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Jan Tack - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of naloxegol in Patients with opioid induced constipation and laxative inadequate response
United European gastroenterology journal, 2015Co-Authors: Jan Tack, Jaakko Lappalainen, Ulysses Diva, Raj Tummala, Mark SostekAbstract:Background: Treatment options for Patients with opioid-induced constipation (OIC) and inadequate response to laxatives (LIR) are few. Objective: Assess the efficacy and safety of orally administered naloxegol in Patients with prospectively confirmed OIC and LIR Methods: We analyzed pooled data from two identical randomized, double-blind, placebo-controlled, Phase 3 trials of naloxegol in Patients with non-cancer pain, OIC and LIR in which naloxegol (12.5mg, n ¼240; 25mg, n ¼241) or placebo (n ¼239) were administered daily. We assessed the response rates, time to first post-dose laxation, spontaneous bowel movements (SBMs), OIC symptoms and Patient-reported outcomes over 12 weeks. Results: OIC response rates for the naloxegol 25-mg (p <0.001) and the 12.5-mg (p ¼0.005) LIR dose groups were higher than placebo. Median times to first post-dose SBM were 7.6, 19.2 and 41.1 hours for the naloxegol 25mg, naloxegol 12.5mg and placebo groups, respectively. Other SBM measures, daily symptoms of OIC, and both the Patient Assessment of Constipation-Symptoms and Patient Assessment of Constipation-Quality of Life scores improved from baseline with naloxegol treatment. Changes from baseline in opioid dose, pain scores and opioid withdrawal scores were similar among treatment groups. Conclusions: Naloxegol was efficacious, generally safe and well tolerated in the Patients with OIC and LIR, while preserving opioid analgesia. ClinicalTrials.gov identifiers: NCT01309841; NCT01323790
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association between health related quality of life and symptoms in Patients with chronic constipation an integrated analysis of three phase 3 trials of prucalopride
Neurogastroenterology and Motility, 2015Co-Authors: Jan Tack, Dominique Dubois, Lieve Vandeplassche, Alain Joseph, Rene KerstensAbstract:Background Prucalopride is a high-affinity 5-HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health-related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride. Methods This was an integrated analysis of data from three pivotal multicenter, double-blind, randomized, placebo-controlled, parallel-group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC-QOL) scores, Patient Assessment of Constipation Symptoms (PAC-SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment. Key Results Patients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC-SYM scores correlated well with an improvement in PAC-QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC-QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of Patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of Patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point). Conclusions & Inferences Improvements in PAC-QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL.
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psychometric performance and clinical meaningfulness of the Patient Assessment of constipation quality of life questionnaire in prucalopride resolor trials for chronic constipation
Neurogastroenterology and Motility, 2010Co-Authors: Dominique Dubois, H Gilet, M Vialadanten, Jan TackAbstract:Background The Patient Assessment of Constipation–Quality of Life (PAC-QOL) is a self-reported questionnaire measuring health-related quality of life (HRQL) of constipated Patients and was used as secondary endpoint in three identical double-blind, randomized, placebo-controlled Phase III clinical trials. These 12-week trials in subjects with severe chronic constipation evaluated the effects of prucalopride, a selective 5-HT4 agonist given orally once daily. Methods To consolidate the main treatment effect results observed in the prucalopride trial populations, analyses were undertaken on the pooled data of the three trials to confirm the psychometric properties of the PAC-QOL and to provide guidance for the interpretation of the clinical significance of its scores. Key Results The evaluation of the psychometric properties confirmed the PAC-QOL reliability, validity and responsiveness to measure the impact of chronic constipation symptoms on HRQL in the prucalopride trials. The 1-point improvement in PAC-QOL scores used as target response level for the main treatment effect analyses was validated as a relevant definition of response for treatment group comparisons. Cumulative distribution curves, drawn for each treatment group to provide more complete information on treatment effects than single minimal important difference point estimates, demonstrated consistent superior effects of prucalopride over placebo on all PAC-QOL scores. Conclusions & Inferences The PAC-QOL questionnaire is a useful measurement tool to assess, from a Patient perspective, the potential therapeutic value of chronic constipation treatments in clinical trials and, by directly reflecting the Patient’s own perspective on constipation and its treatment, eventually also for informing daily medical practice.
