Substance‐related disorders

Re: Injecting drug use in Australia: needle/syringe programs prove their worth, but hepatitis C still on the increase, by Law MG and Batey RG in the 3 March 2003 issue of the Journal (Med J Aust 2003; 178: 197-198). Dr Batey's position was incorrectly given as Director, Gastroenterology Department, John Hunter Hospital. His position is Clinical Chair, Division of Medicine, John Hunter Hospital. The html and pdf versions of the article on the website were corrected on 12 May 2003.

Matthew G Law PhD · Robert G Batey MD FRACP FRCP

Re: Fatal intravenous misuse of transdermal fentanyl (Med J Aust 2002; 177: 552-553) by Mark D Reeves and Corinne J Ginifer. In Box 2A (page 553), the computed tomography scan of the brain was not the correct image. The correct image is given below. The html and pdf versions of this article were corrected on the website on 12 May 2003. A: Brain — arrows indicate areas of low attenuation in basal ganglia.

Mark D Reeves MB BS, FANZCA · Corinne J Ginifer MB BS, FACEM

Smoking presents a substantial health and economic burden to people with schizophrenia. Comorbid use of other substances is common, under-recognised, and associated with a number of serious adverse consequences, such as psychotic relapse and poorer social outcomes. All patients with schizophrenia need to be screened for substance misuse. Effective interventions involve integrated, modified pharmacological and psychosocial strategies.

Dan I Lubman PhD, FRANZCP, FAChAM · Suresh Sundram PhD, FRANZCP

The anti-smoking crusade in Australia is in a sorry state, say the leaders of California's Tobacco Control Program Fear comes in many forms. At the turn of the 20th century, our grandparents were terrified by tuberculosis and polio (to mention only a few of the hideous communicable diseases that plagued the human race). We pulled out all the stops and gladly spent millions to "conquer" the responsible infective agents, at least in the resource-rich nations. As a result, the "plagues" which now terrorise the industrialised world are cardiovascular disease and cancer. These two categories of disease alone are responsible for a majority of all deaths, illnesses, disabilities and the lion's share of medical care costs. The leading responsible agent for these is tobacco. Yet, we tolerate this agent, subsidise it with government funds, and passively accept the tobacco industry argument that our societal ethos accepts its use (that is, it's "normal" and "expected"), and those who oppose its use are, by implication, "intolerant" and "puritanical". There are few examples of so deadly an error in human history. We need to recognise that this problem is caused by an agent (tobacco) as virulent as the tubercule bacillus or the poliovirus. Furthermore, this agent is being skilfully marketed by an industry which is, sans hyperbole, an immensely profitable organisation that has grown by strategically buying social and political influence. An egregious example of this is the relationship between the big tobacco lobbyists and most of the major political parties in Australia.1 Tobacco use remains the single largest underlying preventable cause of death in Australia. The tragic irony is that these deaths are so very preventable. Yet tobacco control measures in Australia have stalled, primarily due to a monumental paucity of funds and political will. Sadly, the Australian crusade is actually a non-crusade. Because of complacency, you are falling far short of what could be achieved if you were once again to become global leaders in tobacco control. Needless to say, tobacco companies are constantly and very effectively working behind the scenes to diminish the gains that have been made to date. Tobacco use in Australia will probably fail to decline, and could even increase, unless a proactive campaign to regenerate your flagging efforts is undertaken. To that end the Cancer Council of New South Wales invited us to visit in November 2002 to transfer some of the California Tobacco Control Program's expertise, irreverence, passion and technology to our Australian counterparts. From 1988 (the year before the California program was launched) to 2001, annual per capita consumption of cigarettes in California declined by 60% to 50 packs per capita. During the same period, annual per capita consumption in the entire nation (including California) declined by only 34%, to just over 100 packets per capita (twice the rate in California).2 The comparable statistic for Australia is currently derived to be about 75 packs per capita annually. From 1988 to 1997, the decline in lung and bronchial cancer rates in California was five times the rate of the decline in the rest of the nation.3 Furthermore, prevalence rates of youth tobacco use in California declined 47% (from 11.2% in 1997 to 5.9% in 2001).4 What worked in California will also work in Australia. The California experience demonstrates that a comprehensive approach designed to change social norms and expectations around tobacco use will reduce both its use and tobacco-related morbidity and mortality. This approach involves media-supported advocacy for laws and voluntary policies that discourage tobacco use, especially at the community level. The objective of this approach is to change the social environment in such a way as to make tobacco use less desirable, less acceptable, and less accessible to adults and youth. The four broad priority areas, or policy themes, of the California program are: Protecting people from exposure to secondhand tobacco smoke; Exposing and countering tobacco industry influences in Californian communities; Reducing the availability of tobacco by regulating tobacco retailers; and Providing support for smoking cessation services. Having studied the dynamics of your political and governmental system, we identified four areas for Australia to work on. Firstly, the insidious influence of the tobacco industry on both sides of your parliamentary aisle is a huge drawback. The fact that a former premier of New South Wales is currently the chairman of your biggest tobacco company says it all. Secondly, your allocation of funds to tobacco control is ludicrous. Our largest State, California, has spent over US$1 billion in 12 years to achieve these results. In your largest State, New South Wales, you spent less than US$2 million last year. Thirdly, your governmental bureaucracy needs to be infinitely more agile and aggressive. Throughout our trip, we were complacently assured by government officials that some of these interventions "would not work" in Australia. We used to hear the same arguments in California. We just ignored them and pushed ahead aggressively to become the first major governmental organisation to take this "legally constituted tobacco industry" head on, by publicly ridiculing them for their falsehoods (as to the addictive, atherogenic, mutagenic and carcinogenic properties of tobacco smoke) and questioning their amoral marketing practices. You must give the leaders of your tobacco control program permission to be caustically critical of the tobacco industry and its surrogates as an official government policy. Lastly, your constituency of anti-tobacco control advocates is too civil by far. Even as we enjoyed success after success, we were continuously and usefully criticised, prodded and even pilloried by an ever-vigilant anti-tobacco constituency to do more and more, to good avail. In expressing these criticisms, we speak as respectful co-labourers in the field of tobacco control. Our own efforts were inspired by Australia's pioneering initiatives in tobacco control 20 years ago. Australia has had phenomenal success in the implementation of certain measures like advertising bans and point-of-sale restrictions (price and pack warnings being good examples of these), but none of these is a fundamental threat to the operation of the industry. Thus, having seen your once-proud effort diminished considerably, we have ventured to speak frankly in the hope that this may contribute to restoring your tobacco control efforts to their former glory. Our best advice? The allocation of funds to tobacco control in Australia is negligent, bordering on the farcical. At a minimum, you have to spend $50 million per year in New South Wales and well over twice that for all of Australia. This could fund an aggressive tobacco control program capable of producing a sea change in community norms around tobacco use. Your focus should be on increasing the tax on all tobacco products, as well as promulgating a total ban on smoking in all indoor venues, including bars, pubs and clubs. Smoking bans are, contrary to the tobacco industry's propaganda, good for health reasons, good for business, and good politics, as has been amply illustrated in California.5-7 A key point to remember is that a good adult campaign is also a good youth campaign. There is a clear divide between your political leaders "cosying up to" the tobacco industry and the preferences of your population, as expressed by polling and survey data.8-10 During our visit, we were repeatedly confronted with the question as to why your political leaders were not responding to these expressed needs. In conclusion, we do not delude ourselves that this will be easy to achieve given the organised opposition of the monolithic tobacco industry behemoth and its front groups and political influence in Australia. However, there is no shortage of anti-tobacco control expertise in Australia, where some of the world's leading tobacco control experts reside. You have the talent and technical expertise for an effective program. So, why are Australian authorities emulating the ostrich and sticking their heads in the sand? The anti-tobacco constituency needs to sound the clarion call: "In tobacco control in Australia: what aren't we doing and why aren't we doing it?".

