6 December 2008

APSAD Annual Scientific Conference 2008 [part I]

APSAD Annual Scientific Conference 2008

Australasian Professional Society on Alcohol and other Drugs.

November 23 - 26, 2008 Part I (Sunday 23 Nov).

Dear Colleagues,

This year's APSAD conference was a fine affair. I must have been to 15 or more of these in most State capitals, Cairns and Canberra. I missed last year’s Fest in Auckland but those who attended said it was excellent. Like national leaders’ meetings with their funny hats, shirts and coats, each APSAD conference is characterised by its own conference attaché bag. This natural-inspired over-the-shoulder model was one of the few I could imagine using in the future.

The venue was splendid, Darling Harbour being just an 8 minutes (downhill) walk from Town Hall station which made me into a commuter again. With medical practice responsibilities I was a part-time conference goer. Thus these notes are incomplete and (as usual) opinionated.

The Sunday afternoon pre-conference session had been booked by the only drug company with a major stake in our field. Reckitt-Benckiser is manufacturer of buprenorphine which is the only registered alternative to methadone, the latter being a generic drug with small bread-and-butter profit lines in comparison. The sponsors began with the topics of pharmaceutical abuse and innovations in addiction management, then ending with two presentations on the potential cardiac complications of methadone before a panel discussion to which I had been invited (and generously funded).

Adrian Dunlop spoke eloquently about the past, present and future of addiction treatments.

Dr Eric Strain covered some historical details of non-medical use of pharmaceuticals in the US, giving some results on prevalence and consequences from household surveys over 25 years. Apparently most users obtained their supplies from one doctor; many from friends or relatives with less only ~1% or less from the internet. Australian figures may be quite different as people are entitled to attend more than one doctor on Medicare. Another speaker quipped that if Australia had a Bill of Rights, it would include being able to attend “as many doctors as you like”. Dr Strain touched on the gap between occasional use and dependent use, something some of us may still forget because of the selected referrals we receive. The other major differences between American street heroin users and those abusing pain killers is that the latter are more likely to be employed, white race and non-injectors. Dr Strain was too modest to mention his own research on buprenorphine abuse and perhaps too polite to mention the reported non-medical use of buprenorphine, including a naloxone combination product which became the drug of choice (mostly injected) by more than half those presenting for treatment in Wellington, New Zealand (see Robinson 1993).

Dr Nick Lintzeris gave some pointers about pharmaceutical abuse in Australia. His talk ending with a plea to put methadone treatment, including side effects, into context both globally, as well as for individual patients. In his rather frequent exposure during the conference, he reminded us that there are much more relevant issues for opioid therapy as patients get older such as testosterone levels, calcium leaching, osteoporosis, dental, viral and bowel problems.

Jason White detailed the rather sparse literature on cardiac complications in methadone recipients. He seemed persuaded that the connection between methadone and torsade is significant and that methadone treatment could be restricted or further regulated as a result. As a demonstration of patients on ‘normal’ methadone treatment coming to torsade, he cited Pearson and Woosley’s report of 59 FDA notifications from 1969 to 2002. While not fully documented, from the limited data 12 could have been on ‘standard’ MMT, 8 of whom were over 40 years of age. This leaves just 4 reported ‘standard’ MMT cases in the USA over a 33 year period in the age group we normally start on MMT. Justo’s more recent literature review found only 6 of 40 cases reported could have been on ‘standard’ MMT cases without other triggering factors (85% had one or more of these known causes of QT prolongation aside from high methadone doses).

QT prolongation on the cardiograph has long been know to occur in about a quarter of methadone patients yet its only serious consequence, ‘torsade de pointes’ tachycardia, hardly ever seems to occur in young patients (<40>40 years of age, electrolyte disturbance, etc.

As our patient population on maintenance treatment gets older so we must be more vigilant about this and other eventualities. As with other related medical issues, close attention should be paid to cardiac status. This may include an ECG in those taking over 150mg, those prescribed other ‘at risk’ medications or those with HIV or personal/family history of unexplained syncope or fainting.

