These elephants aren’t causal, either

•September 29, 2014 • Leave a Comment

It’s been a while since I’ve fired up the blog, and longer since I did a journal club, but this article from BMJ has gotten right up my nose – partially because of the article, and partially because it’s been doing the rounds in the news media (and as an aside, include the link, you broekens).

I really think this article is being quoted for entirely the wrong reasons (although to noble ends) and – because I enjoy being devil’s advocate even to myself, I’m going to discuss why. What the article is, however, is an interesting application of Big Data – and a salutary lesson in the importance of antimicrobial stewardship.

We are well aware than antimicrobial resistance is increasing – in Australia as well as overseas. This study has very commonly been widely reported in the media as being due to rising resistance (generally using the term “SUPERBUGS!!”)

So lets look at it.

Methods

Antibiotic prescription data was collected from the Clinical Practice Research Datalink - data from 700 primary care practices, containing records from over 14,000,000 individuals.  Prescription data is collected from practice software.

Episodes of treatment with a single antibiotic were collected between 1991 and 2012, and linked with indications for prescription recorded in the database.  Four conditions were selected, to represent common presentations to general practice – they were:

  • Upper Respiratory Tract Infections (URTI)
  • Lower Respiratory Tract Infections (LRTI)
  • Skin and Soft Tissue Infections (SSTI)
  • Otitis Media (OM)

Prescribing data was then interrogated for “treatment failure” – which for the purposes of the study was defined as (my emphasis):

  • Prescription of a different antibiotic within 30 days
  • Admission to hospital with an infection-related diagnosis within 30 days
  • Presentation to the emergency department within 3 days of prescription
  • GP referral to an infection-related specialist within 30 days of prescription

(Anybody who has listed to me talk for more than 5 minutes on anything to do with antibiotics can probably see where I’m going with this).

Results

The results include some impressively bignums:

  • More than 4 million prescriptions for URTIs (38.6%)
  • More than 3 million for LRTIs (28.7%)
  • 2.5 million for SSTIs (23.4%)
  • 1 million for Otitis media (9.2%)

The headline figure is an antibiotic “failure” rate of 14.7% – by diagnosis:

  • 12% for URTIs
  • 16.9% for LRTIs
  • 12.8% for SSTIs
  • 12% for OM

And 94.4% of these “failures” were the result of a repeat prescription rather than a referral or ED presentation.

There’s also quite a bit of data of interest to people like me on which antibiotic was prescribed.

Interestingly, some of the media reports have focused on the finding that failure rates for second-line antibiotic prescription were higher than first line – more of that shortly.

Discussion

Antibiotic resistance has increased.  This we know, data tells us so.

1 / 7 (yes, by the way, media, 14.7% expressed as a fraction is closer to 1/7 than 1/10) general practice prescriptions resulted in a repeat prescription.

Superbugs cause GP prescriptions to fail, right?

Whoa, Nellie!

Correlation is not causation.

xkcd: Correlation. By Randall Monroe. CC-BY-NC

Interpreting antibiotic use data is quite challenging.  Part of this reason is because documentation is terrible – one of the benefits of this study at least is that the data seems to be quite robust in terms of diagnoses recorded.

The data I mainly work with in my hospital stewardship program is pharmacy dispensing data – the number of tablets (or ampoules) that leave the pharmacy shelves.  There isn’t any reference to what the antibiotics are actually being used for. This is why our clinical audits are such an important part of a good stewardship program.

This study at least looks at a restricted set of diagnosis groups, so we have some idea about the why as well as the how much.

What it doesn’t cover is the appropriateness of treatment. We know that around one quarter to half of prescriptions are not in keeping with best practice guidelines for the treatment of the condition being treated.  That’s not to say the treatment is ineffective – indeed, I rarely find any patients not receiving effective treatment, but just not the most optimum treatment.

That last sentence is actually correct – the number of times I see a treatment failure due to antibiotic resistance is small. (I can’t quantify this yet, ask me in five years).

So what else could cause it?

Obviously there are limitations to the data, so that a patient could represent with a different infection and receive a second course of antibiotics for a new issue and be  considered a failure from the point of the trial.

In this study, however, I can actually see two elephants in the room.

Need For Treatment

Of the diagnostic groups selected, there is quite good evidence that two-and-a-bit of them do not actually require antimicrobial treatment.

