ABSTRACT
Methylnaltrexone is a methylated form of the mu-opioid antagonist naltrexone that blocks peripheral effects of opioids without affecting centrally mediated analgesia. The authors conducted a ...3-month open-label extension trial of methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC). Following completion of a 2-week double-blind (DB) trial, 82 patients with OIC who did not respond to laxatives received subcutaneous (SC) methylnaltrexone as needed for up to 3 months. Patients received 0.15 mg/kg as a first dose, adjusted to 0.3 mg/kg or 0.075 mg/kg as needed (maximum of one dose per 24 hours). Mean laxation response (rescue-free bowel movement within 4 hours) rates (DB phase, months 1, 2, 3 open-label phase) were 45.3%, 45.5%, 57.7%, and 57.3%, respectively, for patients treated with DB methylnaltrexone and 10.8%, 48.3%, 47.6%, and 52.1%, respectively, for patients treated with DB placebo. Median time to laxation among responders was 45 minutes (range 0-4 hours) for all doses. Approximately 50% of patients reported improvement in constipation distress. Patient and investigator global clinical impression of change scores also improved. There were minimal changes in pain scores and opioid withdrawal symptoms. Adverse events included abdominal pain and nausea, mostly mild or moderate in severity. SC methylnaltrexone administered PRN (as needed) for up to 3 months continued to rapidly induce laxation in advanced illness patients with OIC.
Percutaneous endoscopic gastrostomy (PEG) provides a reliable route for nutrition and hydration in ALS patients with dysphagia. We performed a retrospective analysis of the CNTF and BDNF databases to ...determine the clinical status of ALS patients within 30 days preceding PEG insertion. This analysis revealed an approximately 50% reduction of function across multiple measures of ALS disease status. A trend to earlier intervention with PEG was apparent upon review of published studies and the CNTF and BDNF studies. By comparing the rate of decline pre- and post-PEG, nutritional supplementation via PEG stabilized the weight loss experienced by patients. Death within 30 days post-PEG was associated with a marked reduction in forced vital capacity (FVC) and identified a group of ALS patients in whom PEG should be cautiously performed. These data emphasize the importance of sequential measurement of FVC in managing ALS patients to guide the timing of nutritional intervention with PEG.
Neurotrophin-3 improves functional constipation Parkman, Henry P; Rao, Satish S C; Reynolds, James C ...
The American journal of gastroenterology,
06/2003, Letnik:
98, Številka:
6
Journal Article
Recenzirano
Neurotrophin-3 (NT-3) is a neurotrophic factor involved in the growth, development, and function of the nervous system. In preliminary studies, s.c. recombinant methionyl-human NT-3 enhanced transit ...throughout the GI tract and increased stool frequency in normal and constipated subjects. Our aim was to assess 1) the dose-related effects of NT-3 on bowel function, colon transit, and symptoms of chronic constipation, and 2) its safety.
This was a double-blind, randomized, placebo-controlled phase II study. A total of 107 patients with a diagnosis of functional constipation (Rome II criteria) were randomized to receive 4 wk of double blind, s.c. injections of either placebo, 3 mg, or 9 mg NT-3 once per week (qW) or three times per week (TTW); or 9 mg NT-3 TTW for 1 wk, then qW. The primary endpoint was the change in number of spontaneous, complete bowel movements per week. Colon transit was assessed before and at end of treatment.
Compared with placebo, patients who received 9 mg NT-3 TTW showed significant increases in frequency of spontaneous, complete bowel movements and total bowel movements, as well as dose-related softening of stool and improved ease of passage. The number of days per week without a bowel movement also decreased, colon transit improved, as did constipation-related symptoms. Weekly dosing was ineffective. Transient injection-site reactions, seen in one third of patients receiving NT-3 TTW, were the most frequent adverse event.
NT-3, administered TTW, increased stool frequency, enhanced colon transit, and improved symptoms of chronic constipation. NT-3 seems to be a novel, safe, and effective agent for the treatment of functional constipation.
