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About antibiotic resistance and the price of drugs

Many headlines stated today that UK wants to tax pharmaceutical companies again in order to contribute to a pooled fund against antimicrobial resistance (AMR). The proposed ‘pay or play’ mechanism is a bit more subtle than that. The report (full text here) is also suggesting other financing mechanisms (including the improvement of existing ones) as well as describing potential non-financial measures to reduce these resistances in the first place. Actually, financial measures occupy only about 6% of the report. But headlines need to be catchy. Let’s see a broader picture on tackling antibiotic resistance …

The WHO summarizes well the situation: “Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance occurs when bacteria change in response to the use of these medicines. Bacteria, not humans, become antibiotic resistant. These bacteria may then infect humans and are harder to treat than non-resistant bacteria. Antibiotic resistance leads to higher medical costs, prolonged hospital stays and increased mortality.

An illustrative diagram that shows the difference between a drug resistant bacteria and a non-resistant bacteria.

For Belgium, the Joint Programming Initiative on Antimicrobial Resistance displays a long list of governmental bodies and initiatives that study and/or tackle AMR. The Belgian Scientific Institute of Public Health has a dedicated program against AMR. Despite that, a recent study showed that, in 9 European countries, 99% of bacteria Streptococcus pneumoniae taken from nose of people aged 4 or more show antibiotic resistance (S. pneumoniae causes many types of pneumococcal infections like pneumonia or meningitis). The same study showed that Belgium has the worst resistance rate against the antibiotic cefaclor (fortunately authors also show there is little resistance against the most common antibiotics used against S. pneumoniae). A study from last year in 8 European countries (including Belgium) showed that approximately 4 out of 5 Staphylococcus aureus (another bacteria) isolates from individuals without specific health issues were resistant to at least one antibiotic and more than 7% of them are multidrug resistant. And we are talking here about Belgium, a country with a well developed healthcare system, following best practises in antibiotic stewardship and often considered as an example for the reduction of antibiotic consumption outside hospitals.

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Coming back to the UK report, a big part of it advocates more or less what the 2015 WHO country situation analysis on antimicrobial resistance described too: countries need a plan to fight AMR, surveillance and laboratory capacities should be raised (no data = no knowledge of the situation and no capability to measure progression), antimicrobial medicines should be correctly used, public awareness campaigns should be deployed, and the prevention and control of infections allow to tackle the issue at the source.

The question raised in the report is also how to accelerate the discovery of new antimicrobial medicines? The report advocates for a “global innovation fund for early stage and non-commercial R&D”. And it correctly points that there are currently little incentives for companies to invest in research for products that will ultimately be priced very low (also thanks to generics) for a high volume to produce. Because in “normal times” (periods of “usual drug resistance”) competition between existing products drives prices down. However, if resistances become too high (and they will because they are selected over non-resistant bacteria), none of the existing medicine will be effective anymore, the willingness to pay for innovative drugs will be high but the time to develop them will still be in decades (i.e. too late to tackle the resistances).

Intervention 9 of the UK report tackle this issue with a complex reward mechanism (“the carrot”). But then the next section describes a very simple tax in one page (“the stick”). This ‘pay or play’ mechanism that was highlighted in the press and should indeed be the simplest mechanism that can be applied at a country level.

However, another mechanism could be to make the antimicrobial market attractive again. Allow for (moderately) increased prices on existing drugs (even the ones with competition from generics) and pharmaceutical companies will see opportunities to develop new medicines. Yes, they will become richer thanks to these price increases – but these funds are (partially) re-invested in research and development.

Photo credits: What Is Drug Resistance? by NIAID (licence CC-by) and B0006889 MRSA (clusters of methicillin-resistant Staphylococcus aureus (MRSA) bacteria) by Wellcome Images (licence CC-by-nc-nd).

Is it worth buying a coffee machine at work?

As I moved to a new office, I met new colleagues and one of them brought her own coffee machine and placed it on her desk. It’s a bright red Nespresso machine, a kind of statement that the owner doesn’t drink the free coffee offered in kitchenettes on all floors:

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Given that the company has a professional Nespresso machine downstairs (i.e. similar quality of coffee but with capsules of different shapes), I was wondering if this is really worth buying. The calculation is simple …

On one hand, the “public” Nespresso machine sells 1 capsule at 0.50€ and pours the water (through the capsule) in a cardboard cup.

On the other hand, the cheapest personal Nespresso machine you can buy in Belgium costs 199.00€. The cheapest personal Nespresso capsule you can buy costs 0.35€ (let’s forget for a moment you have to buy them in multiple of 10 and there are savings to be made if you buy large quantities).

Therefore the upfront cost of the personal Nespresso machine tells me it’s more expensive to have my own machine on my desk. But after how many capsules (i.e. cups of coffee) does it become cheaper to have my machine? The equation is easy: 199.00 + 0.35 * x = 0.5 * x (where x is the number of cups of coffee). Solving it tells me I need to consume 1,327 capsules from my machine in order to get my coffee cheaper than on the “public” machine. That is more than 3.6 years if I drink 1 coffee per day – only slightly less than a year if I drink 4 coffees per day (which is a lot).

