Assessment of a Stool Symptom Screener and Understanding the Opioid-Induced Constipation Symptom Experience.

BACKGROUND: Many patients with chronic opioid-induced constipation (OIC) seek treatment to relieve their symptoms. A symptom screener may be useful in identifying symptomatic OIC patients. AIM: The aims of this study were to assess patient understanding of Stool Symptom Screener content and to evaluate how patients described their constipation experience, to better understand the relationship between constipation symptoms and patterns of laxative use. METHODS: Adult OIC patients were recruited through five clinical sites across the USA. Patients were classified as either frequent or non-frequent laxative users. Patients participated in a semi-structured interview to assess their understanding of a Stool Symptom Screener and to discuss their constipation symptoms and laxative use experience. Interview transcripts were reviewed using content analysis. Descriptive statistics were used to characterize the sample. RESULTS: Sixty-six OIC patients participated: 39 frequent laxative users (mean age 53.3 years) and 27 non-frequent laxative users (mean age 55.5 years). Both patient groups described high levels of symptom burden on the Stool Symptom Screener as well as anecdotally. Both patient groups generally understood the Stool Symptom Screener items and felt the questions were relevant to their symptom experience. Most (95.5%) reported that they could remember their constipation symptoms "easily" over the previous 2 weeks. No qualitative differences were found between frequent and non-frequent laxative users in how they described their OIC symptom experience. CONCLUSION: OIC patients understood this Stool Symptom Screener, and its content was relevant to this highly symptomatic patient sample. Pain and bloating may be considered as additional symptoms for future versions of the screener. An emerging conceptual model of the OIC experience, laxative use, and symptoms is presented.

Esomeprazole formulary exclusion: impact on total health care services use and costs.

Esomeprazole was excluded from the United Healthcare formulary for all commercial health plan members January 1, 2007. A retrospective analysis of the Ingenix LabRx database (September 1, 2005, through June 30, 2007) evaluated the effect of this exclusion on health care utilization and costs in a real-world setting. Total medical care services, including pharmacy claims, were examined for 6 months before and after the esomeprazole exclusion. Patients aged ≥ 18 years were included if they had continuous health plan enrollment (September 1, 2005, through June 30, 2007), ≥ 1 esomeprazole prescription during the index period (March 1 through August 31, 2006), and ≥ 2 esomeprazole prescriptions (with no switch to another proton pump inhibitor [PPI]) during the baseline period (sliding 6-month window from September 1 through August 31, 2006). During the 6-month post-exclusion period (January 1 through June 30, 2007), 19.5% of patients remained on esomeprazole, 43% switched to another PPI, and 37.5% had no prescription PPI claims. Compared with the previous 6 months, post-exclusion was associated with increased health care utilization, including a 4.2% increase in number of inpatient visits, and a 2.7% increase in other services (eg, laboratory testing, ambulatory procedures). Esomeprazole prescriptions decreased by 76.5%, whereas overall pharmacy claims for all drug classes (including gastrointestinal drugs) increased by 5.2%. Six-month prescription drug costs decreased by $177/patient (95% confidence interval [CI], $160-$194/patient), whereas costs for total medical services increased by $450/patient (95% CI, $259-$640/patient), resulting in a net increase of $273/patient (95% CI, $137-$408/patient). Total and gastrointestinal-related medical services costs were significantly higher for those switching to another PPI versus those continuing esomeprazole. Inpatient utilization contributed most (44.5%) to increased costs of nongastrointestinal comorbidities. This study provides real-world evidence that formulary exclusions can lead to unintended increases in overall health care utilization and costs that exceed anticipated pharmacy budget savings.

Modified Severity of Dyspepsia Assessment pain scale: a new tool for measuring upper abdominal pain in osteoarthritis patients taking NSAIDs.