From Australia’s Therapeutic Guidelines: Antibiotic:

The benefits of antibiotic therapy in pharyngitis, tonsillitis, nonsuppurative otitis media and sinusitis are limited. Routine use of antibiotics in these conditions should be avoided, to limit potential adverse effects and to reduce selection of bacterial resistance, both in individuals and in the community.

(pharyngitis, tonsillitis and sinusitis are all in the umbrella group of URTIs, non-suppurative OM is the less severe – and more common – end of the otitis spectrum).

It continues:

If aiming to prevent… complications or to shorten the illness, antibiotics are not mandatory. Valuable symptomatic relief is provided by paracetamol or nonsteroidal anti-inflammatory drugs. Antibiotics shorten the illness when bacterial causes are likely, by less than one day, and slightly reduce the risk of acute otitis media as a complication (a Cochrane review suggested that nearly 200 people would require treatment to prevent one case of otitis media). Therefore antibiotics may be indicated by balancing these modest benefits against possible harms (eg rashes and other adverse effects, and bacterial resistance).

Further more, a large and well-designed randomised-controlled trial late in The Lancet Infectious Diseases in 2012 found that amoxicillin (the most common antibiotic prescribed in the BMJ trial) for LRTIs other than pneumonia (and certainly a more common LRTI diagnosis than pneumonia) was no more effective than placebo.

So.  If antibiotics are not generally indicated or have been shown to be ineffective to treat a goodly number of these conditions, why are we then surprised than antibiotics are failing to improve things?

Diagnostic Error

Antimicrobial guidelines are diagnosis-based – if you suspect this problem, use these antibiotics.  It is worth noting that second-line antibiotics in this paper were more likely to result in “failure” – suggesting that where it is possible to do so, prescribing according to guidelines is a good idea.

What it doesn’t cover is the case when the diagnosis is actually incorrect.  This can be simple – “I think your sore throat is probably bacterial” (note that as above, this doesn’t mandate antibiotic use anyway) or more complex.

I’ll use the Skin/Soft Tissue Infections as an example.

The most common SSTI I see as an infection doctor is cellulitis – bacterial infection of the skin / subcutaneous tissues. Usually caused by Group A Streptococcus or Staphylococcus aureus.

Cellulitis – from http://deadlymicrobes.com – believed to be fair use

There are however, other causes of red legs -

Commonly, we see changes of varicose eczema (also known as lipodematosclerosis)in people who have swollen legs due to heart disease:

Varicose eczema – from dxline.info – believed to be fair use

Clots in legs can also present similarly -

DVT – from WebMD – believed to be fair use

Or more simply, antibiotics could be given for a complication rather than the primary problem – and in the case of recurrent lower limb cellulitis, often we see that a patient will keep getting recurrent infections until the primary cause (usually tinea pedis) is treated.

Conclusion

I don’t have any firm figures for these speculations of mine.   But I’m not telling you that “1/10 prescriptions fail because of superbugs”.  What I am telling you is that a retrospective study of the represcription of antibiotics with a nebulous definition of failure, for a group of conditions that are generally self-limiting might not be the Superbugs are Destroying the World article it is being portrayed as.

What the article is, however, is a great pointer of why we need better antimicrobial stewardship – in the community as well as in hospital.

On Impossibility:

•March 8, 2014 • 2 Comments

An Open Letter – from the anonymous SMO to the Premier  of Queensland and the Minister for Health

These words are not mine – but the opinions in them are common to many of us.

[9-Mar 1700: One clinical example edited at request of the unknown SMO and a couple of rogue apostrophes removed]

 

Date: 7 March 2014 10:48:17 PM AEST
Subject: Nothing here is impossible Mr Springborg

Dear Minister Springborg and Premier Newman,

We have been told that your legislative changes are irreversible, and the train carrying these individual contracts has already pulled out of the station,
and cannot be stopped.

We sincerely hope that your talks with the SMO representatives around the concerning issues in the contracts result in a successful outcome for all.

If SMOs are not convinced that our ability to continue to practice public health medicine with safety is secured, then the state will be in grave danger of losing its’ brightest and best.

Please listen:    We say to you that nothing in your legislation, and the individual contracts, is irreversible. This train wreck can most certainly be stopped.