Dileep G Bal MD, MS, MPH · Donald O Lyman MD, DT, DTPH · David F Veneziano MPA

Needle/syringe programs have resulted in enormous savings in both lives and dollars Sixteen years after needle/syringe programs (NSPs) were first introduced in Australia, after a period of civil disobedience and amid intense controversy, the recent report Return on investment in needle and syringe programs in Australia1 has convincingly confirmed the effectiveness of NSPs in reducing HIV and hepatitis C virus (HCV) infection among injecting drug users. The report also draws attention to the program's low cost and high cost-effectiveness. Commissioned by the Commonwealth Department of Health and Ageing, the report summarises 778 years of data from 103 cities around the world. In cities that had ever had NSPs, there had been an average annual decrease in HIV prevalence of 18.6%, compared with an average annual increase of 8.1% in cities without such programs. Australia's NSPs were estimated to have cost Commonwealth and State governments $122 million by 2000, but the return on this investment was the prevention of an estimated 25 000 HIV and 21 000 HCV infections. By 2010, our NSPs will have prevented an estimated 4500 deaths from AIDS and 90 deaths from HCV. The savings to governments for HIV and HCV were estimated to be at least $2.4 billion (allowing for conventional government 5% annual discounting of future costs) or as much as $7.7 billion (without discounting). By any reckoning, this represents an enormous saving in both lives and dollars. In light of these outcomes, opposition to NSPs amounts to public health vandalism and financial recklessness with taxpayers' dollars. However, in spite of these gratifying health outcomes for investments in NSPs, the annual incidence of HCV in Australia continues to rise. Hepatitis C is a very common chronic infection in Australia. At least 80% of infected people have acquired HCV through injecting drug use. A recent report2 estimated that in Australia in 2001 there were about 210 000 people with HCV antibodies, of whom 53 000 had cleared their HCV infection, 151 000 were living with chronic HCV infection and 6500 were living with HCV cirrhosis. Furthermore, according to the report, despite the effectiveness of NSPs in reducing HCV incidence among injecting drug users (IDUs), there were 16 000 people exposed to HCV during 2001, representing a 45% increase on the estimated 11 000 incident HCV infections in 1997.3 The report also projected that the long-term sequelae of HCV infection, such as cirrhosis, liver failure and hepatocellular carcinoma, would all treble by 2020. These two reports1,2 raise several important questions. First, why have NSPs been so successful at limiting HIV infection among IDUs, but less effective in reducing HCV infection? One important reason for the apparent discrepancy is the greater infectiousness of HCV by blood–blood spread compared with HIV, and consequently its heightened transmission among IDUs. Another factor is the higher baseline HCV levels (of the order of 50%–70%) prevalent among IDUs when NSPs were introduced in Australia in the late 1980s.4 At that time, only one in 200 IDUs undergoing treatment in Sydney were infected with HIV.5 HIV appears to have entered IDU populations in Australia in the early 1980s, about 20 years after HCV.6 Second, why has HCV incidence continued to increase so rapidly in Australia throughout the 1980s and 1990s, despite early and vigorous implementation of NSPs? The answer appears to be a combination of the increase in the number of young people who inject drugs7 and the continued high incidence of HCV infection among IDUs, and in particular among young people who have recently started injecting drugs (around 20% of IDUs are infected with HCV within three years of commencing injecting).8 The heroin shortage in Australia beginning in 2000 may have interrupted the increase in the number of IDUs, but whether a shortage will persist is uncertain. It is too early to estimate the net costs and benefits of the heroin shortage, but one benefit has been the 25% drop in deaths from drug overdose between 1999 and 2000.9 Finally, what should be done? Alternative strategies that need to be considered (in combination with NSPs) include medically supervised injecting centres, drug law reform, a trial of medically supervised prescription of illicit drugs for treating refractory drug users, introduction of harm-minimisation strategies into prisons, and education programs to encourage people who do or might inject drugs to consider non-injecting routes of administration. Such strategies must be debated in the community and properly evaluated. As each new HCV infection is estimated to cost healthcare systems more than $10 000,10 such strategies make sound health and financial sense. Many IDUs ultimately abandon injecting illicit drugs — it is in everyone's interests that they are still healthy when they do so, to maximise the likelihood that they will lead normal and useful lives. With the recent confirmation of the effectiveness of NSPs in preventing HIV transmission, it is important that society continues to support these programs. This may appear self-evident, but closing down NSP centres is often politically popular, especially in marginal electorates in tight elections. We must not become complacent just because a feared epidemic of HIV among IDUs has not eventuated. There is no guarantee that it will not happen in the future, as has been seen in some other countries.11 Any loss of resolve in the commitment to NSPs increases the likelihood of an HIV epidemic among IDUs, with potentially disastrous consequences for other at-risk populations (such as female sex workers or Indigenous Australians) and thence for the wider community.

Matthew G Law PhD · Robert G Batey MD FRACP FRCP

To the Editor: I wish to draw attention to a draconian anomaly in the National Health Act 1953 (Cwlth). All GPs encounter patients "shopping" for narcotics and/or tranquillisers. The Doctor Shopper phone line (which enabled GPs to rapidly obtain information from the Health Insurance Commission to identify non-genuine patients) was a boon in guiding GPs' management of such situations. Concern over the new private sector amendments to the Privacy Act 1988 (Cwlth) led to an examination of the legal standing of the Doctor Shopper phone line, and it has now been cancelled. Concerned GPs are now limited to requesting that a "patient" sign a voluntary release of their Pharmaceutical Benefits Scheme record. This tells the "patient" that they have been rumbled, and they move on to the next practice on their list. If they have signed the Privacy Release Form, then the GP will receive a printout of the drugs they have received under the Pharmaceutical Benefits Scheme in the previous six months. This is accompanied by a letter informing the doctor that he or she "cannot make a record of, divulge or communicate to any person, any information with respect to the affairs of the person whose information has been released. To do so attracts a penalty of $5000 and/or imprisonment for a period not exceeding two years". So, under the provisions of the National Health Act (subsection 135A), even putting this information in the medical records of a multidoctor practice would appear to be illegal. It is clearly illegal to warn other doctors outside the practice. There is no corresponding legislation which affects doctor shoppers. So the "right-doers" can finish up in jail, while the "wrong-doers" can, with impunity, continue to play their dissembling, time-consuming, and sometimes harassing, games.

Max Kamien

To the Editor: "Chop-chop" tobacco is illicit tobacco that has been grown and clandestinely distributed by farmers and wholesalers and sold on without government intervention or taxation. There is no quality control over this illicit substance, which may be adulterated or "bulked up". It is sold illegally "under the counter" by weight for rolled cigarettes by unscrupulous tobacconists and grocers. This type of tobacco, which has been roughly chopped up (hence "chop-chop"), is very cheap compared with legally produced manufactured cigarettes. The prevalence of the use of chop-chop in the smoking community is unknown. However, the Australian Taxation Office (ATO) has a keen interest in the distribution of this substance, and estimates that many millions of dollars are lost in revenue from the illegal sale of chop-chop. Arrests and fines initiated by the ATO have so far occurred primarily in Queensland and Victoria. Results of analysis of chop-chop vary from batch to batch, but samples have been shown to contain nicotine (Professor G Starmer, Department of Pharmacology, and Mr B Tattam, Mass Spectrometry Unit, Department of Pharmacy, University of Sydney, personal communication). It may also be fumigated with bleach and may be bulked up to add weight (M Rushton, ATO, personal communication). Although most people smoke it because it is cheap, many have misguided beliefs, for which there is no evidence, that it is "better" than other forms of tobacco. Results of a survey of 44 consecutive patients attending the Smokers' Clinics of the Central Sydney Area Health Service 43% currently using "chop-chop" 84% smoke it because it is cheaper 58% believe it is better for you 74% believe it has no additives 16% believe it has no nicotine 63% know it is not legal A retrospective survey was carried out to assess the prevalence of and attitudes towards illicit tobacco smoking among patients attending the Smokers' Clinics of the Central Sydney Area Health Service (approved by the CSAHS Ethics Committee, June 2002). Patients were routinely asked the type of tobacco they smoked and their beliefs regarding this type of tobacco. The results are shown in the Box. Many of the patients attending the Smokers' Clinics (dedicated exclusively to patients who smoke and have chronic obstructive pulmonary disease [COPD]) smoke this type of illegal tobacco. Several patients volunteered that smoking chop-chop precipitated an acute exacerbation of their COPD. Four patients have recently presented to a hospital emergency department for exacerbation of COPD after smoking chop-chop. Although smokers are loath to volunteer their use of this illegal tobacco, smokers and clinicians should be warned that smoking chop-chop does not constitute a positive health move, is not less harmful, and may be quite dangerous. Quitting smoking altogether is the best health move.

