Jack A. DiPalma

A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation.

OBJECTIVES:Polyethylene glycol (PEG) 3350 (MiraLAX) is currently approved for the short-term treatment of occasional constipation. This study was designed to compare the safety and efficacy of PEG laxative versus placebo over a 6-month treatment period in patients with chronic constipation.METHODS:Study subjects who met defined criteria for chronic constipation were randomized in this double-blind, placebo-controlled, parallel, multicenter study to receive PEG laxative as a single daily dose of 17 g or placebo for 6 months. Baseline constipation status was confirmed during a 14-day observation period. As a primary efficacy variable, treatment success was defined as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were assessed. An Interactive Voice Response System (IVRS) recorded daily bowel movement experience and study efficacy and safety information. Laboratory testing at baseline and monthly for the study duration was analyzed for hematology, blood chemistry including amylase, GGT, uric acid, lipids, and urinalysis.RESULTS:A total of 304 patients were enrolled and received treatment at one of 50 centers. Successful treatment according to the primary efficacy variable was seen in 52.0% of PEG and 11% of placebo subjects (P < 0.001). Similar efficacy was seen in a subgroup of 75 elderly subjects. According to the primary efficacy definition (based on individual treatment weeks), 61% of PEG treatment weeks versus 22% of the placebo weeks were successful (P < 0.001). There were no significant differences in laboratory findings or adverse events except for the gastrointestinal category where diarrhea, flatulence, and nausea were the most frequent with PEG although they were not individually statistically significant compared with placebo. Similar results were observed when analyzed for differences due to gender, race, or age.CONCLUSIONS:PEG laxative is safe and effective for use in patients with chronic constipation for 6 months.

Urinary excretion of polyethylene glycol 3350 and sulfate after gut lavage with a polyethylene glycol electrolyte lavage solution

Ingestion of an electrolyte lavage solution containing polyethylene glycol 3350 and sulfate is an effective method of cleansing the colon for diagnostic studies. Polyethylene glycol and sulfate are considered poorly absorbed from the gastrointestinal tract. Because of the quantities administered, concern exists about potential toxicity of absorption of even a small percentage, particularly for polyethylene glycol. We measured the urinary excretion of both polyethylene glycol and sulfate in normal subjects and inflammatory bowel patients. Absorption of polyethylene glycol can be assessed by measuring recovery in urine, as 85%-96% of an intravenous load is excreted in urine. Similarly, appreciable sulfate absorption would exceed renal tubular reabsorption and result in increased urinary excretion. Mean percent polyethylene glycol load recovered in urine was minimal and similar for normal (0.06%) and inflammatory bowel (0.09%) subjects. Urinary sulfate excretion after lavage was also similar for both groups and was not different from baseline. These results do not suggest the likelihood of toxicity due to polyethylene glycol 3350 or sulfate absorption during gut lavage with this solution.

Does lactose maldigestion really play a role in the irritable bowel

Patients who met International Congress of Gastroenterology criteria for irritable bowel syndrome (IBS) and had breath hydrogen lactose testing were interviewed to determine whether detection of lactose maldigestion (LM) had an impact on their symptoms. Of 199 patients initially evaluated, 161 (81%) were contacted and asked to rate their symptoms. At baseline, 47 (29%) of the IBS group had LM. Before testing, 23 (49%) were aware that ingestion of lactose-containing food was associated with their gastrointestinal symptoms. Lactose-maldigesting IBS subjects (IBSLM, n = 47) and those who had IBS and no LM (n = 114) were similar in terms of age, sex, and ethnic background. Interviews performed 41 +/- 1.1 (SEM) months after baseline evaluation revealed no significant differences in abdominal pain, altered bowel habits, bloating/distension, mucus, and relief with defecation among those with IBS or LMIBS. Overall symptoms resolved, improved, did not change, or worsened in a manner not statistically different between IBS and IBSLM groups. IBSLM subjects (a) felt that identifying LM helped them gain awareness of food-symptom relationships (78.7%), (b) experienced some improvement in symptoms (83%), (c) were avoiding lactose foods (87.2%), or (d) used lactase enzyme supplements (38.3%). Identifying LM did not significantly affect rated variables.

A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications.

Objectives: Medications often cause constipation and little data are available concerning treatment interventions. This study was designed to evaluate the safety and efficacy of polyethylene glycol (PEG) 3350 laxative (MiraLax) for relief of constipation from medicines associated with symptoms of constipation. Methods: Study subjects were enrolled who met defined criteria for chronic constipation and were also taking medications that were associated with a reported side effect incidence of more than 3% constipation. Subjects were randomized into a double-blind, parallel, multicenter study where they received 17 g per day of PEG laxative or placebo for 28 days. The primary efficacy variable, “Treatment Success,” was defined as relief of ROME II criteria for constipation over the last 7 days of the treatment period. Various secondary measures were also assessed. Daily bowel movement experience, patient perception of efficacy, and safety information were recorded in a diary. Laboratory testing was performed at baseline and at end of study for hematology and blood chemistry, including BUN, calcium, electrolytes, and TSH. Results: One hundred patients were enrolled at 4 study centers. Successful treatment according to the primary efficacy variable was seen in 78.3% of PEG and 39.1% of placebo subjects (P < 0.001). Similar results were observed in a subgroup of 28 elderly subjects. Secondary measures of number of bowel movements, complete bowel movements, satisfactory bowel movements, straining at stool and stool consistency also showed statistically significant results in favor of PEG compared with placebo (P ≤ 0.01) after the first week of treatment. There were no differences inpatient reported scores for gas, cramping, or bloating between PEG and placebo. No significant differences in laboratory findings or adverse events, including the gastrointestinal category, were observed. Diarrhea and flatulence occurred more frequently with PEG treatment, although they were not individually statistically different from placebo. Similar results were observed when these symptoms were analyzed for differences due to gender, race, or age. Conclusions: PEG laxative is safe and effective for use in treating constipation in patients taking constipating medications.

Management of severe gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) affects more than one third of the population. It is generally a chronic condition and has the potential to be serious. Some patients with GERD experience persistent daytime or nighttime heartburn and some sustain severe damage, including ulceration, stricture, and Barretts esophagus, which can predispose to development of adenocarcinoma. Extraesophageal manifestations of GERD can include otolaryngologic, respiratory, and cardiac problems. Severe GERD responds best to agents that suppress gastric acid secretion. Of these, proton pump inhibitors (PPIs) provide the most effective control of gastric acidity and are, therefore, the medical treatment of choice. In fact, nonresponse to a PPI should raise the suspicion that the diagnosis is not GERD. Proton pump inhibitors are quickly becoming the treatment of choice for GERD, especially for severe or refractory cases. For patients whose GERD is refractory even to PPIs or who are unwilling to face years of PPI therapy, antireflux surgery remains an option.

Prediction of lactose malabsorption in referral patients

Two hundred forty-two patients referred for various gastrointestinal complaints were evaluated for clinical parameters that would predict findings of lactose malabsorption. Breath hydrogen and blood glucose lactose tests were performed after ingestion of 50 g lactose. Presenting complaints, duration of symptoms, and patient demographics such as age, sex, and ethnic heritage were not different between lactose malabsorbers and absorbers as defined by the breath hydrogen lactose test. Foodrelated symptoms in general and after specific foods such as milk, ice cream, cheese, and yogurt were also similar between groups. Prior to testing, 30% of malabsorbers (N=161) and 36% of absorbers (N=81) reported lactoserelated symptoms (P=NS). The blood glucose response to lactose was abnormal in 60% of malabsorbers and 15% of absorbers. This study confirmed our impression that it is difficult to predict lactose absorption status by clinical parameters. The majority of our lactose malabsorber patients were unaware of lactose-associated symptoms. Furthermore, symptom assessment, demographics, food history, and blood glucose testing did not predict abnormal hydrogen responses to lactose.

