Samstag, 22. Dezember 2012

Gunownership and gun-related mortality?

Sorry, for the time being I have fallen in love with evidence-based politics & policy, statistics and economy, so this might not be the last post on this topic. I've caught the disease thanks to Nate Silver, Paul Krugman & friends, Freakonomics, et al.
Broadly speaking, the topic is relevant to this blog, which is about avoiding unnecessary death and suffering - even though biomedical research is certainly more crucial than gun laws. What good is healthy life-extension if you have been shot, right?

After the Newtown killings and post-Breivik, I would like to add to the discussion something above the evidence-free back and forth we often see in the media and elsewhere. In this case I have simply taken a very superficial look at the academic literature to see what the consensus on gun issues might be.

My working hypothesis is that societal dysfunction and lax gun regulation are both contributors to the composite endpoint of gun-related homicides, suicides and other crimes like armed robbery. No surprises here. But what are the individual contributions of each? I guess both matter although:
"There is, however, the possibility that accessibility alone does not produce more lethal violence. A society could, for example, have high firearm accessibility but due to a lack of structural deprivation its citizens simply do not use firearms either against each other or on themselves." (1)

And two weaker arguments against gun control:
"Another argument from the political debate over gun control is the argument that an equal distribution of firearms has a deterrent effect (Lott 2000). If everyone is similarly armed a thoughtful attacker will ‘‘think twice’... [but this] does [not] appear to hold empirically (Donohue 2003)...
Finally there is the argument that mere competence may reduce the lethality of weapons like firearms."
I'll let the researchers speak with all quotes from (1):

Dienstag, 27. November 2012

Cliffnotes on vegetarianism: Yes, you should eat less meat and more veggies.

Ever since I read the 1999 meta-analysis of vegetarian diets and mortality (2) I wanted to see a follow-up. Finally, some epidemiologists gave it another try.

Enter Huang et al. 2012 (1):
Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97).”
"Begg’s funnel plot and Begg’s test showed a slight significant publication bias in all-cause mortality, cancer incidence, ischemic heart disease and circulatory disease. No publication bias was observed in cerebrovascular disease."
Nonetheless the risk ratio for cerebrovascular disease is not materially different from the other risk estimates, arguing against the null hypothesis. What this may suggest is inadequate statistical power.
And there was some heterogeneity between studies
and residual confounding or bias always remain a big problem in observational studies of this sort. However, sensitivity analysis showed that heterogeneity did not unduly influence the data. 

If it were not for supportive evidence from other study designs, including well designed controlled trials, I wouldn't consider this study to be all that solid evidence. But we do have evidence that:
  • dietary patterns like "prudent", Mediterranean, vegetarian + (marine) n-3
  • food groups like legumes, vegetables, fruit, nuts, olive and n-3 rich plant oils, whole-grains
  • dietary substances abundant in plant foods like fibre, potassium, magnesium, vitamin K, antioxidants, plant protein, secondary plant metabolites, etc. are healthy
and that plants lack many detrimental substances found in foods of animal origin like heme iron, saturated fat, cholesterol, toxic compounds formed due to cooking and heat, BCAA & methionine rich protein.

NB: the above is a simplification and much more could be said on the topic. There is evidence that a vegetarian diet can be further optimized by including low fat dairy and either a source of marine n3 fatty acids or regular intakes of ALA (=n3 of plant origin).. that lowish intakes of white meat can be acceptable... that vegetarian diets can be improved by supplementation and much more.

(1) Ann Nutr Metab. 2012;60(4):233-40. doi: 10.1159/000337301. Epub 2012 Jun 1.
Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review.
Huang T, Yang B, Zheng J, Li G, Wahlqvist ML, Li D.

(2) Am J Clin Nutr. 1999 Sep;70(3 Suppl):516S-524S.
Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Key et al.

Samstag, 17. November 2012

Barack Obama defended the presidency and why the heck should I care?

