Evidence Matters' posterous

Paracetamol linked to blood cancers

The People's Medical Journal (aka Daily Mail Health section) has a striking headline: Paracetamol found to have link to blood cancers

Paracetamol is such a widely-recommended and popular painkiller that such a finding is startling and worrying in its implications. Thankfully, we have people such as Dr Alicia White who contributes to the invaluable Behind the Headlines who has written a very useful guide, How to read health news.

Dr Alicia White states:
The most important rule to remember is: don’t automatically believe the headline. It is there to draw you into buying the paper and reading the story.

And in this case, she is absolutely on point. Although the story leads off with the following:
Regular users of paracetamol have an increased risk of developing blood cancers, researchers have found.
...
The findings will terrify the millions in America and worldwide who pop the pills to cure minor ailments without so much as a second thought.

Buried in paragraph 10, after the frightening introduction and ominous warnings from one of the study's researchers, Professor Emily White, we read:

there is no proof that acetaminophen causes cancer, and the new results need to be confirmed before they are used in any treatment decision.
[para 12]  people who use lots of painkillers could be dealing with medical problems that set them up for cancer down the road. [NB bold is my emphasis]

It is quite striking that the more staid and helpful piece from CBS News on the same topic also quoted Professor Emily White but in a much more constructive, informative fashion, higher up the piece.

 

How big is the risk?
"A person who is age 50 or older has about a 1 percent risk in 10 years of getting one of these cancers," study co-author Dr. Emily White, professor of epidemiology at the Fred Hutchinson Cancer Research Center in Seattle, told Reuters. "Our study suggests that if you use acetaminophen at least four times a week for at least four years that would increase the risk to about 2 percent."
The study tracked painkiller use among nearly 65,000 men and women 50 to 76 years of age. The researchers found that 577 people developed a blood cancer, and the risk of cancer nearly doubled in frequent users of acetaminophen.

Not only does CBS use a Reuters item to inform its readers of the actual size of the risk early on in the story (information that is given much later in the Daily Mail account) but it also (as recommended by Dr Alicia White) links to the original paper for more information: Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risks of Hematologic Malignancies: Results from the Prospective Vitamins and Lifestyle (VITAL) Study.

Ben Goldacre had discussed the importance of where you print such information: The Daily Mail cancer story that torpedoes itself in paragraph 19

by the time you get to a story length of eight to 11 paragraphs, on average, your readers read only half the story....
Caveats in paragraph 19 are common. This evidence strongly suggests that they are also a sop: they permit a defence against criticism, through the strictest, most rigorous analysis of a piece. But if your interest is informing a reader, they are plainly misleading.

 

Such reporting from the Daily Mail is what prompts people such as Tess1959 to ask: 

is there any way the mail could be banned from publishing anything remotely related to medicine? Or banned completely?


Nothing Special has an interesting overview of the Daily Mail and its advertising revenues: Kill the Daily Mail. Albeit the figures relate to the Tuesday Good Health sections there are useful insights into the Health section as a circulation driver and source of advertising. As Dr Alicia White so wisely remarks: 

Would you read an article called, “Coffee pretty unlikely to cause cancer, but you never know”? Probably not.

 

 

 

Meeting to Discuss A London Food CraftSpace

Have you ever looked at a recipe that calls for a specific technique and thought, "I'd really like to see someone do that"? Do you regularly pine for access to a well-equipped public kitchen to try out new foods and ideas that you don't have the space, fridge capacity or equipment for at home? Would you like a place where not only do people know your name, they also want to discuss how to achieve a smoke ring on barbecue, the pH of beetroot and how the hardness of water has altered the colour of your stock?

Do you wish there were a public space to cook, eat and chat with other people about food? A place for beginners and those with experience to share tools and knowledge on both individual and group projects? The name for this collaborative place might just be London Food CraftSpace.

The multi-talented Florian Siepert of Foodtri.ps discussed the notion with several attendees at the recent t Fire & Knives Mixed Grill event in London and with others since. There has been a basic sous-vide event hosted at London HackSpace who were generous enough to allow us to use their facilities and also afforded an opportunity to look at some of their superb range of equipment (in addition to computers, soldering irons and woodworking devices there is a MakerBot Cupcake CDC 3D modeller and a laser cutter).

Similarly to London HackSpace, pooling resources might allow us to assemble a place where we can get together and share our experiences and knowledge and perhaps swap ideas on affordable solutions for tools that it would be impractical to buy for occasional use or for which we lack the space. With the appropriate facilities, there might be general interest classes in bread-making or courses in remarkably niche topics such as hydrocolloids for the terrified. There would be scope both for individual experimentation and collaborating on larger projects.