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development and psychometric evaluation of the Patient Assessment of upper gastrointestinal symptom severity index pagi sym in Patients with upper gastrointestinal disorders
Quality of Life Research, 2004Co-Authors: Anne M Rentz, Nicholas J. Talley, Jan Tack, Peter J Kahrilas, Vincenzo Stanghellini, C De La Loge, Elyse Trudeau, Dominique Dubois, Dennis A RevickiAbstract:Objective: Describe the development and evaluation of a new self-report instrument, the Patient Assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM) in subjects with gastroesophageal reflux disease (GERD), dyspepsia, or gastroparesis. Methods: Recruited subjects with GERD (n=810), dyspepsia (n=767), or gastroparesis (n=169) from the US, France, Germany, Italy, the Netherlands, and Poland. Subjects completed the PAGI-SYM, SF-36, a disease-specific HRQL measure (PAGI-QOL), and disability day questions. Two-week reproducibility was evaluated in 277 stable subjects. We evaluated construct validity by correlating subscale scores with SF-36, PAGI-QOL, disability days, and global symptom severity scores. Results: The final 20-item PAGI-SYM has six subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Internal consistency reliability was good (α =0.79 0.91); test–retest reliability was acceptable (Intraclass correlation coefficients α =0.60 0.82). PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p < 0.0001), PAGI-QOL scores (all p < 0.0001), disability days (p< 0.0001), and global symptom severity (p < 0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability days (all p < 0.0001), where greater symptom severity was associated with more disability days. Conclusions: Results suggest the PAGI-SYM, a brief symptom severity instrument, has good reliability and evidence supporting construct validity in subjects with GERD, dyspepsia, or gastroparesis.
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cross cultural development and validation of a Patient self administered questionnaire to assess quality of life in upper gastrointestinal disorders the pagi qol
Quality of Life Research, 2004Co-Authors: Christine De La Loge, Dennis A Revicki, Nicholas J. Talley, Jan Tack, Anne M Rentz, Peter J Kahrilas, Vincenzo Stanghellini, Elyse Trudeau, P Marquis, Dominique DuboisAbstract:Summarize the Patient Assessment of Upper GastroIntestinal Disorders-Quality of Life (PAGI-QOL©) development and provide results on its reliability and validity from the international psychometric validation in dyspepsia, GastroEsophageal Reflux Disease (GERD), and gastroparesis. Methods: Subjects completed the pilot PAGI-QOL at baseline and 8 weeks; and a subsample also at 2 weeks. Other Assessments were: Patient Assessment of Upper GastroIntestinal Disorders-Symptom Severity Index, SF-36, number of disability days. Results: 1736 Patients completed the PAGI-QOL at baseline. The questionnaire was reduced, producing a 30-item final version covering five domains: Daily Activities, Clothing, Diet and Food Habits, Relationship (REL), and Psychological Well-Being and Distress. Internal consistency was excellent (Cronbach’s α range: 0.83–0.96). Test–retest reproducibility was good: intraclass correlations coefficients were over 0.70 except for the REL scale (0.61). Concurrent validity between the PAGI-QOL total score and all SF-36 subscale scores was good with moderate (0.52) to strong (0.72) correlations. PAGI-QOL scores showed excellent discriminant properties: Patients who had spent some days in bed, had missed some days at work, and were kept from usual activities had much lower PAGI-QOL scores than those who did not (p < 0.0001). Conclusion: The PAGI-QOL is a valid and reliable instrument assessing quality of life in Patients with dyspepsia, GERD, or gastroparesis.
