Biorefinery development for the conversion of softwood residues into sustainable aviation fuel: Implications from life cycle assessment and energetic-exergetic analyses

Background: Opioid-induced constipation (OIC) may increase the risk of fecal impaction and mortality in patients with advanced illness. Methylnaltrexone (MNTX) is efficacious for OIC.Objective: The purpose of this analysis was to evaluate cumulative rescue-free laxation response with repeat MNTX dosing in patients with advanced illness who were refractory to current laxative regimens and to assess the influence, if any, of poor functional status on response to MNTX treatment.Methods: This analysis included pooled data from patients with advanced illness and established OIC who were on a stable opioid regimen in a pivotal, randomized, placebo (PBO)-controlled clinical trial (study 302 [NCT00402038]) or a randomized, PBO-controlled Food and Drug Administration-required postmar-keting study (study 40 0 0 [NCT0 0672477]). Patients in study 302 received subcutaneous MNTX 0.15 mg/kg or PBO every other day, whereas those in study 40 0 0 received MNTX 8 mg (body weight >38 to < 62 kg), MNTX 12 mg (body weight >62 kg), or PBO every other day. Outcomes included cumulative rescue-free laxation rates at 4-and 24-hours postdose for the first 3 doses of study drug and time to rescue-free lax-ation. To assess if functional status influenced treatment outcomes, we performed a secondary analysis on the outcomes stratified by baseline World Health Organization/Eastern Cooperative Oncology Group performance status, pain scores, and safety.Results: One hundred eighty-five patients received PBO and 179 patients received MNTX. The median age was 66.0 years, 51.5% were women, 56.5% had a baseline World Health Organization/Eastern Cooperative Oncology Group performance status score > 2, and 63.4% had a primary diagnosis of cancer. Cumulative rescue-free laxation rates were significantly higher with MNTX than PBO 4-and 24-hours after doses 1, 2, and 3 ( P < 0.0 0 01), and between-treatment comparisons remained significant ( P < 0.0 0 01) regardless of performance status. The estimated time to first rescue-free laxation was shorter for patients receiving MNTX versus PBO. No new safety signals were identified.Conclusions: Repeated use of MNTX represents a safe and effective treatment for OIC in patients with ad-vanced illness regardless of baseline performance status. ClinicalTrials.gov identifier: NCT00672477. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX)(c) 2023 Elsevier HS Journals, Inc.(c) 2023 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )