Vitamin D Deficiency (VDD) and Benefits of Supplementation in Veterans with IBS-D.

Many veterans deployed to Gulf War areas suffer from persistent chronic diarrhea that is disabling and affects their quality of life. The causes for this condition have eluded investigators until recently and recent literature has shed light on the effect of vitamin D on the brain-gut axis. This study focused on determining clinical causes contributing to diarrhea and assessed whether reversing the identified causes, specifically vitamin D deficiency (VDD), could reduce the incidence of diarrhea in Gulf War veterans (GWVs). All patients completed a workup that included serologies (IBD, celiac), routine laboratory tests (CBC, chemistry panels, TSH, T4, CRP), cultures for enteric pathogens (C diff, bacteria, viruses, small intestinal bacterial overgrowth (SIBO)), and upper and lower endoscopies with histology and a trial of cholestyramine to exclude choleretic diarrhea and rifaximin for dysbiosis. A total of 4221 veterans were screened for chronic diarrhea, yielding 105 GWVs, of which 69 GWVs had irritable bowel syndrome with diarrhea (IBS-D). Paired t-tests demonstrated that all GWVs had VDD (t-11.62, df68 and sig(2-tailed) 0.0001) (defined as a vitamin D level less than 30 ng/mL with normal ranges of 30-100 ng/mL) but no positive serologies, inflammatory markers, abnormal endoscopies, cultures, or histology to explain their persistent diarrhea. There was no correlation with age, BMI, or inflammation. Some zip codes had a higher frequency of GWVs with VDD, but the number of deployments had no impact. Treatment with vitamin D supplementation (3000-5000 units), given in the morning, based on weight, reduced the number of bowel movements per day (p < 0.0001) without causing hypercalcemia. We suggest that VDD is important in the etiology of IBS-D in GWVs and that vitamin D supplementation significantly reduces diarrhea.

Strategic Management of Bleeding Small Bowel Gastrointestinal Angiodysplasias (GIADs): A 12 Year Retrospective Review in a Veteran Population and Cost Comparison.

BACKGROUND: Gastrointestinal angiodysplasias (GIADs), also known as gastrointestinal angioectasias, are dilated, abnormally thin-walled blood vessels that occur in the mucosa and submucosa throughout the gastrointestinal tract. As a common cause of small bowel bleeding, GIADs have a significant impact on patient's morbidity and healthcare costs. Presently, somatostatin has been used widely to treat GIADs, but it is unclear if other therapies are as beneficial and cost-effective as somatostatin in managing GIADs. (2) Methods: A retrospective chart review was performed, which included subjects treated with Lanreotide, a somatostatin analog, and other therapies at the VA Loma Linda Healthcare System (VALLHCC) from January 2006 to December 2018. Patients who had symptomatic GIADs were detected by video capsule endoscopy (VCE), a device-assisted enteroscopy (DAE) or, in our case, push enteroscopy (PE) with an Endocuff. (3) Results: Three hundred twelve patients were diagnosed with GIADs. In this group of patients, 72 underwent ablation (endoscopic BICAP) with the addition of Lanreotide (SST), 63 underwent ablation therapy, eight were treated with SST only, 128 received iron replacement only, 25 received iron plus SST therapy, and 61 were observed with no therapy. Each group was followed via their hemoglobin (Hgb) level immediately thereafter, and Hgb levels were then obtained every 3 months for a 12-month period. After ablation therapy, 63 patients maintained stable Hgb levels over the course of the study, suggesting a significant therapeutic effect by controlling active bleeding. The 27 patients receiving ablation +SST therapy did not show improvements when compared to ablation only and the 128 patients who received iron therapy alone. (4) Conclusions: Importantly, 12 years of managing these patients has given us a cost- and time-sensitive strategy to maintain the patients' Hgb levels and avoid hospital admissions for acute bleeding. Iron treatment alone is effective compared to SST treatment in recovering from GIADs. Eliminating SST treatment from therapeutic intervention would save $89,100-445,550 per patient, depending on the number of doses for private care patients and $14,286-28,772 for VA patients, respectively. A suggested therapy would be to perform DAE on actively bleeding patients, ablate the lesions using a coagulation method, and place the patient on iron. If that fails, gastroenterologists should repeat VCE and perform either PE with Endocuff or balloon enteroscopy (all DAEs).