If you're interested in discussing the idea then please sign up at Florian's helpful scheduler and come along to a London Food CraftSpace Meet-up, Sunday, May 8, 8 pm (20:00) at The Drapers Arms, Islington.

Sous Vide London Hackspace March 31

Mrhackspace

 

London HackSpace March 31 2011 Thephotograph shows Michael Riemenschneider and assorted attendees in varying states of visibility (including Tim Hayward) plus the back of several heads (sorry). 

The multi-talented Florian Siepert of Foodtri.ps was the stimulus and facilitator for this introductory Sous Vide Hack event after the success of his talk at the recent t Fire & Knives Mixed Grill event in London. London HackSpace were generous enough to allow us to use their facilities which also afforded an opportunity to look at some of their superb range of equipment (in addition to computers, soldering irons and woodworking devices there is a MakerBot Cupcake CDC 3D modeller and a laser cutter both of which offer exciting facilities for the motivated food hacker).

We started off with a talk from the inspirational Michael Riemenschneider, a chef who held a Michelin star by his mid-twenties and is now in the process of opening his first London restaurant. London HackSpace is a far cry from Michael Riemenschneider's usual venues but he seemed to make cultural adjustments to food and tech geekery in such conditions with admirable rapidity.

The conditions may have been a little crude but, given Medellitin's superbly nerdish account of the origins of sous vide with Sir Benjamin Thompson (creator of Rumford's Soup - an experiment in scientific nutrition, briefly married to Marie-Anne Lavoisier (chemist Antoine Lavoisier's widow), collaborated with Sir Joseph Banks to form the Royal Institution of Great Britain), running this event in London Hackspace felt appropriate in so many ways.

 Michael Riemenschneider uses sous vide for everything from starters to patisserie and has worked with both pro and consumer devices. He gave a comprehensive overview of the gastronomic reasons for sous vide cooking. Although some of these are financial (restaurateurs prefer cooking methods that do not lead to shrinkage of the meat or fish and are flexible enough to reduce competition for cooking rings etc.), Michael Riemenschneider explained that the one of the greatest strengths of the sous vide technique is that it respects the intrinsic quality of ingredients and does not use methods that fight the inherent physical reality of (say) the muscle structure of a piece of meat. 

Slow-cooking is typically the preferred technique for breaking down collagen in some cuts of meat without transforming the surrounding muscle texture into mush. (There are many assumptions about the tenderisation of meat and achieving a desirable texture, it is only by collecting the experience of chefs and others who do this on a regular basis that erroneous beliefs can be corrected. For a very fine discussion of meat tenderisation, see, e.g., this Egullet discussion thread but be warned it has lots of intriguing details about the differences between enzymatic and thermal transformation of protein.)

As one example of the flexibility of sous vide,  Michael Riemenschneider explained that he had recently adapted a beef and barley stew recipe that had been a staple of his grandmother's cooking repertoire. On a personal note, I've used sous vide to adapt some family recipes that depended on (now deprecated) practices such as bringing a boned, stuffed, trussed chicken to a rolling boil, simmering for an hour and then leaving overnight to cook in the residual heat of the water. I haven't tried sous vide as a substitute for stuffing and roasting a chicken or pork shoulder but it's possible that this method may have a useful contribution to make towards re-interpreting the standard roasting technique.

Michael Riemenschneider also argued sous vide is sometimes used to simplify cooking tasks in some kitchens as it is quite difficult to make substantial errors once the food has been prepared correctly and bagged for the water bath. The ability to hold food at the correct temperature before finishing for service is a substantial boon both for restaurant scheduling and harassed domestic hosts with a full dinner table of guests. However, it would be useful to see Michael Riemenschneider expand on that for domestic sous vide users (he runs classes on that and other cookery topics). I imagine that a number of cooks would like a simpler way to organise set piece family occasion dinners such as birthdays, anniversaries, secular or religious festivals.

Michael Riemenschneider has some reservations about the temperature stability of some sous vide systems that are currently available for the domestic market. He expressed his concern that some such systems have exhibited a temperature swing of as much as 5°C which would undermine the usefulness of the sous vide technique for cooking at the lower end of the temperature continuum, especially for foodstuffs such as fish. A substantial temperature over-run might also scramble rather than pasteurise a custard that is intended for (say) ice-cream making.

The temperature swings of domestic systems may be related to the heating elements of the devices (whether stand-alone or the add-on to a controller system) or the volume of water that they contain after the foodstuffs have been immersed. There is a lot more to be written on this topic but I will gather some notes for future posts.

Michael Riemenschneider has a tremendous breadth of experience in using sous vide and favours lower temperatures that he has researched for his protein dishes. Likewise, he has useful guidance and knowledge for preparing fruit and vegetable dishes that typically need higher temperatures because of their pectin and cellulose content.