At this session I was delighted to finally learn the origin of the term ‘ether-a-go-go’ which is from the rhythmic dancing induced in the legs of doomed drosophila drones (flies) under the influence of ether in genetic experiments on channel blockers.

We were then shown a 15 minute video ‘interview’ with Colorado cardiologist Dr Mori Krantz detailing blow by blow the now supposedly conclusive case for methadone’s guilt beyond reasonable doubt in causing fatal arrhythmias. The final proof of any medical argument, we are told, involves randomisation of subjects and so the RCT by Wedam is proffered. This trial, a secondary analysis of ECG tracings obtained incidentally in a 1990s RCT, showed very high rates of QT prolongation in the first 4 months of MMT but no cases of torsade. One of the panellists said to me privately that this appears to be rather persuasive of the safety of methadone rather than the opposite.

As above, hardly anyone has ever seen a case except in patients who are already stressed and in highly complex medical circumstances. I note that since his classic description of 17 non-fatal cases in 2002 (8 were pain management cases), Krantz has only reported two other individual cases of torsade, one of which was attributed to cocaine.

In the video, we are told that because one cannot diagnose an electrical disturbance after death, coroners are unable to detect whether the death was due to cardiac arrhythmia or respiratory depression from the drug. In fact many cases are very clear at autopsy as having the classic findings of post mortem sub-acute lung changes and high blood levels as to leave little doubt about the cause of death. So while Krantz’s proposition may be true for a certain minority, with a 20% mortality, there ought to be 4 times as many (80%) torsade survivors. Yet few if any of these ever seem to get to an emergency room (or ambulance) and have their potentially fatal problem diagnosed with a simple cardiograph tracing. Such reports are exceedingly rare or non-existent. I called one of Australia’s busiest casualty departments to be told that their long-time medical director had never seen a case of methadone associated torsade. He also pointed out that for the past several years modern cardiograph machines have given an automated print-out of QTc, making this information much more available than previously. This just might be the single most important cause of the ‘epidemic’ of electrical changes in the absence of actual symptomatic disease.

Further on in the presentation Krantz states the obvious “it’s not to say that there is an epidemic of cardiac events in America”. Yet elsewhere he has written that a large number of patients are at risk of developing torsade. Fanoe’s Copenhagen syncope study was put up as a written question in the video ‘interview’ (there was no interviewer as such) but Krantz failed to comment on it for some reason. Fanoe showed that out of 800 cases (with no torsade reported) that high rates of syncope (over 20% in most dose groups) in methadone patients was at least in part explained by cardiac conduction problems such as torsade. This is hard to understand for a complication known to occur in less than 1% of patients. Krantz then alluded to Chugh’s Portland study suggesting that it lent support to his torsade theory, yet like so many of the other quoted references, this is another report which does not document any torsade cases at all.

Do I belabour the point? If this is a serial killing, Miss Marple, where are the bodies?
[more about lives saved in another conference posting shortly]

Comments by Andrew Byrne ..

Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)
Dependency Medicine,
75 Redfern Street, Redfern,
New South Wales, 2016, Australia
Email - ajbyrne@ozemail.com.au
Tel (61 - 2) 9319 5524 Fax 9318 0631
Surgery web page: http://www.redfernclinic.com/#news

Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence 1993 33;1:81-6

Strain EC, Stoller K, Walsh SL, Bigelow GE. Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent opioid abusers. Psychopharmacology (Berl) 2000 Mar;148(4):374-83

Justo D. Methadone-Induced Long QT Syndrome vs Methadone-Induced Torsades de Pointes. Arch Intern Med 2006 166:2288

Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial. Arch Intern Med 2007 167;22:2469-2473

Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. 2002 137:501-504

Krantz MJ, Rowan SB, Mehler PS. Cocaine-related torsade de pointes in a methadone maintenance patient. J Addict Dis. 2005;24(1):53-60

Krantz MJ, Garcia JA, Mehler PS. Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsade de pointes. Pharmacotherapy 2005 25:611-614

Fanoe S, Hvidt C, Ege P, Jensen GB. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart 2007;93;1051-1055

Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. American Journal of Medicine 2008 121: 66-71

5 December 2008

APSAD Annual Scientific Conference 2008 [part II]

