold clients which is presented in sec-tionn 4.1 and used a multiplier method to re-estimate the estimated numberr of problematic opiate users born In The Netherlands or Surinamm -N-2807 95% C125B8-3048- given in chapter 2. However, not all OD deathss belong to the population of problematic opiate users. There are alsoo deaths due to drugs other than opiates, suicide with drugs among non-drugg users and deaths resulting from intestinal drug smuggling. Thereforee we limited the overdose deaths to those registered with the Centrall Methadone Register CMR. Hence, we assume that after 20 yearss of large scale low-threshold methadone treatment, including methadonee treatment at police stations, almost alt current
problem-P M A M A H U A M problem-P problem-P
GG « n r a I D i s c H s i l a n 1 4 1
aticc opiate users are already registered with the CMR."3 Twenty-two casess have been identified in the period 1999-2001 of those born in Surinamm or the Netherlands and who are registered with the CMR. Givenn the incidence rate of 2.7/1000 person years py, these 22 cases aree expected to occur within 8148 person years of observation time. Thiss is equivalent to a three year observation period of a population withh an average size of 2716 individuals, an estimate in line with the estimatee of 2807 derived in chapter 2.
Similarly,, section 3.1 shows that the TB incidence rate among thee MHS population is estimated as 5/1000 py. Again» this offers an opportunityy to use the multiplier method as an indicator of preva-lence.. In the 12-year period from 1989 through 2000, 2 54 TB cases havee been observed among drug users. This is an average of 21.2 casess each year; equivalent to an average size of a population of 4233 drugg users. Again, this is consistent with the prevalence of 4130 users -95%Cll 3753-456$- estimated in chapter 2. The coherence between the incidencee rates presented in sections 3.1 and 4.1 and the estimated prevalencee of opiate users presented in chapter 2, seem to support ea<i*MUherss validity.
TJlL-JTi-ends s
P/evaréncee is defined as the total number of cases at a single moment Inn time. Prevalence trends over time are the result of the difference betweenn the number of people entering the population and the num-berr of users leaving the population. This is represented by:
the number of initial heroin users and those relapsing to heroin use,, releases from prison and other ciosed institutions and users migratingg to Amsterdam less
** the number of mortalities, the number abstaining even if this is
temporary'temporary',, admissions to prison or to other closed institutions
andd migration out of Amsterdam.
Inn this section we will present indicators of prevalence trends con-cerningg the numbers of opiate users and the drug related problems.
Inn chapter 2, no statistically significant dependence between quarterlyy low-threshold treatment and the police sample was observed.. Therefore, we used the 2-sample c/RC with quarterly police andd treatment samples to describe prevalence trends. Figure 2A shows thee average quarterly values per annum -the average of four
esti-mates-mates- and the estimated values based on two sample C/RC estimates
withh annual police and low-threshold treatment samples which are usuallyy reported.'3 The quarterly sample estimates show a modest net decreasee between 1989 and 2000. The annual sample estimates lead too a more pronounced decline of problematic opiate users. This can be explainedd by the reduction in the number of foreign heroin users tem-porarilyy residing in Amsterdam. This decrease results in a gradual
1 4 2 2
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n
AnnualAnnual samples
AverageAverage quarterly samples
Dutch,Dutch, etnic minority Foreign Foreign 8000 0 7000 0 6000 0 5000 0 4000 0 3000 0 2000 0 1000 0 cn n oo o cn n o o en n C O O CTl l O ) ) IN N en n cn n 199 3 3 199 4 4 CTl CTl en n 199 6 6 199 7 7 CO O en n en n en n en n en n o o o o o o o o o o IN N 75 5 77 0 65 5 60 0 55 5 50 0 45 5 40 0 35 5 30 0 25 5 20 0 II 5 -O O r--O l l s s N N en n cc c r » » 01 1 en n r---0 1 1 o o co o CO O 0 1 1 IN N co o cn n r oo i ^ -000 co CT1CT1 CTl L OO eo r-> 000 00 co CTii en en o o i e n n coo co enn e n o o er--en n er--en n cn n cn n en n en n * * er--en n en n en n en n en n I - .. co enn en enn en er r en n en n o o o o o o 1 1
A.. Estimated number of problematic opiate users C/RC estimation B.. OD mortality all illicit drugs
33 5 33 0 22 5 22 0 II 5 II 0 1 2 0 0 0 1000 0 8 0 0 0 6 0 0 0 4 0 0 0 2 0 0 0 0 0 en n 0 0 0 en n o o en n en n — — en n en n IN N en n o i i ro o en n en n T T en n en n i n n en n en n IC C en n en n i-v v en n en n oo o en n en n en n en n en n o o o o o o IN N _ _ o o o o o o en n o» » _ _ en n en n en n en n ro o en n en n t t CTl l cn n m m en n en n (O O en n cn n r~ ~ cn n cn n 0 0 0 cn n cn n cn n en n cn n c c o o o o IN N
C.. TB cases among opiate users D.. Number of syringes exchanged
P M A M A H U A M P P
GG a n e r a I D i s c i s s i o n 1 4 3
reductionn of the violation of the closed population assumption over timee and leads to a decreasing overestimation. If the results of quart-erlyy samples are used, a slowly decreasing trend remains.