For comprehensive information about sous vide as a technique for the home cook and specific cooking times for foodstuffs, participant Alastair Instone from the School of Food recommends: Cooking Issues nicely illustrated Low Temperature Cooking Charts (pdf) and Doug Baldwin's Practical Guide to Sous Vide Cooking. None of those present had seen it but Nathan Myhrvold et al's Modernist Cuisine is the current reference standard for those who are uncannily interested in the technical aspects of food preparation. (Kilkennyormonde Hotel recently tweeted a job for a pastry chef for which one of the highlighted inducements is the opportunity to read and use Modernist Cuisine.)

Michael Riemenschneider explored some of the advantages of vacuum packing foodstuffs before preparing them in a water bath. However, for people who would like to experiment with the technique but don't have a vacuum sealer, Cooking Issues has written Sous Vide and Low Temp Primer Part II: Cooking Without A Vacuum that illustrates how to use the immersion technique to exclude air and report that this is sufficient for cooking meat or fish.

After Michael Riemenschneider's talk we had some pulled pork and salt beef that had been lurking evilly in a couple of the sous vide systems that I had set up earlier (evilly because they were repurposed lab equipment and several attendees commented that the meat looked like laboratory specimens and the only thing missing that would completely unnerve them was a human head). One of the accompaniments was Cucumber Freezer Pickles and as these were well received I'll put the technique for that in a separate post.

This is a collection of notes rather than the write-up the day deserves however, if I wait until I have to do the event justice then this won't be timely (and, yes, I'm mortified that I can't rectify the photograph orientation at present). I'll add more notes about the systems on show (including the infamous 'swamp cool box' method from which Michael Riemenschneider almost physically recoiled) in some follow-ups and when I've finally received some of the components that I ordered weeks ago. To be clear, I don't have any direct or indirect associations with any of the products etc. that are mentioned in this post.

Some additional links to items that were mentioned.

Michael Riemenschneider uses Grant waterbaths in a range of capacities (up to 54 litres). Prices for 5 litre domestic-size systems seem to be from around £570 in UK, albeit these offer a 2 digit display and control to ±1.0°C rather than the costlier 3 digit display and finer degree of  ±0.2°C or better which is customary in professional systems.

The admirable Kenji of Serious Eats wrote up a very fine account of a 'swamp' sous vide system: Cook your meat in a beer-cooler: the worl'ds best (and cheapest) sous-vide hack [Update: Kenji has a video from TedxCambridge on Science & Craft of Food about the Beer Cooler Sous Vide.] The version we had on display had some additional insulation in the form of a fleece and survival blanket sandwich, and a quilted wrap-around. We'd also dropped some polystyrene beads into the box to improve the thermal holding capacity. This version of the box had a tweaked immersion heater that helps to maintain the temperature of the water inside the cooler. Both Tim Hayward and Alastair Instone spotted an opportunity to provide extra insulation by drilling holes into the lid of a cooler box and filling it with expanding foam filler.

It's possible to heat appropriate volumes of water using combinations of aquarium heaters or immersion heaters used by homebrewers. I'm currently awaiting some nicely-sized immersion heaters from China but there are various systems available (e.g., search for heaters such as the Electrim 75 Thermostatic Immersion Heater - there are firms that will tweak them (safely) so that they will heat up to 60°C rather than the standard range although, in my experience, this restricts its effectiveness to smaller volumes of water such as 15 rather than 25 litres).

I enthused about Techni-Ice ice-packs for improving temperature stability for general food uses. In my experience similar ice-packs are expensive to purchase in the UK and I've typically obtained them from eBay if I need it in volume (search for Techni Ice HDR 4 Play Reusable Ice Pack, because direct links to eBay time out after a while. However, I have bought it from HT Mart on eBay). If anybody knows about a cheaper, reliable supply, please speak up in the comments.

Alex and Aki's Ideas in Food - both  Aki Kamozawa and H. Alexander Talbot's blog and book.

Useful Twitter accounts

Twitter Florian Siepert 
 
Twitter Michael Riemenschneider (He is currently running a Cookery School Voucher offer for his every 50th new follower)

Twitter The Admirable Kenji (The Food Lab) of Serious Eats 

Twitter Medellitin (Pablo Escolar)
Twitter Aki Kamozawa of Ideas in Food

Slow-poached eggs

Clotilde tweeted that she had attempted Momofuku slow-poached eggs but difficulties in regulating the temperature of the water had resulted in hard-boiled eggs rather than the desired custardy, soft-poached texture.