APSAD Annual Scientific Conference 2008 [part II]
November 23 - 26, 2008

The plenary sessions on Tuesday were excellent, starting out with an American statistician, Rosalie Liccardo Pacula talking about the new generation RAND drug use modelling. This appears to be an enormously detailed, almost 4-dimensional system of looking longitudinally at multiple individual markers as well as societal/drug changes. Already they are able to predict drug trends with far fewer people than household surveys but there is still more work to be done to hone this new tool. Like all statistical models, it is only as good as the information fed into it. [http://www.apsad2008.com/abstract/300.asp]

Next we heard Prof Ross Homel giving a talk about complex family interventions, often involving three generations, with the emphasis on child safety, development and education. He gave numerous examples of what they are doing in a non-Government organisation associated with Mission Australia. There were vastly diverse interventions from group therapies, vocational referrals to literacy programs. Their main aim was to embed such programs into schools where there was a high proportion of disadvantaged children.

It was most appropriate that Prof Ann Roche gave the Rankin Oration this year. She did a broad overview of our field and her involvement in it looking back and then giving some views about the future using many clever and apposite quotes from Woody Allen, Elenor Roosevelt, the Dalai Lama and others. One memorable quote from the conference was a post-modern concept for the single woman to ask of any man she dates: �Is this really the man I want to look after my children on weekends?�

Greg Dore then revealed just what we all needed to know about hepatitis C. He dealt with the progress of the epidemic since it was first formally recognised in our communities around 1990. With no initial symptomatology in most patients, it is hard to determine the true incidence. However, by looking at the prevalence in young age groups one can determine changes from time to time. This would seem to indicate that although there are still many reported new cases each year, fewer of these appear to be true new infections as the prevalence in younger people is dropping more rapidly than in the overall population. [http://www.apsad2008.com/abstract/294.asp]

The range of treatments was detailed, pointing out the major improvements in recent years. We can now expect up to 80% �cure� rates (absent viral PCR at 6 months) in genotypes 2 and 3 with around 50% for genotypes 1 and 4. With several innovations such as closer viral load monitoring, liver "fibro-scans" and treatments for anti-viral side-effects, better results can be expected in the next few years. It is only by combining all of our resources, including GPs, addiction clinics, pharmacies and liver specialists that we will be able to address this epidemic which has a high proportion of patients on opioid therapies.

A talk was then given by Marina Davoli from Rome about the Cochrane Collaboration and internet library. Australia has had a special contribution to several areas and we have the only free access for internet users. Australian and New Zealand have also contributed much more serious research than other comparable western countries by population. This underlines all the evidence based interventions we use today.

I missed the session chaired by Dr Deborah Zador on opioid overdose but happily the conference abstracts are all available on the internet (see below). Dr Zador wrote some of the most important seminal studies on the subject in the 1990s. Two papers were given about naloxone, both its distribution amongst the drug using population and intriguingly by the intranasal route by paramedics in the overdose situation. The �Good Samaritan� provisions and international developments were detailed by Paul Dietze and Simon Lenton. [http://www.apsad2008.com/session/353.asp]

Bethany Butler reported some more results in an on-going study of several thousand NSW cases starting for the first time on methadone (~2500) or buprenorphine (~3500). There was no significant difference in the overall mortality in the groups (~65 subjects in each) but an excess mortality (~5-fold) in the methadone group in the first 2 weeks of treatment (7 versus 2). As well as direct toxicity, this might also be explained by methadone patients being in a higher risk group to start with. Even so, only a randomised trial can scientifically compare the two treatments and this is probably no longer ethical as most patients know which drug they want (see Pinto). It is certainly gratifying that when used in the normal course of practice that patients on each of these drugs have a marked drop in mortality. This study found those who remained in treatment were about three times less likely to die.

Next Louisa Degenhardt gave a paper on her group�s investigations of all deaths in NSW opioid maintenance cases since 1985, showing some differences over time. Overall 0.9% of subjects died each year of follow-up: 0.6% for those in treatment compared with 1.2% for those who had left. There was with a much higher chance of dying in the first two weeks of treatment when rate was 4.2%. This latter has dropped significantly since the early 1990s and does not apply at all to buprenorphine cases. The authors state that the treatments have the same mortality rates since those on buprenorphine have a lower retention rate, consistent with the comparative literature.