Thiss decrease or stabilization is also reflected in the trends of fatall OD cases in Amsterdam in the period 1976-2001 Figure 2B- In interpretingg these figures it should be noted that OD deaths other than thosee among opiate users are included.114 The number of TB cases in thee period 1989-2000 shows the initial increase which is discussed in sectionn 3 . 1 , followed by a stable or decreasing trend • Figure 2C- The annuall number of syringes exchanged shows a major reduction over timee • Figure 2D* The number of exchanged syringes is not only influ-encedd by the number of heroin users but also by the proportion of injectorss and number of injections per injector.
C o v e r a g ee a n d t i m e
Inn chapter 2 we showed that in the first quarter of 1997 the propor-tionn of problematic opiate users who were reached by methadone pro-grammess coverage was 40%. If we use coverage of an intervention as ann epidemiological indicator, thé population which is considered to be reachedd by an intervention should be similar to the population which isis actually affected by it. Because methadone patients form a dynamic population,, the percentage which has been in contact w i t h a methadonee programme increases with the observation period. For example,, the number of people reached within a month is always lowerr than the number reached within a year. This leaves the question off which period to choose. We state that this period should be equal too the duration of the effect of the intervention.
However,, methadone treatment consists of a multitude of inter-ventions.. TB screening is considered to be effective if conducted once everyy six months. Therefore, the proportion reached by TB screening shouldd be the proportion of problematic opiate users screened no longerr than six months previously. The pharmacological effect of methadonee will disappear soon after leaving treatment. Considering thiss single aspect, those who are contacted no longer than one week agoo could be considered as covered. Each intervention has its own periodd of effectiveness, and thus its own coverage. In a dynamic patientt population, preventive measures with a longer duration of effectt are able to cover a higher proportion of drug users. This should bee taken into account when choices are made between different types off interventions.
Methadonee patients are not the only dynamic population, the totall population of problematic opiate users in Amsterdam is also dynamic.. Some of the opiate users who were contacted in the past no longerr belong to this population, due to factors such as migration, mortalityy and stable abstinence. If we want to calculate the proportion
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n
off opiate users who are contacted over a longer period of time, we shouldd be aware that not all opiate users who have been contacted in thiss period still belong to the population of current opiate users. Otherwise,, coverage will be increasingly overestimated with an increasingg period of time. To give an extreme example: 14 717 opiate userss have been in contact with some form of voluntary out-patient methadonee treatment in Amsterdam since 1985. However, at the time off w r i t i n g , the majority of those contacted no longer belong to the populationn of Amsterdam opiate users. In order to determine the real proportionn of opiate users which has been covered over a longer periodd of time, coverage among a representative sample of the popu-lationn of problematic opiate users should be studied.
C o v e r a g ee a n d r e l e v a n c e
Whetherr we can consider 40% coverage of methadone programmes overr a three month period to be a satisfactory result mainly depends onn whether the relevant section of the problematic heroin user popu-lationn is actually reached. If those with thé most severe social and medicall problems are reached, the potential benefit of methadone maintenancee treatment will probably be greater than if this group is excludedd from treatment.
Inn Amsterdam those with thé more severe problems are probably over-representedd among the population covered by the programme. Thee positive dependence between treatment and hospital admission suggestss that particularly those heroin users with severe health prob-lemss are reached by methadone programmes. In addition, among a samplee of heroin users arrested by the police, the main reason for not participatingg in methadone maintenance treatment was the absence or perceivedd absence of health problems.t,s
Thee low-threshold character of methadone treatment probably increasess the coverage to the relevant proportion of opiate users. Individuall opiate users may experience periods with fewer, less severe problemss and periods with more severe problems. Apparently, not all off them need treatment all of the time. It is important that during the specificc periods in which the need for treatment exists, treatment can bee offered. The low-threshold service implies that heroin users can receivee treatment without delay. This will probably enhance the cov-eragee of the relevant proportion of heroin users. Nevertheless, not all opiatee users with serious health problems who - according to the healthh and/or police services - 'should' apply for treatment, actually doo so. This group needs to be actively approached by the health ser-vices. .
G e n e r a a
P M A M A H U A M P P
D i s c u s ss i o n 1 4 8 8
t u r ee d i r e c t i o n s o f s t u d y o n t h i s t o p i c
Continuationn of the various studies to monitor the prevalence andd incidence of drug usage in Amsterdam is important. However, besidess the indicators of prevalence, indicators of problematic use of drugss • but also alcohol- should also be monitored. Although the sub-titlee of chapter 2 is 'the importance of case-definition' the term pro-blematicc opiate user which we used in this chapter is not clearly defined.. The MHS treatment registration needs to be improved in order too define the concept of a problematic opiate user more specifically in termss of the frequency and kind of drugs used and additional social, physicall and mental health deficits.