I wondered if something like a Kuhn-Rikon Hot Pan (an insulated pot) might be useful because it should be possible to heat the water to the desired temperature, put the pan in the heat-retaining shell to maintain that temperature, and then remove the eggs at the appropriate time. However, desirable as such pans are, they're fairly expensive in the UK.

I have a strong urge to rig up make-do systems so I took a 3 litre pan, digital thermometer, fleece blanket and survival (foil) blanket and put them all together. I took a guess that I needed to heat the water to 64°C if I wanted to have a water temperature of approx. 62 °C after immersing 3 medium-size eggs. I took a temperature reading of 64 °C and replaced the pan lid after placing the eggs. The entire pan was placed onto a sandwich of survival blanket and fleece blanket which was brought up and round the pan and secured with a bungee strap.

I left the pan for 45 minutes, unwrapped the pan, took a temperature reading (approx 60 °C)  and cracked open 2 eggs. The results are below and I've broken the yolk of one of them to show that it has thickened and flows reasonably well. Because I was uncertain about the outcome I used fairly elderly eggs so the results would have been much better with fresh (not least because the yolk wouldn't have stuck to the shell so much). However, I'm reasonably confident that this method would work with some trial and error.

Next time, I would use fresh eggs and start from an initial temperature of 65 °C. Another experiment would be to cut a snug hole for the pan in a polystyrene block which would hold the temperature very well (put a pillow/cushion or survival/fleece blanket sandwich on top for added heat-retention). I think that the temperature dropped a degree or so more than I had anticipated because I hadn't pre-warmed the fleece blanket that formed part of the insulation. I might also pre-warm the eggs by immersing them in a jug of water from the hot-tap for a minute or so before immersing them in the pan as that would also mitigate some of the temperature drop.

It will be obvious that I only take photographs under duress so apologies for the quality of the following which I offer in the spirit of technical illustration rather than gastronomic delight. I should also mention that I loathe the appearance of eggs and it was only my technical curiosity that enabled me to try this out.


(download)

London HackSpace: Sous Vide event March 31

There has been a lot of talk around Sous Vide devices and their use in the past few years: Professional kitchens have been using them for a while to cook ingredients so that they reach very precise temperature levels, thus creating steaks that are perfectly rare throughout and eggs with perfectly runny yolks and firm whites.

A consumer market is beginning to emerge in this field, but are these devices really worth the extraordinary amounts charged for them? And what are DIY ways around this? All this and more will be discussed at:

Sous Vide Hack Day

March 31st, 7pm

Unit 24
Cremer Business Centre
37 Cremer Street
London E2

Hoxton Rail

Admission: £5 donation to London Hackspace

 

Program:

The multi-skilled Florian Siepert is the MC of this event.

Talk by Michael Riemenschneider, the swiss born chef who held a Michelin star by his mid-twenties, then went on to do high level cookery classes and is now in the process of opening his first London restaurant. Michael claims to use sous vide for everything from starters to patisserie and has worked with both pro and consumer devices. He'll share insights into the gastronomic reasons for sous vide cooking.

Demo of several systems put together by Evidence Matters and Hackspace London of various versions of DIY sous vide equipment from a modified cool box, slow cookers to Gallenkamp laboratory water heaters, chamber vacuum sealers and more. There will be an overview of how to assemble a basic kit for home use and more advanced projects featuring PID/Arduino/Auber elements to achieve even more precise results. We'll partially disassemble a DIY sous vide kit and put it back together.

We can discuss some of the options available to home users of sous vide and the proposed system that we are refining (we had hoped that the various parts would have arrived from China and Hong Kong by now but they haven't. Nonetheless we want to evaluate some of these because they are approximately a third of the price of system components that are available in the UK. If people feel inspired by this event we should be able to put together a full day workshop to assemble a DIY sous vide system.).

Fortunately demoing Sous Vide machines also makes it necessary to cook things in them. So, yes, there will be many samples of food.

So here it is: An extravaganza with exciting guests, food and permutations of electrical equipment. What could possibly go awry?

New Yorker, Can a Stressful Childhood Make You a Sick Adult?

Paul Tough has what looks to be an interesting piece in the New Yorker: The Poverty Clinic: can a stressful childhood make you a sick adult?


The abstract describes a particularly common observation (adult with multiple health problems has had stressful childhood) and the topic feels particularly timely when there are news reports that: single parents are to be charged for resorting to the Child Support Agency to enforce the collection of child maintenance payments; the introduction of flexible working regulations for parents is to be cancelled for firms with fewer than 10 employees; and there is some disquiet/vigorous discussion about NHS reforms, the fate of Sure Start Centres and other services that may have an impact on the health of children or the support available to them. 


