Australia's overuse of antibiotics driving rate of drug-resistant infections
theguardian.com
theguardian.com
https://www.nrdc.org/resources/us-livestock-industries-persi...
https://extension.umn.edu/news/over-counter-livestock-antibi...
Starting June 11, 2023, all currently available over-the-counter antibiotics for livestock will be available only as prescription medications. This new rule will impact all livestock species. Over-the-counter antibiotics are moving to prescription only to provide more veterinary oversight. Similar to the Veterinary Feed Directive, placing antibiotics under the supervision of veterinarians should result in more judicious use and less antibiotic resistance.
This change includes but is not limited to the following: Penicillin, Oxytetracycline, Sulfa antibiotics and Mastitis tubes. Some medications are not considered crucial for human medicine and will remain over-the-counter. This includes the following: Ionophores including Rumensin and Bovatec, Parasiticides, such as Ivermectin, Oral pre/pro/postbiotics, and topical non-antibiotic treatments.
Livestock producers must have a valid Veterinary-Client-Patient Relationship (VCPR) in place before they can be prescribed antibiotics by a veterinarian. A VCPR is a working relationship between a veterinarian (veterinary clinic) and a client. Ideally, a VCPR is a documented agreement between both parties that includes a dedicated visit to the animal location(s) the client operates. This visit and documentation must occur at least once every year to maintain the VCPR.
> Antibiotics are chemotherapeutic agents used for the clinical management of infectious diseases in humans, plants and animals. However a sizeable fraction of antibiotics produced every year all over the world is used for non-therapeutic purposes. In US alone, about 24.6 million pounds of antibiotics are used in animal agriculture annually and a substantial portion of this is used as growth promoters and not for the treatment of infections...
Evidences available in the literature speak volumes on the beneficial effects obtained from antibiotics used as a feed additive. Pigs supplemented with antibiotics in their feed require 10–15% less feed to achieve a desired level of growth.
https://www.frontiersin.org/articles/10.3389/fmicb.2014.0033...
Constantly feeding antibiotics to animals makes factory farms more profitable.
Has there been any research to determine why growth improves with diminished gut bacteria?
I've seen some theories tossed around to explain the mechanism, but there is no consensus, aside from the fact that it does work.
Unfortunately, it's also led to us having human disease that no longer responds well to antibiotics that are safe to use in humans.
For instance, with Extensively Drug Resistant Tuberculosis:
> Second-line drugs are more toxic than the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression, hallucinations, and deafness. Patients are often hospitalized for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.
https://en.wikipedia.org/wiki/Extensively_drug-resistant_tub...
Even after you fall back on lesser used antibiotics with severe side effects, the cure rate for XDR TB is below 40%.
In the US, poultry industry and federal/state governments have spent endless effort "programming" people to think that it's their responsibility if they get sick because the meat or eggs they purchased were contaminated and they didn't take enough preventative steps (like cooking it to the point of it being nearly inedible.)
Most US poultry is rinsed in chlorinated water, eggs are washed as well (which ends up destroying the egg's natural coating, so they have to be refrigerated) and so on.
Not washing the eggs means the outside might have some chicken crap on it, but A) you wash that off before breaking the egg, and B) you're cooking anything the eggshells come into contact with.
I personally want zero medicine, chemicals or vaccines in my food. It’s frankly gross.
Further, it is your fault if you eat bad meat. We have a responsibility for our own bodies and what we put in them. The fact people can sue is why they wash with bleach.
Eggs in the US are washed (by law) before sale, which removes their natural protective coating, therefore requiring they be refrigerated. In other places eggs are sold unwashed and can be left out.
"Washing them, removes the protective coating, requiring refrigeration"
Right, so why do they require refrigeration, if they are sanitized?
Further, if they're not sanitized, you can leave them out? What exactly is that protective coating and how does it somehow make the eggs less safe to sanitize them?
https://tellus.ars.usda.gov/stories/articles/how-we-store-ou...
US eggs are fine to leave out, they just lose some moisture. That's also true of the ones which are unwashed btw, but washed eggs degrade faster. Both unwashed and washed are better refrigerated.
The theory is that sanitizing process makes the shell more permeable, which makes it easier for random bacteria in the environment to infect the egg; thus it risks going rotten faster. Refrigeration slows down the growth of these microbes, thus counteracting the increase in permability.