Endocuff-assisted push enteroscopy increases the detection of proximal small-bowel gastrointestinal angiodysplasias.

Gastrointestinal angiodysplasias (GIADs) are the most common causes for suspected small bowel bleeding. Fifty percent of GIADs do not need treatment due to bleeding cessation, while 45% have high re-bleeding rates, that significantly impact patient outcome and health resource utilization. We suspected that this high re-bleeding rate occurs because not all lesions are detected with present standard of care. This study evaluates whether device-assisted enteroscopy (DAE) utilizing the Endocuff (EC) device could improve GIAD detection. A retrospective chart review of a prospective data collection was performed from January 2006 to December 2018 at VA Loma Linda Healthcare System (VALLHCS) on both inpatients and outpatients referred for active and chronic suspected small bowel bleeding. The patients were initially monitored for bleeding lesions via video capsule endoscopy (VCE) after negative upper and lower endoscopy. GIADs observed between 0% to 40% small bowel transit time (SBTT) were referred for push enteroscopy (PE) with and without (±) the EC device. Twenty-five consecutive patients underwent PE ± EC. No patient had VCE done after PE ± EC. Using PE-EC, GIADs were detected in 9 of 25 (36%) of patients. Importantly, PE+EC detected GIADs in 23 of 25 (92%) patients. The sum of GIADs detected without EC was 26 ± 0.06 vs. 112 ± 0.2 using EC. The average detection rate for PE without EC was significantly lower (1.04 ± 0.06, mean ± SE) as compared to PE with EC (4.48 ± 0.23, mean ± SE, p<0.0005). Additionally, a positive correlation (r=0.51) between capsule enteroscopy (CE) location of GIADs and SBTT was found. The EC device increases the detection of GIADs in the proximal small bowel. We also reconfirm that the location of bleeding GIADs are within the reach of the push enteroscope (PE). Finally, PE + EC may also reduce GIAD miss rates, which may play a role in the reduction of re-bleeding episodes.

Outcomes Comparison of the Veterans' Choice Program With the Veterans Affairs Health Care System for Hepatitis C Treatment.

BACKGROUND: The US Department of Veterans Affairs (VA) has been stressed by the large number of veterans requiring direct-acting antiviral (DAA) medications for hepatitis C virus (HCV) treatment. The Veterans Choice Program provides VA patients more options to receive treatment. This study compared the experience of veterans who received HCV treatment through the Veterans Choice Program and those that received treatment at the VA Loma Linda Healthcare System (VALLHCS) in fiscal year (FY) 2016. METHODS: A chart review was performed on all veterans referred by VALLHCS to Choice for HCV treatment during FY 2016, and matched to veterans who received treatment at VALLHCS. Data collected included Fibrosis-4 score (Fib-4), platelet count, days elapsed between time of referral and time of appointment (wait time), rate of sustained virologic response at 12 weeks (SVR12), reason for treatment failure, and cost effectiveness. RESULTS: One hundred veterans were referred to Choice; 71 were seen at least once by a Choice provider, and 61 completed a treatment course. Mean Fib-4 and platelet count was 1.9 and 228,000 for the Choice population and 3.4 and 158,000 for the VALLHCS population, respectively. There was no difference in SVR12 rate. Mean wait time was 42 days for Choice vs 29 days for VALLHCS (P < .001). Choice health care providers incurred a mean $8,561.40 in additional costs per veteran seen. CONCLUSIONS: While treatment success rates were similar between Choice and VALLHCS, the degree of liver fibrosis was more advanced in the VALLHCS population. The wait time for care was longer with Choice compared with a direct referral within the VA. While Choice offers a potential solution to providing care for veterans, the current program has unique problems that must be considered.

Endocuff assisted colonoscopy significantly increases sessile serrated adenoma detection in veterans.