Finally, the session was given information about significant reductions in local ambulance attendances during the opening hours of the Sydney injecting centre (MSIC) as well as comparisons with the 2 years prior to its opening.

On the Wednesday morning we heard a plenary talk by Nicholas Lintzeris on the directions of treatment in the 21st century. He alluded to the shortage of doctors working in the field, the use of new medications requiring less supervision and models of treatment from elsewhere such as France. His subtext seemed to be individualising treatments rather than having rules and one-size-fits-all. He quoted the average age of methadone prescribers approaching the average daily dose! [Which is now about 75mg!] The speaker also did a study with Adam Winstock regarding attitudes towards withdrawal from treatment.

Next, those of us nursing a headache from the previous night�s dinner at L�Aqua Restaurant were given a fascinating talk by Sharon Walsh who is working in Kentucky on the effects of non-medical use of pharmaceuticals. She reminded us that in some areas there is now as much or more such abuse as for heroin. [This was also reported recently from inner Sydney in an ABC radio story which was nominated for a Walkley Award.] The emergence of prescription drug abuse may mean that we need to alter our approach and will increase the need for treatment services. Despite street and prescription drug use having essentially the same dependency diagnosis, these occur in quite different demographics (see Dr Strain�s talk from Sunday). The new RACP Policy on Prescription Opioids and Chronic Non-malignant Pain was introduced in another session, mapping out a plan for problematic use of prescription opioids in Australia and New Zealand [http://www.apsad2008.com/session/374.asp].

Dr Walsh reported on her results in human laboratory studies on oxycodone (Oxycontin; Prolodone), hydromorphone (Dilaudid) and hydrocodone. The latter is not available in Australia but is a constituent of Vicodin, a commonly abused drug in America. While hydromorphone is thought to be about 7 times stronger than morphine for its analgesic effects, in experiments on recreational users the differences between these three drugs were only marginal. [http://www.apsad2008.com/session/380.asp]

Despite running short of time, the next speaker Mark Tyndall spent some minute or two giving a hilarious description of the harm reduction aspects of pedestrians running red �WALK� signs. Next the hapless visiting Canadian described his shock at being taken to a surf beach where crashing waves buffeting swimmers who risked life and limb against the elements which were anything but �pacific� of late. His implication, I think, was that life savers are the equivalent of harm reduction services for drug users.

Returning to his subject, a square kilometre of western urban Canada, there were an estimated 6000 drug users, mostly injectors, of whom 25% had already contracted HIV and 90% hepatitis C. Services were and are grossly inadequate despite statistics which show disastrous rates of just aboot everything one would not want in one�s neighbourhood (crime, public injecting, overdose, deaths, hospital admissions, HIV cases, infections, etc). The Vancouver injecting centre is slightly larger in scale and opening hours, but shares all the essential characteristics of the Sydney injecting centre at Kings Cross (on which some say it was modelled). It has registered over 10,000 Canadian drug users (not all injectors as in Sydney). There are moves to close down this centre despite a wealth of public health research showing benefits to drug users and the community generally at modest cost (or even a net saving to the health system). Its closure would be a most pointed and poignant natural experiments in public health, comparable perhaps with the Broad Street pump exposure in London in the 1800s.

Next I attended a break-out session in which Carla Treloar spoke about the impressions people had about hepatitis C (http://www.apsad2008.com/session/388.asp). The myths were myriad. Defeatist misconceptions abounded. Some of her quotes were classics. Clearly our first job with hepatitis C is to inform people about the truth. Yes, the disease is still difficult and poorly understood. But we now have simple ways of determining the stage of the disease (�fibroscans�, risk criteria, etc) and we have reasonable and tolerable treatments with success rates up to 80%.

Nick Lintzeris reported some findings of an excellent intervention started some years ago in western Sydney in which OTP patients were offered a rapid vaccination program for hepatitis B. The results and a literature review showed that people at risk should probably be given a booster just about any time they are prepared to take one when it is available, even in quite short succession or as a booster down the line. Strict and appointment based regimens are perhaps not best suited to our patient group and so haphazard inoculations are probably more effective than no inoculations at all.