Renee Bittoun

Fentanyl is a synthetic opioid with a potency about 200 times that of morphine. It has been misused since it was first introduced, mostly by medical and paramedical personnel because of limited access. Illicit manufacture of fentanyl and its analogues ("China White") occurs sporadically and has been associated with regional fatal epidemics in the United States.1 With the introduction of a transdermal delivery system for fentanyl (Durogesic, Janssen-Cilag) for managing chronic and cancer pain, there is a widening pool of individuals with access. Prescribed transdermal fentanyl patches can be sold or stolen. Clinical recordA 35-year-old woman with a history of intravenous drug use was brought by ambulance to the emergency department after an intravenous overdose of the contents of a transdermal fentanyl patch. The ambulance had been called to a private home where there were two people unconscious, a man and a woman. Both appeared to have had acute narcotic overdoses. It was later confirmed that they had shared (and injected intravenously) the contents of a transdermal fentanyl patch (5 mg) found at the scene. Both patients were rapidly assessed by the ambulance officers, and the initial resuscitation concentrated on the male patient, who, at first assessment, appeared to be in a more critical state. He was unrousable and was reported to have Cheyne–Stokes respiration. His blood sugar level was checked (10.5 mmol/L) and he was given 1.2 mg naloxone intravenously. He recovered consciousness within five minutes and subsequently absconded from the scene while the second patient was being treated. In the interim, the female patient had suffered a cardiorespiratory arrest. Cardiopulmonary resuscitation was commenced, with the assistance of police officers who were also in attendance. According to ambulance records, her initial rhythm was electromechanical dissociation, which subsequently deteriorated into ventricular fibrillation. A direct current countershock (200 J energy) was applied. The patient went into asystole. She was intubated and intermittent positive pressure ventilation with 100% oxygen was started. Naloxone 1.6 mg, adrenalin 10 mg (total dose) and atropine 2 mg were administered intravenously. Subsequently, she developed a narrow complex tachycardia with a rate of 130 beats/minute and had a palpable cardiac output. The total time spent at the scene was 40 minutes, and transport time to hospital took 5 minutes. On arrival at the emergency department she was unconscious, with a Glasgow Coma Score of 3. Her pupils were dilated and non-reactive to light. She was making occasional attempts at respiration and was ventilated as above with 100% oxygen. Her heart rate was 120 beats/minute in sinus rhythm, systolic blood pressure 55 mmHg and oxygen saturation 97%. One litre of Haemaccel and a noradrenalin infusion were administered, resulting in an initial improvement in systolic blood pressure to 95 mmHg. It was evident that she had vomited at the scene, and clinical signs were consistent with aspiration, which was later confirmed on chest x-ray. Laboratory results for arterial blood, serum and urine are shown in Box 1. She was transferred to the intensive care unit, where she subsequently developed diabetes insipidus, abnormal liver function, disseminated intravascular coagulation and had ongoing haemodynamic instability. The next day, cerebral computed tomography (CT) scan showed changes in the basal ganglia and mild generalised cerebral swelling consistent with severe hypoxia (Box 2A). A CT scan of her abdomen showed generalised changes in the bowel wall and mesentery consistent with bowel necrosis (Box 2B). Surgical intervention was considered to offer little in view of the severe neurological damage and multiorgan failure. Following extensive discussion with family members, inotropic support was withdrawn and she died soon afterwards. DiscussionSurprisingly, this is the first report of death caused by intravenous misuse of a fentanyl patch, although there have been fatalities after oral ingestion.2 Non-fatal inhalational misuse has been reported.3 In one death (a funeral home employee who obtained a patch from a deceased person in a nursing home), the route of administration was never determined.4 Finally, there is a report of respiratory arrest from intentional intravenous misuse of transdermal fentanyl in a patient with chronic pain.5 Transdermal fentanyl is used in the management of both acute and chronic pain.6 In Australia, it is listed on the Pharmaceutical Benefits Scheme for pain caused by malignant neoplasia, but it has increasingly found a role in the management of chronic non-malignant pain. Durogesic patches are available in four sizes, the smallest designed to deliver 25 μg/h of fentanyl (total 2.5 mg fentanyl), the largest 100 μg/h (total 10 mg fentanyl) (Box 3). Extracting the contents of a patch can lead to a large variation in the dose administered, making a dangerous habit perilous. The pharmacokinetics of fentanyl only add to the danger. Fentanyl is highly lipid-soluble and has a large volume of distribution (60–300 L). A 2 μg/kg dose leads to high immediate serum concentrations (up to 11 ng/mL) that fall rapidly to less than 1 ng/mL after one hour.7 The offset of action is mainly by redistribution. An effective analgesic concentration of fentanyl ranges from 0.3–0.7 ng/mL.8 Serum concentrations in health professionals who died after fentanyl misuse have ranged from 0.1–5 ng/mL,1 in keeping with the average concentration of 3 ng/mL found in a larger series of deaths from fentanyl misuse.9 The serum fentanyl concentration in our case accords with concentrations given in other published cases. The absence of detectable opioid in the urine was consistent with a recent overdose. Alterations to the formulation or presentation of the patch might make it harder to misuse the drug intravenously, although previous experience with temazepam in several countries has shown that such changes are not necessarily the answer. In response to the ease of misuse of temazepam, the pharmaceutical industry produced a gel-filled formulation that would be as "resistant" as possible to injecting. However, it has since been shown that the gel-filled preparation is readily injectable,10 and results in more medical complications, including superficial thrombophlebitis, abscesses and deep venous thrombosis. There are several case reports of ischaemic necrosis of digits resulting from intra-arterial injection of temazepam.11 To date, all reported deaths from misuse of fentanyl patches have been the result of other than intravenous misuse. Prescribers need to be alert to the potential for misuse and the consequent risk of fatality. They need to impress on patients the importance of secure storage of patches. Stricter regulation of fentanyl patches could be enforced by accounting for patches after they have been dispensed (eg, ensuring that, on the death of a patient issued with patches, unused medications are returned). A more draconian measure would be to require that used patches be returned before more can be issued. However, this would not prevent the theft of patches, and would put the onus of returning used patches on patients already suffering from debilitating pain. It is clearly necessary to continue to strictly control the availability and prescribing of these patches, which potentially are a highly sought after product on the black market. However, it is also important to avoid widespread public warning of the risk, which might serve only to advertise a novel activity for risk-takers. 1: Laboratory results in a patient after intravenous misuse of transdermal fentanyl Arterial blood (reference range) pH 6.88 (7.36–7.44) Pco2 62 (36–44) mmHg Po2 170 (85–100 mmHg on room air) Bicarbonate 11.3 (22–26) mmol/L Base excess – 22.6 mmol/L Haemoglobin 114 g/L Serum Paracetamol Negative Salicylate Negative Benzodiazepines Negative Tricyclic antidepressants Negative Fentanyl 2.0 ng/mL Ethanol 0.16 g/L Urine Cannabinoids Negative Opioids Negative Amphetamine Negative 2: Computed tomography (CT) scans A: Brain — arrows indicate areas of low attenuation in basal ganglia. B: Abdomen — arrows show changes consistent with bowel necrosis. 3: Transdermal fentanyl patch Fentanyl, dissolved in ethanol (a flux enhancer) and gelled with hydroxyethyl cellulose, is held in a drug reservoir between a backing layer and a rate-controlling membrane on an adhesive base.

Mark D Reeves MB BS, FANZCA · Corinne J Ginifer MB BS, FACEM

To the Editor: I read with great interest the article by Byard et al,1 as well as the previous work by these authors on paramethoxyamphetamine (PMA)-related fatalities in South Australia.2 In 2001, I encountered a similar fatal "outbreak" in Belgium: six fatal cases, four of them in the Antwerp metropolitan area.3,4 Striking similarities between the Belgian and Australian fatalities include the clinical symptoms, the autopsy findings and the history of alleged "ecstasy" intake. Pure PMA tablets were found on a victim with an "xTc" logo pressed onto the surface of the tablets.3 I agree with Byard et al1 that the sudden "outbreaks" of death from PMA intoxication probably do not result from contamination during the synthesis of 3,4-methylene-dioxymethamphetamine (MDMA). In Belgium, there are strong indications that the resurgence of PMA resulted from a legal loophole. Early in 2001, PMA was encountered for the first time in the blood sample of a young girl who presented to an emergency department for alleged ecstasy intoxication. A few weeks later, the first fatal case was reported, and over a period of a few months five other fatal cases were seen. After the first two deaths, PMA captured a lot of media attention and even evoked some political disturbance. By the end of 2001, PMA and its precursor molecule, p-methoxyphenylacetone, were placed on the list of regulated and restricted substances (and hence the unauthorised possession of these products became a criminal offence). Afterwards, no more fatalities were reported. I therefore hypothesise that illicit amphetamine manufacturers were aware of the (temporary) legal vacuum in Belgian law before the deaths occurred and substituted PMA for MDMA because PMA precursors were easier to obtain and less strictly controlled by legislation. It has been suggested in the Australian illicit drug report 1994,5 as well as by Byard et al,1 that manufacturers of PMA may have been deliberately marketing it as another drug (eg, MDMA) or may have promoted it specifically as a drug to augment the effects of MDMA. If this is the case, there may be serious implications for criminal liability, as we now know that PMA intoxication has a significantly worse clinical outcome than MDMA intoxication (including a greater likelihood of QRS-interval prolongation, extreme hyperthermia, seizures and a significantly lower score on the Glasgow Coma Scale).6

Werner Jacobs

To the Editor: We write to alert policy makers and clinicians to the challenge presented by rising cannabis use in north-east Arnhem Land, in the Northern Territory, given that many current cannabis users were previously petrol sniffers. In the past five years, there has been a rise in cannabis use and evidence of expansion of supply links in the Miwatj region.1 There are concerns that rising cannabis use is associated with social effects: increased family violence, drug–alcohol psychosis, self-harm and suicide, and community disruption. Policy makers seeking to foster initiatives to minimise harmful outcomes must develop general policies that can have local effects in a varied Northern Territory population. NT police have targeted cannabis in remote communities. A Substance Abuse Select Committee and Illicit Drugs Task Force, each with Indigenous representation, will report to the NT government during 2002. We recently began collecting baseline data to allow us to evaluate the effects on patterns of use of cannabis (and related harm) of community-wide interventions. These interventions will be similar to those implemented for petrol sniffing,2 but with a focus on improved availability of appropriate drug education. We have selected a random sample of about a third of the residents (aged 13–34 years) from two communities. From this sample, current cannabis users (at least weekly) and past petrol sniffers have been identified by using health worker consensus classification, supported by data from review of the health clinic chart and self-report, if available. These data for 145 males and 141 females are presented in the Figure. Among males aged 20–34 years, 74% are current cannabis users and, of these, 60% are former petrol sniffers. To date, 57 cannabis users have agreed to interview (34 males and 23 females) and, of these, 38 met DSM-IV criteria for cannabis dependence.3 A particular health concern is that persistent cannabis use may compound any residual cognitive impairment from petrol sniffing. Current cannabis users among people aged 13–34 years in northeast Arnhem Land Results for samples from two remote communities in the Miwatj region, assessed by using health worker consensus classification, self-report data, and supporting data from health clinic chart review.

Alan R Clough · Sheree Cairney · Paul Maruff · Robert Parker

Re the article "The contribution of airway structure to early childhood asthma", by McKay KO and Hogg JC, in the 16 September supplement to the Journal, Early childhood asthma: what we know and what we need to know (Med J Aust 2002; 177: S45-S47). The last two lines of the figure caption on page S46 were omitted. The full caption should read: "The vessels in the submucosa (a) are smaller than the vessels in the adventitia (c), and the vessels that pass through the muscle layer (b) connect them. These two sets of vessels are perfused in series, providing a basis for a difference in the nature of the inflammatory reaction in the submucosa and lumen compared with the peribronchiolar space." The html and pdf versions of the article were corrected on Monday 30 September 2002.