Dominique Dubois - One of the best experts on this subject based on the ideXlab platform.
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association between health related quality of life and symptoms in Patients with chronic constipation an integrated analysis of three phase 3 trials of prucalopride
Neurogastroenterology and Motility, 2015Co-Authors: Jan Tack, Dominique Dubois, Lieve Vandeplassche, Alain Joseph, Rene KerstensAbstract:Background Prucalopride is a high-affinity 5-HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health-related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride. Methods This was an integrated analysis of data from three pivotal multicenter, double-blind, randomized, placebo-controlled, parallel-group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC-QOL) scores, Patient Assessment of Constipation Symptoms (PAC-SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment. Key Results Patients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC-SYM scores correlated well with an improvement in PAC-QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC-QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of Patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of Patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point). Conclusions & Inferences Improvements in PAC-QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL.
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psychometric performance and clinical meaningfulness of the Patient Assessment of constipation quality of life questionnaire in prucalopride resolor trials for chronic constipation
Neurogastroenterology and Motility, 2010Co-Authors: Dominique Dubois, H Gilet, M Vialadanten, Jan TackAbstract:Background The Patient Assessment of Constipation–Quality of Life (PAC-QOL) is a self-reported questionnaire measuring health-related quality of life (HRQL) of constipated Patients and was used as secondary endpoint in three identical double-blind, randomized, placebo-controlled Phase III clinical trials. These 12-week trials in subjects with severe chronic constipation evaluated the effects of prucalopride, a selective 5-HT4 agonist given orally once daily. Methods To consolidate the main treatment effect results observed in the prucalopride trial populations, analyses were undertaken on the pooled data of the three trials to confirm the psychometric properties of the PAC-QOL and to provide guidance for the interpretation of the clinical significance of its scores. Key Results The evaluation of the psychometric properties confirmed the PAC-QOL reliability, validity and responsiveness to measure the impact of chronic constipation symptoms on HRQL in the prucalopride trials. The 1-point improvement in PAC-QOL scores used as target response level for the main treatment effect analyses was validated as a relevant definition of response for treatment group comparisons. Cumulative distribution curves, drawn for each treatment group to provide more complete information on treatment effects than single minimal important difference point estimates, demonstrated consistent superior effects of prucalopride over placebo on all PAC-QOL scores. Conclusions & Inferences The PAC-QOL questionnaire is a useful measurement tool to assess, from a Patient perspective, the potential therapeutic value of chronic constipation treatments in clinical trials and, by directly reflecting the Patient’s own perspective on constipation and its treatment, eventually also for informing daily medical practice.
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development and validation of the Patient Assessment of constipation quality of life questionnaire
Scandinavian Journal of Gastroenterology, 2005Co-Authors: Patrick Marquis, Dominique Dubois, Christine De La Loge, Anne Mcdermott, O ChassanyAbstract:Objective Chronic constipation is characterized by difficult, infrequent, or seemingly incomplete bowel movements. The Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire was developed to address the need for a standardized, Patient-reported outcomes measure to evaluate constipation over time. Material and methods Items for the PAC-QOL were generated from the literature, clinical experts, and Patients. Following principal components and multi-trait analyses, 28 items were retained forming four subscales (worries and concerns, physical discomfort, psychosocial discomfort, and satisfaction) and an overall scale. Validation studies were conducted in the United States, Europe, Canada, and Australia, to evaluate the internal consistency reliability (Cronbach's alpha), reproducibility (Intraclass Correlation Coefficients (ICCs)), validity (analysis of variance models), and responsiveness (effect size) of the PAC-QOL scales. Results The PAC-QOL scales were internally consistent (Cronbach's...