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. Colonoscopy is the gold standard for the detection of CRC. There are many colonoscopy quality measures and among these the adenoma detection rate (ADR) has demonstrated a significant impact in reducing mortality from CRC. The primary aim of our study was to compare ADR and distribution of polyp type in patients undergoing Endocuff-assisted colonoscopy (EAC) versus standard colonoscopy (SC) in a VA system. METHODS: Retrospective data was collected from 496 patients who underwent routine screening, surveillance and diagnostic colonoscopies either via SC from January 6, 2014 through March 12, 2014 or EAC from September 24, 2014 through February 19, 2015. A total of 54 patients were excluded based on a personal history of CRC and prior resection, incomplete colonoscopy due to poor bowel preparation, and removal or loss of Endocuff (EC). Primary outcomes measured and compared were ADR and types of polyps found. RESULTS: The overall ADR in the EAC group was higher at 59.91% versus 50.66% for SC, accounting for a 9% increase (P=0.0508). EAC was able to detect a total of 59 sessile serrated adenoma/polyps (SSA/Ps) compared to SC only detecting 8 (P≤0.0001). There was a significant increase in the SSA/P detection rate with EAC at 15% versus 3% in the SC group (P≤0.0001). CONCLUSIONS: EAC significantly increases the detection of SSA/P and has shown a trend in improving ADR in our veteran population.

Training mid-career internists to perform high-quality colonoscopy: a pilot training programme to meet increasing demands for colonoscopy.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the USA. Despite a recent rise in CRC screening there remains an increasing demand for colonoscopy, yet a limited supply of gastroenterologists who can meet this need. OBJECTIVE: To determine if a mid-career general internist (GIN) could be trained to perform high-quality colonoscopes via an intensive training programme. DESIGN: A GIN trained 2-3 days/week, 4-5 hours/day, for 7 months with an experienced gastroenterologist. Their independent performance was then compared with that of a gastroenterology attending (GA), with and without a gastroenterology fellow (GF). MAIN MEASURES: The primary outcome was to compare caecal intubation rates, adenoma detection rates (ADRs), interval CRC rates and complications between the three groups. KEY RESULTS: 989 patients were initially included in the study, and 818 were included in the final analysis. Caecal intubation rates were 95%, 94% and 93% for the GIN, GA+GF and GA, respectively (p=0.31). The overall polyp detection rates were 68%, 39% and 44% among the GIN, GA+GF and GA, respectively (p<0.0001). The ADRs were 56%, 33% and 34% for the GIN, GA+GF and GA, respectively (p<0.0001). Three complications occurred, all within the GA group. No interval cancers were diagnosed within a 5-year surveillance period, across all three groups. CONCLUSIONS: The GIN attained high success rates in all quality measures. Training mid-career GINs to perform high-quality screening colonoscopes, through a standardised curriculum, may be a reasonable approach to address the growing demand for colonoscopists.

Gastrointestinal Angiodysplasia: Diagnosis and Management.

Gastrointestinal angiodysplasia (GIAD) are red flat arborized lesions that are found throughout the entire gastrointestinal tract. GIAD can vary in size and have a range of presentation from occult to life-threatening bleeding. The typical presentation is intermittent bleeding in the setting of iron deficiency anemia. Endoscopy is the primary means of diagnosis and endoscopic therapy is noted to be initially effective. However, rebleeding can be as high as 40% to 50% in patients with small bowel GIAD. This review describes the pathophysiology for the development of GIAD and the current roles of endoscopic, medical, and surgical therapy in its treatment.

At-line determination of pharmaceuticals small molecule's blending end point using chemometric modeling combined with Fourier transform near infrared spectroscopy.

