Douglas L. Seidner

The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis

BACKGROUND & AIMS Two case-control studies have shown that folate may protect against neoplasia in ulcerative colitis. This historical cohort study was performed to better define this association. METHODS The records of 98 patients with ulcerative colitis who had disease proximal to the splenic flexure for at least 8 years were reviewed. Documented folate use of at least 6 months was deemed a positive exposure. RESULTS Of the patients, 29.6% developed neoplasia and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia for patients taking folate was 0.72 (95% confidence interval [CI], 0.28-1.83). The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate; RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no folate). Folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08). CONCLUSIONS Although not statistically significant, the RR for folate supplementation on the risk of neoplasia is < 1 and shows a dose-response effect, consistent with previous studies. Daily folate supplementation may protect against the development of neoplasia in ulcerative colitis.

A Randomized Clinical Trial of Ciprofloxacin and Metronidazole to Treat Acute Pouchitis

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch–anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1 ± 2.3 to 3.3 ± 1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7 ± 2.3 to 5.8 ± 1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9 ± 1.2 versus 3.8 ± 1.7; p = 0.002), symptom score (2.4 ± 0.9 versus 1.3 ± 0.9; p = 0.03), and endoscopic score (3.6 ± 1.3 versus 1.9 ± 1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Teduglutide Reduces Need for Parenteral Support Among Patients With Short Bowel Syndrome With Intestinal Failure

BACKGROUND & AIMS Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intestinal failure (SBS-IF). We performed a prospective study to determine whether teduglutide reduces parenteral support in patients with SBS-IF. METHODS We performed a 24-week study of patients with SBS-IF who were given subcutaneous teduglutide (0.05 mg/kg/d; n = 43) or placebo (n = 43) once daily. Parenteral support was reduced if 48-hour urine volumes exceeded baseline values by ≥ 10%. The primary efficacy end point was number of responders (patients with >20% reduction in parenteral support volume from baseline at weeks 20 and 24). RESULTS There were significantly more responders in the teduglutide group (27/43 [63%]) than the placebo group (13/43 [30%]; P = .002). At week 24, the mean reduction in parenteral support volume in the teduglutide group was 4.4 ± 3.8 L/wk (baseline 12.9 ± 7.8 L/wk) compared with 2.3 ± 2.7 L/wk (baseline 13.2 ± 7.4 L/wk) in the placebo group (P < .001). The percentage of patients with a 1-day or more reduction in the weekly need for parenteral support was greater in the teduglutide group (21/39 [54%]) than in the placebo group (9/39 [23%]; P = .005). Teduglutide increased plasma concentrations of citrulline, a biomarker of mucosal mass. The distribution of treatment-emergent adverse events that led to study discontinuation was similar between patients given teduglutide (n = 2) and placebo (n = 3). CONCLUSIONS Twenty-four weeks of teduglutide treatment was generally well tolerated in patients with SBS-IF. Treatment with teduglutide reduced volumes and numbers of days of parenteral support for patients with SBS-IF; ClinicalTrials.gov Number, NCT00798967.

Effects of Long-Chain Triglyceride Emulsions on Reticuloendothelial System Function in Humans

Parenteral administration of long-chain triglyceride emulsions has been shown to have deleterious effects on reticuloendothelial system function in animal models. It is unknown whether this interference occurs in humans with clinically relevant doses of intravenous fat. Two studies were done. Eighteen patients were prospectively enrolled for study. Patients received full feeding by continuous total parenteral nutrition (amino acids 1.5 g/kg/day and dextrose 4.5 g/kg/day) with 33.1 kcal/kg/day. Forty-three % of the nonprotein calories were provided as soybean oil emulsion (Travamulsion 20%) and was administered intravenously over 10 hr (0.130 g/kg/hr). Reticuloendothelial system function was determined by measuring the change in the clearance rate of intravenously injected 99mTc-sulfur colloid (TSC) in each patient. In study 1 (n = 10), one day of lipid (10 hr) was infused, with the clearance of 99mTc-sulfur colloid measured before the lipid was infused and then during the last hour of the 10-hr infusion. In study 2 (n = 8), the clearance rates were measured before the lipid emulsion was begun, and then during the last hour of the infusion on the 3rd day. Clearance rates for TSC after 10 hr of lipid infusion in study 1 did not differ (0.27 +/- 1/min to 0.26 +/- 0.1/min, p greater than 0.10). However, after 3 days of lipid infusion (10 hr/day), a statistically significant reduction in TSC was seen (0.46 +/- 0.08/min-0.27 +/- 0.03/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man.