Clinical trial: an efficacy evaluation of reduced bisacodyl given as part of a polyethylene glycol electrolyte solution preparation prior to colonoscopy

Background  In an attempt to further improve patient preparation experience with reduced volume gut lavage solutions using 2‐L sulphate‐free electrolyte lavage solution plus 20‐mg bisacodyl (HalfLytely with Bisacodyl Tablets Bowel Prep Kit, Braintree Laboratories, Inc., Braintree, MA, USA), a low bisacodyl dose preparation was developed using 10 mg bisacodyl.

Safety issues regarding colonic cleansing for diagnostic and surgical procedures.

There are various methods available to cleanse the colon in preparation for diagnostic and surgical procedures. The popular options are diet and cathartic regimens, gut lavage and phosphate preparations. Each method has its own unique characteristics and safety profile. Diet and cathartic regimens are based on traditional methods of colonoscopy preparation and remain an acceptable and safe alternative for patients unwilling or unable to tolerate other bowel preparations. Gut lavage methods involve ingestion of 2–4L of osmotically balanced solutions containing polyethylene glycol, which have been shown to be safe and effective for colon cleansing, including for special patient populations with cardiac, renal or hepatic dysfunction. Phosphate preparations have also been shown to be safe and effective for colon cleansing and are generally better tolerated than counterpart gut lavage solutions. However, this method has safety concerns for some patients with cardiac, renal and hepatic dysfunctions.

Bowel cleansing with polyethylene glycol electrolyte lavage solution.

We reviewed our experience with an oral gut lavage solution (GoLYTELY), used as a rapid bowel cleansing preparation, and the prospective clinical trials reported in the literature to compare the overall experience with this type of preparation for colonoscopy and colon surgery. Five studies (546 patients) compared GoLYTELY to standard preparations for colonoscopy, while three trials (177 patients) have studied surgical patients. After evaluating patient tolerance, quality of colonic cleansing, and changes in microflora and colonic gas, GoLYTELY was found to be safe, rapid, and effective. It is well tolerated by patients and may become the preferred method of bowel cleansing.

Enzyme replacement for lactose malabsorption using a beta-D-galactosidase.

We evaluated 10 healthy symptomatic lactose malabsorbers for effect of an oral beta-D-galactosidase derived from Aspergillus oryzae (Lactrase, Kremers Urban Company, Milwaukee, WI, U.S.A.) on symptom and breath hydrogen response to challenge with 50 g lactose. Basally and at 30-min intervals for 8 h after lactose challenge, end-alveolar breath samples were collected and analyzed for hydrogen using gas chromatography. Symptoms were scored at 30 min and hourly for 8 h, rating bloating, cramps, nausea, pain, diarrhea, and flatulence. Four challenges were performed on 4 separate days with at least 3 days between challenges. The first two challenges served as baselines. Just before ingestion of 50 g powdered lactose dissolved in 200 ml water, beta-D-galactosidase capsules were given orally as a 250-mg dose for the third challenge and a 500-mg dose for challenge 4. Hydrogen excretion, quantified by using a trapezoidal method for computing area under the discontinuous curve of breath hydrogen concentration, was decreased in subjects receiving beta-D-galactosidase (baseline I, 346.0 ppm/h; baseline II, 367.2 ppm/h; 250-mg galactosidase, 208.2 ppm/h; 500-mg galactosidase, 178.0 ppm/h; p ≤ 0.05). Other analyzed parameters of H2 excretion were also decreased. Analysis of symptom response scores showed a dose-related decrease for bloating and flatus (p ≤ 0.05) and no statistical difference in the other assessed symptoms. We conclude that beta-D-galactosidase from Aspergillus oryzae, when given just before ingestion of lactose by lactose malabsorbers, can produce a dose-dependent reduction (statistically significant for the 500-mg dose) in breath hydrogen excretion, bloating, and flatus.