Biomedical subjects

Dominique Dubois

Publications and source records attributed to Dominique Dubois.

15 recordsLinked to original sources

PubMed2006

Descriptive and prognostic value of patient-reported outcomes: the bortezomib experience in relapsed and refractory multiple myeloma.

PURPOSE: Bortezomib, a boronic acid dipeptide, has been recently introduced as a new approach to treating multiple myeloma (MM). The goal of this work was to evaluate the added value of patient-reported outcomes (PRO) in the interpretation of bortezomib clinical trial outcomes. PATIENTS AND METHODS: Two hundred two patients with relapsed, refractory MM were treated with bortezomib as part of the SUMMIT (Study of Uncontrolled Multiple Myeloma Managed with Proteasome Inhibition Therapy) study. Patients were administered the following four PRO measures at several time points: the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, and the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG) Neurotoxicity (Ntx) scale. Minimal important difference (MID) thresholds were used to define patients as improved, stable, or worsened. A survival analysis was conducted to assess the predictive power of PRO data. RESULTS: For the total population, there was a positive change between baseline and best end point. Consistent with the clinical responses, change in PRO scores showed statistically significant differences between response groups with PRO improvement in patients with complete response (CR) or partial response (PR), mostly stable scores in patients with minor response or no change, and deterioration in most scores for patients with progressive disease. Change in scores for neuropathy-related symptoms was reasonably stable. In contrast, fatigue scores significantly improved for patients with CR or PR. When various MID thresholds were applied, the proportion of improved patients exceeded 35% for several domains within all change group definitions. Moreover, survival analysis results demonstrated the additional prognostic information PRO data can provide to supplement clinical data. CONCLUSION: This study demonstrated the complementary value for PRO assessments in further interpreting clinical response, the impact of adverse effects, and patient prognosis in clinical trials.

Adult↗

PubMed2006

Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain.

BACKGROUND: The Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire is a 12-item self-report instrument divided into abdominal, rectal and stool domains. AIMS: This study aimed to (1) evaluate the psychometric properties of PAC-SYM in assessing the symptoms and severity of opioid-induced constipation; (2) test for differences in opioid-induced constipation between Durogesic fentanyl transdermal reservoir (TDF) and oral sustained-release morphine (SRM) in patients with chronic low back pain (CLBP). METHODS: In a 13-month, open-label, parallel-group study, 680 patients were randomised to receive either TDF (n=338) or SRM (n=342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC-SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC-SYM scores between treatment groups were also evaluated. RESULTS: The study included 677 patients, of whom 638 were opioid-naïve. Mean PAC-SYM scores for constipated patients were substantially higher than for non-constipated patients, demonstrating good clinical validity for PAC-SYM. The PAC-SYM could detect changes in bowel function over the treatment period, indicating responsiveness. Homogeneity of each symptom domain exceeded Cronbach's alpha coefficient of 0.70, suggesting good internal consistency and reliability. Changes in mean PAC-SYM scores from baseline to Visit 5 and Visit 17 were significantly lower for the TDF group than for the SRM group, indicating that the TDF group experienced less severe constipation. CONCLUSION: PAC-SYM is a reliable, valid and responsive measure of the presence and severity of opioid-induced constipation symptoms.

Administration, Cutaneous↗

PubMed2005

Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study.

BACKGROUND & AIMS: This study examined the prevalence of upper gastrointestinal (GI) symptoms and symptom groupings and determined impact on disability days in a nationally representative US sample. METHODS: A telephone survey of 21,128 adults was conducted including questions about the presence of upper GI symptoms during the past 3 months. Respondents were categorized as symptomatic (ie, reported GI symptoms once per month) or asymptomatic. The survey included questions about missed work, leisure activity, or household activity days. Symptom groupings were identified by using factor analysis, and cluster analysis was used to assign respondents into distinct groups on the basis of these symptom groupings. RESULTS: The prevalence of an average of 1 or more upper GI symptoms during the past 3 months was 44.9%. The most common symptoms experienced during the past 3 months were early satiety, heartburn, and postprandial fullness. Factor analysis identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting; (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five respondent clusters were identified; the largest clusters were primarily early satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%). Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom profile (4%). Symptomatic respondents reported significantly more missed work, leisure, and household activity days than asymptomatic respondents (all P < .0001). CONCLUSIONS: Factor analysis separated GI symptoms into groupings reflecting gastroesophageal reflux disease and dyspepsia: early satiety, postprandial fullness, and loss of appetite; bloating and abdominal pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated with significant loss of work and activity days.