Of course, this simple calculation doesn’t take into account electricity, water, cleaning cups or the cups themselves ; they are considered free in both situations (which they are, in practice). It doesn’t take into account neither the convenience of not having to stand up, go down a few stairs to the “public” machine. But, for the future, it doesn’t take into account neither the benefit of having moved more during office hours (more than just sitting the whole day).

So, given some assumptions, having my own Nespresso machine on my desk is probably not economically viable at a reasonable time horizon, unless I drink a lot of coffee and if I value the convenience of not losing a few minutes to go down to the “public” machine. But going downstairs for a coffee prevent me from sitting for too long at my desk and it allows me to meet other colleagues downstairs. I’ll keep this habit!😉

How to redesign a numeric keypad?

In an interesting blog post on Smashing Magazine, C.Y. Gopinath explained the design choices he made to build a new calculator for smartphones (iPhones more specifically). He started with an interesting summary of the reasons and origins of the numerical keypads of phones and calculators (keyboards, ATM, etc.). This is what drove me to read his post. Indeed I posted a photo on Flickr that showed the difference, a few years ago.

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While reading the post, I was happy the author of the app did some research on the traditions behind this keyboard layout as well as the reasons and studies that lead to these layout. The article also contains links to further details, if necessary, and interesting comments from Harry Blanchard and Michael Long.

However I think the author mixed several things before re-designing his numerical keypad …

Circular design with numbers already exists in the real world: the analog watch (also mentioned in a comment). I guess most if not all humans above 10 years old are used to this design and the way it starts with “0” (well, “12”) at the top and “6” at the bottom. So when I saw Gopinath’s app screen, I was wondering if there is a reason or if there are research showing the tilt is beneficial and will not confuse for the user.

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Comparison of C.Y. Gopinath’s calculator app (left) and a regular clock on a smartphone (“HTC Sense – Home” from Cha già José on Flickr, CC-by-sa, right)

Citing research from Bell Laboratories is great: very few apps did this amount of research and still show “revolutionary” user interfaces based only on the gut feeling of a designer on steroids (when there was a designer) (to be fair, some new designs achieve their goals). However the period during which they were conducted (early/mid-last century) has most probably a large role to play in the choices and habits of respondents. One thing in particular is that people most probably would use these numerical keyboards sitting on the table (like phones on table) and use their finger (or fingers but I expect the index being the single most used finger) of one hand.

What could be the response now? Only research would tell. My feeling is to start from habits of smartphone users. My own use would consider the following facts:

  1. so far smartphones are still square / rectangle objects
  2. most smartphones are still small enough to be held with only one hand and one finger on the same hand would be used (the thumb)
  3. if smartphones are too big to be used with only one hand, either you hold it with 2 hands and use your 2 thumbs (text messaging) or you hold it with 1 hand and use one finger from the other hand.

I did not (yet) witness cases where the user types on a smartphone with many fingers, like a typist would use all his/her fingers on a keyboard.

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Two ways to hold and interact with a smartphone: with one hand on top (from Iriss on Flickr, CC-by-nc) and with two hands below (from Freestocks.org, public domain)

Therefore I would rather see another “radical” design like this one (case phone held with 2 hands, using 2 thumbs to type):

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My example of mock-up smartphone with digits on the side, reachable by thumbs if placed on the sides (I guess it needs some more research, of course)

I was also wondering why the author added so many gesture and swiping left, right, center. In his assessment of other calculators, it was mentioned that they offered little or no feedback. How these gestures can be intuitive or discovered by the user? I must admit I didn’t install the app but I guess there should be a tutorial for all these gestures. In my opinion, these tutorials are however the admission that these features were not intuitive, that the discoverability principle was forgotten, most probably on the altar of minimalism …

Although I appreciated the author’s research and share most of the author’s comments on current numerical keyboards, I don’t think the current implementation solves the issues of user-friendliness, discoverability and the greater goal of making kids love maths. Ironically, the “Edit History” page of the app shows the standard, old-fashioned numerical keyboard …

Fedora 23 on a Dell XPS13 (part 1)

Taking advantage of a trip to Canada and a very favourable CAN$:€ exchange rate, I bought a Dell XPS13 (9350 or “late 2015”), following excellent reviews from around the web. Dell sold a ‘developer edition‘ of this laptop (shipping with Ubuntu Linux) but unfortunately it was out of stock on Dell US and I couldn’t find the item on the Dell Canada website. So I bought the Windows version with a touchscreen (it was Black Friday :-)).

fedora_infinity_140x140Here is how to install Fedora 23 on it (and probably most other Linux distribution) … I will focus on three aspects (in brief: everything works out of the box, except the wireless card that needed some additional action):

  1. How to boot and install Fedora Workstation
  2. What works and what doesn’t work out of the box
  3. Some things to do after installation (additional software)

Read more…

Jadoo and static website generators

Coming back from holidays, I fired my RSS reader and, among many interesting posts, I found this one from Smashing Magazine about static website generators being the Next Big Thing on the web (and a follow-up deep-diving into four of them).

The first paper describes how the web started as something static, became all dynamic and is progressively coming back to something more static, at least for some specific tasks. The interesting thing is that the author also describes pros and cons of each stage and why the web jumped to the next level.

jadooWhile reading this, I couldn’t help thinking of Jadoo, a pet project I started in 2007. Its goal was to get rid of the complexity and number of resources required to run a dynamic blog system. Following some notes from Alexandre Dulaunoy, it was written in Python and already used concepts now hidden under buzzwords😉 like templating and a rudimentary meta-data organization. At that time, there was nothing like Markdown, assets management, caching, Github, … (not as widespread as today at least). There is an initial post and an update – then I gave up (reasons inside). Note drawbacks I wrote at that time are still drawbacks of current static website generators (manual update and local edition only). All these ideas in 2007, one year before Jekyll …😉

P.S. The irony is that posts about Jadoo were later transferred to WordPress – and this blog is also npw currently hosted on WordPress!

Apple HealthKit already created some disruptions …

… At least in the minds of people.

Marketing is a powerful persuasion tool and you sometimes need a few early applications to create 243076870_1166dfc14e_zthe impression that something radically new came and is changing an area.

I like to listen to podcast while doing repetitive activities that don’t require my brain too much. One of the podcasts I listen to is the Clinical Air from the Pharma Talk serie. A few weeks ago, I listened to episode #14 about consumer electronics in clinical research. It was all about the Apple HealthKit. In a sense it was very interesting to hear about it as it contained more details than its Wikipedia page for the moment ; another top-level summary of its capabilities is found in this Rahlyn Gossen’s blog post (Rahlyn was one of the guests of this episode). Episode #14 was published on July 21, 2015.

Tonight I listen to episode #12 about digital startups and applications for clinical research. It struck me that the discussion was more serious, more focused on actual startups and apps, what they try to solve, how they would/should evolve in the future, etc. Apple was mentioned only once, as part of provocative titles of articles in the press at that time. Because “that time” was August 29, 2014 (when episode #12 was published), one month before Apple announcement.

For some things, we’ll have to dig for information before big marketing campaign, in order to find out interesting content that explore various areas instead of being funneled in the same direction …

Photo credit: Birds: a tragedy by Shannon Kokoska on Flickr (licence CC-by-nc-nd).

Happy to use Zotero since a few weeks

Source Material - by Josh DiMauroFor my work I need to reference a lot of statements, mainly with papers and books in the biological / medical literature. Usually “professionals” use two proprietary software, Reference Manager or EndNote (both owned by Thomson Reuters). But there are a few very interesting free alternatives (see this comparison of reference management software).

I switched from Mendeley to Zotero a few weeks ago and I’m very happy. Here is why … Read more…

Medicines coming soon at a printer near you!

The terminator may not come at any time soon but medicines should be coming soon at a printer near you …

Mid last year, Gartner mentionedmedical applications [of 3D printing] will have the biggest impact in the next two to five years“. With 3D printing you can already create a lot of physical artifacts and medical applications go from building medical equipments to prosthetic parts, but also blood vessels, bone, heart valve, cartilage, etc. Complete organs are not too far, with companies like Organovo already printing functional liver assays, prospects to restore a body by replacing or consolidating personalized parts seem interesting.

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On the other side, restoring a body function by providing personalized molecules was a dream so far. Preventing body malfunction via similar systems is too.

Plan view of Cronin's robotic systemI recently watched and read about Lee Cronin’s laboratory work and these dreams may come true, one of these days. In a TEDxGateway video in 2013, Prof. Cronin explained briefly how he did it. Last December, they published their method with a basic application in Nature Communications. What I also liked is that, beyond the technical capabilities, this research is based on common components (right) and free software that are available for everyone. And Cronin also insisted on compatibility between “recipes” and the possibilities to exchange them as well as source code – one day, will their software be released on Github like some of their 3D models as STL files?

Cronin also talks about pharmaceutical companies releasing blueprints for drugs that could save plenty of lives in emerging economies, for instance. In my opinion, this is however where the technology goes much faster than the ideological framework we live in: pharma companies will not likely suddenly release recipes for drugs that bring them money (no for-profit company in any other sector would, by the way) and the regulatory framework for healthcare is far from ready to accommodate these advances.

Prevention could also benefit from these advances. Synthetic vaccines are in production since two decades at least. If safety is the first argument often put forward in their favor, rapid prototyping and versatile production could one day become possible. It seems it was already tested for flu vaccines. Now imagine to move the “engineering” part in a computer, sending the recipe for the best-adapted vaccine directly to “vaccine printers” in regions where health hazards are likely to occur or as early as they occur … We would also face many corporate and regulatory hurdles. But it wouldn’t be the first field where technology would push broader changes …

Happy New Year 2015!

May your 2015 be filled with magic, dreams and good madness!

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