Some 9 cases of bacterial endocarditis in Newcastle area were reported next by Andrew Taylor. These formed a small minority of the total number of such cases in the region. Candida and staphylococcus aureus were common pathogens. The costs of such treatment to the health care system were high and the savings in prevention substantial.

The final segment of the conference for me at least was our own pet topic, hepatitis C outcomes. Carolyn Day, Paul Haber and colleagues reported on the barriers to addressing this public health priority (http://www.apsad2008.com/abstract/263.asp). From the low rates of assessment and treatment, even some prominent and well run clinics seem not to have effective strategies for testing and referring their patients. Some have no idea what proportion of their patients have been tested. Where resources allow, this can be pro-active, �on-site� and direct to hepatology services. Alternatively, referral to the individual patient�s GPs may be the best way to handle such matters in some situations. It is no longer acceptable to do nothing as advocated by some, claiming that �the treatment is worse than the disease�(!!). Some clinic practices seem so calcified that they have not even managed the change from methadone syrup (containing alcohol, caramel, sorbitol, gum, etc) to the safer �pink� methadone, despite majority patient support where the transfer was done some years ago (eg. NSW prisons; Rankin Court, Langton Centre, Clinic 36, Regent House, etc). At a recent health department forum at North Sydney some senior salaried clinicians described every barrier to improved treatment except themselves!

Next I moved to the session on intervention outcomes where Richard Hallinan reported our own 6 year experience prioritising hepatitis C assessments in OTP cases in Redfern (http://www.apsad2008.com/abstract/270.asp). We used some simple criteria devised by Greg Dore to indicate the likelihood of disease progression with liver fibrosis or cirrhosis. Some findings were given from 315 consecutive assessments with follow-up results for 30 cases having anti-viral treatment. Pegylated interferon alpha plus ribavirin were monitored in a shared care model with specialist hepatology services, with encouraging results thus far showing an overall 74% sustained viral response.

Comments by Andrew Byrne ..

Surgery web page: http://www.redfernclinic.com/#news

Opera blog: http://www.redfernclinic.com/opera/critique/blog/

New York in 2008: http://ajbtravels.blogspot.com/

New York diaries 1922: http://bpresent.com/harry/code/10b_bowery.php

Travel log: http://www.redfernclinic.com/c/2007/10/lord-howe-island-naturalists.php4

Vincent Dole in Nepal Diary: http://vincentdolehimalaya.blogspot.com/

Old photos of Sand Souci: http://sanssouciphotos.blogspot.com/

Pinto H, Rumball D, Maskrey V, Holland R. A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Journal of Substance Use 2008 13;2:73-82

�Current policy puts too much emphasis on protecting society from methadone, and not enough on protecting society from the epidemic of addiction, violence and infections that methadone can help reduce.�

Institute of Medicine 1995

Tiny tobacco "tea-bags" commonly used in USA, unregulated!


Dear Readers,

This contains some information which is quite interesting. In some American states there are currently significant numbers of tobacco �suckers� compared with traditional smokers (eg. West Virginia 16% vs. 27%). Apparently these products have not been formally approved yet they were never banned and thus are legal and marketable. We await some good research on their use but most believe that they are probably safer than smoking.

Comment by Andrew Byrne .. (see excerpt below). http://www.redfernclinic.com/#news

MORGANTOWN, W.Va. (AP) -- They're discreet, flavorful and come in cute tin boxes with names like ''frost'' and ''spice.'' And the folks who created Joe Camel are hoping Camel Snus will become a hit with tobacco lovers tired of being forced outside for a smoke.

But convincing health officials and smokers like Ethan Flint that they're worth a try may take some work.

Snus -- Swedish for tobacco, rhymes with ''noose'' -- is a tiny, tea bag-like pouch of steam-pasteurized, smokeless tobacco to tuck between the cheek and gum. Aromatic to the user and undetectable to anyone else, it promises a hit of nicotine without the messy spitting associated with chewing tobacco. Just swallow the juice.