I could take a piece of meat way past ita expiration date, bleach it in hydrogen peroxide, and sell it to you as fresh, and you would never know.
Thats what food industry does. https://active-oxygens.evonik.com/en/markets/food-and-bevera...
Only folks that care about food safety. Refrigeration is sometimes cultural: Folks in Norway usually refrigerate eggs, even though they look unwashed, but eggs sit on a shelf at stores in Sweden.
I personally want zero medicine, chemicals or vaccines in my food. It’s frankly gross. So don't eat. Everything has chemicals. You probably don't want to eat sick animals (that's what medicine is for) and vaccines help make sure your food is safer - especially for salmonella. Or produce all of your own food. Good luck grinding wheat, canning and avoiding botulism, feeding animals (or farming even more), and not dying when food runs out.
Further, it is your fault if you eat bad meat. We have a responsibility for our own bodies and what we put in them. The fact people can sue is why they wash with bleach.
This is a horrible misunderstanding of what you have control over. You can handle all meat properly and still get sick: Unvaccinated chickens tend to have salmonella, for example, and it can make you sick. You simply can't see whether or not the spinach you are eating is contaminated by animal droppings either. You don't - and never will - have control over everything you put in your body.
They don't wash with bleach because people can sue: They wash with bleach because they aren't taking other measures to make sure your eggs are safer and because some cultures will reject food if it has little bits of poop and feathers on the shell.
How would you know you're eating bad meat?
So I have to pay $500 to get some vet to come out in 1-2 days, to tell me what I already know. In that time, my cattle can die, it can spread all costing me more and benefiting no one. Further, because I can only sell a head for $750-2000 this basically wipes out any potential profit.
This is basically just helping the big players who keep a vet on staff or in a high concentrated area. Most of the small farms in my area are just going to get screwed.
Finally, I’m curious how much evidence there is animals use of antibiotics impact humans. Most diseases don’t spread from animal to human, so I don’t suspect it’s all that impactful. On the other hand, it could be to reduce animal-to-animal diseases. That would make sense.
All that being said, to be honest, I think this is an effort to limit the things we saw during Covid. Basically, people realized they could get any drugs for animals cheap and easy. It’s screwing up the medical system, making it as cheap as drugs in the rest of the world.
But, the net effect is what you say. What other solutions are there? Tax them so other uses aren't economic, perhaps?
There's a ton, and it all points to antibiotic overuse in agriculture as the main culprit.
Antibiotics and their metabolites don't just stay in animals, they exist in their waste and percolate throughout the environment, water supply, etc, causing antibiotic resistance in bacteria in the environment.
Antibiotic resistance in bacteria is mainly from misuse in humans and animals, and disease spread between the two, along with ineffective waste treatment and the leaching of antibiotics into the environment[1]. About 80% of antibiotics sold in the US are used in agriculture[2], where they are given to animals not to treat infections, but to prevent them and to stimulate growth.
Here are some diagrams from the CDC[3][4], and some articles[5][6][7] from the CDC.
> Most diseases don’t spread from animal to human, so I don’t suspect it’s all that impactful.
Over 60% of infectious diseases in humans are spread from animals, and 75% of new diseases in humans are spread from animals[3].
[1] https://en.wikipedia.org/wiki/Antimicrobial_resistance
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638249/
[3] https://upload.wikimedia.org/wikipedia/commons/5/52/Antibiot...
[4] https://upload.wikimedia.org/wikipedia/commons/5/52/Antibiot...
[5] https://www.cdc.gov/drugresistance/food.html
[6] https://www.cdc.gov/foodsafety/challenges/antibiotic-resista...
[7] https://www.cdc.gov/drugresistance/environment.html
[8] https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html
Think of it like the black death in humans. When this disease suddenly made the jump to humans, some people had naturally higher resistance and some had lower resistance, all just due to random genetic variation. The disease spared people who were more resistant and killed people who were less resistant, and now humans today carry genes that protect us from this disease, even though we have not had another black plague for hundreds of years. Even if we eradicated the disease entirely, we will probably still carry resistance for thousands of years. It's just a part of our genetic makeup now.