Karen O McKay LLB PhD · James C Hogg MD PhD

Hollywood celebrity Pamela Anderson's announcement that she has hepatitis C was a major talking point at this recent conference. Unlike similar announcements of HIV infection, Ms Anderson has not positioned herself as a celebrity campaigner — there is no princess or pop star championing the rights of people with hepatitis C or demanding extra funding for research or services. Hepatitis C has been characterised as an "epidemic of difference",1 affecting people from a wide variety of ethnic, cultural and class backgrounds, with implications for the ability of people with hepatitis C to organise and advocate for changes in policy to improve their lives. Until recently, a study by Crofts et al (1997) was the only example of academic research to focus on hepatitis C-related discrimination and to highlight the part played by healthcare professionals.2 It is timely that many presentations from the recent Third Australasian Conference on Hepatitis C, held in Melbourne in March 2002, highlighted the discriminatory attitudes and practices of some healthcare workers when treating and working among people with hepatitis C. Presentations discussed both institutional and interpersonal discrimination against people with hepatitis C. The relatively low level of community and government concern regarding this epidemic was alluded to in several presentations, suggesting a form of systemic discrimination. There have been more than 160 000 notified cases of hepatitis C since antibody testing became available in 1990.3 Alex Wodak (Director, Alcohol and Drug Service, St Vincent's Hospital, Sydney) described the estimated incidence of 16 000 new infections in 2001 as one every 33 minutes.4 Given the high prevalence and estimated incidence of the hepatitis C epidemic, Nick Crofts (Head, Epidemiology and Social Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health [Burnet Institute], Melbourne) questioned whether the government response might have been quicker and better funded if hepatitis C primarily affected people other than injecting drug users.5 Similarly, conference presentations from people with hepatitis C, community organisations and researchers challenged the positioning of hepatitis C (in their view) as a "second-class" disease. These presentations indicated that people with hepatitis C are tainted as past or current drug users and suffer attitudes of blame from healthcare professionals, often described as "userphobia". Grant McNally (Chair, United Kingdom Assembly on Hepatitis C) summarised the effects of these negative attitudes on people with hepatitis C: they take for granted and come to expect substandard levels of healthcare.6 Academic presentations documented the effects of discrimination on prevention, testing, living with hepatitis C, quality of life, treatment and prognosis. A paper by Michael Kerger (Manager, Centre for Harm Reduction, Burnet Institute), Campbell Aitken (Research Fellow, Centre for Harm Reduction, Burnet Institute) and Nick Crofts discussed piloting peer-delivered hepatitis C testing and counselling at a needle and syringe program.7 The authors highlighted current injecting drug users' fear of discrimination following disclosure of their injecting status to doctors. This fear meant that users often did not present for hepatitis C testing. Max Hopwood (Senior Research Officer, National Centre in HIV Social Research, University of New South Wales, Sydney) and Erica Southgate (Research Fellow, National Centre in HIV Social Research) reported that people with hepatitis C at times feel pressured by healthcare workers to reveal their hepatitis C status.8 They described how some people with hepatitis C were refused medical treatment and had their positive serostatus disclosed to other healthcare workers without permission. Similarly, in discussing women's experiences of living with hepatitis C while using drugs, Mary O'Brien (Researcher, Australian Centre for Research into Sex, Health and Society, La Trobe University, Melbourne)9 reported that participants in their study who were current injecting drug users were treated less favourably by healthcare professionals than women with hepatitis C who were not currently injecting drugs. Sandy Gifford (Professor, School of Health Sciences, Deakin University, Melbourne) presented a paper noting the harmful impact of hepatitis C-related discrimination on participants' quality-of-life measures, including physical and emotional health scores.10 The participation of people from the affected communities provided opportunity for elaboration and reflection on research from the perspective of those primarily affected by hepatitis C. People with hepatitis C spoke informally of feelings of guilt, shame, low self-esteem and self-worth that arose as a result of their interactions with some healthcare professionals. They claimed that internalising stigma led to missed opportunities for care and support from social networks and had implications for people's access to healthcare services. Deb Warneke (Metropolitan Educator, Hepatitis C Council of South Australia) and Richard Hanssens (Representative, Hepatitis C Resource Centre, Christchurch, New Zealand) provided personal views and case studies of the effect of hepatitis C in other domains of life experience —within family circles and the workplace.11,12 These conference papers support the report of the New South Wales Anti-Discrimination Board Enquiry, which found that hepatitis C is a highly stigmatised condition and discrimination is rife, especially in healthcare settings.13 The report states that discrimination results either from an inadequate knowledge of the virus and how it is transmitted, or from a confounding of injecting drug use with hepatitis C virus infection. Both the conference presentations and the Enquiry report acknowledge that not all healthcare workers discriminate against people with hepatitis C. However, it is time for healthcare professionals to acknowledge and address hepatitis C-related discrimination. No short term practical solutions to healthcare workers' discrimination against hepatitis C-positive injecting drug users were proffered. A paper by Piergiorgio Moro (Education and Community Development Officer, Hepatitis C Council of Victoria) suggested that a long term solution would involve organisation and lobbying by the hepatitis C-positive and injecting drug use communities to effect legislative change.14 As implied in many of the conference papers, marginalising people with hepatitis C will impede measures to prevent the further spread of the virus throughout the community, and will contribute much to the burden borne by people with hepatitis C.

Carla J Treloar BSc(Hons), PhD · Max N Hopwood BA(Hons) · Stuart K Loveday BCom

In Australia, the lifetime use of cocaine is rising, with 3% of the population aged over 14 using cocaine in 1991, increasing to 4.5% in 1998, and cocaine use accounting for 10% of all deaths secondary to illicit drug use in 1998. Cocaine is prepared from the leaves of the plant Erythroxylon coca, and is available as cocaine hydrochloride (a water-soluble powder or granule which can be taken orally, intravenously or intranasally) and as "freebase" or "crack" cocaine (heat stable, melting at high temperatures, thus allowing it to be smoked). Acute myocardial infarction (AMI) is the most commonly reported cardiac consequence of cocaine misuse, usually occurring in men who are young, fit and healthy and who have minimal, if any, risk factors for cardiovascular disease. The mechanism by which cocaine induces AMI is largely not understood. Cocaine effect should be seriously considered in any young patient with minimal risk factors for cardiac disease presenting with AMI, dilated cardiomyopathy, myocarditis or cardiac arrhythmias.

Gabriella Vasica MB BS(Hons), BSc(Hons) · Christopher C Tennant MPH, MRCPsych, FRANZCP