I refuse to believe that politics must be about ideology. Most politics and policy deals with reality and as such ought to be evidence-based. As it happens, there is usually a party that sides with reality more closely. So why was this election critical?

There are good reasons why the US election is an international issue most importantly globalisation, but we also should emphasize with the American people. Of course, Barack Obama is not a good president, far from it, but the only realistic alternative was cataclysmic.Therefore the election can be considered a small win for science over noise, which was perfectly predicted in advance by the famous poll aggregator Nate Silver.

To understand why, let's look at science and health policy: With the Republican slash and burn approach to the budget, funding for the National Institute of health (NIH) and National Institute of Aging (NIA) would be in jeopardy. We already know funding for the NIH wasn't exactly rosy during the last Republican administration.
However, research may be crippled by other means too. Remember that it was the Republican George W. Bush who appointed and listened to bioethicists like Leon Kass, who is not only anti-abortion and anti-stem cell research, but also firmly opposed to life extension. With such monstrous friends who needs enemies? I doubt a republican president would be less radical today, given the strong grip the Tea Party has on the GOP.
And this is not offset by any benefits to the free market, i.e. pharma companies, that I know of.
Tens of thousands die due to a lack of insurance each year, and it took a Democrat to broaden coverage against fierce opposition. Colour me unimpressed, Republicans.
On the other hand, if a Supreme Court of the United States (SCOTUS) appointee leads to an overturn of Roe v. Wade, allowing bans on abortion, tens, probably hundreds, of thousands will die as an (in)direct consequence of medical complications and of being born into dysfunctional families.

A SCOTUS and president that kills Roe v. Wade may enable the teaching of creationism in school, even if it is just by a back-door.
The Republicans continue to deny the scientific fact of AGW and ecological problems, and under such an administration reckless exploitation of the environment will continue to erode the long-term growth potential of the US.

Republican economic policy paints a picture just as bleak:
While Obama generally embraces very successful new Keynesian economics, that saved (or could have saved) millions of jobs. His opponents call for pernicious tax cuts for the rich, severe spending cuts in a depressed economy, undermine Social Security, continued deregulation, etc., showing their disdain for the poor.

The republican war mongers brought us two unnecessary wars that cost trillions, which could have been spent on - oh, I don't know - education,  research, biogerontology and the global fight against poverty. Foreign policy is one of the key the reasons why Republican politicians are despised in most developed countries.

The Republican track record on social issues is even more horrifying: jingoism, homophobia, racism, misogyny ("the war on women"), prudery and radical evangelical Christianity are rampant in their party from the bottom rungs to the top - with few exceptions.

Disaster has been averted, for now.

Mittwoch, 7. November 2012

What can you do to help us slow, prevent or reverse aging?

You can donate…

Donate to the SENS foundation, or the MFoundation. Or aka imminst, if you like grassroots efforts.

…or do something else
  • Spread the word: blog, tweet, post, like it, talk about it.
  • Critize it! A good scientist will always change his or her opinion given new evidence. Discuss and provide constructive criticism.
  • Do the science, or support the science. Get a degree and support your local university.
  • Buy a book or two. You can learn more about the topic of healthy life extension. Ending Aging is a good start, or another book on biogerontology (no particular recommendation yet)
  • Get political and petition your government. Contact local politicians. Vote accordingly.
  • Indirectly, promote a world view that values: humanism, atheism and agnosticism, critical thinking, equality, LGBT and women’s rights, a healthy diet, the fight against poverty, science, education, freedom and smart growth, environmentalism, liberal and progressive social democracy and the free distribution of knowledge.
  • Look out for yourself: eat a healthy mostly plant based, low or moderate calorie diet. Work out, don't stress, don't smoke etc. However, never forget that only biomedical research will lead to true advances.

There’s much more, other Ideas from...

... Longecity

... Dr. Aubrey de Grey's

...The MFoundation

this post was adapted from the above sources.

