Jorge L. Herrera

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.

Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection.

Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin α and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (−238A) and TNF3 (−308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the −238G/A and −308G/A dimorphic sequences. Polymorphisms in the TNFα promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection.

A Randomized, Multicenter Comparison of Polyethylene Glycol Laxative and Tegaserod in Treatment of Patients With Chronic Constipation

OBJECTIVE: Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. This study was designed to compare the efficacy of each product over a 4-wk treatment period.METHODS: Study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information.RESULTS: A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P = 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P = 0.019) and had significantly greater improvement in constipation symptoms (P = 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events.CONCLUSIONS: While PEG laxative and tegaserod are safe for their intended use in chronic constipation, PEG had superior efficacy, caused fewer headaches, and produced greater improvement of constipation symptoms. Trial is registered at: http://www.clintrials.gov. Unique registration number: NCT00153140

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.

Acetaminophen overdose in pregnancy.

Acetaminophen (APAP) is the most common drug overdose in pregnancy. Available data regarding APAP overdose in pregnancy is limited to case reports and a small prospective case series. APAP has been demonstrated to cross the placenta and in toxic doses may harm the fetal and maternal hepatocytes. Fetal hepatocytes metabolize APAP into both active and toxic metabolites. These toxic metabolites may cause fetal hepatic necrosis. N-acetylcysteine (NAC) has also been demonstrated to cross the placenta and may bind toxic metabolites in both the mother and the fetus. Limited data suggest that the majority of morbidity and mortality from APAP overdose can be averted by initiation of NAC within the first 16 hours of ingestion and possibly even later. NAC may be safely administered during pregnancy and should be initiated early after APAP overdosage. The literature was reviewed through the use of OvidMEDLlNE® database, encompassing 1966 to the present. Searches were conducted using the key words acetaminophen, paracetamol, N-acetylcysteine, overdose, and hepatotoxicity. The search was further refined by selecting articles that contained these search words together with the key word pregnancy. Only English language papers were reviewed. Articles were selected on the basis of relevance to the topic. Pertinent citations found in the selected articles were also reviewed.

An open-label study of chronic polyethylene glycol laxative use in chronic constipation.

Polyethylene glycol 3350 (MiraLAX, Braintree Laboratories Inc., Braintree, MA, USA) is approved for the short‐term treatment of occasional constipation.

Iron depletion is not effective in inducing a virologic response in patients with chronic hepatitis C who failed to respond to interferon therapy

OBJECTIVE:Some studies have suggested that increased iron stores may impact negatively on the response to interferon in patients with chronic hepatitis C infection. We performed this prospective trial to determine the effects of iron depletion on ALT and HCV-RNA levels in patients with chronic hepatitis C infection and to assess whether the response to interferon in patients who had previously failed to respond to interferon was enhanced by iron depletion.METHODS:Patients with chronic hepatitis C resistant to interferon therapy and no evidence of iron overload underwent weekly phlebotomies until the serum ferritin level was below lower limits of normal for the subjects age and sex. Patients were then started on interferon-α2b, 3 million units subcutaneously three times per week for a period of 24 weeks. Iron studies, ALT, and HCV-RNA levels were monitored at baseline, after phlebotomy and at 12 and 24 weeks of interferon therapy.RESULTS:Thirty-three patients were enrolled, 28 completed the study. A mean of 7.2 units of blood were removed to achieve iron depletion. ALT levels decreased significantly with phlebotomy (142 IU/L before phlebotomy vs 82 IU/L after phlebotomy; p < 0.001), but log HCV-RNA levels remained unchanged (6.49 before phlebotomy vs 6.51 after phlebotomy). Interferon therapy did not improve ALT levels further. HCV-RNA levels were minimally reduced during interferon therapy (log HCV-RNA 6.49 before interferon vs 6.00 after 24 weeks of interferon therapy). Two patients achieved a virologic end of treatment response, both relapsed within 3 months after discontinuation of interferon. No patient achieved a sustained virologic response.CONCLUSIONS:In patients who previously failed treatment with interferon, iron depletion induced by phlebotomy improves ALT levels but is ineffective in achieving viral eradication in patients retreated with interferon 3 million units three times per week.

Case Report: Esophageal Metastasis from Breast Carcinoma Presenting as Achalasia

Metastatic breast carcinoma to the esophagus most often presents with a mid-esophageal stricture. Involvement of the gastroesophageal junction by breast carcinoma is distinctly unusual. The authors report the case of a 78-year-old woman who presented with clinical and radiologic features of achalasia secondary to breast carcinoma, metastatic to the gastroesophageal junction. Metastatic breast cancer to the gastroesophageal junction should be added to the list of conditions mimicking achalasia.

Management of Acute Variceal Bleeding

Acute variceal bleeding (AVB) is the most common cause of upper gastrointestinal hemorrhage in patients with cirrhosis. Advances in the management of AVB have resulted in decreased mortality. To minimize mortality, a multidisciplinary approach addressing airway safety, prompt judicious volume resuscitation, vasoactive and antimicrobial pharmacotherapy, and early endoscopy to obliterate varices is necessary. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) has been used as rescue therapy for patients failing initial attempts at hemostasis. Patients who have a high likelihood of failing initial attempts at hemostasis may benefit from a more aggressive approach using TIPS earlier in their management.

Immune globulin and vaccine therapy to prevent hepatitis a infection

The hepatitis A virus is usually transmitted person-to-person due to fecal-oral exchange of virus. Approximately 30,000 infections are reported each year in the United States, with the actual incidence being much greater. Prophylaxis with immune globulin has had a minimal impact on the overall incidence of hepatitis A. The recent availability and proven efficacy of a hepatitis A vaccine offers the hope that the incidence of infection may be substantially reduced. Pre- and postexposure prophylaxis should be targeted to individuals at increased risk of either acquiring infection, transmitting infection, or developing fulminant hepatitis, or to help control epidemics. This article reviews the current literature and discusses recommendations for pre- and postexposure prophylaxis against hepatitis A virus.