Back to bacteria, even if antibiotic resistance does come at a high cost to the organism and there is selective pressure against it in the absence of antibiotics, it is still very unlikely that we can get back to the way it was when antiobiotics were new. Once a deleterious trait appears in a population, it has a way of sticking around (e.g., see numerous deadly genetic diseases carried by humans).
Basically, the cat is out of the bag. We need to drastically reduce our use of modern antibiotics to buy ourselves time to develop new antibiotics--and we need to keep the new antibiotics very tightly controlled.
> Australian animal industries are one of the lowest users of antimicrobials in the world
https://www.amr.gov.au/about-amr/amr-australia/animal-health
Assuming the data is accurate, it would seem antibiotic use (not sure how that compares with antimicrobials in general) is not particularly low compare to other countries.
From the cited paper itself:
> The top 5 consumers in 2020 were China, Brazil, India, USA, and Australia
But also:
> In contrast, Australia now also appears among the top 5 –however, in the absence of any public report of AMU since 2010 [29], usage for Australia was obtained through extrapolation, as with other countries that do not report data. Therefore, predictions may not accurately reflect the current country efforts to reduce AMU.
So it's not clear if the data actually is accurate (and the paper really is about how accurate data is missing for many countries).
There's also financial reasons to do so, with livestock the financial reasons are likely reversed.
Beside that, anti-biotics also have side effects that can make you more sick, their use is not just unnecessary but counter productive. Some of the side effects can be serious and long term, like changing your gut bacteria.
Antibiotic Resistance from the Farm to the Table. September 11, 2014. Available at: http://www.cdc.gov/foodsafety/from-farm-to-table.html. Accessed September 14, 2015.
https://www.who.int/news/item/07-11-2017-stop-using-antibiot...
ANTIBIOTIC RESISTANCE—LINKING HUMAN AND ANIMAL HEALTH https://www.ncbi.nlm.nih.gov/books/NBK114485/
Much of modern medicine depends on antibiotics. The above resources give clear and compelling evidence that overuse of antibiotics in livestock is associated with increases in drug-resistant infections in humans.
Farmers don't use antibiotics for fun. It increases meat production by 5-10%. So expect meat prices to go up by about that amount if the practice gets banned.
Bacteria transfer genes from one species to another, so an innovative new genetic mutation that allows one kind of bacteria to shrug off antibiotics more effectively won't stay only in that species of bacteria or only on that farm.
> Horizontal gene transfer is the movement of genetic information between organisms, a process that includes the spread of antibiotic resistance genes among bacteria, fueling pathogen evolution.
That would massively drive up meat prices and anger voting consumers who won't be able to afford meant anymore, and also anger voting meat producers who will go bankrupt from slumping sales and have to lay off workers, all of which who will direct their anger at the politicians who restricted the use of antibiotics in animal farms. So not gonna happen politically.
Consumers have to either accept higher meat prices (not gonna happen), or accept that we're too many consumers on the planet for everyone to be fed with organically grown meat (also not gonna happen), so we just kick the can down the road and sweep the dirt under the rug until the titanic hits the iceberg and there's no way forward anymore.
Here in the rich EU countries we have some rules and regulations on meat production, but enforcement is very lax and it's an open secret that those certification seals of approval are basically worthless as animals are still caged together crowded in their own filth, with massively infected open wounds full of puss, and pumped full of antibiotics just to stay alive long enough to become burgers. You should Google those images if you want to become vegan but lack the motivation.
It's a political tragedy of the commons that's found in a lot of other areas in our lives/society which we know for a fact are wrong and are harming us (or others from less fortunate parts of the world), but we still stick to them because they're very profitable industries generating $$$ and jobs, and they're such a tight part of our daily lives, they're nearly impossible to undo today, like all the pollution from car dependence, microplastics, the cheap cocoa and coffee industries driven by slave labor, etc.
See the dead body spaghetti episode from Rick and Morty, it's pretty good satire on our collective hypocrisy on this topic.
We know those are all bad, but we choose to look the other way and not do anything about it because we love our lifestyles with cheap car traveling, cheap shipping, cheap meat, cheap coffee, cheap clothing, etc. and all the associated profits.
I am quite far from the vegan ideology, but still willing to recognize that there is something untenable about our current relationship with livestock.
It would be great if fake meat would be able to drop demand for real meat, leading to less need for factory farming. But if that happens, it's very far in the future.
Recall that the US (and many other highly industrialised, wealthy countries) had filthy environments in the 1960s. Then, the world awoke to environmentalism and a huge number of regulations were passed to clean-up. Few people are asking to go back to the pre-1960s environment. And, yes, following these new environmental rules is not cheap. It would be much cheaper to produce chemicals (and whatever else) if manufacturers could pollute like the 1950s.
You're forgetting the massive off-shoring of dirty environmentally damaging manufacturing and mining that has moved from the wealthy countries to Asia and Africa, and allowed said rich countries to become 'clean' while still having access to cheap stuff and not be economically affected by the move to green.
It's a trick that doesn't work as well with organic farming.
Not sure about the definitions about prophylaxis and metaphylaxis but I was under the impression any systemic use of antibiotic use in healthy animals was outlawed e.g. in the EU.
EDIT: Thank you to responses below.
There may be local regulations or labellings to (e.g. some organic labeling means no antibiotic and so on). But as a first rule I just try to avoid meat from "bad" countries. E.g. we get quite a lot of imported Brazilian beef in stores and I know it's terrible both for deforestation and antibiotics so I avoid that completely. Some interesting differences in the map is e.g. between Australia And NZ.
https://journals.plos.org/globalpublichealth/article/figure?...
or read through the two major cited articles:
Mulchandani et al. (2023) Global trends in antimicrobial use in food-producing animals: 2020 to 2030 https://journals.plos.org/globalpublichealth/article?id=10.1...
Delia Grace (2015) Review of Evidence on Antimicrobial Resistance and Animal Agriculture in Developing Countries https://assets.publishing.service.gov.uk/media/57a0897e40f0b...
There's some devil in the details, of course, are the antimicrobials used in animals the same as those used in humans? ie. Does increasing resistance in animals to X product result in resistance to Y product as used in humans?
Australia thinks it has the right solution here: https://www.amr.gov.au/about-amr/amr-australia/animal-health
How does the economics of shipping frozen and refrigerated lamb to Europe work out for this to make business sense?
There can also be other forces at play. For example, we have just transitioned from la Nina (which brings high rainfall to this part of the world) to el Nino (which brings drought), so a lot of farmers will be downsizing their flocks.
Changes in wool prices can also affect lamb prices.
EU law is pretty strict about labelling meat coming from the EU/outside the EU so that could be one way.
Meat should be an expensive food. it’s costs for the environment and the humanity are too high.
What amount of suffering in the world would cause you to even consider the option of eating less meat? Is it something you’re willing to contemplate? Not just animal suffering either. Think of the complicated web of problems that come out of people eating too much meat. The antibiotic use discussed in this thread. The methane byproduct discussed in countless others. The inhumane conditions of most butchers (for workers! Let’s forget the animals still).
It’s okay if none of that bothers you. We’re only human. I’m a former vegan, I’ve likely considered it all more than strictly necessary. I don’t think anyone _has_ to be anything. But for what it’s worth it _could_ be about more than an individual’s health.
That would be a different discussion, with a different answer. I was only replying to the comment above mine.
Yes... animals produce waste & suffer from infections...
Inhumane conditions exist in the minority in every industry. You're claiming most butchers/abattoirs have inhumane conditions in an industry that I'm certain you've never worked in.
You're a former vegan but I see that you're still brain-washed by the material that you were hand fed.
that would require people cut back on meat consumption
I’m simply asking you consider something beyond the meals you want to partake in.
You’re absolutely correct- I never have worked in that industry. My family has worked the chicken industry in Georgia and South Carolina. I’ve seen the result of that labor first-hand. If that brain washed me then so be it. That labor is inhumane. It is hardly the only inhumane labor that we rely on.
The thing is I believe you’re capable of seeing more than your comment lets on. I wasn’t hand-fed some propaganda and I don’t think you were either. It’s a weird world out here.
The experience overseas is so much more loose that I wonder what the author is on, no pun intended. In Indonesia the health care system was so broken that I actually became kind of a low level expert in antibiotics myself, and would regularly self-diagnose and "prescribe" myself whatever, which I could just walk into any pharmacy, demand, and get. In Thailand it's a little stricter but not much.
So with two much larger countries right nearby with much laxer rules it's hard for me to take seriously the notion that tiny, isolated Australia's moderately bad GP habits, if that is even true, is having much of an effect on anything.
Thats right there in the heading. No country should have freaking 1/3 of the population using antimicrobials in a single year.
https://www.safetyandquality.gov.au/publications-and-resourc...
OK, I have to admit I'm surprised it's that high. As you'd expect, it's heavily biased towards the elderly. It's good that a light is being shone on it.
But the article is written as if Australia is some kind of global prime suspect in driving resistance trends, and I continue to doubt whether that is actually the case.
> Australia ranks seventh-highest in the developed world for antimicrobial community prescribing rates. Australia’s hospital antimicrobial use is estimated to be nearly three times that of the European country with the lowest use, the Netherlands.
So we are top 10 but not the single worse offender, at least by this metric.
I suspect the other thing is how often Australians go to the doctor. Americans tend to be pretty hesitant to see doctors due to pricing of health care. In Australia, if you're sick, you go to the doctor. This is true even for common colds. Some stats, in 2010 Americans saw the doctor on average around 3.9 times a year (and this number is on a downward trend from the previous survey)[0]. In Australia this number is a bit harder to break down. Some politicians have cited that on average people see a doctor 11 times a year. Medicare stats breakdowns put that number at somewhere closer to 7[1]. Either way, it's a significant increase in comparison to Americans. It's more common to go see the doctor.
Unfortunately the article doesn't cite their sources here. One thing I'd be very curious about is what percentage of doctor visits result in antibiotics when comparing Australia vs the United States. My hypothesis is that despite cultural pressures, it may actually be that prescription rates per visit are quite similar between the two countries, and it's just that Australians seen the doctor more often.
[0] https://www.census.gov/newsroom/releases/archives/health_car... [1] https://www.servicesaustralia.gov.au/sites/default/files/doc...
Whether it's 7 or 11, I don't know anyone middle-aged (20-50) anywhere near that number.
So if Australia is top of the list, I'd certainly want to know more about the sources of the data. If hospitals have started giving out prophylactic antibiotics, that for example would skew the statistics and help identify the source of the problem.
I'd joke that by then the issue would have either gone away or I'd be dead.
I live in suburban Melbourne and have no problems getting a same day appointment. There are at least 5 GP clinics within a 5 minute drive.
How about healthcare? Single-payer or is it the wild West like America where if you don't have health insurance, you're stuffed with arbitrary debt and bankruptcy at random?
Leers at the UK with their fancy-pants NHS that even those on the right of politics mostly defend.
One of my colleagues there seemed to be having a pretty bad cold so he exited our meeting. One hour later he was back, said he took antibiotics, and felt fine now.
My jaw dropped. Dutch doctors are the opposite, as expats commonly complain about. Our first method of treatment (for various symptoms) is to send you back home and sit it out for a few days. Or just take some aspirins.
The idea being that your body will heal itself over various ills, and that this is the preferred way.
My mind was also blown when I heard that in many countries, people have medical cabinets at home. It being common that the typical non-senior adult has a stock with a wide array of medicines.
I was raised on zero medicines, unless there's something critically wrong. Even taking an aspirin makes you a bit of a wimp.
Cultural differences I guess.
My partner is a GP (French originally) and when she discussed antibiotics being used in France it was quite eye-opening. Most of the antibiotics prescribed in Sweden have not been in use for years in France because there's too much resistance already. On the other hand many of the antibiotics that she considered really basic were considered "super strong", rarely used in Sweden, e.g. Augmentin.
It's probably true for some rare cases, though on average very likely doing more harm than good.
Even if antibiotics did fix his cold (highly unlikely), there's no way it worked in an hour. He got something to pep him up for sure.
I had covid recently and a woman at work who had identical symptoms but wasn’t testing positive went to the GP and was prescribed antibiotics.
Whether it was placebo or not, it did usually seem to make me feel better.
Those two sentences contradict each other; it is a very irresponsible thing to do. Also, yes, if every time you have a cold, you get antibiotics and they make you feel better, it is placebo.
Not necessarily. Azithromycin, a common antibiotic used for upper respiratory infections, has anti-inflammatory effects separate from it's antibacterial effects[1]. So it may make patients feel better even if they have a viral infection. Thus perpetuating the patient's belief that they "needed" antibiotics.
