Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients
Ontology highlight
ABSTRACT:
DISEASE(S): Opioid-induced Constipation,Constipation,Cancer
PROVIDER: 2094150 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:OBJECTIVE:The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350?+?E) compared to PEG4000 without electrolytes (PEG4000). METHODS:In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350?+?E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ?1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ?3 per week with <1 episode of fecal incontinence. RESULTS:Ninety-seven subjects were included, of whom 82 completed the study. Mean reduction in TSS was -3.81 (95% CI: -4.96 to -2.65) and -3.74 (95%CI: -5.08 to -2.40), for PEG3350?+?E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68). Daily sachet use was: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350?+?E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P?=?0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. CONCLUSIONS:Noninferiority regarding long-term constipation-related symptoms of PEG3350?+?E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents.
| S-EPMC5753830 | biostudies-literature
Project description: Not available
| S-EPMC8090930 | biostudies-literature
Project description:Adsorption on a functionalized surface can be an effective way of purifying polyphenols from complex plant extracts. Polymeric resins that rely on hydrophobic interactions suffer from low selectivity, weak affinity towards polyphenols, and lack tunability therefore making the purification of polyphenols less efficient. In this study, a purification process for the recovery of polyphenols from grape pomace extract was successfully developed using hydrogen bonding affinity ligands grafted on silica particles and PEG-assisted elution solvents. Bare silica (SiO2) and polyethylene glycol (mPEG)-grafted silica microparticles with molecular weights of 2000 and 5000 were tested to determine their polyphenol binding and release characteristics. Functionalizing the surface of bare silica with mPEG ligands increased the adsorption capacity by 7.1- and 11.4-fold for mPEG-2000 and mPEG-5000 compared to bare silica particles, respectively. This was likely due to the introduction of more polyphenol binding sites with mPEG functionalization. Altering the molecular weight (MW) of mPEG grafted on silica surfaces provided tunability in the adsorption capacity. A complete recovery of polyphenols (~99.9%) from mPEG-grafted silica particles was achieved by utilizing PEG-ethanol or PEG-water cosolvent systems. Recovered polyphenols showed up to ~12-fold antioxidant activity compared to grape pomace extract. This study demonstrates that mPEG-grafted silica particles and elution of polyphenols with PEG cosolvents can potentially be used for large-scale purification of polyphenols from complex plant extracts and simplify the use of polyphenols, as PEG facilitates remarkable solvation and is an ideal medium for the final formulation of polyphenols.
| S-EPMC6630576 | biostudies-literature
Project description:Cassava is an important tropical and sub-tropical root crop that is adapted to drought environment. However, severe drought stress significantly influences biomass accumulation and starchy root production. The mechanism underlying drought-tolerance remains obscure in cassava. In this study, changes of physiological characters and gene transcriptome profiles were investigated under dehydration stress simulated by polyethylene glycol (PEG) treatments. Five traits, including peroxidase (POD) activity, proline content, malondialdehyde (MDA), soluble sugar and soluble protein, were all dramatically induced in response to PEG treatment. RNA-seq analysis revealed a gradient decrease of differentially expressed (DE) gene number in tissues from bottom to top of a plant, suggesting that cassava root has a quicker response and more induced/depressed DE genes than leaves in response to drought. Overall, dynamic changes of gene expression profiles in cassava root and leaves were uncovered: genes related to glycolysis, abscisic acid and ethylene biosynthesis, lipid metabolism, protein degradation, and second metabolism of flavonoids were significantly induced, while genes associated with cell cycle/organization, cell wall synthesis and degradation, DNA synthesis and chromatin structure, protein synthesis, light reaction of photosynthesis, gibberelin pathways and abiotic stress were greatly depressed. Finally, novel pathways in ABA-dependent and ABA-independent regulatory networks underlying PEG-induced dehydration response in cassava were detected, and the RNA-Seq results of a subset of fifteen genes were confirmed by real-time PCR. The findings will improve our understanding of the mechanism related to dehydration stress-tolerance in cassava and will provide useful candidate genes for breeding of cassava varieties better adapted to drought environment.
| S-EPMC4813147 | biostudies-literature
Project description:With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.
| S-EPMC10622525 | biostudies-literature
Project description:AimTo evaluate the efficacy and safety of polyethylene glycol (PEG) 3350 in subjects with self-reported occasional constipation.MethodsEligible subjects ≥ 17 years of age were randomized to receive either placebo or PEG 3350 17 g once daily in this multicenter, double-blind trial. Evaluations were conducted before (baseline) and after a 7-d treatment period. The primary efficacy variable was the proportion of subjects reporting complete resolution of straining and hard or lumpy stools. Secondary efficacy variables assessed the severity of the subjects' daily bowel movement (BM) symptoms, and preference of laxatives based on diary entries, visual analog scale scores, and questionnaires.ResultsOf the 203 subjects enrolled in the study, 11 had major protocol violations. Complete resolution was noted by 36/98 (36.7%) subjects in the PEG 3350 group and 23/94 (24.5%) in the placebo group (P = 0.0595). The number of complete BMs without straining or lumpy stools was similar between both groups. Subjects receiving PEG 3350 experienced significant relief in straining and reduction in hardness of stools over a 7-d period (P < 0.0001). Subjects reported that PEG 3350 had a better effect on their daily lives, provided better control over a BM, better relief from constipation, cramping, and bloating, and was their preferred laxative. Adverse events (AEs) were balanced between the PEG 3350 and the placebo groups. No deaths, serious AEs, or discontinuations due to AEs were reported. This trial is registered at clinicaltrials.gov as NCT00770432.ConclusionOral administration of 17 g PEG 3350 once daily for a week is effective, safe, and well tolerated in subjects with occasional constipation.
