Clinical and Histologic Remission in an Adult Crohn's Disease Patient Following the Specific Carbohydrate Diet and Its Impact on Healthcare Costs.

Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract. While the etiology is not fully elucidated, the intestinal microbiome is believed to initiate and maintain immune activation in CD. The intestinal microbiome is highly responsive to its environment, including host dietary patterns. As such, dietary interventions have the potential to modulate intestinal microbiome composition and function and improve disease outcomes. We present a retrospective chart review of an adult male with complicated Crohn's disease who was non-responsive to medical management. The patient began the specific carbohydrate diet (SCD) in February 2017 and maintained it for 42 months. The patient tolerated the SCD well and has been asymptomatic for 40 months on the SCD. Stool fecal calprotectin (FCP) decreased from 493 ug/g at baseline to 70 ug/g at month three and remained in the normal range thereafter. Endoscopy with biopsy at month 12 showed normal histology in the colon and terminal ileum. Magnetic resonance enterography (MRE) showed resolution of prior jejunal inflammation. Inflammatory bowel disease (IBD) associated healthcare costs were $42,688 in the 12 months preceding the intervention and $2,797/year with SCD. This represented a 94% reduction in healthcare insurance costs and a 91% reduction in out-of-pocket patient expenses. This case highlights the rapid and sustainable benefits of the SCD intervention in Crohn's disease from both a clinical and economic standpoint.

New frontiers-accelerator mass spectrometry (AMS): Recommendation for best practices and harmonization from Global Bioanalysis Consortium Harmonization Team.

The technique of accelerator mass spectrometry (AMS) is applicable to the analysis of a wide range of trace elemental isotopes. However, in the context of the pharmaceutical industry, it is invariably used to measure radiocarbon ((14)C). There are two broad modes of application: analysis of total (14)C sometimes termed "direct AMS" and analysis of specific (14)C-labelled analytes in a variety of matrices following some method of isolation. It is the latter application which is within the remit of the GBC team, and the team has made efforts to propose harmonized recommendations for the validation of AMS when used in a regulatory bioanalytical mode, i.e. the quantification of specific analyte(s) using liquid chromatography with off-line detection by AMS now known as "LC + AMS". The GBC team has reached a position where they have agreed to many aspects, but also differ on some aspects of what constitutes a bioanalytical assay validation in support of clinical studies using this technology. The detail of most of this will be covered under separate publication(s), but for the purposes of this paper, we have outlined the points of consensus. The purpose of this article is not to provide a roadmap for validation of LC + AMS assays, but to highlight agreements amongst the industry representative experts and the practitioners, as well as identifying specific areas essential for establishing assay quality but where additional discussion is required to reach agreement.

Precision and accuracy in the quantitative analysis of biological samples by accelerator mass spectrometry: application in microdose absolute bioavailability studies.

Determination of the pharmacokinetics and absolute bioavailability of an experimental compound, SCH 900518, following a 89.7 nCi (100 µg) intravenous (iv) dose of (14)C-SCH 900518 2 h post 200 mg oral administration of nonradiolabeled SCH 900518 to six healthy male subjects has been described. The plasma concentration of SCH 900518 was measured using a validated LC-MS/MS system, and accelerator mass spectrometry (AMS) was used for quantitative plasma (14)C-SCH 900518 concentration determination. Calibration standards and quality controls were included for every batch of sample analysis by AMS to ensure acceptable quality of the assay. Plasma (14)C-SCH 900518 concentrations were derived from the regression function established from the calibration standards, rather than directly from isotopic ratios from AMS measurement. The precision and accuracy of quality controls and calibration standards met the requirements of bioanalytical guidance (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical Method Validation (ucm070107), May 2001. http://www.fda.gov/downloads/Drugs/GuidanceCompilanceRegulatoryInformation/Guidances/ucm070107.pdf ). The AMS measurement had a linear response range from 0.0159 to 9.07 dpm/mL for plasma (14)C-SCH 900158 concentrations. The CV and accuracy were 3.4-8.5% and 94-108% (82-119% for the lower limit of quantitation (LLOQ)), respectively, with a correlation coefficient of 0.9998. The absolute bioavailability was calculated from the dose-normalized area under the curve of iv and oral doses after the plasma concentrations were plotted vs the sampling time post oral dose. The mean absolute bioavailability of SCH 900518 was 40.8% (range 16.8-60.6%). The typical accuracy and standard deviation in AMS quantitative analysis of drugs from human plasma samples have been reported for the first time, and the impact of these parameters on quantitative analysis was further assessed using the Z factor. The use of the lowest achievable LLOQ(Z=0) derived from statistical analysis of the control and low-concentration standards for AMS measurements is proposed in future studies.

Accelerator mass spectrometry-enabled studies: current status and future prospects.

Accelerator mass spectrometry is a detection platform with exceptional sensitivity compared with other bioanalytical platforms. Accelerator mass spectrometry (AMS) is widely used in archeology for radiocarbon dating applications. Early exploration of the biological and pharmaceutical applications of AMS began in the early 1990s. AMS has since demonstrated unique problem-solving ability in nutrition science, toxicology and pharmacology. AMS has also enabled the development of new applications, such as Phase 0 microdosing. Recent development of AMS-enabled applications has transformed this novelty research instrument to a valuable tool within the pharmaceutical industry. Although there is now greater awareness of AMS technology, recognition and appreciation of the range of AMS-enabled applications is still lacking, including study-design strategies. This review aims to provide further insight into the wide range of AMS-enabled applications. Examples of studies conducted over the past two decades will be presented, as well as prospects for the future of AMS.

Quantitation of in vivo human folate metabolism.

BACKGROUND: A quantitative understanding of human folate metabolism is needed. OBJECTIVE: The objective was to quantify and interpret human folate metabolism as it might occur in vivo. DESIGN: Adults (n = 13) received 0.5 nmol [(14)C]pteroylmonoglutamate (100 nCi radioactivity) plus 79.5 nmol pteroylmonoglutamate in water orally. (14)C was measured in plasma, erythrocytes, urine, and feces for >/=40 d. Kinetic modeling was used to analyze and interpret the data. RESULTS: According to the data, the population was healthy and had a mean dietary folate intake of 1046 nmol/d, and the apparent dose absorption of (14)C was 79%. The model predictions showed that only 0.25% of plasma folate was destined for marrow, mean bile folate flux was 5351 nmol/d, and the digestibility of the mix (1046 + 5351 nmol/d) was 92%. About 33% of visceral pteroylmonoglutamate was converted to the polyglutamate form, most of the body folate was visceral (>99%), most of the visceral folate was pteroylpolyglutamate (>98%), total body folate was 225 micromol, and pteroylpolyglutamate synthesis, recycling, and catabolism were 1985, 1429, and 556 nmol/d, respectively. Mean residence times were 0.525 d as visceral pteroylmonoglutamate, 119 d as visceral pteroylpolyglutamate, 0.0086 d as plasma folate, and 0.1 d as gastrointestinal folate. CONCLUSIONS: Across subjects, folate absorption, bile folate flux, and body folate stores were larger than prior estimates. Marrow folate uptake and pteroylpolyglutamate synthesis, recycling, and catabolism are saturable processes. Visceral pteroylpolyglutamate was an immediate precursor of plasma p-aminobenzoylglutamate. The model is a working hypothesis with derived features that are explicitly model-dependent. It successfully quantitated folate metabolism, encouraging further rigorous testing.