BACKGROUND: This study evaluated the electronically administered modified Severity of Dyspepsia Assessment (mSODA) pain scale, a six-item measure of upper abdominal pain intensity, for daily use in osteoarthritis patients taking nonsteroidal anti-inflammatory drugs. METHODS: Once the mSODA pain scale was isolated, cognitive debriefing interviews (n = 30) were used to examine its appropriateness in the target population. Following administration of the instrument in two Phase III pivotal trials, the data were analyzed to examine reliability, validity, responsiveness, and the minimal important difference. RESULTS: Using a subset of trial data (n = 90 patients), the mSODA pain scale proved to be a unidimensional, highly internally consistent instrument (α = 0.93) with good test-retest reliability (intraclass correlation coefficient 0.77). Construct validity was established via moderate correlations with other similar patient-reported outcomes. Additionally, known-groups validity demonstrated that the mSODA pain scale could distinguish between subjects who did and did not report gastrointestinal symptoms and antacid use (both P values ≤ 0.05). The mSODA pain scale was also responsive to change in heartburn at weeks 6 and 12 (Guyatt's statistic = 1.7 and 2.6, respectively), and the minimal important difference obtained via ½ SD was 5.7 (range 2-47). CONCLUSION: This research suggests that the mSODA pain scale is both feasible and valid for assessing dyspepsia in patients taking nonsteroidal anti-inflammatory drugs for relief of symptoms of osteoarthritis.

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study.

BACKGROUND: Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents. METHODS: This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits. RESULTS: Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units. CONCLUSION: GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents. TRIAL REGISTRATION: D9614C00098; ClinicalTrials.gov Identifier NCT00241501.

The impact of proton pump inhibitor compliance on health-care resource utilization and costs in patients with gastroesophageal reflux disease.

OBJECTIVE: Standard pharmacotherapy for patients with gastroesophageal reflux disease (GERD) includes treatment with proton pump inhibitors (PPIs). This study examined the effect of GERD patients' compliance with PPI therapy on health-care resource utilization and costs. METHODS: This was a retrospective study of more than 25 million managed care lives in the United States from January 2000 through February 2005. Administrative claims data were obtained from the National Managed Care Benchmarks database, developed by Integrated Health Care Information Solutions. GERD-diagnosed patients who had at least two PPI dispensings were extracted and grouped into two treatment categories based on their PPI medication possession ratio (MPR): compliant (MPR > 0.8) and noncompliant. A regression-based difference-in-differences approach was used to estimate the effect of compliance on the frequency and costs of inpatient and outpatient visits and pharmacy costs. Statistical controls included health plan type, patient age, baseline use of nonsteroidal antiinflammatory drugs, and comorbidities. RESULTS: Of the total 41,837 patients studied, 68% were compliant. On an annual, per-patient basis, PPI compliance resulted in 0.47 fewer outpatient visits (P = 0.040), 0.03 fewer inpatient visits (P = 0.015), and 0.47 fewer hospitalization days (P = 0.001) from the pre-PPI use period, compared to noncompliance. PPI therapy increased pharmacy costs for both groups, but the total annual health-care costs were reduced for both groups. Compliant patients experienced a greater decline in total cost from the pre-PPI period compared to noncompliant patients (declines of $3261 vs. $2406 per patient per year, P = 0.012). CONCLUSIONS: Both health-care resource use and costs were reduced after initiation of PPI therapy. Additional reductions from the pre-PPI period were further observed by compliance with PPI therapy.

Impact of compliance with proton pump inhibitors on NSAID treatment.