| S-EPMC4848251 | biostudies-literature
Project description:The aims of this study were to compare the bowel-cleansing efficacy, patient affinity for the preparation solution, and mucosal injury between a split dose of polyethylene glycol (SD-PEG) and low-volume PEG plus ascorbic acid (LV-PEG+Asc) in outpatient scheduled colonoscopies.Of the 319 patients, 160 were enrolled for SDPEG, and 159 for LV-PEG+Asc. The bowel-cleansing efficacy was rated according to the Ottawa bowel preparation scale. Patient affinity for the preparation solution was assessed using a questionnaire. All mucosal injuries observed during colonoscopy were biopsied and histopathologically reviewed.There was no significant difference in bowel cleansing between the groups. The LV-PEG+Asc group reported better patient acceptance and preference. There were no significant differences in the incidence or characteristics of the mucosal injuries between the two groups.Compared with SD-PEG, LV-PEG+Asc exhibited equivalent bowel-cleansing efficacy and resulted in improved patient acceptance and preference. There was no significant difference in mucosal injury between SD-PEG and LV-PEG+Asc. Thus, the LV-PEG+Asc preparation could be used more effectively and easily for routine colonoscopies without risking significant mucosal injury.
| S-EPMC4780453 | biostudies-literature
Project description:Manuscript Name: "Addressing Bioreactor hiPSC Aggregate Stability, Maintenance and Scaleup Challenges Using a Design of Experiment Approach" Evaluation of core pluripotent genes showed that expression levels were similar between samples with a clear indication of a primed phenotype. In addition, we evaluated several well-known oncogenes notable TP53, MYC, NANOGP8, EEF1A2 and KLF4 were expressed with similar transcript levels between samples, though KLF4 had low overall expression. It was observed that a few genes indicative of forward differentiation were expressed with TSR genes TDGF1, LEFTY1 and IL17RC and the trophectodermal genes KRT8 and TEAD4 showing comparable expression levels. Expression of the primary primitive streak gene NODAL was observed at low transcript levels in both samples. Examining the top differentially expressed genes we noted that there were several genes involved in ectodermal differentiation and some key signaling pathway components that were significantly downregulated in response to the presence of PEG and HS. Down-regulated ectodermal genes included SOX1, OLIG3, LHX5 and OTX2 as well as some less known ones. The pathways most downregulated were the TGFβ family as suggested by BMP2 and BMP4 down regulation, though the previously mentioned levels of TDGF1, LEFTY1 and NODAL remained consistent to cultures lacking additives. Wnt family signaling components down regulated were Wnt4, FRZB, FZD5 and FRZ8. Also a decreased in retinoic acid signaling components were noted as indicated by decreased CYP26A1, CYP26C1, DHRS3 and CRABP2 transcript levels.
2024-04-16 | GSE264081 | GEO
Project description:The objective of the study is to examine the effect of adding a strict low-residue lunch on the day before colonoscopy has on clinical efficacy and patient tolerability of bowel preparation, with patients receiving split-dose Polyethylene Glycol Based Lavage.
The primary outcomes will be 1) quality of preparation in cleansing the colon and 2) patient satisfaction
| 2126299 | ecrin-mdr-crc
Project description:MethodsThis multicenter, double-blind, placebo-controlled, parallel-group trial included adults with chronic idiopathic constipation randomized to polyethylene glycol 3350 17 g (n = 204) or placebo (n = 100) once daily for 24 weeks. Post hoc analyses were performed using the US Food and Drug Administration endpoint (≥3 complete spontaneous bowel movements/week and an increase of ≥1 complete spontaneous bowel movement/week from baseline for ≥9/12 weeks, including 3 of the last 4 weeks) along with additional efficacy and safety outcomes.ResultsThe proportion of patients meeting the new endpoint was significantly higher with polyethylene glycol 3350 vs placebo (42% vs 13%; P < 0.0001). Reductions in the mean number of hard/lumpy stools/week (-2.1 vs -0.9; P = 0.0014) and the weekly mean five-point cramping rating (-0.3 vs -0.1; P = 0.0272) also significantly favored polyethylene glycol 3350. The proportion of subjects with gastrointestinal adverse events decreased markedly after the first week of treatment in the polyethylene glycol 3350 group.ConclusionUsing the current US Food and Drug Administration-recommended responder definition and other secondary outcomes, once-daily polyethylene glycol 3350 demonstrated substantial and sustained efficacy and safety over 24 weeks in patients with chronic idiopathic constipation. Trial Registration. The original trial was registered with https://clinicaltrials.gov Trial: NCT00153153.
| S-EPMC9481403 | biostudies-literature