A Bayesian Hierarchical 13COBT to Correct Estimates Associated with a Delayed Gastric Emptying

The use of a Bayesian Hierarchical Model (BHM) to interpret breath measurements obtained during a 13C Octanoic Breath Test (13COBT) is demonstrated. The statistical analysis was implemented using WinBUGS, a commercially available computer package for Bayesian inference. A hierarchical setting was adopted where poorly defined parameters associated with a delayed Gastric Emptying (GE) were able to "borrow" strength from global distributions. This is proved to be a sufficient tool to correct model's failures and data inconsistencies apparent in conventional analyses employing a Non-linear least squares technique (NLS). Direct comparison of two parameters describing gastric emptying ng ( tlag -lag phase, t1/ 2 -half emptying time) revealed a strong correlation between the two methods. Despite our large dataset ( n = 164 ), Bayesian modeling was fast and provided a successful fitting for all subjects. On the contrary, NLS failed to return acceptable estimates in cases where GE was delayed.





References:
[1] Mariani G, Boni G, Barreca M, "Radionuclide gastroesophageal motor
studies", J Nucl Med, vol.45(6), pp:1004-1028, 2004.
[2] Abell TL, Camilleri M, Donohoe K, "American Neurogastroenterology
and Motility Society and the Society of Nuclear Medicine. Consensus
recommendations for gastric emptying scintigraphy: a joint report of the
American Neurogastroenterology and Motility Society and the Society
of Nuclear Medicine", J Nucl Med Technol, vol.36(10), pp:44-54, 2008.
[3] Siegel JA, Urbain JL, Adler LP, Charkes ND, Maurer AH, Krevsky B,
Knight LC, Fisher RS, Malmud LS, "Biphasic nature of gastric
emptying", Gut, vol.29, pp:85-89, 1988.
[4] Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ,
Vantrappen G, "Measurement of Gastric Emptying Rate of Solids my
Means of a Carbon-Labeled Octanoic Acid Breath Test",
Gastroenterology, vol.104, pp:1640-1647,1993.
[5] Maes BD, Ghoos YF, Geypens BJ, Mys G, Hiele MO, Rutgeerts PJ,
Vantrappen G, "Combined Carbon-13-Glycine/Carbon-14- Octanoic
Acid Breath Test to Monitor Gastric Emptying Rates of Liquids and
Solids", J Nucl Med, vol.35, pp:824-831, 1994.
[6] Maes BD, Mys G, Geypens BJ, Evenepoel P, Ghoos YF, Rutgeerts PJ,
"Gastric emptying flow curves separated from carbon-labeled octanoic
acid breath test results", Gastrointest Liver Physiol, vol.38, pp:169-175,
1998.
[7] Sidossis LS, Coggan AR, Gastaldelli A, "A new correction factor for use
in tracer estimations of plasma fatty-acids in non-anesthetized pigs", Am
J Physiol - Endocrinol Metab, vol.32, pp:649-656, 1995.
[8] Schrauwen P, van Aggel-Leijssen DPC, Lichtenbelt WDV, "Validation
of the (1,2-C-13)acetate recovery factor for correction of (U-C-
13)palmitate oxidation rates in humans", J Physiol Lond, vol.513,
pp:215-223, 1998.
[9] van Hall G, "Correction factors for C-13-labelled substrate oxidation at
whole-body and muscle level", Proc Nutr Soc, vol.58, pp:979-986, 1999.
[10] Schrauwen P, Blaak EE, van Aggel-Leijssen DPC, "Determinants of the
acetate recovery factor: implications for estimation of (13-C) substrate
oxidation", Clin Sci, vol.98, pp:587-592, 2000.
[11] Bluck LJ, Coward WA, "Measurement of gastric emptying by the 13Coctanoate
breath test-rationalization with scintigraphy", Physiol Meas,
vol.27, pp:279-289, 2006.
[12] Samsom M, Bharucha A, Gerich JE, Herrmann K, Limmer J, Linke R,
Maggs D, Schirra J, Vella A, Worle HJ, Goke B, "Diabetes mellitus and
gastric emptying: questions and issues in clinical practice", Diabetes
Metab Res Rev, vol.25, pp:502-514, 2009.
[13] Horowitz M, Collins PJ, Cook DJ, Harding PE, Shearman DJC,
"Abnormalities of Gastric Emptying in Obese Patients", Int J Obes,
vol.7, pp:415-421, 1983.
[14] Jackson SJ, Leahy FE, Jebb SA, Prentice AM, Coward WA, Bluck LJC,
"Frequent feeding delays the gastric emptying of a subsequent meal",
Appetite, vol.48(2), pp:199-205, 2007.
[15] Jackson SJ, Leahy FE, McGowan AA, Bluck LJC, Coward WA, Jebb
SA, "Delayed gastric emptying in the obese: an assessment using the
non-invasive C-13-octanoic acid breath test", Diabetes Obes Metab,
vol.6(4), pp:264-270, 2004.
[16] Jackson SJ, Bluck LJC, Coward WA, "Use of isotopically labelled
octanoic acid to assess the effect of meal size on gastric emptying",
Rapid Commun Mass Spectrom, vol. 18(10), pp:1003-1007, 2004.
[17] Schofield W, "Predicting Basal Metabolic Rate, New Standards and
Review of Previous Work", Hum Nutr Clin Nutr, vol.39C, pp:5-41,
1985.
[18] Evenepoel P, Geypens B, Luypaerts A, Hiele M, Ghoos Y, "Digestibility
of Cooked and Raw Egg Protein in Humans as Assessed by Stable
Isotope Techniques", Journal of Nutrition, vol.128, pp:1716-1722, 1998.
[19] Schommartz B, Ziegler D, Schadewaldt P, "Significance of diagnostic
parameters in (C-13)octanoic acid gastric emptying breath tests",
Isotopes Environ Health Stud, vol.34, pp:135-143, 1998.
[20] Gelman A, Carlin JB, Stern HS, Rubin DB, "Bayesian Data Analysis",
Chapman & Hall, TX: Statistical Science, 2004.
[21] Lunn DJ, Thomas A, Best N, Spiegelhalter D, "WinBUGS - a Bayesian
modelling framework: concepts, structure and extensibility", Stat
Comput, vol.10, pp:325-337, 2000.
[22] Gilks WR, Richardson S, Spiegelhalter DJ, "Markov Chain Monte Carlo
in Practice", Chapman & Hall, TX: Interdisciplinary Statistics, 1996.
[23] Pilloneto G, Sparacino G, Magni P, Bellazzi R, Cobelli C, "Minimal
model Si=0 problem in NIDDM subjects: nonzero Bayesian estimates
with credible confidence intervals", Am J Physiol Endrocrinol Metab,
vol.282, pp:564-573, 2000.