Alcohol accounted for an estimated 3668 deaths and 95 917 hospital separations in Australia in the 1996–97 financial year.1 Alcohol-related deaths in Australia declined from 460 per million population in 1990 to 369 per million in 1997.2 The net economic cost of alcohol to the economy in 1992 was estimated to be $4.5 billion (this estimate includes increased healthcare expenditure and costs to industry from impaired productivity, increased accidents and absenteeism).3 Prevention and treatment of alcohol-related problems has been improving in recent decades. In the 1980s, brief interventions4 were developed for problem drinkers who reject abstinence or are unsuitable for this treatment goal. Brief interventions involve a combination of techniques, including motivational interviewing, feedback to patients of likely adverse consequences of current drinking, self-monitoring of drinking, developing a contract for future drinking, providing strategies to cut down drinking, and regular follow-up. Most clinicians try to discourage patients with life-threatening complications from alcohol from pursuing brief interventions. Recently, more effective pharmacological treatments have been developed for alcohol dependence. The aetiology, natural history, compliance with and response to treatment of alcohol dependence are similar to those for other common, chronic, relapsing–remitting conditions readily accepted by the medical profession as worthy of treatment.5 Treatment of alcohol dependence has been shown to substantially reduce healthcare costs in the period after compared with the period before treatment.6 PharmacologyThe main drugs used to treat alcohol dependence are acamprosate and naltrexone. Their profiles are shown in Box 1. EfficacyThis review is restricted to major studies providing the highest-quality evidence. Studies were preferred if they were larger, had a longer study duration and were more recent. Studies or reviews with a more rigorous design were preferred. Only one study directly compared acamprosate and naltrexone.10 AcamprosateThere have been 16 randomised controlled trials (RCTs) comparing acamprosate and placebo, two systematic reviews of acamprosate only (by the same principal author),11,12 and one cost-effectiveness study of acamprosate compared with placebo13 (E1) (for an explanation of level-of-evidence codes, see Box 2). The efficacy of acamprosate has been evaluated in a large number of well-designed studies involving large numbers of participants with six to 12 months of treatment or follow-up. These reports have drawn very consistent conclusions. Fourteen showed a statistically significant beneficial effect for acamprosate on several measures of alcohol consumption, including time to first drink, total abstinence rate and duration of cumulative abstinence (the proportion of drinking days per unit time). Many studies have also found a satisfactory retention in treatment and reduction in laboratory indices of alcohol consumption (γ-glutamyltransferase, carbohydrate-deficient transferrin). However, one randomised controlled trial of acamprosate versus placebo showed only a modest treatment effect and poor compliance.15 Unlike the other studies, patients in this study began treatment an average of 25 days after the last drink; 32% had relapsed before starting drug therapy. The cost-effectiveness study estimated that treatment with acamprosate resulted in net savings of 528 euros (equivalent to approximately A$880) per patient over 24 months compared with no pharmaceutical treatment.13 NaltrexoneThere have been 11 randomised controlled studies comparing naltrexone with placebo, one meta-analysis16 and one systematic review17 of the use of opioid antagonists for alcohol dependence (E1). Naltrexone has been assessed in fewer studies overall, with smaller numbers of participants, and only one study18 extended beyond three months' duration. Naltrexone has been shown to have a statistically significant beneficial effect on several measures of alcohol consumption, including time to first drink, time to first episode of heavy drinking, duration of cumulative abstinence and number of standard drinks consumed. The Cochrane review17 also noted that such benefits were lost six months after completion of treatment. The meta-analysis concluded that in the seven existing studies of naltrexone versus placebo, involving 804 patients, naltrexone produced a modest benefit: a reduction in relapse rates of 14% and an improvement in abstinence rates of 10%. All seven studies were of three months' duration. The incidence of at least one adverse event or discontinuation of treatment because of adverse events was comparable. However, nausea, somnolence, abdominal pain, anorexia and vomiting were significantly more common in patients treated with naltrexone. The systematic review concluded that the short-term benefits of naltrexone included an increase in total abstinence, and a reduction in the percentage of drinking days and the number of standard drinks of alcohol consumed. However, six months after the completion of treatment, the benefits of treatment were generally lost. Overall, the observed effects have been modest, and there is no evidence that these benefits extend beyond the duration of treatment. Intention-to-treat analyses of two recent studies comparing naltrexone and placebo resulted in largely unimpressive findings.18,19 However, in one of these studies,19 the overall completion rate was much lower than other studies. In a recent study of older, predominantly male, patients, 12-step facilitation counselling was used in conjunction with naltrexone,18 whereas other studies tended to use coping-skills therapy or relapse-prevention training. Two recent Australian studies showed a reduction in relapse rate for naltrexone compared with placebo;20,21 one of these was conducted in a standard clinical setting without extensive psychosocial intervention.21 Acamprosate and naltrexoneIn the only direct comparison of both drugs, there was no difference between treatments in time to first drink10 (E2). However, patients treated with naltrexone had a significant benefit in several measures of alcohol consumption compared with the acamprosate group. At the end of the first year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed, defined as having five or more drinks in a day. However, in this study patients and the doctors were aware of the treatment received. A meta-analysis for both drugs found that both drugs exerted significant, but modest, effects on drinking outcomes, with sizeable variability in results between studies22 (E1). More recent and more rigorous studies of naltrexone have found less favourable outcomes than earlier research. One systematic review concluded that both drugs achieved similar results, but naltrexone was not as well tolerated.23 Another systematic review of a similar selection of the literature concluded that both drugs reduced the frequency and severity of drinking over most of the aforementioned end-points.24 A multi-centre, placebo-controlled trial of naltrexone and acamprosate, alone or in combination, is in progress and may resolve some of these differences.25 Specific indicationsFormulating guidelines for pharmacotherapy of alcohol dependence is difficult because of the paucity of data from direct comparison of acamprosate and naltrexone. However, acamprosate should probably be considered the first-line treatment for patients with moderate to severe alcohol dependence, because of the larger body of supporting evidence and the benefits extending after treatment. Naltrexone is indicated for alcohol-dependent patients in whom acamprosate has not proved effective or has not been well tolerated, or for individuals whose lifestyle or past history indicates that compliance with taking medication is poor. The use of naltrexone for managing heroin dependence is controversial. However, there may be a place for prescribing naltrexone to alcohol-dependent patients who are also dependent on heroin. DiscussionDefining clear guidelines for use of the two main pharmacotherapies (acamprosate and naltrexone) is difficult in the present state of knowledge. This difficulty stems from the fact that the various studies have examined the use of these drugs over varying groups of outcome measures and study durations. Studies of acamprosate have generally used absolute-abstinence-based measures as the primary outcomes, while naltrexone studies have also measured more relative "harm-reduction" measures, such as relapse to heavy drinking or total amount of alcohol consumed. Acamprosate appears to have a prolonged action for up to a year after therapy has ceased, but compliance with a medication requiring thrice-daily administration is often difficult. On the other hand, naltrexone has well documented efficacy, at least in the initial three months of treatment, and is easier to take on a once-daily basis. Consideration of the outcomes desired by the patient, compliance history, other drug therapy and medical conditions may all influence the choice made by the prescriber. In patients with alcohol dependence who also suffer from chronic pain, naltrexone will cause some not insurmountable problems. In this situation, or in acute pain, analgesia can be provided by non-opioid drugs such as non-steroidal anti-inflammatory drugs (including parenteral ketorolac). Other approaches could include local or regional anaesthesia. Attempting to overcome blockade with high doses of opioids is dangerous and not recommended outside an intensive care unit. Opioid withdrawal may be precipitated in alcohol-dependent patients treated with naltrexone if they have also been taking heroin recently. Naltrexone has been used (with uncertain benefit) for treating heroin dependence, but to avoid the problem of precipitating heroin withdrawal naltrexone should only be introduced in patients who have abstained from opioids for seven to 10 days. The optimal duration of acamprosate or naltrexone treatment has not been established, but six months should be considered a minimum, and 12 months a more desirable duration of treatment. It is generally recommended that naltrexone should be avoided in patients with advanced liver disease or elevated results on liver function tests. Higher than recommended doses of naltrexone may elevate liver function test results, but these dangers may be overstated. It is not clear how severe liver damage has to be before naltrexone administration becomes dangerous. Avoiding naltrexone in patients with decompensated liver disease is prudent; naltrexone should also be used with caution in patients with less severe forms of hepatic impairment. Some authors recommend that naltrexone be avoided in patients with aspartate transaminase levels three times greater than normal, while others set the limit at five-times normal. Few studies have included many patients with the combination of severe alcohol dependence and mental illness. It is therefore unclear what effect mental illness has on the efficacy of acamprosate or naltrexone. However, one study included patients with stable mental illness and showed that they could be treated safely.20 There are no existing studies on the effectiveness and safety of the combination of acamprosate and naltrexone, but there is no theoretical reason preventing the combined use of these drugs. Acamprosate and naltrexone have been approved under the Pharmaceutical Benefits Scheme (PBS) for use in treating alcohol dependence, provided that the patient is in a comprehensive treatment program for alcohol dependence with the goal of maintaining abstinence. Each authority prescription lasts for two months. There is no stated limit to the duration of treatment, but further extension of PBS authority requires an additional application each time. The PBS subsidy reduces the price (30 days' supply) from $170.10 (acamprosate) or $167.28 (naltrexone) to $22.40 (both drugs). Product information for naltrexone states that treatment duration is up to 12 weeks. However, the length of treatment is at the discretion of the prescriber. Other drugsDisulfiram inhibits acetaldehyde dehydrogenase, so that alcohol consumption results in a build up of acetaldehyde, causing extremely distressing symptoms, including flushing, syncope, nausea, vomiting and diarrhoea. It is available in 200-mg tablets; the usual starting dose is 100 mg daily increasing to 300 mg maximum, with 200 mg being the usual dose. It has been available for many years for treating alcohol dependence, but is prescribed rarely as compliance is often poor. Evidence of efficacy is limited, although this may be partly due to difficulties in trial design24 (E1). Nalmefene has similar properties and a proposed similar mechanism of action to naltrexone26 (E2). It is not currently used to treat alcohol dependence other than in research settings. Ondansetron, a selective 5-HT3-receptor antagonist, has been shown in one study to have a beneficial effect on early-onset alcohol dependence27 (E2), presumably by modulating dopamine release in mesocorticolimbic dopamine pathways. There is insufficient evidence to justify its routine use at present. Other psychoactive drugs, such as lithium and some selective serotonin-reuptake inhibitor antidepressants, have been suggested, but no positive effect on alcohol dependence has been demonstrated in addition to the documented benefits in treating depression and other psychiatric conditions24 (E1). General managementWhen pharmacotherapy is included in the management of alcohol dependence, doctors should ensure that patients are also followed up closely and regularly, and should draw up a comprehensive treatment plan with each patient. This should include attempts to resolve any psychosocial issues. Prescribers are required to obtain a Health Insurance Commission (HIC) authority before prescribing acamprosate. The comprehensive plan can be provided by general practitioners using, where required, Expanded Primary Care (EPC) items. Engaging allied health professionals, such as alcohol and drug counsellors, may help patient management and also helps fulfil HIC requirements. A comprehensive treatment plan should be tailored to the needs of the individual patient and may need to involve combinations of modalities, including detoxification, counselling, referral to self-help groups or group therapy. The diagram in Box 3 may help guide doctors through the stages of managing patients who drink hazardous or harmful quantities of alcohol. Box 4 provides advice for patients, as well as telephone numbers for help-lines throughout Australia. 1: Profiles of acamprosate and naltrexone Acamprosate Action: Chronic exposure to alcohol causes a decrease in the inhibitory γ-aminobutyric acid (GABA)-ergic system and a corresponding increase in activity of the excitatory glutamate system in the central nervous system.7 Acamprosate, which has a similar structure to GABA, enhances GABA transmission by increasing the number of sites for GABA uptake. Acamprosate also interferes with the action of glutamate at various sites, such as n-methyl-d-aspartate (NMDA) receptors, and has also been shown to affect calcium channels, which increase in number as alcohol dependence develops.8 Dose: Acamprosate comes as 333 mg tablets, with the recommended daily dose for adults weighing over 60 kg being six tablets (1998 mg) orally in three divided doses, with meals. Adults weighing under 60 kg should take four tablets (1332 mg) per day. Usual practice is to start at half these doses and increase by one tablet a week. Metabolism: Only 10% of acamprosate is absorbed, of which 90% is excreted unchanged into urine. Adverse effects: Acamprosate is well tolerated, and its predominantly gastrointestinal adverse effects (commonly diarrhoea) usually resolve spontaneously. Side effects are minimised by gradual dose increases. Other low-grade side effects, including mild abdominal pain, are reported by some patients. Rash or isolated pruritus, paraesthesiae, decreased libido and confusion have all been reported at low frequencies. Drug interactions: Tetracyclines may be inactivated by the calcium component in acamprosate during concurrent administration. Contraindications: Acamprosate is contraindicated in patients with known hypersensitivity to the drug, renal insufficiency or cirrhosis with severe hepatic decompensation. The safety of acamprosate in pregnancy or lactation has not been established. Naltrexone Action: Naltrexone, a potent opioid-receptor antagonist, blocks the effects of endogenous opioids, which increase after alcohol consumption.9 Dose: Naltrexone is administered orally at 25 mg for 1–2 days, and then increased to the standard dose of 50 mg daily. Metabolism: Naltrexone undergoes extensive first-pass metabolism in the liver to β-naltrexol. Although a much weaker antagonist than naltrexone, the half-life of β-naltrexol is longer, and plasma concentrations of the metabolite are always higher than those of the parent drug. The mean elimination half-life values for naltrexone and 6-β-naltrexol are four hours and 13 hours, respectively. Adverse effects: Naltrexone is generally well tolerated. A number of studies indicate that non-specific and systemic symptoms, including headache, back-pain, flu-like symptoms, nausea and anorexia, have been more commonly reported by patients receiving naltrexone than those receiving placebo. However, there are also reports that side effects are no more common in patients taking naltrexone than in those taking placebo. Drug interactions: Naltrexone blocks the action of opioid analgesics, which can be problematic in clinical practice. Contraindications: Naltrexone is contraindicated in patients receiving long-term opioid therapy for chronic pain or heroin dependence. 2: NHMRC level-of-evidence codes Evidence for the statements made in this article is graded according to the National Health and Medical Research Council system14 for assessing the level of evidence. E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E31 Level III-1: Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method). E32 Level III-2: Evidence obtained from comparative studies with concurrent controls and allocation not randomised, cohort studies, case–control studies, or interrupted time series with a parallel control group. E33 Level III-3: Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. E4 Level IV: Evidence obtained from case-series, either post-test, or pre-test and post-test. 3: Managing patients who drink hazardous or harmful quantities of alcohol 4: Advice for patients Alcohol dependence is a chronic, relapsing–remitting condition. Treatment is moderately effective and comparable with that for many other chronic medical conditions. Inducing remission is usually less difficult than preventing relapse. It may help to attend self-help groups such as Alcoholics Anonymous <http://www.alcoholicsanonymous.org.au/> or the less well established Rational Recovery <http://www.rationalrecovery.net/>, although these interventions are difficult to evaluate and do not appeal to all. Self-help groups are also available for family members and children <http://www.al-anon.alateen.org/meetings/international.html>. As the risk of relapse is high, it is important to try to identify high risk factors and then to develop strategies to avoid these. Relapse should be dealt with by undergoing detoxification when required. It is helpful to attend follow-up with a doctor with whom you can establish a strong therapeutic relationship. Telephone counselling services are available 24 hours a day, seven days a week: Alcohol and drug telephone help-lines in Australia ACT: "Alcohol & Drug Programs" (02) 6205 4545 NSW: "Alcohol and Drug Information Service (ADIS)" 9361 8000 in Sydney, 1800 422 599 elsewhere in the State NT: "Alcohol & other Drug Service" (08) 8922 8399; Central Australia (08) 8951 7580 QLD: "ADIS" (07) 3236 2414; 1800 177 833 SA: "ADIS" (08) 8274 3333; 1300 13 13 40 TAS: "ADIS" 1800 811 994 (from interstate call 03 9416 1818) VIC: "Directline" (03) 9416 1818; 1800 136 385 WA: "ADIS" (08) 9442 5000; 1800 198 024