The abstract crams in some of the principle arguments that underpin research into allostasis and allostatic load. Crudely, the relevant argument here is that the concept of stress is described via numerous mechanisms. These encompass physiological stress reactions in response to home circumstances, working/educational conditions, inter-personal conflict, ability to control the personal environment and a sense of optimism/pessimism about future prospects. The notion of 'allostatic load' involves considering the cost of constantly responding or adapting to a stressful environment which may produced repeated cycles of adaptive responses (allostasis) that facilitate homeostasis in the short term but may lead to wear and tear on the body and brain.


The abstract stirred the memory of a study at the Philadelphia Child Guidance Clinic (pdf). 

Diabetic children who experience chronic bouts of ketoacidosis had been widely treated with beta-adrenergic antagonists. This often proved ineffective, and it was hypothesized that the metabolic disturbance is induced by parental conflict expressed through the child (“who is right, Daddy or Mommy?”). This was directly observed in “stress interviews”. The parents’ fatty acid levels would rise but soon return toward baseline, whereas the child’s would remain elevated for hours (Figure 2A). Clearly, potent psychological demands were driving multiple physiological mechanisms to override the beta-adrenergic mechanism. Salvador Minuchin, the clinic director, described this as a poignant demonstration that “behavioral events among family members can be measured in the bloodstream of other family members” (Minuchin, 1974).

The children stabilised readily in hospital but tended to relapse when they re-entered the family home. When the parents were coached in techniques that allowed them to resolve their conflicts directly, and without involving the children, the children could be stabilised at home without the use of the beta-blocker. There was an improvement in the children's medical outcome as a result of a successful intervention between people other than themselves.


I know very little about allostasis and allostatic load. However, I've been reminded of claims about it many times over the past few months as more and more reforms are announced that remove some of the present support for families and children. I'm awaiting the announcement of the 3rd Sector or Big Society interventions that will go beyond what was previously available and improve the outcomes for children (both in childhood and as adults). However, according to Ingrid Wolfe's interesting tweets on the paucity of well understood quality indicators for Child Services, such improvements are not imminent.


Minuchin S (1974) Families and family therapy. Cambridge MA: Harvard University Press

Hack your own Sous Vide at London HackSpace March 31

Sous Vide is a method of vacuum-sealing food under pressure and cooking it at precise, controlled temperatures that showcase the texture and flavour of the foodstuff. A fair number of cooks are interested in the sous vide food preparation technique but have neither the funds nor space to purchase a standard system. There's a lot of interest in hacking a sous vide system to fit personal finances and available space. March 31 is an opportunity to do this with some guidance and access to necessary materials and gadgets in a good workshop space.

Updated details for the Hack your own Sous Vide event.

Date: 31 March, start time 7pm (19:00)

Laboratory 24
Units 23 & 24
Cremer Business Centre
37 Cremer Street
London E2 8HD

Entrance is opposite the interesting Geffrye Museum

Google Map

Course Organisers: Florian Siepert & EvidenceMatters

Cost: order your own components (suggestions below) and bring your own cooking appliance to hack (suggestions below). On the day we will need a donation of approx. £20 to contribute to venue hire and cost of other components.

Outcome: a flexible, temperature-controlled cooking device that will be usable for sous vide methods. This device will not provide the fine-grained temperature control of high-end models (that typically allow control to 0.1 degree C) but is comparable to the mid-range systems that are available for approx £350+ in UK.

Please order the following components: to be confirmed as we want to make sure that UK stockists have enough but we should be able to recommend  a controller and probe very shortly.

Suggested appliances for hacking. It's possible to hack small appliances such as slow cookers, rice cookers, wet bain marie or similar appliance that offers some simple degree of temperature control. It is more straightforward to adapt appliances with simple controls because they are easier to turn one and off in response to the temperature range: these techniques will also make it possible to retain the original use of the device. An appliance with a programmable digital interface would need it to be disabled which would make it impractical to use the appliance for its original purpose (eg, digital rice cooker; single induction hob).

Examples of suitable appliances: Lidl Electric Fruit Preserver/Jam Maker/Mulled Wine Heater (similar ones are available in UK from other sources but at approx. double the cost); Amazon currently has a 6.5l Morphy Richards Slow Cooker for approx. £25; Tesco and Argos have 3.5l slow cookers for approx. £16. The small volume slow cookers are restrictive in what they can cook but are adequate for small pieces of meat or fish.

I intend to bring along a vacuum chamber sealer and a couple of my own hacked set-ups so that people can take a look at those during the event.

Please confirm your interest and ask any related questions in comments.

Florian, London HackSpace and I look forward to seeing you March 31.