You are dealing with a group of people who understand what is truly irreversible and impossible, as they have stood in the face of death and tried to stare death down,
bargained against time with their knowledge, skills, equipment and courage, and sometimes failed, and often times not.

When you have to tell parents that their child has autism and intellectual impairment and that their lives will forever be filled with difficulty and challenge, and watch their grief unfold – that is irreversible.

When you watch a child bleed to death before your eyes as you pump blood in their arm only to see it pour out of the gaping hole in their skull, where it has been sheared off from a motor vehicle accident -
that is irreversible.

When you tell parents that their baby has cerebral palsy and will never walk or talk, or even eat independently, because their brain is malformed or damaged beyond repair   –  that is irreversible.

Nothing here with your individual contract legislation is impossible to change – we’ll tell you what is impossible.

When parents beg you to save a child’s life after a second failed bone marrow transplant for leukaemia, as you’re watching them die from an infection they have no white blood cells left to fight  –  that is impossible.

When you’re trying to bring back a heart beat in a child who has been pulled from the bottom of a pool, an hour after its heart beat stopped  –  that is impossible.

Don’t you dare sit there and tell us that this legislation is irreversible and that stopping this contract roll out is impossible.
Because we know that all it takes is a show of hands in a parliamentary room, and the swipe of a pen across a piece of paper.

No fancy machines, no million dollar drugs, no transplanted tissues, no 12 hour operations, and no miracles of fate.

Just understanding and good will from your colleagues and yourselves. And if you’re up all night to achieve that, then welcome to our lives.

We have each others’ backs, us medicos  –  we always have and always will.

Because we have all stood there with the sick and the dying, and we know how lonely that journey is without colleagues at our shoulders, and support and resources at our backs.

So we will stand together, even if we have to walk away, together  – until you listen, and pull on the brakes, and stop this train wreck from playing out to its end.

Please enter the discussions with good will, and open minds and hearts, and leave your egos on the coat rack outside.

The health of the state is in your hands – please don’t throw it away.

Sincerely,
Senior Medical Officers of Queensland Health.

PS To all of our colleagues – please don’t walk away or sign just yet – stand at our shoulders because we’ve got your backs.

PPS Please someone send this to every QLD SMO.

Dear Chemo

•December 1, 2013 • Leave a Comment

Originally posted on drkategranger:

Dear Chemo,

I thought I’d commit some of my thoughts about you to paper. I’ll warn you that this may make for uncomfortable reading at times and I may seem a little harsh.

There is no doubt that just under two years ago when we first encountered each other you managed to save my life. I completely get that and am deeply grateful to the doctors and nurses who helped to prescribe you and infuse you into my damaged body that was teetering on the edge of remaining alive. I had always been a little stand offish about entering into a relationship with you though. I had seen what you could do to my own patients back when I toyed with the idea of becoming a Haematologist.

The first time we came together I will never forget the nausea and vomiting you caused. It was horrendous. I didn’t eat for…

View original 480 more words

HIV, Stigma and teh Jernlisms (again)

•November 27, 2013 • 2 Comments

This Sunday is World AIDS Day.  The theme for our local campaign is “Zero”.

Zero new infections. Zero AIDS-related deaths. Zero discrimination.

The Queensland Government HIV strategy aligns nicely with these messages. The four priority areas are:

  1. Implement a comprehensive prevention campaign.
  2. Promote increased uptake of testing.
  3. Ensure 90% of positive patients are on treatment
  4. Increase community awareness and reduce stigma and discrimination

It’s point 4 that I’m going to talk about today.

You may have seen me retweet a couple of links yesterday on HIV in Greece.  I’ve included the photos below in case they get eaten by the internet.

ImageTweet posted by timmyconspiracy

There was also a screenshot of the primary report that this was based on – from WHO’s Review of Social Determinants of Health in the European Region. The relevant section is page 112 of the PDF at the other end of that link, which I’ve reproduced below (also from timmyconspiracy).

Image

Surely if the WHO put it in one of their technical reports, it must be the real deal, hey?  It was certainly taken as authoritative by several sources in the media.