This article summarizes the development and validation of a Fourier transform near infrared spectroscopy (FT-NIR) method for the rapid at-line prediction of active pharmaceutical ingredient (API) in a powder blend to optimize small molecule formulations. The method was used to determine the blend uniformity end-point for a pharmaceutical solid dosage formulation containing a range of API concentrations. A set of calibration spectra from samples with concentrations ranging from 1% to 15% of API (w/w) were collected at-line from 4000 to 12,500cm-1. The ability of the FT-NIR method to predict API concentration in the blend samples was validated against a reference high performance liquid chromatography (HPLC) method. The prediction efficiency of four different types of multivariate data modeling methods such as partial least-squares 1 (PLS1), partial least-squares 2 (PLS2), principal component regression (PCR) and artificial neural network (ANN), were compared using relevant multivariate figures of merit. The prediction ability of the regression models were cross validated against results generated with the reference HPLC method. PLS1 and ANN showed excellent and superior prediction abilities when compared to PLS2 and PCR. Based upon these results and because of its decreased complexity compared to ANN, PLS1 was selected as the best chemometric method to predict blend uniformity at-line. The FT-NIR measurement and the associated chemometric analysis were implemented in the production environment for rapid at-line determination of the end-point of the small molecule blending operation.

Gastrointestinal angiodysplasia is associated with significant gastrointestinal bleeding in patients with continuous left ventricular assist devices.

BACKGROUND AND STUDY AIMS: Patients with a continuous-flow left ventricular assist device (LVAD) have a 65 % incidence of bleeding events within the first year. The majority of gastrointestinal bleeding (GIB) is from gastrointestinal angiodyplasia (GIAD). The primary aim of the study was to determine whether GIAD was associated with a higher rate of significant bleeding, an increased number of bleeding events per year, and a higher rate of transfusion compared to non-GIAD sources. PATIENTS AND METHODS: This retrospective cohort study included 118 individuals who received a LVAD at a tertiary medical center from 2006 through 2014. Patients were subdivided into GIB and non-GIB for comparison of patient demographics, comorbid conditions, and laboratory data. GIB was further divided into sources of GIB, GIAD, obscure, or non-GIAD to establish severity of bleeding, rate of re-bleeding, and transfusion rate. RESULTS: GIAD is associated with an increased number of bleeding events compared to non-GIAD sources of GIB (2.07 vs 1.23, P = 0.01) and a higher number of bleeding events per year (0.806 vs. 0.455 P = 0.001). GIAD compared to non-GIAD sources of GIB was associated with an increased incidence of major bleeding (100 % vs 60 %, P = 0.006) and increased rates of transfusion (8.8 vs 2.95 units, P = 0.0004). Cox Regression analysis between non-GIB and GIAD demonstrated increased risk with age (P = 0.001), history of chronic kidney disease (P = 0.005), and length of stay after LVAD implantation of more than 45 days (P = 0.04). History of hypertension (P = 0.045), diabetes mellitus (P = 0.016), and male gender was associated with decreased risk (P = 0.04). CONCLUSION: Patients with a continuous-flow LVAD who develop a GIB secondary to GIAD have a higher rate of major bleeding, multiple bleeding events, and require more transfusions to achieve stabilization compared to patients who do not have GIAD.

Increased amygdala fMRI activation after secretin administration.

It has recently been reported that secretin activates gene expression in the central nucleus of the amygdala in rats. To examine the neurophysiological effects of secretin on amygdalar activation in humans, the authors measured Blood Oxygen Level Dependent functional magnetic resonance imaging signal change during facial affect processing in a placebo-controlled double-blind study. The authors studied 12 healthy male subjects who were presented with three stimulus conditions: viewing happy, fearful, and neutral faces, before and after infusion with either secretin or placebo. To test whether treatment was associated with distinct patterns of activation, the two conditions (Pre and Post) were subjected to a subtraction analyses in SPM99 and hypotheses regarding the activation of the left and right amygdala were tested using a region-of-interest approach. Subtraction of treatment minus baseline activation during the fear condition yielded significant (p=.001) activation in the right amygdala and a nonsignificant increase in activation in the left amygdala. No significant differences were seen between the treatment conditions for the amygdala when viewing happy or neutral faces. These preliminary findings indicate that secretin may alter responsivity to affective stimuli. The presence of increased activation of the amygdala during the viewing of fearful faces is consistent with findings from animal studies and suggests a mechanism by which secretin may modulate social behavior.