OBJECTIVE: To assess the impact of patient compliance with proton pump inhibitor (PPI) therapy on nonsteroidal anti-inflammatory drug (NSAID) treatment duration and upper-gastrointestinal (GI) complications in patients with gastroesophageal reflux disease (GERD). STUDY DESIGN: Retrospective cohort study. METHODS: Study subjects were GERD patients receiving cotherapy with a PPI and a cyclooxygenase-2-selective (COX-2-selective) or nonselective NSAID. Patients compliant and noncompliant with PPI therapy were compared on NSAID treatment duration and incidence of upper-GI events. Kaplan-Meier analysis and a multivariate Cox proportional hazards model were used to compare durations of NSAID treatment, controlling for baseline characteristics. The incidences of GI events were compared using incidence rate and Poisson regression models. The analyses were conducted separately for patients taking COX-2-selective NSAIDs and those taking nonselective NSAIDs. RESULTS: In both patient groups taking a COX-2-selective agent (n = 12,562; 70.9% compliant) and nonselective NSAID (n = 17,487; 69.9% compliant), mean NSAID treatment duration was significantly longer (84.0 days and 20.8 days longer, respectively) in PPI-compliant patients than in noncompliant patients. Compliance with PPI therapy was associated with a greater reduction in the incidence of GI events than noncompliance in both patients taking a COX-2-selective NSAID (6-fold vs 5-fold; P = .026) and patients taking a nonselective NSAID (8-fold vs 6-fold; P = .002). CONCLUSIONS: In GERD patients receiving NSAIDs, those who were compliant with PPI therapy had a longer NSAID treatment duration and better GI tolerability than those who were noncompliant.

Treatment of chronic posterior laryngitis with esomeprazole.

OBJECTIVE: To evaluate the efficacy of acid-suppressive therapy with the proton pump inhibitor esomeprazole on the signs and symptoms of chronic posterior laryngitis (CPL) in patients with suspected reflux laryngitis. STUDY DESIGN: Prospective, multicenter, randomized, parallel-group trial that compared twice-daily esomeprazole 40 mg with placebo for 16 weeks. METHODS: Eligible patients had a history of one or more CPL symptoms (throat clearing, cough, globus, sore throat, or hoarseness) and laryngoscopic signs indicating reflux laryngitis based on CPL index (CPLI) scores measured during a screening laryngoscopy. Patients were randomized to treatment if their 7-day screening diary-card recordings showed a cumulative primary symptom score of 9 or higher and they had 3 or more days with moderately severe symptoms based on a 7-point scale. Efficacy was assessed by changes in symptoms as recorded by patients and investigators and by changes in CPLI scores based on laryngoscopic examinations. RESULTS: The patients' primary CPL symptom at final visit (primary efficacy end point) was resolved in 14.7% (14/95) and 16.0% (8/50) of patients in the esomeprazole and placebo groups, respectively (P=.799). Esomeprazole and placebo were not significantly different for change from baseline to the final visit in mean total CPLI (-1.66+/-2.13 vs. -2.0+/-2.55, respectively; P=.446) or any other secondary efficacy end points based on patient diary card or investigator assessments. CONCLUSION: This study provides no evidence of a therapeutic benefit of treatment with esomeprazole 40 mg twice daily for 16 weeks compared with placebo for signs and symptoms associated with CPL.

Effect of esomeprazole on nighttime heartburn and sleep quality in patients with GERD: a randomized, placebo-controlled trial.

OBJECTIVES: Sleep disturbances are common in patients with gastroesophageal reflux disease (GERD). This study examined the effects of esomeprazole on nighttime heartburn, GERD-related sleep disturbances, sleep quality, work productivity, and regular activities. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn (recorded by patient diary during screening). Patients received oral esomeprazole 40 mg (n = 220) or 20 mg (n = 226) or placebo (n = 229) once daily for 4 wk. The primary outcome was relief of nighttime heartburn. Secondary outcomes included resolution of sleep disturbances, sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and work productivity measured by the Work Productivity and Activity Impairment Questionnaire. RESULTS: Nighttime heartburn was relieved in 53.1% (111/209), 50.5% (111/220), and 12.7% (28/221) of patients who received esomeprazole 40 mg, esomeprazole 20 mg, and placebo, respectively. Differences (95% CI) versus placebo were 40.5% (32.4%, 48.5%) and 37.8% (29.9%, 45.7%) and were highly significant (p < 0.0001). GERD-related sleep disturbances resolved in significantly more (p < 0.0001) patients who received esomeprazole 40 (73.7%) or 20 mg (73.2%) than in those who received placebo (41.2%). Both esomeprazole groups had greater PSQI global score changes from baseline (p < 0.0001 vs placebo) and more (p < 0.0001 vs placebo) work hours saved per week per patient compared with baseline (esomeprazole 40 mg, 11.6 h; esomeprazole 20 mg, 12.3 h; placebo, 6.2 h). CONCLUSIONS: Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity.