Adolescent↗

PubMed2005

Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire.

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 alpha >0.80) and reproducible (ICCs >0.70, except for the satisfaction subscale ICC=0.66). PAC-QOL scale scores were significantly associated with abdominal pain (p<0.001) and constipation severity (p<0.05). Effect sizes in patients reporting improvements in constipation over a 6-week period were moderate to large, with subscale effect sizes ranging from 0.76 to 3.41 and the overall scale effect size=1.77. Similar findings were observed in validation studies conducted in Europe, Canada, and Australia. CONCLUSIONS: The PAC-QOL is a brief but comprehensive assessment of the burden of constipation on patients' everyday functioning and well-being. Multinational studies demonstrate that the PAC-QOL is internally consistent, reproducible, valid, and responsive to improvements over time.

Adult↗

PubMed2005

Economic analysis of on-demand maintenance therapy with proton pump inhibitors in patients with non-erosive reflux disease.

AIM: To evaluate the costs and effectiveness of on-demand maintenance therapy with oral esomeprazole, lansoprazole, omeprazole, pantoprazole or rabeprazole in patients with endoscopy-confirmed non-erosive reflux disease (NERD) in the UK. METHODS: A probabilistic model was developed to compare the costs and effectiveness of five proton pump inhibitors (PPIs) in endoscopy-negative, symptomatic NERD patients who had complete resolution of heartburn symptoms following 4 weeks of open-label acute PPI treatment. The total annual expected costs (euro, 2003 values) and utilities gained per patient were measured over a 1-year horizon from the perspective of the UK NHS. Model uncertainty was addressed by sensitivity analyses. RESULTS: The base-case annual median costs and utilities gained with on-demand PPI therapy were: 123 euro and 0.89 for rabeprazole 10mg; 176 euro and 0.90 for pantoprazole 20mg; 190 euro and 0.89 for esomeprazole 20mg; 195 euro and 0.91 for lansoprazole 15mg; 201 euro and 0.90 for omeprazole 20mg; and 210 euro and 0.91 for omeprazole 10mg. Differences in costs, but not in outcomes, were statistically significant. The results were robust to sensitivity analyses. CONCLUSIONS: In this analysis, on-demand use of rabeprazole for the management of NERD incurred the least cost in comparison with the other PPIs evaluated. Utility gains were comparable for all on-demand PPIs. The place of on-demand PPIs in therapy, however, requires further evaluation.

Anti-Ulcer Agents↗

PubMed2004

Cross-cultural development and validation of a patient self-administered questionnaire to assess quality of life in upper gastrointestinal disorders: the PAGI-QOL.

OBJECTIVE: 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 alpha 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.

Cross-Cultural Comparison↗

PubMed2004

Focal expression and final activity of matrix metalloproteinases may explain irregular dysfunctional endometrial bleeding.

Irregular dysfunctional bleeding of the endometrium (ie, metrorrhagia without organic lesion) is common in women, whether treated or not with ovarian hormones. Several matrix metalloproteinases (MMPs) become normally expressed and/or activated at menstruation and cause extracellular matrix breakdown. We therefore explored whether episodes of irregular dysfunctional bleeding could be associated with untimely MMP activity. By histology, foci of stromal breakdown were exclusively found in the endometrium of metrorrhagic women at bleeding. In these foci, 1) expression of estrogen receptor-alpha and progesterone receptor was altered; 2) collagenase-1 (MMP-1), stromelysin-1 (MMP-3), and gelatinase B (MMP-9) became detected in stromal cells, together with MMP-9 in neutrophils; and 3) gelatinase A (MMP-2) was more expressed and immunolocalized at the membrane of stromal cells. By biochemistry, endometrial lysates from nonbleeding metrorrhagic patients contained more latent and active MMP-2 and -9 than age-matched controls; at bleeding, collagenase activity, MMP-9, and active MMP-2 were strikingly increased whereas tissue inhibitor of metalloproteinases-1 (TIMP-1) was considerably decreased. As a functional assay, in situ gelatin zymography revealed large areas of gelatinolytic activity only in endometrium of bleeding patients. Altogether, these results strongly suggest that inappropriate focal expression and activation of several MMPs, combined with decreased inhibition, trigger irregular dysfunctional endometrial bleeding.

Adult↗

PubMed2004

Responsiveness and interpretation of a symptom severity index specific to upper gastrointestinal disorders.

BACKGROUND AND AIMS: Determining clinically meaningful change of patient-reported outcome measures is important for evaluating effectiveness of treatments for gastrointestinal (GI) diseases. This study evaluates responsiveness of the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) in gastroesophageal reflux disease (GERD) and dyspepsia. METHODS: The PAGI-SYM was based on a review of the published literature and interviews with patients and clinicians. Items were developed to be linguistically and culturally appropriate for multicountry studies. The PAGI-SYM includes 6 subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Subjects with GERD (n = 810) or dyspepsia (n = 767) participated in this multicountry, observational study. All subjects completed the PAGI-SYM, a global symptom relief questionnaire, and a measure of patient-rated change in GI-related symptoms, the Overall Treatment Effect (OTE) scale. Responsiveness was evaluated at 8 weeks by comparing groups by disease, symptom relief, and OTE (improved, stable, and worsened). RESULTS: Subjects reporting symptom relief reported significantly lower (better) PAGI-SYM scores than those reporting no symptom relief ( P < 0.0001 to P < 0.0005). Subjects with improvements in overall GI symptoms exhibited significant decreases in PAGI-SYM subscale scores compared with those who remained the same or worsened (all P values < 0.0001). Effect sizes ranged from 0.21-1.28, and standard errors of measurement ranged from 0.29-0.63, depending on subscale and disease sample. CONCLUSIONS: The PAGI-SYM is a brief symptom severity instrument that measures common GI symptoms. Results suggest that the PAGI-SYM is responsive and sensitive to change in clinical status in subjects with GERD or dyspepsia.

Adult↗

PubMed2004

Responsiveness and interpretation of a quality of life questionnaire specific to upper gastrointestinal disorders.

BACKGROUND AND AIMS: The Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) has been developed and validated to assess quality of life in gastroesophageal reflux disease, dyspepsia, and gastroparesis. The aim of this work was to assess responsiveness of the PAGI-QOL to clinical changes and provide guidance for the interpretation of score changes. METHODS: The analysis was based on 2 observational multicenter, longitudinal, 8-week observation studies, one in the United States and one in 5 European countries. The Overall Treatment Effect scale completed by patients and clinicians at 8 weeks was used to define groups of improved, worsened, and stable patients. Responsiveness was assessed by describing the change in PAGI-QOL scores for each of these groups, comparing these changes over time, and calculating effect sizes and standardized response means. These data were used to define the minimal clinically important difference. RESULTS: A total of 1736 patients with upper gastrointestinal disorders were analyzed. High sensitivity to change over time was demonstrated, with effect sizes and standardized response means in improved patients for the PAGI-QOL total score ranging from 0.79-1.41. A change of 0.4 for the PAGI-QOL total score might be considered as the minimal clinically important difference when comparing pretreatment and post-treatment PAGI-QOL total scores. CONCLUSIONS: The PAGI-QOL questionnaire is a responsive and clinically relevant instrument for assessing quality of life in patients with upper gastrointestinal disorders.

Adolescent↗

PubMed2004

Gastroparesis Cardinal Symptom Index (GCSI): development and validation of a patient reported assessment of severity of gastroparesis symptoms.