Inn addition, rather than studying a more abstract proportion of opiatee users who are contacted by the health services, we should definee the population of opiate users, and other groups in a similar situation,, who 'should' apply for treatment but is not yet in contact withh the health services. Cooperation with the police and citizens of Amsterdamm is of the utmost importance to enable this population to bee found. However, the public mental health services should guard againstt a situation in which they mainly focus on the prevention of nuisance.. The reporting point for extreme nuisance to which people cann report neighbours who cause a nuisance, for example with excess noise,, smell or aggression,"6 could be extended into a 'reporting point
forfor extreme nuisance and severe care deficit'. Once a concrete
popu-lationn is defined, the methods used to make and maintain contact with thiss population e.g. support project- should be evaluated."7
BB I D I T Y
ectionn 3.1 describes the incidence of TB among methadone patients recordedd between 1 989 and 1 992. At that time, TB was a possible new threatt together with HIV. Similarly, with the decreasing incidence of Hivv among drug users and the increasing treatment possibilities, the threatt of a major TB epidemic among opiate users has declined. Althoughh HIV prevalence among methadone patients born in Surinam orr the Dutch Antilles is rare, TB incidence within this group of users wass no lower than in other groups of opiate users. It is therefore expectedd that despite the reduction in new Hiv cases, TB will continue too show a rather high prevalence within the population of opiate users.. Consequently, TB screening remains important to protect other patients,, health workers and the general population. TB incidence amongg GP methadone patients was no higher than among the general Amsterdamm population. Therefore, the extension of TB screening to thesee patients is not necessary.
P M A M A H U A M P P
G e n e r a ll D l i c u s s l o n
AA further reduction of TB could possibly be attained by giving thee highest risk group preventive treatment with tuberculostatics. The highestt risk group consists of opiate users who are both HIV and Purifiedd Protein Derivative PPD seropositive.1'8 Randomized controlled trialss in HIV-infected adults have shown that preventive therapy sig-nificantlyy decreased the risk of T8 and death in HIV and PPD positive individuals.119 9
T88 among drug users is of particular importance because their irregularr lifestyle does not enhance treatment compliance. This risk factorr encourages the development of multi-drug resistant strains of TB.IÏ00 Methadone treatment programmes provide a framework to enhancee T8 treatment compliance. In this respect, daily contact in the newlyy implemented heroin treatment facilities may offer an opportu-nityy for Directly Observed Treatment DOT to treat TB infection in activee heroin users.
X O P D D
Inn section 3.2 we found an impaired pulmonary function among methadonee patients. In contrast to TB, COPD is likely to cause more problemss in the future population of ageing and chronic heroin users. Thee chronic use of cigarettes is probably a major causal factor of this impairment.. Consistent with other studies, we observed an extremely highh prevalence and low quit rate of heavy cigarette smoking among methadonee clients.«' Almost all patients have smoked cigarettes since theyy were young adolescents. Therefore, cigarette smoking could not bee identified as a separate risk factor in this study.
Sectionn 3.2 suggests that the inhalation of heroin results in addi-tionall pulmonary impairment. Moreover, the large variation in the spirometricc results among most chronic heroin inhalers suggests that iff the inhalation of heroin is causally related to pulmonary impair-ment,, other risk factors will also play a role in the causal mechanism, forr example a high histamine response to opiates.1" Although chasing
thethe dragon might be related to lung function impairments; the health
riskss faced by 'chasers' are minor compared to the health risks faced byy intravenous heroin users.1" COPD is a slow progressive disease^ whichh generally implies that these opiate users have survived decades off cigarette and heroin addiction before the disease manifests itself. Manyy of the health risks faced by injecting users, for example the risk off OD mortality and the risks of viral or bacterial infections, are not applicable,, or are only marginally significant to those users who inhalee heroin instead. Within the heroin co-prescription study, heroin wass inhaled by 6B% of the experimental group. Patients could change fromm injecting to inhaling but not the other way around. In this form off treatment the potential hazard of inhaling heroin should always be balancedd against the potential gains which are obtained by treatment
P M A M A H U A M P P
GG • n • r a I D i s c u s s i o n 1 4 7
withh methadone and co-prescribed heroin.1** Other factors which may enhancee or limit actual oxygen uptake may be altered due to heroin co-prescription.. Therefore, based on the results of this study we can nott predict whether the net effect of co-prescribing heroin for inhala-tionn on the patients actual oxygen uptake will be positive or negative.
futurefuture research directions concerning TB an4 COPD
Concerningg TB we may conclude that the extension of TB screening to GPP methadone patients is not necessary. Instead, the cost effective-nesss of screening among the homeless residing in shelters with a high degreee of mobility125 could be investigated.*26 Concerning pulmonary function,, we may consider periodical spirometry among methadone patients.. This may increase the awareness of pulmonary impairment amongg both health workers and patients. Hence, it could be an incen-tivee for the improvement of COPD treatment on the one hand and reductionn of cigarette and drug use on the other.
