Erratum: Development of opioid-induced constipation: post hoc analysis of data from a 12-week prospective, open-label, blinded-endpoint streamlined study in low-back pain patients treated with prolonged-release WHO step III opioids [Corrigendum].
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ABSTRACT: [This corrects the article on p. 459 in vol. 8, PMID: 26300655.].
Erratum: Development of opioid-induced constipation: post hoc analysis of data from a 12-week prospective, open-label, blinded-endpoint streamlined study in low-back pain patients treated with prolonged-release WHO step III opioids [Corrigendum].
Journal of pain research 20151112
[This corrects the article on p. 459 in vol. 8, PMID: 26300655.]. ...[more]
Project description:BACKGROUND:Opioid-induced constipation is the most prevalent patient complaint associated with longer-term opioid use and interferes with analgesic efficacy, functionality, quality of life, and patient compliance. OBJECTIVES:We aimed to compare the effects of prolonged-release (PR) oxycodone plus PR naloxone (OXN) vs PR oxycodone (OXY) vs PR morphine (MOR) on bowel function under real-life conditions in chronic low-back pain patients refractory to World Health Organization (WHO) step I and/or II analgesics. RESEARCH DESIGN AND METHODS:This was a post hoc analysis of the complete data set from a prospective, randomized, open-label, blinded endpoint (PROBE) streamlined study (German pain study registry: 2012-0012-05; European Union Drug Regulating Authorities Clinical Trials [EudraCT]: 2012-001317-16), carried out in 88 centers in Germany, where a total of 901 patients requiring WHO step III opioids to treat low-back pain were enrolled and prospectively observed for 3 months. Opioid allocation was based on either optional randomization (n=453) or physician decision (n=448). In both groups, treatment doses could be adjusted as per the German prescribing information, and physicians were free to address all side effects and tolerability issues as usual. The primary endpoint was the proportion of patients maintaining normal bowel function throughout the complete treatment period, assessed with the Bowel Function Index (BFI). Secondary analyses addressed absolute and relative BFI changes, complete spontaneous bowel movements, use of laxatives, treatment emergent adverse events, analgesic effects, and differences between randomized vs nonrandomized patient groups. RESULTS:BFI changed significantly with all three WHO step III treatments, however significantly less with OXN vs OXY and MOR despite a significantly higher use of laxatives with the latter ones (P<0.001). The percentage of patients who maintained normal BFI scores despite opioid treatment was 54.5% (164/301) with OXN and was significantly superior to those seen with OXY (32.8% [98/300]) (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.77-3.44; P<0.001) or MOR (29.7% [89/300]) (OR: 2.84, 95% CI: 2.03-3.97; P<0.001). Absolute BFI changes of ?12mm 100 mm horizontal visual analog scale (VAS100) vs. baseline were seen for OXN in 41.4%, for OXY in 68.7%, and for MOR in 72.3%. Complete spontaneous bowel movements decreased at least by one per week in 10.3% with OXN vs 42.3% for OXY (OR: 6.39, 95% CI 4.13-9.89; P<0.001) and 42.0% for MOR (OR: 6.31, 95% CI: 4.08-9.76; P<0.001). Overall, 359 treatment emergent adverse events (78 [OXN], 134 [OXY], and 147 [MOR]) in 204 patients (41 [OXN], 80 [OXY], and 83 [MOR]) occurred, most affecting the gastrointestinal (49.3%) and the nervous system (39.3%). Treatment contrasts between randomized vs nonrandomized patients were insignificant. CONCLUSION:In this post hoc analysis of data from a real-life 12-week study, OXN treatment was associated with a significantly lower risk of opioid-induced constipation, superior tolerability, and significantly better analgesic efficacy compared with OXY and MOR.
Project description:Consideration of a previous unrecognized twinning of the original investigated crystal of the title compound [Kia et al. (2009 ?). Acta Cryst. E65, o301] led to improved reliability factors and to a slightly higher precision for all geometric parameters. The crystal under investigation was twinned by pseudo-merohedry with [100, 00, 00]?as the twin matrix and a refined twin domain fraction of 0.9610?(5):0.0390?(5). The results of the new crystal structure refinement are given here.[This corrects the article DOI: 10.1107/S1600536809001068.].
Project description:An error in the original formulation of the title compound in the paper by Sadiq-ur-Rehman, Sherzaman, Ali, Shahzadi & Helliwell [Acta Cryst. (2007), E63, m2329] is corrected.The title compound in the paper by Sadiq-ur-Rehman, Sherzaman, Ali, Shahzadi & Helliwell [Acta Cryst. (2007), E63, m2329] was an unexpected product which seemed to have nitrate coordinated to three Sn atoms. However, it was noticed that the charges do not balance and that it is most likely that the nitrate is in fact a carbonate. Regrettably, there is no material to carry out microanalysis, but a plausible mechanism has been suggested to explain the unexpected formation of the product. Trimethyl-tin chloride will react with methanol in the presence of a base (4-hydroxy-piperidine) to give trimethyl-tin methoxide, which will rapidly hydrolyze in air to give the hydroxide. Both the methoxide and the hydroxide will react with atmospheric CO(2) to give the carbonate (Bloodworth et al., 1967 ?; Blunden et al., 1984 ?; Sato, 1967 ?). Me(3)SnCl + MeOH + base ? Me(3)SnOMe + base·HCl Me(3)SnOMe + H(2)O ? Me(3)SnOH + MeOH Me(3)SnOH + CO(2) ? Me(3)SnOCO(2)HMe(3)SnOCO(2)H + Me(3)SnOMe ? Me(3)SnOCO(2)SnMe(3) + MeOH. The carbonate then forms a coordination copolymer with trimethyl-tin chloride. The name of the title compound is corrected to poly[?(3)-carbonato-?(3)-chlorido-nona-methyl-tri-tin(IV)], [Sn(3)(CH(3))(9)(CO(3))Cl] (M(r) = 586.84).[This corrects the article DOI: 10.1107/S1600536808017091.].
Project description:The chemical name and formula in the paper by Castillo, Luque, De la Pinta & Román [Acta Cryst. (2001), E57, m384-m386] is corrected.[This corrects the article DOI: 10.1107/S1600536801012909.].
Project description:INTRODUCTION:Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST). METHODS AND ANALYSIS:FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60?years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357?µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3?years. The primary endpoint is first occurrence of the Anti-Platelet Trialists' Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3. ETHICS AND DISSEMINATION:FAST (ISRCTN72443728) has ethical approval in the UK and Denmark, and results will be published in a peer reviewed journal. TRIAL REGISTRATION NUMBER:FAST is registered in the EU Clinical Trials Register (EUDRACT No: 2011-001883-23) and International Standard Randomised Controlled Trial Number Register (ISRCTN No: ISRCTN72443728).
Project description:To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors.Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1).The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10% false discovery rate.Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.