BACKGROUND: Patient-rated symptom assessments are needed for evaluating the effectiveness of medical treatments and for monitoring outcomes in gastroparesis. OBJECTIVE: This paper summarizes the development and psychometric evaluation of a new instrument, the Gastroparesis Cardinal Symptom Index (GCSI), for assessing severity of symptoms associated with gastroparesis. METHODS: The GCSI was based on reviews of the medical literature, patient focus groups, and interviews with clinicians. A sample of 169 patients with a documented diagnosis of gastroparesis participated in the psychometric evaluation study. Patients completed the GCSI, the SF-36 Health Survey, and disability days questions at baseline and after 8 weeks. A randomly selected sub-sample of 30 subjects returned at 2 weeks to assess test retest reliability. Clinicians rated severity of symptoms, and both clinicians and patients rated change in gastroparesis-related symptoms over the 8 week study. RESULTS: The GCSI is based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). Internal consistency reliability was 0.84 for the GCSI total score and ranged from 0.83 to 0.85 for the subscale scores. Two week test retest reliability was 0.76 for the total score and ranged from 0.68 to 0.81 for subscale scores. Construct validity was supported, given that we observed significant relationships between clinician assessed symptom severity and GCSI total score, significant differences between gastroparesis and dyspepsia patients (n = 760) on GCSI total (p < 0.0001) and subscale scores (p < 0.03 to p < 0.0001), moderate and significant relationships between GCSI total and SF-36 scores, and significant associations between GCSI total score and reports of restricted activity and bed disability days. Patients with greater symptom severity, as rated by clinicians, reported more symptom severity on GCSI total score. GSCI total scores were responsive to changes in overall gastroparesis symptoms as assessed by clinicians (p < 0.0001) and patients (p = 0.0004). CONCLUSION: The findings of this study indicate that the GCSI is a reliable and valid instrument for measuring symptom severity in patients with gastroparesis.

Adolescent↗

PubMed2004

Cost-effectiveness analysis of extended-release formulations of oxybutynin and tolterodine for the management of urge incontinence.

INTRODUCTION: Oxybutynin and tolterodine are two drugs widely used for the management of overactive bladder and urge urinary incontinence. The once-daily, extended-release formulations benefit from being well tolerated and efficacious. However, their costs, compared with generic immediate-release (IR) oxybutynin, are significantly greater. This study compared the cost effectiveness of oxybutynin extended-release (Oxy-XL), tolterodine extended-release (Tol-ER), tolterodine immediate-release (Tol-IR) and oxybutynin immediate-release (Oxy-IR). STUDY DESIGN: A cost-effectiveness model. METHODS: A systematic review that identified appropriate randomised clinical trials provided evidence on efficacy. Empirical models of drug effects (number of incontinent-free weeks) and persistence (proportion of patients still on therapy) were constructed in order to determine clinical effectiveness which was combined with cost data (direct medical costs to the UK NHS, year 2001 values) to calculate the drugs' cost-effectiveness from the perspective of the NHS. Univariate sensitivity analyses were conducted to test the robustness of the results. PATIENTS: Hypothetical cohort of patients with urge incontinence associated with overactive bladder. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost per incontinent-free week for Oxy-IR (versus no treatment) ranged from pound sterling 2.58 to pound sterling 16.59. Oxy-XL and Tol-ER were more effective than Oxy-IR but at additional costs per incontinent-free week. Tol-IR did not appear to be a cost-effective option as it was less effective and more costly than the extended-release formulations. Uncertainty surrounding the health and cost consequences of early discontinuation affected these results, although the model results were robust to parameter uncertainty. CONCLUSION: Oxy-IR, Oxy-XL and Tol-ER appear to be cost-effective options for the management of urge incontinence from the NHS perspective. A decision among the treatments depends on the acceptable cost per additional incontinent-free week.

Adult↗

PubMed2003

Risk factors for chronic constipation based on a general practice sample.

OBJECTIVES: Many factors have been associated with the occurrence of constipation, particularly poor diet and lack of exercise. However, the importance of medications and general medical illnesses in constipation remains more uncertain. We aimed to identify risk factors for constipation from among patient clinical, therapeutic, and demographic characteristics. METHODS: The sample was composed of patients explicitly diagnosed with chronic constipation (n = 7251), those diagnosed with constipation of unspecified chronicity (n = 6441), and a sample of controls (n = 7103). All were drawn from a general practice research database representing more than 10 yr of data collection. RESULTS: A large number of clinical and therapeutic factors were independently associated with chronic constipation over and above age and gender. Primary neurological diseases were strongly associated with constipation but accounted for few cases. Opioids (OR = 1.6, population attributable risk [PAR] = 2.6%), diuretics (OR = 1.7, PAR = 5.6%), antidepressants (OR = 1.9, PAR = 8.2%), antihistamines (OR = 1.8, PAR = 9.2%), antispasmodics (OR = 3.3, PAR = 11.6%), anticonvulsants (OR = 2.8, PAR = 2.5%) and aluminum antacids (OR = 1.7, PAR = 3.0%) were associated with the highest risk among medications. CONCLUSIONS: Constipation is common in primary care, and multiple medications seem to be an important contributing factor. Concurrent diseases are also associated but at most are only contributing to a minority of cases.