Robert Graham MB BS · Alex D Wodak FRACP · Greg Whelan FRACP

"Hey doc, whaddaya reckon? Is this sore infected? Do I need antibiotics? Mind if I walk with you?" So starts my clinical day as I walk from my parked car and potential patients fall in for street therapy. An informal consultation frequently ensues. Street drug users are in a hurry. Appointments and time management have no place in their chaotic lives. Setting aside time to see a doctor is well down the list of priorities. Most are in an endless rotating door — scamming at least a hundred dollars a day for heroin is the main game. Informal street consults are the way I dispense medical advice to this marginalised group. Most have no GP and have never sat in a waiting room; nor are they likely to. Time is precious as they push the limits of endurance to survive on the streets. Tolerating this exotic clinical behaviour has given me access to an unusual underclass of patients who rarely see doctors at all. I treat drug dependence within general practice in Kings Cross in Sydney. It is a magnet to drug users and is the epicentre of street drug culture in Australia — users flock here from all over the country. But first let me tell you what it is that makes the Cross different from anywhere else in Australia. Demographically, Kings Cross is a village perched on a hill between Rushcutters Bay and Woolloomooloo with the highest population density in Australia. Few of its denizens travel by car, and so the streets are always full of people at all hours of the day and night. From its halcyon days as a place where actors, artists and writers lived to now, when drug users rub shoulders with yuppie designers, journalists and movie makers, the Cross has seen more than its share of eccentric and odd behaviour, holding, as it does, an edgy juxtaposition of the marginalised with the mainstream. If nothing else, the Cross and its habitués are tolerant of extreme diversity. My practice is unique in that around half of my patients are injecting drug users. By the time they make it into treatment, a large proportion have depleted their finances and their health. Wasted, demoralised, often with criminal charges for break-and-enter or stealing hovering over their heads and the prospect of a jail sentence awaiting them, they attend my rooms. Their recent history is littered with failed attempts at home detoxification or geographical relocation to beat the heroin habit. Desperate family members will drag them in, trying to coerce them into treatment. This is rarely successful. Untreated serious infections are commonplace. Hepatitis C, chronic airways limitation, psychiatric comorbidity and serious injuries complicate their initial presentation. For them, I facilitate treatment with pharmacotherapies like methadone, buprenorphine and naltrexone. These treatments fit well into a primary care setting, allowing users a window of sobriety, a chance to "chill out" and reassess their lives. However, none of these treatments is a panacea. Many will start treatment only to fall out and resume again at another time. Others manage to stick it out, putting up with the rigour of attending treatment centres to requalify as functioning members of society. There is a clear correlation between staying in treatment and improved outcomes in this population. But, for me, the most important thing is to establish a therapeutic alliance with these once-feral individuals — no matter how tenuous this may appear — and slowly, over time, to observe the re-integration of personality and lost talent. For many have rare gifts and capacities that have fallen into disuse over years of addiction. This process is among the most gratifying experiences in medicine that I can think of. A psychiatrist once told me that treating addiction was the most difficult area of medicine to work in. I should adjust my expectations down from what I had been used to. In treating drug dependence, "there is no such thing as failure, just varying degrees of success", he said. This adage has stuck with me over the years. It really means that any engagement with a drug user is a success of sorts, and that to keep them in treatment, even for a few weeks, may give them that glimmer of hope to revisit treatment options in the future. In the past year I have had referrals from the nearby Medically Supervised Injection Centre. Some of these clients had never considered treatment as an option, but have had some gentle counselling in the "chill out room" after they have used their drug of choice. If they have experienced overdoses, there is some urgency in commencing treatment and I try to minimise the bureaucracy involved in providing them with a substitution treatment. My guess is that my street consultations while I walk to coffee, lunch or back to my car in the evening will continue. Sometimes I will examine an abscess under a street light, listen to a wheeze on Darlinghurst Road and maybe get asked if I want to buy some marijuana by the 15-year-old kids who sell the stuff on the streets every night. "Sorry doc, I didn't recognise you for a moment."

Raymond C Seidler MB BS

Objectives: To determine whether naltrexone is beneficial in the treatment of alcohol dependence in the absence of obligatory pyschosocial intervention.Design: Multicentre, randomised, double-blind, placebo-controlled trial.Setting: Hospital-based drug and alcohol clinics, 18 March 1998 – 22 October 1999.Patients: 107 patients (mean age, 45 years) fulfilling Diagnostic and statistical manual of mental disorders (4th edition) criteria for alcohol dependence.Interventions: Patients with alcohol dependence were randomly allocated to naltrexone (50 mg/day) or placebo for 12 weeks. They were medically assessed, reviewed and advised by one physician, and encouraged to strive for abstinence and attend counselling and/or Alcoholics Anonymous, but this was not obligatory.Main outcome measures: Relapse rate; time to first relapse; side effects.Results: On an intention-to-treat basis, the Kaplan–Meier survival curve showed a clear advantage in relapse rates for naltrexone over placebo (log-rank test, χ21 = 4.15; P = 0.042). This treatment effect was most marked in the first 6 weeks of the trial. The median time to relapse was 90 days for naltrexone, compared with 42 days for placebo. In absolute numbers, 19 of 56 patients (33.9%) taking naltrexone relapsed, compared with 27 of 51 patients (52.9%) taking placebo (P = 0.047). Naltrexone was well tolerated.Conclusions: Unlike previous studies, we have shown that naltrexone with adjunctive medical advice is effective in the treatment of alcohol dependence irrespective of whether it is accompanied by psychosocial interventions.

Noeline C Latt MB BS, MRCP, MPhil · Stephen Jurd MB BS, FRANZP · Jennie Houseman BPharm, MA(ClinDrugDepStud) · Sonia E Wutzke BSc(Psych)(Hons), MPH, PhD

The great majority of smokers are chronically dependent on tobacco. This dependence arises from the rituals and sensory associations of smoking that are reinforced, within seconds, by a rapid burst of nicotine from the cigarette. All forms of nicotine replacement therapy (NRT) — gum, patches and inhaler — and bupropion are safe and effective for increasing smoking cessation rates in the short and long terms. Other than those who are minimally dependent, all patients willing to quit should be offered one of these therapies unless contraindications exist. The effectiveness of drug treatments is multiplied when associated with effective counselling or behavioural treatments. While NRT is not recommended during pregnancy or in patients with cardiac disease, if the alternative is smoking NRT is almost certainly safe. Combination NRT (more than one therapy) may be indicated in patients who have failed monotherapy in association with withdrawal symptoms. There are some specific contraindications to the use of bupropion. Its subsidised availability should not influence prescribers to ignore these.