PurposeOpioid-induced constipation (OIC) is a common side effect of opioid therapy. Methylnaltrexone (MNTX) is a selective, peripherally acting μ-opioid receptor antagonist, with demonstrated ...efficacy in treating OIC. We pooled results from MNTX clinical trials to compare responses to an initial dose in patients with chronic cancer and noncancer pain. Patients and MethodsThis post hoc analysis used pooled data from 3 randomized, placebo-controlled studies of MNTX in patients with advanced illness with OIC. Assessments included the proportions of patients achieving rescue-free laxation (RFL) within 4 and 24 hours of the first study drug dose, time to RFL, current and worst pain intensity, and adverse events, stratified by the presence/absence of cancer. ResultsA total of 355 patients with cancer (MNTX n = 198, placebo n = 157) and 163 without active cancer (MNTX n = 83; placebo n = 80) were included. More patients treated with MNTX compared with those who received placebo achieved an RFL within 4 (cancer: MNTX, 61.1% vs placebo,15.3%, p<0.0001; noncancer: MNTX, 62.2% vs placebo, 17.5%, p<0.0001) and 24 hours (cancer: MNTX, 71.2% vs placebo, 41.4%, p<0.0001; noncancer: MNTX, 74.4% vs placebo, 37.5%, p<0.0001) of the initial dose. Cumulative RFL response rates within 4 hours of the first, second, or third dose of study drug were also higher in MNTX-treated patients. The estimated time to RFL was shorter among those who received MNTX and similar in cancer and noncancer patients. Mean pain scores declined similarly in all groups. The most common adverse events in both cancer and noncancer patients were abdominal pain, flatulence, and nausea. ConclusionAfter the first dose, MNTX rapidly induced a laxation response in the majority of both cancer and noncancer patients with advanced illness. Opioid-induced analgesia was not compromised, and adverse events were primarily gastrointestinal in nature. Methylnaltrexone is a well-tolerated and effective treatment for OIC in both cancer and noncancer patients.
Methodologic errors have compromised previous attempts to establish the relationship between mood and menstruation in women with the premenstrual syndromes. These syndromes cannot be diagnosed by ...history and require confirmation with longitudinal, prospective ratings. In this paper we present the characteristic pattern of mood changes in women with and without menstrually-related mood syndrome. The theoretical and diagnostic implications of the pattern differences are discussed.
INTRODUCTION: Use of mechanical ventilation (MV), administered either invasively via tracheostomy, or more commonly non-invasively (CPAP, BiPAP), appears to be increasing in ALS. No prospective ...databases exist that describe the behavior of physicians and patients and the criteria for instituting MV in ALS. METHODS: 387 placebo patients in a Phase III trial of r-metHuBDNF were followed for 9 months. Although the use of MV was not the primary end-point of the trial, information was gathered regarding it by cataloging respiratory adverse events and tracking health resource utilization. RESULTS: 35 of 387 patients utilized MV during the trial. Twenty-eight (7%) patients received BiPAP. Seven (2%) were tracheotomized without first receiving BiPAP. Forced vital capacity (FVC): BiPAP patients had a mean ( &A SEM) FVC% of 71.8 &A 2.8% and ALSFRS of 27.7 &A 1.0 at baseline; non-BiPAP patients had a mean baseline FVC% of 88.7 &A 1.0%, and an ALSFRS of 30.3 &A 0.3. Symptom duration at entry was similar for both groups (2.1 &A 0.4 years vs. 2.1 &A 0.1 years). At the time of first use of BiPAP, average FVC% was 47.5 &A 4.0% and ALSFRS score was 22.4 &A 1.5. The range of FVC% at start of BiPAP was 15A87. The nine-month survival was 67.9% for BiPAP patients vs. 86% for non-BiPAP patients. The use of BiPAP varied tremendously among the 38 study sites, with some not employing it at all and others using it in as many as 40% of patients. CONCLUSIONS: Of the 9% of placebo patients who received MV, BiPAP patients were more rapidly progressing than non-BIPAP patients, and showed a greater eventual mortality rate. Patients began MV at a wide range of values of FVC%, and centers differed in their prescribing practices. Factors influencing BiPAP use are complex, and not strictly related to FVC%. (ALS 2001; 2: 19A22)
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