The trouble is, it’s just not true. (Official WHO erratum here: thanks, Paul Davis for pointing out I forgot to link this)

You’ll notice the statistic about HIV infections in the WHO report isn’t specifically referenced.  Reading around this, it is variably attributed to a statement by the Greek Health Minister (can’t find any primary evidence of this) or based on an article (actually a letter) in The Lancet.  This letter says specifically:

“A significant increase in HIV infections occurred in late 2010…with half of the currently observed increases attributable to infections among IV drug users.

“An authority report described accounts of deliberate self-infection by a few individuals to obtain access to benefits of €700 per month and faster admission onto drug substitution programmes.”

That second sentence was referenced to the Report of the ad-hoc Expert Group of the Greek Focal Point on the Outbreak of HIV/AIDS in 2011. Its points were:

  • The increase in cases occurred without any change in harm reduction interventions
  • Increased law-enforcement crackdown on IVDUs resulted in less access of drug use support workers to the users
  • Increased needle-sharing and unsafe sexual practices
  • An important factor in these risk behaviours are the economic crisis

and finally:

“An additional factor the committee believed worth considering is the well founded suspicion[my emphasis] that some problem users are intentionally infected with HIV because of the benefit they are entitled to…and also because they are granted “exceptional admission” to the substitution programme.”

Further background is in the EMCDDA report on HIV/AIDS among IDUs in Greece:

I won’t block quote big sections of the report, but abstracting it for you, the issues identified were very similar

  • Most of the increase in cases were centered on Athens
  • Increase in prostitution by users unable to fund their habit in other ways due to the economic crisis
  • Opioid substitution clinics in Athens have a long waiting list so less IVDUs in Athens are on a program
  • Very limited coverage of needle/syringe programs in Greece compared to other countries in Europe.

So let’s be very clear on this.  Some Athenian drug dependency doctors put in a report they had a “well founded suspicion that some problem users” were self-infecting in 2011 and this managed to make its way into a WHO report as saying that “half of new infections in 2013″ were self-infected.

Obviously WHO dropped the ball with this one.  An authoritative scientific report on social determinants to make an outrageous claim without reference is really just not good enough.  But where was the critical journalism of this report?  The UKs Daily Mail managed to quote the original report with the suspicion quote, but still said “research said around half of new cases could be self-inflicted”.  Based on what?

My thoughts

Why is any of this important in Australia?  Adding the stigma of people deliberately infecting themselves onto the already significant challenges experienced by people who are down-and-out and turning to drugs and prostitution is hardly going to contribute to either better health outcomes or better community acceptance the people or their disease.

Secondly, there is the clear evidence that a policing and enforcement policy on IV drug use not only does not work, but also results in worse health outcomes. I have signed the Vienna Declaration – and I encourage all of you who believed in evidence-based policy to sign it as well.

This year’s Kirby Report found that 2% of newly diagnosed HIV infections were associated with IVDU. This figure is similar to previous years, and is only a small fraction of the figure for some overseas countries – up to 40% according to the most recent UNAIDS report. Maintaining tough on drugs does not work, and any cuts to NSPs or other (evidence-based) harm minimisation programs could potentially open the door to a more generalised HIV epidemic than we currently have.

And none of this helps people who are living with HIV get on with their life, free of discrimination.

My Week on RealScientists

•November 25, 2013 • Leave a Comment

ICYMI, I was tweeting for RealScientists last week.

Welcome blog post is here: http://realscientists.wordpress.com/2013/11/17/superbugs-stewardship-and-sci-fi-welcome-dr-trent-yarwood-to-realscientists/

Farewell post is here: http://realscientists.wordpress.com/2013/11/24/mutate-or-die-farewell-and-thanks-dr-trent-yarwood/

And the storified tweets of the week are here (part 1) and here (part 2).

RS is a great idea – if you’re a scientist (or clinician) I think it’s worth a turn around. Tweet the admins or email them here

.

Law of Unintended Consequences

•October 28, 2013 • Leave a Comment

You’ve probably all heard of the Law of Unintended Consequences.  It even has a page on Wikipedia. In short, it says that things that you do may have results that you did not intend.  Of course these can be unexpected windfalls as well as other, more unfortunate side-effects.  There is also limited benefit to saying “think about the consequences of your actions” because obviously – 1) people don’t and 2) there may well always be unforeseeable unintended consequences.