Prospectivee studies concerning the risk factors of pulmonary impairmentt may disentangle the influence of inhaling heroin and cig-arettee smoking. Moreover, we may be able to define special risk groupss at an early stage. The influence of other mechanisms affecting thee pulmonary function or oxygen transport in general should also be studied.. Besides heroin inhalation, attention should be paid to pneu-moniaa and TB, nutritional status and the use of cigarettes and base-cocaine. .
M OO R T A L I T Y
u . dd . ü $ g h e r m o r t a l i t y r a t e s a m o n g h e r o i n u s e r s HH
Ml„S£Ctïon 4.3 we saw that all cohorts of opiate users show a higher mortalityy rate than expected in the general population of the same age.. This is not a surprise; in contrast to non-heroin users, heroin userss are at risk from fatal poisoning by opiates, which we discussed inn sections 4.1 and 4.2. In addition, opiate users risk death due to dis-easess caused by the contamination of the heroin itself or the para-phernaliaa which they use to administer the drugs. Death due to con-taminationn of • illicit heroin exists but is not a major threat. Bacterial contaminationn of heroin sporadically causes deaths.127 Moreover, lethal leuco-encephalopathyy among those who inhaled heroin was probably causedd by a hitherto unidentified contamination in the early 1980*s.u* Contaminationn of the injection equipment used causes more deaths. Virall infection Hepatitis B. C and HIV- cause life-threatening diseases suchh as liver-cirrhosis and AIDS, bacterial infections cause abscesses, sepsiss and endocarditis.,29
P M A M A H U A M P P
1 4 11 G e n « r * I D l s c u s i f o n
Besidess to the toxic effect of the drugs and the danger of con-taminationn of drugs and the paraphernalia, we should also take into accountt the consequences of the psychiatric syndrome of dependence itself.. As described in the introduction, the diagnosis dependence is characterizedd by the continual use of heroin despite the significant sociall and medical problems related to the use of heroin.130 Most prob-ably,, these consequences of dependence, such as unemployment, hometessness,, prostitution, criminality and poor nutrition indirectly leadd to a higher risk of mortality.
O v e r d o s ee m o r t a l i t y
Sectionss 4.1 and 4.2 focus on death caused by the direct toxic effectt of opiates: death as a result of an overdose. The number of overdosee deaths in the Netherlands is low compared to the number of overdosee deaths reported in other countries.31 We may argue that the policyy in Amsterdam is (ikely to prevent overdose mortality. The main interventionn is large-scale methadone maintenance treatment which hass proven to reduce overdose mortality in international studies and inn a local study among injecting opiate users.1 3 2'n i U The Amsterdam methadonee treatment most probably contributed to a reduction of heroinee use in general and injecting heroin use in particular.1"136 Medicall and social care is provided to those people who continue usingg heroin and the low-threshold character of the programme is importantt in order to reach those with the highest needs. Methadone maintenancee is expected to enhance the tolerance level of the heroin users,, especially because treatment compliance is increasing and higherr dosages of methadone are being used.137 In addition, in Amsterdamm detoxification treatment is mainly limited to those drug userss who are expected to complete this course of treatment success-fully,, possibly leading to a lower proportion of relapses after detoxifi-cationn treatment.13* Moreover, if a potentially fatal overdose occurs, thee provision of professional help is not only secured by a well func-tioningg ambulance system but also by providing an atmosphere in whichh witnesses, who are usually other drug users, feel free to call for professionall help.
Thee Frankfurt policy is modelled on the Amsterdam policy. The sharpp reduction of overdose deaths in Frankfurt shown in section 4.2 isis considered to be the result of implementing this policy. Similar to thee programme in Amsterdam, large scale methadone maintenance treatmentt is one of the main interventions. However, in Amsterdam OD mortalityy rates during treatment and after leaving methadone treat-mentt as presented in section 4.1 do not show a significant difference. Mostt probably, the risk of OD is already low because the vast majority off heroin users in Amsterdam are inhalers. In this situation the poten-tiall for reducing OD mortality with methadone treatment is low. We can
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n
thereforee argue that although the drug policy as implemented in Amsterdamm is likely to reduce OD mortality, the low OD mortality rate amongg the Amsterdam users is not singularly a consequence of this
c kk h e r o i n u s e r e f f e c t
—nsiderr general mortality among opiate users from an epidemi-ologicall perspective there is a complicating factor that hampers a validd description of the risk which is attributable to heroin depend-ence.. In section 4.3 we call this factor the 'sick heroin user effect', afterr the 'healthy worker effect' which hampers a valid description of occupationall risks. The 'healthy worker effect' implies that the employedd population is generally healthier than the non-employed populationn of the same age, and the death rate in this population groupp is lower than the corresponding rates for the general popula-tion.1399 The 'healthy worker effect' can be considered as a particular kindd of • self- selection which is derived from a screening process and thee fact that unhealthy people leave work.140 It causes a bias in study-ingg occupational risks because it tends to give results which are too positive. .