What's even worse is that unnecessary use of antibiotics can affect someone's gut biome and leave them worse off for months, in some extreme cases years. I have had antibiotics only a couple of times in my life (for bleeding injuries) and I noticed the effect on my gut each time. To think that people create this problem when they don't have to is alarming. I hope for their sake their doctors _are_ prescribing them placebos so it's harmless ignorance.
Walking out of the pharmacy with 8 boxes of antibiotics at a time was a fun experience. I can't remember but in Australia I think it was less than $5 a box without insurance.
Yes there's the saying among doctors, for patients with a cold who want medication (e.g. antibiotics): "You can either wait and feel better in a week, or I give you medication and you feel better in 7 days."
It's also not unusual for someone to end up with a bacterial infection because their immune system is weakened from the viral infection.
Your coworker almost certainly didn't repeat everything the doctor said or did, nor should she have to; mind your own business. It's wild that you were not there, don't posses any medical training, but consider yourself more qualified...
Why do you think any real expertise is required for a situation like this? It’s a simple reality that medicine, like any field, is brimming with practitioners who do not follow best practices and even many that are not good at their job. Doctors make terrible decisions all the time. I can give you numerous anecdotes in my life where doctors were dangerously wrong even when presented with very clear evidence.
It's very hard for me to get antibiotics and at the same time I have a high chance of getting nasty bacterial infections with each cold. The last infection 2 years ago has caused me to have a permanent cough. Just wish antibiotics weren't so vilified, they actually serve a purpose. Why can't we reduce use in livestock first?
Meanwhile, my family in India are so used to getting antibiotics and overmedicating in general for everything that they find it weird that doctors here just prescribe basic OTC stuff and rest for a basic viral cold.
When I recently went to the doctor for a cold, they did a strep test which came out negative and handed me a "prescription" of lozenges and an OTC decongestant.
Here they even stopped for many bacterial infections e.g. typical strep infections and so on, so long as the body takes care of it. I.e. no antibiotics just to shorten the disease period.
> ... more than one-third (36.6%) of the population had at least one antimicrobial prescription subsidised by the Australian government in 2022... of antibiotics and antifungals...
The prescriptions were for antibiotics AND antifungals. So any prescription treatment for thrush, athletes foot or similar yeast infections were included in the statistics.
Also from the article is that Australia ranks 7th in the list of over-users. There are 6 other countries that are doing worse.
Like most medicines if you need them you really ought to have them and if you don’t then you shouldn’t.
I believe some of this can be tied to the very rapidly changing demographics in Australia. I have no data to back this up, but I do see quite often amongst parents that they will shop around for a GP that gives them antibiotics because back *home*, that's what they were expected to do.
So it is not uncommon for people to drive 30 minutes to their favourite GP somewhere to get exactly what they want...
There's a GP practice near us that pays really poorly, always young doctors, they never last more than a year, and the owner (an older GP who also works there) just wants happy return customers who are in-and-out. So yeah, they'll prescribe whatever.
There's a better GP practice near me which won't actually do that though, most visits take the full 15 mins, they'll ask loads of questions and give you some tests and/or recommend over the counter stuff, and it's always "come back if it gets worse or doesn't get better by X". They charge for the first consult, but typically just bulk-bill for every visit related to that problem. Even chronic issues they typically bulk-bill.
So yeah, quality varies. it'd be interesting to see some stats around what sort of GP practices prescribe the most antibiotics - Total visits per year, average doctor turnover, etc etc.
Father was a vet, and he made me respect antibiotics. Including, IF you take them THEN finish the entire course as directed. DO NOT stop taking them because you feel better.
I think we gotta normalize being sick, and sitting at home watching Netflix.
I haven't had to worry about this in years but while working in retail I periodically found myself at a GP and being prescribed antibiotics when I would have otherwise stayed home to rest, if I didn't need that medical certificate.
I think if we are serious about antibiotic use in humans, we need to test for pathogens before or during treatment. Is there a mechanism to affordably do a broad spectrum screening of infections?
And the other 6 countries are...?
Is the rate of resistance formation, the same as what you would expect from looking at other countries with the same usage profile of antibiotics? Have all other variables been controlled for?