But there are a couple of pretty straight-forward examples where a very limited amount of thought would prevent quite a significant knock-on effect.  Of course, this knock-on may well create work for someone else, so you probably don’t care all that much.

Imagine you are a doctor.  (Some of you may have to work harder than others).

Imagine a parent brings a child to you with spots.

You’ve never seen a case of measles – because it’s almost been eradicated from Australia.  I’ve only seen one actual case, and I’m an infection specialist (although I’m in my 30s – older GPs have probably seen a bit).

Measles cases in Australia

Measles cases in Australia

Here you have a couple of choices.

1) You could explain that you’ve never seen a case of measles, so you’re not sure if is or not.  You could do some tests and send them home, letting the mum know you’ll tell her when the test results come through.

2) You could call someone who might have more experience to ask for advice.

3) You could confidently declare that it’s measles and tell the child’s parent to keep them home from school so they don’t cause any secondary cases – after all, that’s what it says to do in the Time Out guidelines.

Option 3 happens surprisingly often.

So let’s look at some of the unintended consequences.

  • The mum goes home and wikis Measles – and becomes rather anxious that the article says it used to have a 30% mortality.  She also clicks on Subacute Sclerosing Panencephalitis – and gets a bit worried that her child has an illness that can cause a progressive incurable brain disease
  • The mum helpfully rings the school principle who then anxiously calls the public health unit wanting to know why they weren’t notified directly and should they notify parents and OH MY GOD THE ANXIETY!
  • The mum also tells her friend who tells their friends who tells someone else who works for the local rag which precipitates an email like this:

“Hi, I’m a journalist from the Local Rag and we have reason to believe there are cases of Measles at Local School.  Can you please provide information on this as we intend to run the story on tomorrow’s front page. Our deadline is 4pm”

  • One of mum’s other friends is a conscientious objector to vaccinations and then either presents to the local hospital or rings the public health unit requesting prophylactic immunoglobulin because her child (Storm or Phoenix) isn’t vaccinated and urgently needs less effective and more risky post-exposure treatment because they aren’t immunised.

The mum rings the public health unit to try and address all her questions about the diagnosis of measles.  The public health staff start asking the mum a few questions and explain to her that:

  • There isn’t actually any definite evidence that the case is measles because no testing was done.
  • Some directed questioning reveals that the child almost certainly doesn’t have measles because
    • The child has had two doses of MMR and is almost certain to be immune to measles
    • There have been no cases of measles in the local area in the past few weeks
    • The child and its family have not traveled outside the area and have had no contact at all with anyone who was sick
    • The illness doesn’t actually meet the case definition for measles which is quite specific – rash, fever present at the time the rash comes on and one of (cough, runny nose, conjunctivitis or Koplik spots).
  • This precipitates a round of “but my doctor said…” in which public health staff have to politely and subtly point out that the doctor probably got it wrong while being mindful that they haven’t actually seen the patient and also of professional courtesy

The rest of the day is spent in arranging appropriate testing, reassuring the school principle, drafting a media release explaining that there isn’t measles anywhere and filling in a mountain of paperwork.

Contrast this with:   Admitting you don’t know what it is, looking up the guidelines and doing some appropriate tests, calling public health and letting them sort it out tomorrow.

Let’s be clear:

  • Measles is a rare disease in Australia (although sadly not so rare as it used to be)
  • You probably haven’t actually seen an actual case unless you’ve been in clinical practice for many years
  • There are many causes of morbiliform rashes – and the pre-test probability of it being anything other than measles is quite high.
  • If the child is fully vaccinated, measles is quite unlikely (but not impossible)
  • If the child has been given antibiotics in the past week, consider that it might be a drug eruption.

I hear you saying “that’s all specific public health / infectious diseases knowledge, surely it’s not my job to know that”.  This is quite true, it isn’t really.

But just yesterday, you thought that your knowledge was sufficient to diagnose a rare disease that you’d never seen without any tests, recommend a management plan based on these feelings (which was actually wrong, by the way) and failed to notify your suspicions in accordance with the public health act.  You can’t have it both ways.

The man who admits his ignorance shows it once. The man who conceals it shows it many times

–Proverb

Don’t be such a fucking muppet.

Begin Rant: Hung is good, m’kay?

•August 28, 2013 • Leave a Comment

I agree with this so much I’m just going to reblog it.

 
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