Thee 'sick heroin user effect' can also be considered as a selection process.. First, a selected group starts to use heroin; for example, userss of alcohol or tobacco and users of marijuana are more likely to startt using heroin, and in particular, those who start using these other substancess at a young age are prone to progress to the use of hero-in.i411 Most probably, the mortality risks among those who start using heroinn would also have been higher even if they had not started using heroin.. Additionally, we know that the majority of those who start usingg heroin will not end up being a chronic user.12 The users who con-tinuee heroin use and develop dependence are a selection of the starters.. Subsequently, treatment causes an additional selection. Heroinn users with psychiatric co-morbidity have less favourable treat-mentt outcomes than those with heroin use as a single problem.142 Finally,, relapse often occurs and contributes to the sick heroin user effect.. The risk factors associated with relapse are also associated withh mortality and therefore contribute to the 'sick heroin user
effect'.effect'.11**33,44 ,44
Too summarize, the 'sick heroin user effect' encompasses the selectivee mechanisms at the start of heroin use, the continuation of heroinn use, treatment failure and relapse to heroin use that probably resultss in a lower health status and higher mortality rate among opiatee users than expected in the general population of the same age. Consequently,, when studying the risk factor opiate dependence we tendd to overestimate the number of deaths attributed to heroin dependence.. The influence of the 'sick heroin user effect' may differ in
P M A M A H U A M P P
time,, place and among different ethnic subgroups and may explain somee of the differences in mortality rates in different perfods, regions orr ethnic groups.
Withinn the study described in chapter 4.3 it was not possible to controll for the Influence of the 'sick opiate user effect' on the total populationn of opiate users, nor for the potential differences in this selectionn process between different countries. So, we should be reluc-tantt to attribute the total increase of mortality to the opiate depend-encee itself. Differential selection processes may have influenced the results.. However, the differential selection bias during recruitment of opiatee users by the treatment centres in different countries will prob-ablyy explain a much larger part of the observed differences.
I n t e r n a t i o n a ll c o m p a r i s o n
Sectionn 4.2 attempts to explain why some cities have higher numbers off OD deaths than others. A detailed description of the cities revealed thatt there are many factors which could possibly explain the differ-ences.. Definition and registration practices vary and the cities have differingg risk profiles in terms of characteristics of drug users, the drugss used and implemented facilities.
Wee realise that a clear comparison was hampered by the absence off detailed information about the nature of overdose mortality, for examplee whether OD was accidental or intentional, whether the victim wass alone or with others, what combination of drugs were detected, whetherr the victim was recently detoxified etc. Moreover, to quantify riskk factors we had to rely on the information which was available and itt was not always possible to make comparisons. Additionally, studies too evaluate the effectiveness of measures implemented to reduce OD mortalityy are hardly ever conducted. Therefore, the result of this study isis a qualitative description addressing the potential risk factors or pre-ventivee factors in each city and any possible differences in approach. Thee quantitative relevance of these risk factors in relation to the OD mortalityy rate in each city remains under discussion.
Sectionn 4.3 provides reference rates which can be used to calcu-latee the SMR in mortality studies among opiate users. This study aimed too improve the comparability of mortality studies by improving the abilityy to adjust for differences in age and sex distribution. Within this ongoingg EMCDDA project nine cohorts are constructed. Differences in mortalityy rates and differences in causes of death over the course of timee or between different cohorts are expected to generate additional hypothesess on the topic of mortality among opiate users in the future. Oversimplificationn is a pitfall in studies which are conducted to explainn general differences or specific causes of mortality between differentt regions, as we did in section 4.2. If we attempt to explain the differences,, we start with the net results, in this case, the differences
P M A M A H U A M P P
G e n e r a ll D i s c u s s i o n 1 5 1
inn number of OD deaths. These differences are the result of a rather complicatedd web of causation. Based on literature studies we are awaree of certain risk factors and preventive factors. However, there willl be some risk factors which have not yet been found or factors whichh modify the reported effects. When studying the known risk fac-tors,, it is tempting to construct a scenario which ends at its starting point:: the observed differences in mortality rates. Hence, in order to reachh the net result the importance of the known factors will easily be overratedd or undervalued.
Inn order to generate a scientifically clear epidemiological study itt is preferable to concentrate on a single risk factor, a clearly defined outcomee parameter and a short period of observation time. Differencess in the characteristics of drug users and differences in the policyy measures in different cities, regions and countries do not necessarilyy hamper the results but may offer the possibility to constructt pseudo-experimental study designs instead.
