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.”