Sonntag, 4. November 2012

The Magic of Buying in Bulk

I know this is obvious to some, but I just realised this and it bears stressing: buying in bulk has considerable advantages. This is an easily overlooked benefit of having a stable diet.

Buying in bulk is:
  • practical and efficient, you can save a lot of time at the store.
  • possibly healthier, because storage condition can be optimised, which is particularly important for fatty foods. Especially those containing easily damageable polyunsaturated fatty acids. Retailers often do a terrible job with storage. Nuts and olive oil (EVOO) should be stored cool (8-10°C) and not be exposed to light, for instance, but I have never seen a store do this.
  • ecological, because you need less packaging material.
  • cheaper, since you get discounts.

Montag, 29. Oktober 2012

Helicobacter pylori (Part II): How to test and to treat?

How to test?

Urea Breath Test (UBT), validated stool antigen test and as a close second validated IgG serology (not useful for follow-up, best test if you use acid-suppressing drugs). 

„Several non-invasive H pylori tests are established in clinical  routine.  The UBT [Urea Breath Test (UBT)] using essentially [13C]urea remains the best test to  diagnose H pylori infection, has a high accuracy and is easy to  perform.76 During recent years new formats of the SAT [stool antigen test] (using  monoclonal antibodies instead of polyclonal antibodies, which  lead to a constant quality of the reagents have been developed.  The two formats available are: (1) laboratory tests (ELISAs) and  (2) rapid in-office tests using an immunochromatographic  technique. A meta-analysis of 22 studies including 2499 patients  showed that laboratory SATs using monoclonal antibodies  have a high accuracy both for initial and post-treatment diagnosis  of H pylori.77 These data have been confirmed by more  recent studies.78 79 In contrast, the rapid in-office tests have a  limited accuracy.80 81  Therefore, when a SAT has to be used the recommendation is  to use an ELISA format with a monoclonal antibody as reagent.“

The Urea Breath Test (UBT) and stool antigen testing are acceptable non-invasive tests for H pylori infection in this setting. For UBT, sensitivity is 88-95% and specificity 95%-100%.4 Stool antigen testing may be somewhat less acceptable to patients in some cultures but is equally valid, with a sensitivity of 94% and a specificity of 92%.5

How to treat?

The standard is triple treatment including PPI(acid inhibition) clarithromycin, and amoxicillin (or metronidazole), but can be further improved. Talk to your gastroenterologist.

 Proton pump inhibitor (PPI)-clarithromycin containing triple therapy without prior susceptibility testing should be abandoned when the clarithromycin resistance rate in the region is over 15-20% 
The use of high-dose (twice a day) PPI increases the efficacy of triple therapy [esomeprazole preferred; perhaps slow phase-out vs rebound-reflux disease?]
Extending the duration of PPI-clarithromycin-containing triple treatment from 7 to 10-14 days improves the eradication success by approximately 5% and may be considered
Certain probiotics and prebiotics show promising results as an adjuvant treatment in reducing side effects [I'd recommend lactoferrin because of its safety]

Against inducing antibiotic resistance: hygiene and sanitation (don’t transfer the resistant germs), 100% compliance if possible, state of the art therapy with high acid suppression (increases specificity for the stomach), watch out for local patterns of resistance.

[1a] Management of Helicobacter pylori infection—the Maastricht IV/Florence consensus report. Malfertheiner et al.

Freitag, 19. Oktober 2012

Helicobacter pylori (Part I): should we test-and treat in the very healthy? Points for discussion.

Helicobacter pylori: should we test-and treat in the very healthy? Points for discussion.

Herein I propose that it might be beneficial to treat the ”pathogen” on a case by case basis even though there is no official recommendation for population-wide screening yet. A note of caution: this is based on a preliminary review, but I think it is time to act. As a starter I recommend these two reviews, the authoritative Maastricht IV/ Florence Consensus Report [1a] and a book chapter by Marshall et al. [1b].