Matthew J Peters MD, FRACP · Lucy C Morgan BMed, FRACP

QuestionAre levo acetyl methadol (LAAM) and buprenorphine as effective as methadone for substitution treatment of opioid dependence? Trial details Design: Randomised controlled trial, double-blind. Setting: Outpatient clinic in Baltimore, United States. Participants: 220 people categorised as opioid dependent by DSM-IV;1 groups similar on demographics and drug use history. Exclusion criteria were medical and psychiatric illness requiring long-term medication, and pregnancy. Interventions: (i) Levo acetyl methadol (LAAM) at 75–115 mg, (ii) buprenorphine at 16–32 mg, (iii) methadone at 60–100 mg ("high dose"), or (iv) methadone at 20 mg ("low dose"). LAAM and buprenorphine were given three times a week, methadone daily. LAAM and methadone were given orally, buprenorphine sublingually. Participants attended the clinic daily for two weeks of dose induction, then thrice weekly with take-home doses. The scheduled duration of the trial was 17 weeks. Main outcome measures: Retention in treatment; illicit drug use; participants' global ratings of their drug problem. Main results: Days retained in the study (mean ± SE) — LAAM (i), 89 ± 6; buprenorphine (ii), 96 ± 4; "high dose" methadone (iii), 105 ± 4; "low dose" methadone (iv) 70 ± 4. Significantly more days retained for groups (i), (ii) and (iii) compared with group (iv) (P < 0.001), and group (iii) compared with group (i) (P = 0.02). Trial was completed by 53% of group (i), 58% of group (ii), 73% of group (iii), and 20% of group (iv), with 4, 3, 6 and 26 of groups (i), (ii), (iii) and (iv), respectively, transferred to rescue treatment (standard methadone maintenance). Twelve or more consecutive opioid-negative urine specimens were obtained in 36% of group (i), 26% of group (ii), 28% of group (iii) and 8% of group (iv) (P < 0.005). Conclusion: Compared with low-dose methadone, LAAM, buprenorphine and high-dose methadone substantially reduce the use of illicit opioids. CommentaryRationale for the trialSubstitution treatment with methadone has proven effective in reducing heroin use and providing an opportunity for improvement in health and social functioning for dependent drug users.2 However, methadone maintenance does not suit all people. LAAM, a full opioid agonist, and buprenorphine, a partial agonist, are promising alternatives to methadone maintenance. Buprenorphine has a lower risk of overdose than methadone, and both buprenorphine and LAAM can be given less frequently than daily, providing increased flexibility and reduced costs. Previous research supports the feasibility of substitution treatment with LAAM and buprenorphine, and each of these drugs has been compared with methadone in controlled studies.2 The rationale for this trial by Johnson and colleagues was to compare LAAM and buprenorphine with standard ("high dose") methadone maintenance and a control in a single study. Methadone at 20 mg daily was chosen as the control because it has the capacity to suppress opioid withdrawal, but is only minimally effective as a maintenance treatment. For ethical reasons, a rescue treatment was available for all study participants who responded poorly to experimental treatment. Trial methodsParticipants were stratified, then allocated by random number generation, with participants and clinic staff unaware of group assignments and doses. Each day participants received three solutions (two oral, one sublingual), only one of which contained active medication. Otherwise all groups received equivalent treatment. It seems likely that participants in the "low dose" methadone group might have been able to guess their group allocation, but the adequacy of blinding was not discussed by the authors. There were clear definitions for transfer to rescue treatment, drop-out, and calculation of retention in treatment, and adjustments for missing data. All analyses were based on intention to treat. New informationLAAM and buprenorphine are significantly more effective than "low dose" methadone in reducing illicit opioid use, and of similar effectiveness to "high dose" methadone. Illicit opioid use was somewhat lower for the LAAM group — the use of larger group sizes might have provided sufficient statistical power for a significant difference to be detected. Participants in the "high dose" methadone group were retained in treatment for more days, although the difference achieved statistical significance only for "high dose" methadone compared with LAAM. Most of the difference between "high dose" methadone and LAAM occurred in the first two weeks of treatment. Implications for clinical practiceAs most doses are supervised by a pharmacist, the possibility of less than daily dosing is a practical benefit of LAAM and buprenorphine. This trial shows that thrice-weekly dosing with these medications reduces illicit opioid use to a similar extent to that achieved with standard methadone maintenance treatment, and indicates that both buprenorphine and LAAM are more effective than "low dose" methadone. The lower retention rates associated with LAAM make it necessary to have available an alternative therapy for people who do not respond, and to give particular attention to patients during induction. More participants in the LAAM group were withdrawn because of side effects, but the details of these side effects were not reported, and this needs to be explored further. This report did not describe changes in participants' health and social functioning, which are important in considering the overall effectiveness of treatments for opioid dependence. Buprenorphine is available in Australia, but LAAM is available only under clinical trial arrangements.

Linda R Gowing PhD · Robert L Ali MB BS, DipRACOG, GDPH, FAFPHM · Jason M White PhD

Clinical question"Is subcutaneous (SC) or intramuscular (IM) naloxone as effective as intravenous (IV) naloxone in the treatment of life-threatening heroin overdose?" An emergency department clinician was interested in comparing routes of administration of naloxone in light of anecdotal evidence suggesting that various routes may not be equally efficacious in restoring a patient to spontaneous breathing and consciousness. Search questionPatients presenting to an emergency department for the management of a heroin overdose were the focus of the search strategy. The search question was "How long does it take for patients to return to consciousness after administration of naloxone by various routes?". In order to answer this question, a randomised controlled trial comparing the effects of SC or IM versus IV naloxone would be the ideal study design. SearchThe search terms "heroin", "opioid overdose", "naloxone" and "route of administration" were combined to identify relevant English-language articles published between 1966 and June 2000. Databases and websites searched included the Cochrane Library, Best Evidence, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Smart Search and Bandolier. Studies other than those set in the emergency department (ie, those conducted in hospital wards or post-anaesthetic care units) were excluded, as the clinician had specified that we limit the search to pre-hospital or emergency department settings. The search yielded only one study that compared SC with IV naloxone for treating opioid overdose in this setting. No studies were found comparing the use of IM with IV naloxone. Summary of findingsIn a comparative study using historical controls, Wagner et al1 compared naloxone administered intravenously or subcutaneously to patients in the community with suspected opioid overdose. The two intervention arms were 0.4 mg IV naloxone and 0.8 mg SC naloxone. The study was conducted sequentially in two phases: the IV phase, from 1 June to 30 June 1996, and the SC phase, from 1 July to 1 September 1996. Ambulance attendants in a regional district of British Columbia, Canada, administered naloxone to people meeting the British Columbia Ambulance Services' criteria for suspected overdose (ie, reduced consciousness, history suggestive of opioid use, and respiratory rate of less than 10 breaths per minute). The protocol also included a second dose of SC or IV naloxone if the first dose was not observed to be physiologically effective. The primary outcomes of interest included the time interval from arrival at the patient's side until the respiratory rate rose above 10 breaths per minute, the time interval from arrival at patient's side to naloxone administration, and the duration of bag–valve–mask ventilation. Overall, there was no significant difference between the two modes of naloxone administration with regard to the time interval between arrival at the patient's side and attainment of a respiratory rate greater than 10 breaths per minute (9.3 ± 4.2 minutes [IV] v 9.6 ± 4.6 min [SC]; P = 0.67). There was also no significant difference in duration of respiratory bag–valve–mask ventilation between administration arms (8.1 ± 6.0 minutes [IV] v 9.1 ± 4.8 minutes [SC]; P = 0.20; 95% CI of difference, –2.53 to 0.53). OutcomeWe submitted the report to the emergency physician, stating that the single study in a community setting demonstrated that IV and SC naloxone administration appeared to be equally effective in returning patients suffering from opioid overdose to spontaneous breathing. However, we advised the physician that the study was subject to a number of biases, including the utilisation of historical controls, a lack of clear randomisation, and the recruitment of fewer patients (74) than the 92 required to achieve 90% power. The physician used the information from our report to change the emergency department's policy — the use of IV naloxone was eliminated to reduce the risk of needle-stick injury to staff.

Jason Wasiak MPH · Ornella Clavisi BSc(Hons) MPH

Case reports Case 1: A 22-year-old man complained that he was "burning up" and collapsed after ingesting drugs at a friend's house. He died soon afterwards at a local hospital, despite attempts at resuscitation. His core temperature was 42oC. At autopsy there was evidence of coagulopathy, with scattered bruises, intra-alveolar haemorrhage, and haemorrhagic pleural effusions, ascites and stomach contents. Toxicological blood analysis revealed a lethal level of PMA (1.3 mg/L), together with 0.02 mg/L of MDMA and 0.21 mg/L of methylamphetamine. No alcohol was detected in the blood. Case 2: An 18-year-old man died at his home after ingesting a number of "ecstasy" tablets over five hours, both at a dance club and at home. Two hours after death the core temperature of the body was 39oC. Autopsy revealed focal pericardial haemorrhage, pulmonary congestion and renal tubular necrosis. Toxicological blood analysis showed a lethal level of PMA (1.7 mg/L), with 0.1 mg/L of MDMA and 0.06 mg/L of methylamphetamine. No alcohol was detected in the blood. Case 3: A 19-year-old man died in hospital 40 hours after being brought to the emergency department in respiratory arrest with a body core temperature of 41.6°C. He had taken "two or three capsules" of street drugs of an uncertain nature, both at a "rave" party and then at a friend's home the following day. According to witnesses, he had been advised to take PMA for an enhanced effect after taking MDMA. Laboratory investigations revealed evidence of rhabdomyolysis, with a serum myoglobin level of 328 960 g/L (normal level, < 150 g/L), disseminated intravascular coagulation and marked hyperkalaemia (7.7 mmol/L; normal range, 3.5–5.0 mmol/L). At autopsy there was evidence of coagulopathy, with epicardial petechiae, pulmonary haemorrhage, haemorrhagic gastric and intestinal contents, and haemorrhagic serous cavity effusions. There was also oedema and necrosis of skeletal muscle and renal tubular necrosis. Toxicological blood analysis revealed a lethal level of PMA (0.98 mg/L), with 0.32 mg/L of MDMA. No alcohol was detected in the blood. Analysis of capsules found with the patient revealed PMA with no other amphetamine derivatives. Death from amphetamine use is a well recognised occurrence, with most reported fatalities involving the use of 3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy"). In 1998, a series of six cases of death due to an unusual amphetamine drug, paramethoxyamphetamine (PMA), was reported in South Australia.1 The only other comparable report of deaths due to PMA was that of nine deaths in Ontario, Canada, in the early 1970s.2 In 1998, our group warned that, although PMA substitution for MDMA appeared at the time to be a local Australian problem, there was a possibility that the manufacture and sale of PMA could occur in other countries. Unfortunately, this prediction has been proved accurate, with recent reports of PMA-related deaths in the United States, Europe and Canada.3-5 Initially, it was assumed that PMA was created as a contaminant during the synthesis of MDMA and was being disguised and substituted for MDMA by local dealers attempting to offload the drug.1,6,7 However, this is now considered unlikely, as the chemical precursors of PMA and MDMA are different,3,4 and information received concerning Case 3 (described here) suggests that capsules containing only PMA are being marketed specifically to augment the effects of MDMA. This is an extremely dangerous development, as it is well recognised that PMA has a much greater propensity to produce adverse effects than other ring-derivative amphetamines.6 Death in each of the cases described here was due to PMA toxicity with hyperthermia. PMA levels of higher than 0.3 mg/L and MDMA levels higher than 0.6 mg/L have been found in cases where deaths were attributed to these drugs.1

Roger W Byard MD · Nicholas G Rodgers MB BS · Ross A James FRCPA · Chris Kostakis BSc(Hons) · Andrew M Camilleri BSc(Hons)

To the Editor: Hall et al1 argue that a hydromorphone trial would break the current deadlock in Australia over prescription heroin research. But would it? If hydromorphone was demonstrated to be an effective intervention for treating refractory heroin users, researchers would then wish to compare both hydromorphone and prescription heroin against the gold standard, oral methadone. The Prime Minister has stated publicly that proceeding with a prescription heroin trial "would send a wrong message". This claim is still unsupported by evidence. Clinicians and researchers should steadfastly oppose political interference in medical research from however august a level, especially when there is such a strong rationale for the trial and when researchers have so scrupulously followed scientific process. Such interference would not be tolerated in other areas of medical research and should not be tolerated in this field. The results of a recent large randomised controlled trial2 of prescription heroin in the Netherlands, while yet to be published in a peer-reviewed journal, provide strong additional support for an Australian trial. In contrast, Hall et al1 cite no previous evaluation of the efficacy of hydromorphone in managing heroin dependence. In Switzerland, prescription heroin is reserved strictly for treating refractory patients and accounts for fewer than 5% of all treatment provided.3 The importance of attracting and retaining this group in treatment is probably far greater than their small numbers might suggest, as there is reason to believe that they contribute disproportionately to the immense social costs of heroin use in the community. (By analogy, the heaviest-drinking 10% in a community account for half the total alcohol consumed.) Those who inject heroin very much more frequently than the community mean are probably responsible for a disproportionate share of crime and enlisting new recruits. Prescription heroin was selected as the experimental intervention in studies in Switzerland, the Netherlands, Germany and Spain and is now being considered seriously in Canada. The reasons advanced by Hall et al1 are all cogent arguments for conducting a trial of hydromorphone additional to an evaluation of prescription heroin. Hall et al are concerned about lack of community support for a heroin trial in Australia, but in a recent national opinion poll4 45% of respondents expressed support, while 47% were opposed. The case for an Australian heroin trial, with or without additional trials, remains compelling.