Twitter Florian Siepert 

Twitter Evidence Matters 

Twitter London Hackspace 

Sous Vide Hack Event at London HackSpace

Florian Siepert was a popular speaker at the recent Fire & Knives Mixed Grill and excited a lot of interest not only with descriptions of his food camps but also when he mentioned that he would be interested in leading a 'Hack your own Sous Vide from a slow cooker/other temperature controlled appliance' event in London.

We're very fortunate to have the well-equipped London HackSpace as a venue for the event.

Florian is currently scheduled to be in London from 29 March to 1 April. London HackSpace is hosting a Perl Hackathon from 28-30 March so the current best date looks like Thursday 31 March with class time running from late afternoon into the evening or from early evening onwards.

The cost for the event will include a donation to the London HackSpace and will need to cover the cost of the necessary components and other incidentals. Bring along your slow cookers, rice cookers, automatic jam makers or other suitable appliance to hack.

The Sous Vide Hack Event is now being planned. Please comment below to sign up as an expression of interest and give preferences for particular day or times.

Update We are confirmed at London HackSpace for evening of March 31. More details to follow. Please comment to register interest.

Twitter Florian Siepert

Twitter Fire & Knives

Twitter Fire & Knives Mixed Grill

Twitter Evidence Matters

Twitter London Hackspace

NHS Health Atlas of Variation in Health Care in England & Wales

The NHS Atlas of Variation in Healthcare is a landmark in transparent, useful data. Its creators offer an elegant summary:

Awareness is the first important step in identifying and addressing unwarranted variation; if the existence of variation is unknown, the debate about whether it is unwarranted cannot take place...
Commissioners should consider the opportunities to maximise health outcome and minimise inequalities by addressing unwarranted variation. We hope by extension, to stimulate action to tackle the drivers of un-warranted variation to improve quality for patients and increase value for the NHS.


The Guardian has an overview of the NHS Atlas and reports that there is a coalition of ten health charities (including Diabetes UK and Asthma UK) that see the opportunity to identify variations in provision of care for particular conditions and patient groups.

Ciarán Devane, chief executive at Macmillan Cancer Support said: "The atlas shows that there's not always a direct connection between the amount of money spent by the NHS and the quality of care provided to patients. The number of people living with the different diseases and longterm conditions our ten charities represent is set to increase dramatically. If the NHS stands any chance of coping, it needs to be clear about where best practice is taking place, so that underperforming areas of the country can improve their performance urgently.


The Daily Mail version illustrates its coverage with some good examples of variation in health care but emphasises the more negative implications of the Atlas with the headline: NHS postcode lottery exposed: The shocking maps that let YOU know where you will get good treatment and where to avoid

Three-quarters of all stroke victims are missing out on treatment which would drastically improve their chances of recovery

A report on the shocking extent of Britain’s ‘postcode lottery’ of NHS care revealed that a majority of patients are simply left on hospital wards rather than being looked after in specialised stroke units.

Fewer than 25 per cent of sufferers are being admitted to such centres, despite official recommendations that all those who suffer a stroke should receive this level of care by highly trained doctors and nurses.


There will be good analysis of this Atlas from various organisations over the next few months and the coalition of charities may issue some useful reports.

One interesting aspect of the Daily Mail comments is the number of people who discuss the variations as if they are relatively recent rather than something that been present since the inception of the NHS.It was widely acknowledge that resources had been distributed unevenly. It's possible that variations seemed to excite less outrage in the early years because so many life-saving and life-enhancing treatments didn't exist. (Short History of the NHS has some useful treatment landmarks and overview of NHS re-organisations.)

The excellent Wellcome Trust has an archive of films about the early years of the NHS. Segment 5 of the 1973, LTS' TV programme "The British Way of Health" shows Drs Stone, Gibson and Laing discussing waiting lists and restrictions in the 1970s, even for plastic surgery for young children with extensive birthmarks on the face.

 However, these variations have existed from the inauguration of the NHS. Sharing resources for health in England: Resource Allocation Working Party reported in 1976: its terms of references were:

To review the arrangements for distributing NHS capital and revenue to RHA,s AHAs and Districts respectively with a view to establishing a method of securing, as soon as practicable, a pattern of distribution responsive, objectively, equitably and efficiently, to relative need, and to make recommendations.


Sadly, that noble aspiration was not fulfilled in the 1970s or subsequently, resulting in the variations and inequalities shorthanded in "postcode lottery". The Atlas is particularly helpful in highlighting that marked variation in health care is not always related to health care spending.It will be useful if investigation of the details prompts discussion about the factors that do influence such variations. It is lamentable that it has taken so long to collate the data that have always been lacking from rigorous evaluation.

The Atlas is a landmark in overdue transparency (it makes its methods and data sources readily accessible) and is a starting point for essential conversations about the future of the NHS.

The collective principle asserts that... no society can legitimately call itself civilised if a sick person is denied medical aid because of lack of means. (pg. 100)
The National Health service and the Welfare State have come to be used as interchangeable terms, and in the mouths of some people as terms of reproach. Why this is so it is not difficult to understand, if you view everything from the angle of a strictly individualistic competitive society. A free health service is pure Socialism and as such it is opposed to the hedonism of capitalist society. (pg. 106)
—Aneurin Bevan, In Place of Fear

.Corrections

1 Atlasof Variation in Health Care covers England, not England and Wales.

 

David Smith, B vitamins and Alzheimer's Disease

Several people have voiced concerns about the recently published Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial.

Citation: Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244

Responding to some of the points raised by Carl Heneghan: Vitamin B and slowing the rate of brain atrophy: The numbers don't add up. I had left a series of comments but they were lost. I'll reproduce some of them here.

Heneghan:

A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial from 271. Therefore the study lost a lot of participants – where did they go?

The study authors don't really seem to have 'lost' them although reasons for declining to participate in the scans are not outlined.

A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Smith et al, 2010

It's not implausible that some of the participants might have had shunts, stents or joint replacements of such vintage that not all were readily suited to MRI investigation. Without access to the consent documents, it's not clear if some participants refused scans on the grounds that they wouldn't wish to know if they were in a group with greater brain atrophy and perhaps 'more likely' to develop AD. Unhelpfully, the appended VITACOG protocol does not clarify this matter.

We will also scan the brain by MRI before treatment and then again two years later when the treatment has finished. We can then measure the rate of brain shrinkage in each group. MRI will be voluntary for those who consent to participate in the trial and who don’t have a cardiac pacemaker.

Albeit the authors seem to have mis-judged the participation rate or there were more participants with pacemakers etc. than anticipated because the usable MRI participation rate is approx. 62%. "Participation in the MRI scans will be voluntary and we anticipate that about 80% subjects will volunteer." 187/271 indicates that 69% volunteered.


In the appended methods supplement, Smith et al state:

Eligible participants were asked if they would agree to have two cranial MRI scans, one at the start and one two years later at the end of treatment, but it was emphasized that the scans were voluntary. Although the main outcome of the trial was atrophy rate, we allowed subjects that could not or did not wish to participate in the MRI part of the study to enter the trial in a separate arm: the intention was to evaluate recruiting strategies for such trials (not reported here) for subjects with MCI.

The reference to a "separate arm" is confusing, given that only 187 of the eligible 271 appear to have consented, yet we are quoted (as per Heneghan) adverse event data from n=266.

168 of the 187 volunteers had MRIs that were suitably clear for interpretation.

I'll update this post as I try to re-construct the lost comments. However, It's not clear to me that the reported results and the confidence reposed in them are in line with the authors' description of what the study was powered to observe, as described in the protocol.

Update 1: Before addressing specific issues, I recommend. Does Industry Sponsorship Undermine the Integrity of Nutrition Research/ and Relationship Between Funding Source and Conclusion Among Nutrition-Related Science Articles

The authors provided a competing interests statement.

Dr. A. D. Smith is named as an inventor on two patents held by the University of Oxford on the use of folic acid to treat Alzheimer's disease (US6008221; US6127370); under the University's rules he could benefit financially if the patent is exploited. Drs. Refsum and A. D. Smith report having in the past received speaking honoraria from Recip AB, the company that donated the vitamin tablets, and from Axis-Shield, who make the equipment used to assay homocysteine. These competing interests do not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. None of the other authors have any financial disclosures.

It will never be clear-cut as to just how much information authors should provide in such statements. However, some Twitter exchanges have commented that Drs Smith and Refsum are associated with the contentious work of Patrick Holford. Both Smith and Refsum are members of the Scientific Advisory Board for enterprises from which Patrick Holford derives an income: eg, Food for the Brain and Brain Bio Centre.

Patrick Holford claims that Dr Smith co-taught a Food Is Better Medicine Than Drugs (FIBMTD) seminar expressly targed 'to doctors, by doctors' (see, eg., this video interview of Patrick Holford on RTE's Late, Late Show, dissected in some detail by Holfordwatch, eg. Patrick Holford and his tap-dancing on the Late Late Show). FIBMTD is a book collaboration of Patrick Holford and Jerome Burne and has its own seminar series arguing for a nutrition (but mostly in the form of supplements) approach to health problems with some notable reporting errors

Dr Smith and Patrick Holford are a regular double act in discussing research findings in newspapers such as the Daily Record before they are available for scrutiny. Dr Smith not only provided the foreward for Holford's Alzheimer's Prevention Plan book but is also said to have reviewed the manuscript (albeit, Smith's reviewing standards for non-peer review work have been criticised by HolfordWatch and Professor David Colquhoun and, to be fair, Dr Smith accepted that FFTB research for which he had been a scientific adviser and reviewer had not been  "a proper job" or "rigorous").