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development and psychometric evaluation of the Patient Assessment of upper gastrointestinal symptom severity index pagi sym in Patients with upper gastrointestinal disorders
Quality of Life Research, 2004Co-Authors: Anne M Rentz, Nicholas J. Talley, Jan Tack, Peter J Kahrilas, Vincenzo Stanghellini, C De La Loge, Elyse Trudeau, Dominique Dubois, Dennis A RevickiAbstract:Objective: Describe the development and evaluation of a new self-report instrument, the Patient Assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM) in subjects with gastroesophageal reflux disease (GERD), dyspepsia, or gastroparesis. Methods: Recruited subjects with GERD (n=810), dyspepsia (n=767), or gastroparesis (n=169) from the US, France, Germany, Italy, the Netherlands, and Poland. Subjects completed the PAGI-SYM, SF-36, a disease-specific HRQL measure (PAGI-QOL), and disability day questions. Two-week reproducibility was evaluated in 277 stable subjects. We evaluated construct validity by correlating subscale scores with SF-36, PAGI-QOL, disability days, and global symptom severity scores. Results: The final 20-item PAGI-SYM has six subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Internal consistency reliability was good (α =0.79 0.91); test–retest reliability was acceptable (Intraclass correlation coefficients α =0.60 0.82). PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p < 0.0001), PAGI-QOL scores (all p < 0.0001), disability days (p< 0.0001), and global symptom severity (p < 0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability days (all p < 0.0001), where greater symptom severity was associated with more disability days. Conclusions: Results suggest the PAGI-SYM, a brief symptom severity instrument, has good reliability and evidence supporting construct validity in subjects with GERD, dyspepsia, or gastroparesis.
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cross cultural development and validation of a Patient self administered questionnaire to assess quality of life in upper gastrointestinal disorders the pagi qol
Quality of Life Research, 2004Co-Authors: Christine De La Loge, Dennis A Revicki, Nicholas J. Talley, Jan Tack, Anne M Rentz, Peter J Kahrilas, Vincenzo Stanghellini, Elyse Trudeau, P Marquis, Dominique DuboisAbstract:Summarize the Patient Assessment of Upper GastroIntestinal Disorders-Quality of Life (PAGI-QOL©) development and provide results on its reliability and validity from the international psychometric validation in dyspepsia, GastroEsophageal Reflux Disease (GERD), and gastroparesis. Methods: Subjects completed the pilot PAGI-QOL at baseline and 8 weeks; and a subsample also at 2 weeks. Other Assessments were: Patient Assessment of Upper GastroIntestinal Disorders-Symptom Severity Index, SF-36, number of disability days. Results: 1736 Patients completed the PAGI-QOL at baseline. The questionnaire was reduced, producing a 30-item final version covering five domains: Daily Activities, Clothing, Diet and Food Habits, Relationship (REL), and Psychological Well-Being and Distress. Internal consistency was excellent (Cronbach’s α range: 0.83–0.96). Test–retest reproducibility was good: intraclass correlations coefficients were over 0.70 except for the REL scale (0.61). Concurrent validity between the PAGI-QOL total score and all SF-36 subscale scores was good with moderate (0.52) to strong (0.72) correlations. PAGI-QOL scores showed excellent discriminant properties: Patients who had spent some days in bed, had missed some days at work, and were kept from usual activities had much lower PAGI-QOL scores than those who did not (p < 0.0001). Conclusion: The PAGI-QOL is a valid and reliable instrument assessing quality of life in Patients with dyspepsia, GERD, or gastroparesis.
Juan Camilo Arjona Ferreira - One of the best experts on this subject based on the ideXlab platform.