H. pylori has been causally linked to atrophic gastritis, functional dyspepsia, peptic ulcer, gastric cancer and some rare conditions e.g. MALT lymphoma, iron loss, etc. The evidence for (other) extra-gastric benefits and harms is weak and inconsistent  [1a, 1b]. The pathogen may promote auto-immune diseases, colorectal adenoma, pancreatic and lung cancer, CVD, disturbed glucose homeostasis, neurodegenerative disorders, and more. Whereas potential benefits from H. pylori infection include: reduced asthma, CVD(!), atopy, inflammatory bowel diseases, weight gain, diarrheal diseases etc. („commensal hypothesis“).

On gastric cancer
Preclincal evidence, observational [1a], and non-randomized studies as well as secondary prevention RCTs (randomised controlled trials)* support a role [4]. As predicted, eradication also improves precancerous lesions, at least somewhat - gastric atrophy may improve but metaplasia does not, Rokkas et al. 2007 [3]: this is the point of no return hypothesis.
Recently, follow-up of a large trial and an updated meta-analysis of primary prevention trials was published and both showed a significant reduction in gastric cancer incidence RR=0.66, 0.46-0.95 with n=4 (see supplementary data, Ma et al. 2012) [2]. The meta-analysis looked at N=4+1+1 studies but even excluding the one secondary prevention (Fukase 2008) and another controversial trial (Leung 2004/Zhou 2008) the result was significant. This was an update of the (then-flawed) 2009 analysis [4b]. However, in this large study there was no decrease in all-cause mortality and a non-significant 30% decrease in gastric cancer mortality. This was mostly expected since the predicted decrease in all-cause mortality was ~ 6% and so the study was underpowered to detect a difference. Nonetheless, this result is decent since their eradication treatment was outdated and reinfection rate must be high. On the other hand, the Asian data is difficult to generalize and the study quality wasn’t perfect.
If we compare H. Pylori eradication to the HPV vaccine, as an example of an approved treatment scheme, it still looks favorable in my opinion: HPV studies were better quality and larger, but the non-cancer benefits of HPV eradication are very modest vs. H. pylori eradication and all data for HPV concerns precancerous lesions only!
All in all, I think the weight of evidence supports population wide screening but the evidence is weak. And if we consider preliminary data on extra gastric effects the case for eradication is stronger, if anything.

Montag, 15. Oktober 2012

Please be patient - This Page is Under Construction!

Please be patient - This Page is Under Construction!

A Draft: Pathologic and Cardiovascular Calcification in Relation to Aging (2008-2010)

Some time ago, I was writing a review on this topic but had to stop due to health problems before finishing it. Here, I publish the draft from 2010 almost unmodified. I hope it is fine if I publish it for people to (possibly) learn from it. A big thank you to everyone who helped with the review, especially the SENS- and Methuselah Foundation.
Despite proof-reading, I am sure I made some mistakes, hopefully not too stupid ones. But, really, the reference to the then-controversial, now-disproven "nanobacteria" in the review makes me laugh already. (At least disproven as far as the bacteria part is concerned.) Even back then I only included it for for the sake of completeness, see if you can find it!

ABSTRACT: “In the first part of the review I am going to discuss vascular disorders involving calcification, how they relate to aging and their clinical implications. Second, I will provide a quick overview of mechanisms involved both in age-related calcification and vascular aging.
The remainder of the review is devoted to potential therapies. The third chapter shortly summarises nutritional and lifestyle influences on calcification. Thereafter, theoretical and practical concepts and problems relating to regression will be discussed, including the role of spontaneous, surgical and pharmacological regression. Lastly, in the fifth part, I will summarise the main points, identify specific targets for future research and introduce the reader to several promising “targeted” therapies in preclinical development.

The major conclusions of this review are that calcification is more dynamic than is appreciated. Calcification may regress spontaneously, albeit inefficiently, thus necessitating development of effective drugs. Therapeutic regression would likely alleviate the age-related decline of the cardiovascular system.”