Alex D Wodak FRACP · Alison J Ritter PhD · Charles RR Watson PhD

In reply: We disagree with Wodak and colleagues in a number of respects. If the results of a hydromorphone trial were as good as Wodak et al claim a heroin trial would be, then a heroin trial would be unnecessary. We accept, as did the Dutch and Swiss, that politicians have the authority to make decisions about what medical research is permitted. The heroin trials in Switzerland and the Netherlands were approved by parliament and supported by referenda in cantons and cities in Switzerland. The Australian survey data cited by Wodak and colleagues indicate that a heroin trial would not have been approved if a referendum had been held in 2001. Nor do we think it would be supported by a free vote in Federal Parliament, as it was not supported by a similar vote at the NSW Drug Summit in 1999. Wodak et al present no evidence to support their claim that the delivery of a treatment that costs between A$25 000 and A$45 000 per patient per year in the Netherlands1 to less than 5% of the heroin-dependent population would have a detectable impact at the population level. A hydromorphone trial would provide a way of evaluating the role of injectable opioids in the treatment of heroin dependence. It would not prevent Wodak and colleagues from convincing the community that injectable heroin is the drug of choice to treat refractory heroin dependence.

Wayne D Hall PhD · Richard P Mattick PhD · Jo Kimber BSc (Hons)

A 29-year-old unemployed man presented with pain and swelling of the right hand. He reported two occasions of intravenous drug use during the previous three days: a single heroin dose, followed by temazepam (4 × 10 mg gel capsules, dissolved in hot water). He was right-handed. On both occasions he injected into a superficial blood vessel on the back of the right hand. On presentation, the clinical diagnosis was inadvertent intra-arterial injection of temazepam, with vascular endothelial damage secondary to macrogols (used to increase viscosity in gel capsule manufacture). The patient's condition was managed with elevation of the forearm, aspirin, heparin anticoagulation, empirical parenteral antibiotics and analgesia. Over three days the patient showed substantial improvement, allowing discharge with follow-up in one week. Four days later, he returned with increasing pain. He denied further intravenous drug use. He had normal arterial pulses, but the distal fingers were cool. Fingertip sensation and capillary refilling were diminished. To improve perfusion and limit further thrombus development, an alprostadil infusion and oral nifedipine were introduced. Over 10 days, necrotic areas, involving index, middle and little fingers, developed and required amputation. The picture shows the patient's hand after surgical debridement and amputation of necrotic areas, three weeks after injection of temazepam.*

Gerald FX Feeney MB BCh BAO FRACP · Harry H Gibbs MB BS FRACP

To the Editor: Australia has been successful so far in maintaining a low prevalence of HIV infection among injecting drug users (IDUs). This has been achieved by adopting a harm-reduction approach to the prevention of bloodborne virus transmission, including needle and syringe programs, methadone maintenance and peer-education. Sharing of needles and syringes has declined markedly: cross-sectional surveys among users of needle and syringe programs across Australia have shown a decrease in the prevalence of reported sharing from 31% in 1995 to 15% in 1997.1 However, there is evidence that among some subpopulations, especially those of Indo-Chinese origin, unsafe injecting practices remain common. In a survey of Indo-Chinese IDUs in Sydney and Melbourne, Maher et al reported that 22% of those surveyed had shared needles and syringes in the preceding month.1 Although the Indo-Chinese community is becoming increasingly aware of issues related to drug use, IDUs are under-represented in drug treatment programs.3 There is also evidence that parents send their children back to their country of origin to escape the Australian heroin scene. In a Melbourne survey of Vietnamese IDUs, Kelsall et al reported that 19% of their sample (38 of 200) had returned to Vietnam during the previous five years for drug-related reasons. Of these, 24 reported using heroin in Vietnam, a disturbing finding given that HIV prevalence among IDUs in parts of Vietnam is greater than 50%.4 We analysed HIV surveillance data in Victoria to investigate whether there was an over-representation of Indo-Chinese-born IDUs. Country of birth has been collected as part of HIV notification in Victoria since January 1996. Since then, there have been 38 notifications of HIV infection in individuals reporting intravenous drug use as a risk factor. Of these 38, 11 (29%; 95% CI, 15%–46%) reported an Indo-Chinese country of birth — a higher proportion than expected given the 1996 census finding that 1.5% of Victoria's population was born in an Indo-Chinese country.5 These 11, all men, were significantly younger than other IDUs notified in this time (mean, 23.3 years v 31.3 years, respectively; P < 0.05). Although these numbers are small, they highlight a group at increased risk of HIV who are not currently being effectively reached by prevention services. These data also suggest a hidden route for spread of HIV from Asia into the Australian community. There is an urgent need to provide culturally relevant education and harm-reduction programs to prevent transmission of HIV within this group. The Victorian Department of Human Services is allocating additional resources to working with culturally and linguistically diverse communities on prevention activities to address this issue.

Jane S Hocking · Peter G Higgs · Cathy M Keenan · Nick Crofts

Injectable heroin maintenance has been advocated as a form of treatment for opioid dependence that would attract, and retain in treatment, addicts who have either not sought treatment or who have failed at other forms of treatment, including methadone maintenance. Advocates of heroin maintenance argue that it would increase the proportion of addicts in treatment and reduce heroin use, drug-related crime, and deaths due to overdose.1 A 1991 proposal by a Select Committee on HIV, Illegal Drugs and Prostitution of the ACT Legislative Assembly led to a feasibility study for a heroin trial in the ACT.1 In 1997, the Ministerial Council on Drug Strategy voted in favour of a heroin trial, but the trial did not proceed, as the Federal Government would not amend legislation to allow heroin to be imported for the trial or allocate funds to monitor the use of heroin in accordance with international treaties.2 Dramatic rises in deaths caused by opioid overdose in the late 1990s prompted more calls for a heroin trial.3 The Federal Government refused to countenance a trial, creating a policy deadlock that prevented the evaluation of what proponents2 claimed was a potentially valuable policy option. If we can avoid the fixation on a trial of heroin per se, there is a way out of this policy deadlock. The alternative option we are proposing is to trial hydromorphone (Dilaudid), an injectable opioid that has similar effects to heroin.4,5 Even if the Federal Government's attitude towards a heroin trial were to change, we believe that trialling hydromorphone would be a better option than trialling heroin, for a number of reasons: The subjective effects of hydromorphone are very similar to heroin in experienced heroin users and both have short durations of action.5 Hydromorphone is a registered drug (Schedule 8) in Australia, so it can be prescribed for medical purposes and used in clinical trials. There would be no need to change federal legislation to allow a trial of injectable hydromorphone. Nor would there be any need for oversight of heroin importation and distribution by the International Narcotics Control Board. The use of hydromorphone can be distinguished from the use of heroin by urinalysis,6 thus allowing detection of any covert use of street heroin by trial participants. (A major criticism of the Swiss heroin trials was that this could not be done.)4 Hydromorphone lacks the political symbolism of heroin.5 This would allow a clinical trial to be conducted in the absence of the media sensationalism that would probably attend a trial of heroin maintenance. A protocol for a clinical trial of hydromorphone could be assessed by peer review and funded by the National Health and Medical Research Council. (On the other hand, a trial of hydromorphone might have the disadvantage of discouraging participation of dependent heroin users who only want heroin. Assessing the attractiveness of hydromorphone to the patient population would therefore be an important part of a feasibility study for a clinical trial.) A trial of hydromorphone may reduce the need to inflate the public health benefits of heroin maintenance in order to enlist community support for a heroin trial. Allowing the prescribing of injectable opioids, whether heroin or hydromorphone, would be unlikely to substantially reduce the heroin black market or heroin-related crime. The cost of providing this form of treatment, and the restrictions that the community would probably impose on eligibility for it, mean that too few heroin-dependent people would receive this form of treatment to have a substantial effect on heroin use and its consequences in the population.7 Injectable opioid maintenance would most likely be a treatment option reserved for dependent heroin users who have failed at existing forms of treatment (the model that was trialled in Switzerland).8 Any trial of hydromorphone maintenance for opioid dependence should include an economic evaluation of the comparative costs and benefits of competing forms of maintenance treatment. These could include alternative forms of injectable opioid maintenance using longer-acting agonists such as methadone and partial agonists such as buprenorphine. Oral methadone maintenance should be the comparison condition, as in a recent trial of heroin maintenance.9 For these reasons, we believe a controlled clinical trial of injectable hydromorphone maintenance would break the impasse over a heroin trial and enable the Australian community to decide what role injectable opioid maintenance has to play in the public health response to dependent opioid use.

Wayne D Hall PhD · Jo Kimber BSc (Hons) · Richard P Mattick PhD