I.U>> F u t u r e r e s e a r c h q u e s t i o n s
Thee continued monitoring of mortality rates among methadone patientss in Amsterdam and including more information about risk factorss and causes of death is recommended. Mortality rates due to pulmonaryy diseases are of special importance. Although OD mortality ratess are low and the number of HIV infected deaths has decreased, the totall mortality rate among Amsterdam methadone patients continues too increase steadily.13 Preferably, a national population of drug users in treatment,, as registered in LADIS"2 should be used for this purpose. Thee current EMCDDA study on mortality rates is designed as an open cohortt -i.e. new people may enter the study during the study period-off drug users applying for treatment for the first time. It may be preferablee to transform this study into a study which is able to moni-torr mortality in a dynamic cohort of opiate users too -i.e. during the
studystudy period people may enter but also leave the cohort in order to limitlimit the population to active drug
users-Concerningg OD mortality, it is important to gather international comparablee information concerning social behaviour in relation to overdosee deaths. Differences in the presence and behaviour of bystanderss when an overdose occurs may explain some of the differ-encess in overdose death statistics between different member states. In contrastt to observations in the United Kingdom,145 OD deaths where witnessess are present are rare in Amsterdam.16 This suggests that pro-fessionall help is more often successfully offered in a life threatening situationn in Amsterdam. As mentioned in section 4 . 1 , social factors mayy also explain some of the differences between males and females concerningg the risk of a fatal overdose. Females may use their heroin lesss often alone and/or bystanders may be more willing to offer help
P M A M A H U A M P P
iff a women suffers an overdose. Other relevant topics suitable for internationall comparison are: the influence of prison policy - detoxifi-cationn versus methadone maintenance; on relapse, non-fatal and fatal overdosess after release among various subgroups of opiate users.
Sectionss 4.1 and 4.2 show that similar interventions do not alwayss lead to similar results, which implies that results of studies conductedd elsewhere, predominantly among injecting heroin users, cannott always be directly extrapolated to the Dutch population of heroinn users, predominantly inhaling heroin users. Considering OD mortality,, both the effect of risk reducing measures and the effect of riskk enhancing situations is probably lower in The Netherlands. As we havee discussed earlier, an example of risk reducing measures is the stablee methadone maintenance treatment, and examples of risk enhancingg situations are detoxification in prison and the onset of methadonee treatment. Due to the limited reproducibility of studies concerningg heroin users it may be worthwhile or even necessary to reproducee studies that are conducted elsewhere.
Consideringg the 'sick heroin user effect', we should monitor and quantifyy the selection mechanisms during the start of drug usage, the continuationn of drug usage, treatment and relapse in order to under-standd the social, physical and mental health status and thus the mor-talityy pattern of the drug users. In our opinion different selection mechanismss wilt explain a part of the differences fn morbidity and mortalityy between heroin users of different countries and between userss of different kinds of drugs. In Amsterdam different research groupss focus on different stages of addiction and may be able to focus onn a different part of the selection process, for example contact with drugs,, initial usage, continuation, treatment resistance and relapse. Thesee differential selection processes may also be applicable when studyingg morbidity and mortality among other groups at the margins off society such as the homeless.
P M A M A H U A M P P
R E F E R E N C E S S III Bammer C. Why? Who? How?
EstimatingEstimating numbers of illicit drug users:users: lessons from a case study fromfrom the Australian Capital Territory.Territory. A u s t r a l i a n and New
Zealandd Journal of Public Health 1996;; 20: 493-99.
|22 A b r a h a m MD, Cohen PDA. van Til RJ, Langemeijerr MPS. Licit and i l l i c i t d r u g usee in A m s t e r d a m III: Developments
inin drug use 1987- 1997. CEDRO
C e n t r u mm voor D r u g s o n d e r z o e k . U n i v e r s i t e i tt van A m s t e r d a m . A m s t e r d a mm 1998.
133 van Brussel CHA. Buster MCA.
OCCZOCCZ monitor 1999-2001 .trends enen cijfers '99,'00,'01. GG&GD
A m s t e r d a mm 2 0 0 2 .
|44 Langendam MW. Unpublished
additionaladditional analysis on the drug usersusers cohort. Personal
c o m m u n i c a t i o nn 2 0 0 2 .
|55 Buster MCA, van Brussel CHA. van denn Brink W. An increase in
overdoseoverdose mortality during the firstfirst 2 weeks after entering or re-enteringentering methadone treatment in AmsterdamAmsterdam methadone programmes.programmes. A d d i c t i o n 2 0 0 2 ; 97:
993993 1001 This thesis, section 4.1
|66 Buster MCA. Additional analysis of
thethe local OD register of
Amsterdam,Amsterdam, u n p u b l i s h e d 2 0 0 2 .
\7\7 van Brussel CHA. Buster MCA. Nasseri K,, van Limbeek J, van D e u t e k o m H, v a nn den Brink W. Incidence of
tuberculosistuberculosis among drug addicts inin Amsterdam methadone
programmes.programmes. European j o u r n a l of
p u b l i cc health 1995; 4 : 2 5 3 - 5 7 •• This thesis section 3. I
|88 C o m i n s k y CM. Barry JM. A
capture-recapturerecapture study of the prevalence andand implications of opiate use in Dublin.Dublin. European Journal of Public
Healthh 2 0 0 1 ; / / : 198 200.
|99 Domingo-Salvany A, H a r t n o l l RL. Maguiree A, Brugal MT, A l b e r t i n P, Caylaa JA, Casabona J, Suelves JM.