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long term use of naldemedine in the treatment of opioid induced constipation in Patients with chronic noncancer pain a randomized double blind placebo controlled phase 3 study
Pain, 2018Co-Authors: Lynn R Webster, Srinivas Nalamachu, Bart Morlion, Jyotsna Batapati Krishna Reddy, Yuko Baba, Tadaaki Yamada, Juan Camilo Arjona FerreiraAbstract:The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in Patients with opioid-induced constipation and chronic noncancer pain in a 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on a routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo (n = 623). The primary endpoint was summary measures of treatment-emergent adverse events (AEs). Additional endpoints included opioid withdrawal on the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale, pain intensity on Numeric Rating Scale, frequency of bowel movements, and constipation-related symptoms and quality of life on the Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life scales, respectively. Treatment-emergent AEs (naldemedine, 68.4% vs placebo, 72.1%; difference: -3.6% [95% confidence interval: -8.7 to 1.5]) and treatment-emergent AEs leading to study discontinuation (6.3% vs 5.8%; difference: 0.5% [-2.2 to 3.1)] were reported for similar proportions of Patients. Diarrhea was reported more frequently with naldemedine (11.0%) vs placebo (5.3%; difference: 5.6% [2.6-8.6]). There were no meaningful differences between groups in opioid withdrawal or pain intensity. Sustained significant improvements in bowel movement frequency and overall constipation-related symptoms and quality of life were observed with naldemedine (P ≤ 0.0001 vs placebo at all time points). Naldemedine was generally well tolerated for 52 weeks and did not interfere with opioid-mediated analgesia or precipitate opioid withdrawal. Naldemedine significantly increased bowel movement frequency, improved symptomatic burden of opioid-induced constipation, and increased Patients' quality of life vs placebo.
Lynn R Webster - One of the best experts on this subject based on the ideXlab platform.
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long term use of naldemedine in the treatment of opioid induced constipation in Patients with chronic noncancer pain a randomized double blind placebo controlled phase 3 study
Pain, 2018Co-Authors: Lynn R Webster, Srinivas Nalamachu, Bart Morlion, Jyotsna Batapati Krishna Reddy, Yuko Baba, Tadaaki Yamada, Juan Camilo Arjona FerreiraAbstract:The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in Patients with opioid-induced constipation and chronic noncancer pain in a 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on a routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo (n = 623). The primary endpoint was summary measures of treatment-emergent adverse events (AEs). Additional endpoints included opioid withdrawal on the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale, pain intensity on Numeric Rating Scale, frequency of bowel movements, and constipation-related symptoms and quality of life on the Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life scales, respectively. Treatment-emergent AEs (naldemedine, 68.4% vs placebo, 72.1%; difference: -3.6% [95% confidence interval: -8.7 to 1.5]) and treatment-emergent AEs leading to study discontinuation (6.3% vs 5.8%; difference: 0.5% [-2.2 to 3.1)] were reported for similar proportions of Patients. Diarrhea was reported more frequently with naldemedine (11.0%) vs placebo (5.3%; difference: 5.6% [2.6-8.6]). There were no meaningful differences between groups in opioid withdrawal or pain intensity. Sustained significant improvements in bowel movement frequency and overall constipation-related symptoms and quality of life were observed with naldemedine (P ≤ 0.0001 vs placebo at all time points). Naldemedine was generally well tolerated for 52 weeks and did not interfere with opioid-mediated analgesia or precipitate opioid withdrawal. Naldemedine significantly increased bowel movement frequency, improved symptomatic burden of opioid-induced constipation, and increased Patients' quality of life vs placebo.
Rene Kerstens - One of the best experts on this subject based on the ideXlab platform.
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association between health related quality of life and symptoms in Patients with chronic constipation an integrated analysis of three phase 3 trials of prucalopride
Neurogastroenterology and Motility, 2015Co-Authors: Jan Tack, Dominique Dubois, Lieve Vandeplassche, Alain Joseph, Rene KerstensAbstract:Background Prucalopride is a high-affinity 5-HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health-related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride. Methods This was an integrated analysis of data from three pivotal multicenter, double-blind, randomized, placebo-controlled, parallel-group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC-QOL) scores, Patient Assessment of Constipation Symptoms (PAC-SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment. Key Results Patients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC-SYM scores correlated well with an improvement in PAC-QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC-QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of Patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of Patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point). Conclusions & Inferences Improvements in PAC-QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL.