Update 3: It is notable that Dr Smith's informal colleague, Patrick Holford, has used the results of this paper as a marketing opportunity for homocysteine tests (not the one used in the study) and his own range of supplements (not the ones used in the study although tacitly, perhaps, endorsed by Dr Smith as part of Holford's Alzheimer's Prevention Plan (as above)). See B vitamins stop brain shrinkage preventing dementia (albeit I doubt the author meant the obvious interpretation of such a title).

In line with his own assertions, for which there is no solid evidence base, Holford advises:

The cut-off point for an effect was 10, so you want to make sure your homocysteine level is certainly below 10, although a level below 7 is optimal, especially if you are younger.

It is worth reminding readers that (the last time I looked) assays from different laboratories are not standardised and the results are not, therefore, inter-changeable or able to support the sort of interpretation or recommendation that Holford offers. As for supplementation, Holford ignores some of the concerns surrounding supplementation and the stimulation of some cancers and despite a correct summary of the study's dosages:

Smith’s team studied the effects of giving homocysteine-lowering B vitamins (folic acid 800mcg, B6 20mg and B12 500mcg)

advises:

If your level is raised, you need to supplement a homocysteine-lowering formula of B vitamins and supporting nutrients. For levels above 9, this would look something like 800mcg folic acid, 500mcg B12, 75mg B6, 20mg B2, 15mg zinc, 1.5-3g Trimethylglycine (TMG) and 500g N-Acetyl-Cysteine. If your test revels levels about 15, then you need slightly higher doses.

This last is disingenuous: Holford advises titrating vitamin supplement intake according to tHcy levels and individuals may be thus persuaded to take considerably more than Smith's team has investigated.

Update 4: Henegan has elegantly summarised one of the main causes for concern in the reporting of this study.

Although treatment with vit B after 24 months significantly slowed the rate of brain atrophy by 30% this is a relative measure. The absolute reduction is 0.32% over the length of the trial. The question is; is this clinically significance? Given adherence, was about 75% and 17/83 (21%) of the placebo group had taken supplementary folic acid or vitamin B12. In the active treatment group, and 14/ 84 (17%) in the treatment group did not take, or did not absorb, the vitamins, only 136 were defined as biologically compliant.

Until there is follow-up of this group, and a large, multi-centre trial, it is inappropriate to anticipate that the reported reductions in the rate of brain atrophy will prove to be clinically significant. Drawing upon trials in cardiovascular health, D Eva Lonn provided a useful reflection on the history of potential of the therapeutic manipulation of homocysteine levels and the, to date, disappointing clinical outcomes in populations that are already well nourished.

While the experimental and epidemiological evidence does indeed support a plausible role for homocysteine lowering in CVD prevention in the population at large (as opposed to a limited role in rare genetic disorders), overzealous interpretations of such data have led to extrapolations and unjustified early enthusiasm…

Two obvious questions arise: why did the B vitamin homocysteine-lowering trials conducted to date not demonstrate clinical benefits and is there a role for additional trials or should researchers close yet another chapter, which seemed promising but failed to deliver. The answers to these questions are complex…However, it is possible that the treatment truly has no effect on vascular risk…

In conclusion, B vitamin supplements cannot currently be recommended for the prevention of CVD events (with the exception of rare genetic disorders) and there is no role for routine screening for elevated homocysteine levels. However, ongoing clinical research should provide further evidence on whether there may be any role for homocysteine-lowering B vitamin supplements in CVD prevention and for the overall importance of homocysteine as a CVD risk factor. Lonn, E. Homocysteine-Lowering B Vitamin Therapy in Cardiovascular Prevention—Wrong Again? May, 2008; vol 299: pp. 2086-2087.

It seems that a substantial number of the participants in Smith et al.'s trial were already accustomed to taking vitamin B supplements. It might have been useful if the authors had asked the participants or the study partners to state whether they believed that they were taking the active treatment or the placebo. Depending on the formulation, B vitamins can have a distinctive taste and this might have been sufficient to 'un-blind' some of the participants in the placebo group, and may account for some of the 21% rate of additional supplementation. NB, the supplementary description of the methods mentions attention to the authentic colour of the tablets but not the taste:

The placebo tablet was identical to the vitamin tablet (TrioBe Plus®) except for omission of the vitamins and the addition of iron oxide and ferrous sulphate (0.0055%) to give a colour to match the vitamin tablet.

 

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