Dominique Dubois

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.

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 (Cronbachs 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 (Cronbachs 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.

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.

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.

Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders

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.

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.

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.

Six-month trial of on-demand rabeprazole 10 mg maintains symptom relief in patients with non-erosive reflux disease

Background : Compliance studies have shown that patients with reflux symptoms generally take their medication only when experiencing these symptoms.

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.

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

AbstractSummarize 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.