The economic impact of GERD and PUD: examination of direct and indirect costs using a large integrated employer claims database.

OBJECTIVE: The objective of this study was to examine the relationship of work loss associated with gastro- the relationship of work loss associated with gastro- the relationship of work loss associated with gastro-esophageal reflux disease (GERD) and peptic ulcer disease (GERD) and peptic ulcer disease (PUD) in a large population of employed individuals in the United States (US) and quantify the individuals in the United States (US) and quantify the economic impact of these diseases to the employer. METHODS: A proprietary database that contained work place absence, disability and workers' compensation data in addition to prescription drug and medical claims was used to answer the objectives. Employees with a medical claim with an ICD-9 code for GERD or PUD were identified from 1 January 1997 to 31 December 2000. A cohort of controls was identified for the same time period using the method of frequency matching on age, gender, industry type, occupational status, and employment status. Work absence rates and health care costs were compared between the groups after adjusting for demo graphic, and employment differences using analysis of covariance models. RESULTS: There were significantly lower (p < 0.05) prescription, and outpatient costs in the controls compared to the disease groups, although the eta-square values were very low. The mean work absence attributed to sick days was 2.8 (+/- 2.3) for controls, 3.4 (+/- 2.5) for GERD, 3.2 (+/- 2.6) for PUD, and 3.2 (+/- 2.3) days for GERD + PUD. For work loss, a significantly higher (p < 0.05) rate of adjusted all-cause absenteeism and sickness-related absenteeism were observed between the disease groups versus the controls. In particular, controls had an average of 1.2 to 1.6 days and 0.4 to 0.6 lower all-cause and sickness-related absenteeism compared to the disease groups. The incremental economic impact projected to a hypothetical employed population was estimated to be $3441 for GERD, $1374 for PUD, and $4803 for GERD + PUD per employee per year compared to employees without these diseases. CONCLUSIONS: Direct medical cost and work absence in employees with GERD, PUD and GERD + PUD represent a significant burden to employees and employers.

Validation of a quality-of-life instrument for laryngopharyngeal reflux.

OBJECTIVES: To establish the reliability, validity, and responsiveness of a new, disease-specific assessment tool, the LPR-HRQL, which assesses patient-reported outcomes (PRO) with regard to health-related quality of life (HRQL) of patients with laryngopharyngeal reflux (LPR). DESIGN: A prospective, open-label, repeated-measures study. SETTING: Six centers in 4 states in the eastern United States. PATIENTS: Patients with LPR. INTERVENTIONS: Open-label treatment with 20 mg of omeprazole twice daily. Clinical and PRO HRQL data were collected. Several PRO instruments were administered to patients at each of several time points; these instruments included the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), a general HRQL tool; the Voice Handicap Index (VHI), a symptom-specific tool for assessing voice problems; and the QOLRAD instrument (Quality of Life in Reflux and Dyspepsia), used to assess the impact of gastroesophageal reflux disease. RESULTS: Factor analyses of the LPR-HRQL scales confirmed single dimensions for each. All LPR-HRQL items contributed to internal consistency of scales and had substantial variability permitting useful information. Substantial evidence of convergent and divergent validity with SF-36, VHI, and QOLRAD items was observed. Test-retest validity was adequate for the time interval tested. Changes in domain scores of the LPR-HRQL at 4 and 6 months documented its responsiveness. CONCLUSIONS: The LPR-HRQL displays reliability, validity, and responsiveness, has face validity, and is simple and not burdensome to administer, score, and analyze. Accordingly, it may be used to assist physicians and patients in understanding the HRQL burden of LPR and the impact of therapy.

Simultaneous development of the Pediatric GERD Caregiver Impact Questionnaire (PGCIQ) in American English and American Spanish.

