Carbon‐based compounds emerging as sparkling diamonds for IBS treatment? authors’ reply
Bibliographic record
Abstract
Sirs, We read with interest the letter by Drs Chao and Holtmann on our study with AST-120 for the treatment of irritable bowel syndrome (IBS) symptoms.1 We agree that elimination of non-absorbable carbohydrates and polyols may induce benefit to IBS patients, although the number of IBS patients studied in a controlled study with such intervention remains low.2, 3 In the study with AST-120, patients with symptoms attributable to lactose maldigestion were excluded. Attempts to exclude other non-absorbable sugars and polyols were not specified, but we assume that the experienced clinicians took these types of dietary confounders into account. Fermentable oligo-, di- and monosaccharides and polyols have been implicated in worsening of abdominal pain, bloating and flatulence in IBS.2, 3 The same symptoms improved in our study with AST-120.4 The spectrum of molecules that AST-120 can bind is wide, and it is presently unclear whether this also involves (metabolites of) non-absorbable carbohydrates and polyols. The place of AST-120, relative to other available treatments for IBS, including dietary measures, requires additional (phase 3) studies. Drs Chao and Holtmann raise the issue of confounding by the intake of rescue medication. Loperamide was allowed as rescue therapy for diarrhoea, but its use throughout the study was very low, similar for both treatment groups, and it did not contribute to explaining the differences observed between active and placebo treatment. A final comment relates to the apparent loss of efficacy over placebo in the second half of the double-blind randomised phase of the trial. We think this effect is mainly due to a rise in placebo response, and may be due to the selection of patients that entered the trial, who were perhaps more prone to transient symptoms, as well as the relatively small sample size. Moreover, it is unclear whether patient’s expectations, in a trial design where they were guaranteed to receive active treatment during at least part of the study period, may have contributed to the rising placebo response. These issues will be addressed in subsequent studies. Declaration of personal interests: Dr Jan F. Tack has served as a consultant to Addex Pharma, Almirall, Aryx, AstraZeneca, Danone, Ipsen, Menarini, Movetis, Norgine, Novartis, NPS Pharma, Nycomed, Ocera, Rose Pharma, SK Life Sciences, Smartpill, Sucampo, Theravance, Tranzyme, Xenoport and Zeria Pharmaceutical Co. Dr. Philip B. Miner has served as a consultant to Abbott Laboratories, Altheus Therapeutics, Aryx Pharmaceuticals, AstraZeneca, Inc, Atlantic Pharmaceuticals, Inc, Axcan Pharmaceuticals, Biogen-Idec, Centocor Inc, Pozen Inc., Salix Pharmaceuticals, Sanofi-Aventis, Selexys Pharmaceuticals, Takeda Pharmaceutical Company, UCB Inc, Vecta Ltd and Ventrus Biosciences. He has received grant and research support from Abbott Laboratories, Aryx Pharmaceuticals, AstraZeneca, Inc, Axcan Pharmaceuticals, Biogen-Idec, Centocor Inc, Eisai Co Ltd., Forest Laboratories, GlaxoSmithKline, Lexicon Pharmaceuticals, Prometheus Laboratories, Pozen Inc., Salix Pharmaceuticals, Schering-Plough, Selexys Pharmaceuticals, Takeda Pharmaceutical Company, UCB Inc, Vecta Ltd, Ventrus Biosciences and Wyeth Laboratories (now Pfizer, Inc). Dr Laurent Fischer is an employee of Ocera Therapeutics. Dr M. Scott Harris has served as a consultant to Ocera Therapeutics, Inc., Meda Pharmaceuticals, Inc., Martek Biosciences, International Institute for One World Health, Ardelyx Pharmaceuticals, Theravance Inc., Tranzyme Pharmaceuticals, Combimab Pharmaceuticals, UCB Inc., Kala Pharmaceuticals, Orchid Pharmaceuticals, Radiation Control Technologies, Inc and Napo Pharmaceuticals. He has received grant and research funding from Meda Pharmaceuticals and owns stock and shares in Ocera Therapeutics, Inc and Napo Pharmaceuticals. He was an employee of Ocera Therapeutics during the conduct of this trial. Declaration of funding interests: None.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.003 | 0.007 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.026 | 0.039 |
| Insufficient payload (model declined to judge) | 0.005 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".