Adolescent↗

PubMed2002

Recommended structure for reporting economic evaluation on pharmaceuticals in Belgium.

Pharmaco-economic evaluations become more important for the reimbursement of pharmaceuticals, and will be obligatory for new pharmaceutical drugs for which an added therapeutic value is claimed and a price premium is proposed by the manufacturer. Therefore, it is important to guide purchasers and providers of pharmaceutical care in their efforts related to the evaluation process. Standard Report Format can support the quality, transparency and exhaustiveness of the data submitted. A multidisciplinary task force developed a Standard Report Format for pharmaco-economic evaluations in Belgium.

Belgium↗

PubMed2002

Lack of objective evidence of efficacy of laxatives in chronic constipation.

Laxatives are commonly used to treat constipation and can be bought over-the-counter in many countries, although some preparations need to be prescribed by physicians. A meta-analysis was conducted to quantitatively evaluate the published evidence on the efficacy of laxatives in constipation. We found that large, well-controlled, published studies whose data were comparable were lacking. Of 250 articles, 35 met the inclusion criteria but only 11 yielded usable data (N = 375 patients on laxatives, 174 on placebo). There was an effect of laxatives on stool frequency (mean increase 1.9 stools per week) and stool weight (mean increase 476 g) but this was not clearly distinguishable from that of placebo therapies (1 stool and 434 g, respectively) in studies up to 4 weeks in duration. Similarly, studies of 5-12 weeks yielded no differences overall. These results cannot definitively rule out laxatives as an effective treatment, due to the poor published evidence. Better evidence is required to justify the continued expenditure of funds on laxatives by both patients and formularies.

Adult↗

PubMedDate not supplied

Incorporating the patient's perspective into drug development and communication: an ad hoc task force report of the Patient-Reported Outcomes (PRO) Harmonization Group meeting at the Food and Drug Administration, February 16, 2001.

BACKGROUND: The extent to which patient-based outcomes can be used to evaluate and communicate the effect of new drugs and devices is a subject of much debate. Criteria for evaluating the scientific quality of data to support health-related quality of life (HRQL) and other patient-based labeling and promotional claims in the United States and Europe have been proposed by various scientists and organizations. Since March 2000, a working group composed of members of the International Society for Quality of Life Research (ISOQOL), the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the Pharmaceutical Manufacturer's Association Health Outcomes Committee (PhRMA-HOC), and the European Regulatory Issues on Quality of Life Assessment (ERIQA) met to discuss and coordinate the various recommendations by their respective groups and address the need to harmonize outcomes review criteria within and across United States and European regulatory agencies. Over time, the discussion expanded from HRQL outcomes to include any outcome based on data provided by the patient or patient proxy, that is, patient-reported outcomes (PROs). The working group therefore became known as the PRO Harmonization Group. METHODS: Working with a member of the US Food and Drug Administration (FDA), four key issues requiring clarification were identified: how PROs are defined and put into operation for research purposes; the added value of PROs in the drug review and evaluation process; selected questions related to the PRO measurement and research methodology; and the interest and demand for PRO information by decision makers. On February 15, 2001, all members of the PRO Harmonization Group attended a meeting in Rockville, Maryland, to discuss these four issues further, and on February 16, 2001, a formal presentation was made to representatives from various departments and reviewing divisions of the FDA. These presentations are summarized in this report. RESULTS: All participants agreed that PROs are important for understanding the impact of treatment on patient functioning and well-being. They also stressed the need to communicate PRO information to key decision makers, including regulatory agencies, clinicians, patients and their families, and payers. Finally, the meeting resulted in plans for continuing the dialogue on PRO measurement and interpretation. SUMMARY: The February 16, 2001, meeting represented an important step in harmonizing efforts across various organizations and in opening a dialogue with the FDA around major issues related to methodologic standards for measuring and interpreting PROs in the drug evaluation process.

Advisory Committees↗