Previous study demonstrated that patients who received total parenteral nutrition (TPN) with standard intermittent infusion of long chain triglyceride (LCT) at 0.13 g kg-1hr-1 over 10 hr for each of three days showed a significant decline in 99Tc-sulfur colloid (TSC) clearance rate by the reticuloendothelial system (RES). The present studies evaluated eight patients who received the same total lipid dose of LCT infused continuously as in a three-in-one admixture, and another nine patients receiving the same amount of fat as a medium chain triglyceride (MCT)/LCT (75%/25%) emulsion intermittently over 10 hr at 0.13 g kg-1hr-1 for three consecutive days. Patients were given continuous total parenteral nutrition (TPN) comprised of protein, 1.5 g kg-1day-1, and dextrose, 4.5 g kg-1day-1. RES function was examined by measuring the clearance rates of intravenously injected TSC while receiving TPN containing only protein and dextrose, and again after three days of fat infusion. Mean (+/- SEM) clearance rate constants before and after continuous LCT infusion were 0.38 +/- 0.09 and 0.41 +/- 0.08 min-1, respectively, while those before and after intermittent MCT/LCT infusion were 0.50 +/- 0.18 and 0.73 +/- 0.24 min-1, respectively. In contrast to intermittent LCT infusion, the administration of continuous LCT or an intermittent MCT/LCT mixture does not impair TSC clearance by the RES. These findings suggest that condensing the daily period of LCT infusion at standard dosage may exceed the rate of metabolic utilization, resulting in increased fat removal and diminished TSC uptake by the RES.(ABSTRACT TRUNCATED AT 250 WORDS)

A.S.P.E.N. Position Paper Clinical Role for Alternative Intravenous Fat Emulsions

The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.

An Oral Supplement Enriched With Fish Oil, Soluble Fiber, and Antioxidants for Corticosteroid Sparing in Ulcerative Colitis: A Randomized, Controlled Trial

BACKGROUND & AIMS N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC. METHODS A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model. RESULTS Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001). CONCLUSIONS The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

Definition of Terms, Style, and Conventions Used in A.S.P.E.N. Guidelines and Standards

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is a professional society of physicians, nurses, dietitians, pharmacists, allied health professionals, and researchers. A.S.P.E.N. envisions an environment in which every patient receives safe, efficacious, and high quality patient care. A.S.P.E.N.’s mission is to improve patient care by advancing the science and practice of nutrition support therapy.

The need to advance nutrition education in the training of health care professionals and recommended research to evaluate implementation and effectiveness

Nutrition is a recognized determinant in 3 (ie, diseases of the heart, malignant neoplasms, cerebrovascular diseases) of the top 4 leading causes of death in the United States. However, many health care providers are not adequately trained to address lifestyle recommendations that include nutrition and physical activity behaviors in a manner that could mitigate disease development or progression. This contributes to a compelling need to markedly improve nutrition education for health care professionals and to establish curricular standards and requisite nutrition and physical activity competencies in the education, training, and continuing education for health care professionals. This article reports the present status of nutrition and physical activity education for health care professionals, evaluates the current pedagogic models, and underscores the urgent need to realign and synergize these models to reflect evidence-based and outcomes-focused education.

Liver failure is uncommon in adults receiving long-term parenteral nutrition

BACKGROUND Abnormal liver enzymes and endstage liver disease are reported to occur in 25%-100% and 15%-40% of adult patients receiving long-term parenteral nutrition (PN), respectively. The purpose of this historic cohort study was to investigate the incidence of and possible factors leading to the development of liver disease in our large home PN population. METHODS All patients on home PN for at least 6 months from July 1991 through June 2002 were eligible. Patients were excluded if they had active malignancy, underlying liver disease, or exposure to a hepatotoxin. The presence of PN-associated liver disease was only considered if test results were elevated on more than 1 occasion over at least 6 or more months. The severity of liver-associated enzymes was based on the degree of elevation and was stratified as mild (<2 times normal), moderate (2-5 times normal), and severe (>5 times normal). Severe liver dysfunction was defined as having all of the following criteria: total bilirubin >3 mg/dL; albumin <3.2 g/dL; and prothrombin time >3 seconds prolonged. A cumulative logit model was used to compare age, gender, underlying disease, PN indication, and PN formulas in patients with normal vs abnormal laboratory test results. RESULTS Two hundred eight patients received PN for more than 6 months, 36 had exclusion criteria, and 10 could not be analyzed, because of incomplete laboratory test results, leaving 162 in the study group. The average PN duration was 2.14 +/- 2.19 years (maximum, 10.28 years). Abnormal liver tests occurred in 154 patients, with most having a moderate elevation of alkaline phosphatase or aspartate aminotransferase; severe liver dysfunction occurred in 7 patients; 1 patient had completely normal liver enzymes. On average, patients received a PN formula that was high in amino acids (1.45 +/- 0.65 g/kg/d), modest in energy (24.7 +/- 13.4 kcal/kg/d), and in most cases with enough lipid emulsion to meet essential fatty acid requirements (0.28 +/- 0.25 g/kg/d). Only female gender was found to be associated with a greater likelihood of liver failure (p = .02). There was a trend toward a greater amount of total calories, dextrose calories, and duration of PN exposure leading to the development of severe liver dysfunction. CONCLUSIONS When long-term PN is given with a modest amount of total energy and a minimal amount of lipid emulsion, abnormal liver enzymes are common, but severe liver dysfunction is unusual.