AnalyticalAnalytical considerations in the useuse of capture recapture to
estimateestimate prevalence: Case studies ofof the estimation of opiate use in thethe metropolitan area of
Barcelona,Barcelona, Spain. American Journal
off e p i d e m i o l o g y 1 9 9 8 ; 148: 732-40.
|100 Hickman M, Cox S. Harvey J. Howes S. Farrell M.Frischer M. Stimson C. Taylor C,, Tiling K. Estimating the
prevalenceprevalence of problem drug use in innerinner London: a discussion of
threethree capture-recapture studies.
A d d i c t i o nn 1 9 9 9 ; 94: 1653-62.
111 I Langendam MW. Additional analysis
onon the drug users cohort, personal
c o m m u n i c a t i o nn 2 0 0 2 .
111 2 Landelijk Alcohol en Drugs
RapportageRapportage Syteem, Rapportage 2000.2000. IVV, Houten 2 0 0 1 . IVDU is
alsoalso mentioned in section 3.2 and 4.2 ofof this Thesis
|11 3 Buster MCA. Additional analysis of
CentralCentral Methadone Register data.
Inn 2001 95% o f the arrested Dutch or Surinamm h e r o i n users w h o received m e t h a d o n ee at a police s t a t i o n have beenn registered b e f o r e .
111 4 Nationale Drugs Monitor
JaarberichtJaarbericht 2001. Trimbos I n s t i t u u t .
Utrechtt 2 0 0 2 .
|155 Terpstra MJA, van Brussel CHA. van Limbeekk J. Politie veldwerk: bij de
hulpverleninghulpverlening onbekende druggebruikersdruggebruikers in Amsterdamse politiebureaus,politiebureaus, een voorzorg onderzoek.onderzoek. CC&CD A m s t e r d a m .
A m s t e r d a mm I 9 9 4 .
1166 van Mierlo R. Bestrijding extreme
overlastoverlast binnenstad: jaarverslag 1999.1999. Gemeente A m s t e r d a m .
A m s t e r d a mm 2 0 0 0 .
\\7\\7 Jaarrapportage Support 2001.
CC&CDD A m s t e r d a m , A m s t e r d a m 2 0 0 2 .
|188 Selwyn PA, Hartel D. Lewis VA. Schoenbaumm EE, V e r m u n d SH. Klein RS,, et al. A prospective study of
thethe risk of TB among i.v. drug usersusers with HIV infection. New
Englandd Journal of Medicine 1989;
320:320: 545-50.
| I 99 W i l i n s o n D, Squire SB, Garner P.
EffectEffect of preventive treatment for tuberculosistuberculosis in adults infected withwith HIV: systematic review of
randomisedrandomised placebo controlled trials.trials. British Medical Journal 1 9 9 8 ; 317:317: 625 29.
1200 Wilox PA. Drug resistant
tuberculosis:tuberculosis: world-wide trends, problemsproblems specific to eastern
EuropeEurope and other hotspots, and thethe threat to developing
countries.countries. C u r r e n t o p i n i o n in
p u l m o n a r yy m e d i c i n e 2 0 0 1 ; 7: 148-53.
122 I Richter KP. Gibson CA. A h l u w a l i a JS. Schmelzee KH. Tobacco use and quit
attemptsattempts among methadone maintenancemaintenance clients. American
Journall of p u b l i c health 2 0 0 1 ;
91:91: 296-99.
1222 W i t h i n g t o n DE. Patrick JA. Reynolds F.
HistamineHistamine release by morphine andand diamorphine in man.
Anaestesiaa 1 9 9 3 ; 48: 26 29.
|233 van Haastrecht HJA. van A m e i j d e n EJC.. van den Hoek JAR. et a l .
PredictorsPredictors of mortality in the AmsterdamAmsterdam cohort of HIV positive andand HIV negative drug users.
Americann Journal of E p i d e m i o l o g y 1996;; 143: 380-91.
|244 Central C o m m i t t e e on the t r e a t m e n t o ff h e r o i n a d d i c t s . Medical
co-prescriptionco-prescription of heroin, two randomizedrandomized controlled trials.
http://www.ccbh.nl-P M A M A H U A M http://www.ccbh.nl-P http://www.ccbh.nl-P
rr a I D i s c
1255 Buster MCA, van Laere IRAL.
DynamiekDynamiek en problematiek in socialesociale pensions & internaten.
CC&CDD A m s t e r d a m . A m s t e r d a m 2 0 0 1 .
|266 Rendleman NJ. Mandated
tuberculosistuberculosis screening in a communitycommunity of homeless people.
