Biomedical subjects

Dominique Dubois

Publications and source records attributed to Dominique Dubois.

8 recordsLinked to original sources

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↗

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↗