A m e r i c a nn Journal of Preventive M e d i c i n ee 1 9 9 9 ; 17: 108-13.
|22 7 Hagmann M. Deaths among heroin
usersusers present a puzzle. Science
2 0 0 0 ;; 288: 1941.
|288 Wolters EC, van W i j n g a a r d e n CK, Stam FC,, Rengelink H, L o u s b e r g RJ,
Schipperr ME, Verbeeten B.
LeucoencephalopathyLeucoencephalopathy after inhalinginhaling "heroin" pyrolysate. The
Lancett 1 9 8 2 ; 2: 1233-37.
|299 van Haastrecht HJA, van A m e i j d e n EJC,, van den Hoek JAR, Mientjes CHC, Baxx JS, C o u t h i n h o RA. Predictors of
mortalitymortality in the Amsterdam cohortcohort of positive and HIV-negativenegative drug users. American
Journall of e p i d e m i o l o g y 1996; 143:
380-380- 91.
|344 Langendam MW, van Brussel CHA,
CouthinoCouthino RA, van Ameijden EJC. TheThe impact of
harm-reduction-basedbased methadone treatment on mortality.mortality. A m e r i c a n Journal of Public
Healthh 2 0 0 1 ; 91: 774-80.
|355 van Brussel CHA, Buster MCA. Care
forfor the future; opiate users in
AmsterdamAmsterdam 19961998. CG&CD
A m s t e r d a m .. A m s t e r d a m 1999.
|366 Langendam MW, van Brussel CHA, C o u t h i n oo RA, van A m e i j d e n EJC.
MethadoneMethadone maintenance and cessationcessation of injecting drug use: resultsresults from the Amsterdam CohortCohort Study. A d d i c t i o n 2 0 0 0 : 9 5 ;
5 9 1 - 6 0 0 . .
133 7 Buster MCA, Reurs H. Jaarraportage
CentraleCentrale Methadon Registratie 1998.1998. CMR, CC&CD A m s t e r d a m ,
A m s t e r d a mm 1 9 9 9 .
1388 Magura S, Rosenblum A. Leaving
methadonemethadone treatment. Lessons learned,learned, lessons forgotten, lessonslessons ignored. Mount Sinai Journal
off Medicine 2 0 0 1 ; 68: 62-78.
|422 Krausz M, D e g k w i t z P, Kuhne A. et al.
Co-morbidityCo-morbidity of opiate
dependencedependence and mental disorders.
A d d i c t i v ee Behaviors 1998;
23:23: 767-83.
|433 Hser Yl, Hoffman V, Crella CE, A n g l i n MD.. A 33-year follow up of
narcoticnarcotic addicts. Archives of
generall p s y c h i a t r y 2 0 0 1 ; 58: 503-08.
|444 Hser Y, McCarthy WJ, A n g l i n MD.
TobaccoTobacco use as a distal predictor ofof mortality among long term
narcoticnarcotic addicts. Preventive
Medicinee 1 9 9 4 ; 23: 61-69.
|455 Cossop M, Stewart D, Tracy S, Marsdenn J. A prospective study of
mortalitymortality among drug misusers duringduring a 4-year period after seekingseeking treatment. Addiction 2 0 0 2 ; 97:97: 39-47.
|300 Diagnostic and statistical manual
ofof mental disorders. Fourth edition.edition. A m e r i c a n Psychiatric
A s s o c i a t i o n ,, W a s h i n g t o n DC 1 9 9 4 .
| 3 II European Monitoring Centre for
DrugsDrugs and Drug Addiction annual reportreport 2001. EMCDDA. Lisbon 2 0 0 2 .
1322 C a p l e h o r n JRM. D a l t o n SYN, Haldar F, Petrenass A M , Nisbet JG. Methadone
maintenancemaintenance and addicts' risk of fatalfatal heroin overdose. Substance
usee and misuse 1 9 9 6 ; 31: 711-21.
|333 G r o n b l a d h L, Ó h l u n d LS, Gunne LM.
MortalityMortality in heroin addiction, the impactimpact of methadone treatment.
Actaa Psychiatrica Scandinavica 1990;
82:82: 223 27.
|399 Fox AJ, G o l d b l a t t PO. Longitudinal
study.study. Socio demographic mortalitymortality Differentials. Her
Majesty'ss Stationary Office, London 1 9 8 2 .. I n : Breslow NE and Day NE.
StatisticalStatistical Methods in Cancer research.research. Volume II -The design andand analysis of cohort studies.
pagee I 7. I n t e r n a t i o n a l Agency for Researchh on Cancer, Lyon 1 9 8 7 .
|400 Li CY, Sung FC. A review of the
healthyhealthy worker effect in
occupationaloccupational epidemiology.
O c c u p a t i o n a ll Medicine 1 9 9 9 ;
49:49: 225-29.
|44 1 Golub A . J o h n s o n BD. Variation in
YouthfulYouthful risks to progression fromfrom alcohol and tobacco to marijuanamarijuana and to hard drugs acrossacross generations. American
Journall of Public Health 2 0 0 1 ;