BACKGROUND: The objective of this study was to develop simultaneously a new questionnaire, the Pediatric GERD Caregiver Impact Questionnaire (PGCIQ), in American English and American Spanish in order to elucidate the impact of caring for a child with GERD. METHODS: Two focus group discussions were conducted in American English and American Spanish to develop a relevant conceptual model. Focus group participants were the primary caregivers of children with GERD (newborn through 12 years of age). Participant responses were qualitatively analyzed to identify potential differences in caregiver perspectives by the caregiver's language, socio-economic status and demographic profile as well as the child's age and disease severity level. Items in the PGCIQ were generated simultaneously in English and Spanish by reviewing results of qualitative analysis from focus groups in each language. The PGCIQ was finalized in both languages after testing content validity and conducting an in-depth translatability assessment. RESULTS: Analysis of focus group comments resulted in the development of a first draft questionnaire consisting of 58 items in 10 domains. Content validity testing and an in-depth translatability assessment resulted in wording modification of 37 items, deletion of 14 items and the addition of a domain with five items. Feedback from the content validity testing interviews indicated that the instrument is conceptually relevant in both American English and American Spanish, clear, comprehensive and easy to complete within 10 minutes. The final version of the PGCIQ contains 49 items assessing ten domains. An optional module with nine items is available for investigative research purposes and for use only at baseline. CONCLUSION: The PGCIQ was developed using simultaneous item generation, a process that allows for consideration of concept relevance in all stages of development and in all languages being developed. The PGCIQ is the first questionnaire to document the multidimensional impact of caring for an infant or young child with GERD. Linguistic adaptation of the PGCIQ in multiple languages is ongoing. A validation study of the PGCIQ is needed to examine its psychometric properties, further refine the items and develop an appropriate scoring model.

The impact of laryngopharyngeal reflux on patient-reported quality of life.

OBJECTIVES/HYPOTHESIS: The objectives were to assess patient-reported outcomes, specifically, the health-related quality of life of patients with laryngopharyngeal reflux, and to compare those reported levels with the health-related quality of life of patients with gastroesophageal reflux disease and a general population. STUDY DESIGN: Prospective study. METHODS: As part of a prospective study to validate a health-related quality of life instrument for laryngopharyngeal reflux, patient-reported data were collected before the initiation of therapy. Use of the Short Form-36 (SF-36), a generic instrument, allowed the health-related quality of life of the patients with laryngopharyngeal reflux to be compared with benchmarks existing for patients with gastroesophageal reflux disease and a general U.S. population. RESULTS: The 117 patients with laryngopharyngeal reflux often reported multiple symptoms, most frequently, chronic throat-clearing (85.5%), globus (82.1%), and hoarseness (80.3%). Their mean health-related quality of life was statistically significantly worse than that of a general U.S. population in seven of the eight SF-36 domains. The most dramatic differences between patients with laryngopharyngeal reflux and the general population were in social functioning and bodily pain (P <.001). Mean scores for patients with laryngopharyngeal reflux were significantly lower than those for patients with gastroesophageal reflux disease in social functioning (P <.001) and vitality (P =.0017). In five of the six remaining domains, patients with laryngopharyngeal reflux reported lower mean scores than did patients with gastroesophageal reflux disease, but those differences were not statistically significant. CONCLUSION: The study's assessment of health-related quality of life suggests that laryngopharyngeal reflux has a significant negative impact on the lives of patients. Although its impact is similar in some respects to that of gastroesophageal reflux disease, laryngopharyngeal reflux has a more significant impact on patients' social functioning and vitality.

Health-related quality of life improves with treatment-related GERD symptom resolution after adjusting for baseline severity.

Severity and frequency of gastroesophageal reflux disease (GERD) related symptoms are associated with impaired health-related quality of life (HRQL). This study evaluated the association between baseline heartburn severity and endpoint HRQL of patients treated for heartburn and the relationship between complete resolution of heartburn symptoms and HRQL outcomes after controlling for baseline severity. We completed a secondary analysis of clinical symptom and HRQL data from three clinical trials in adult patients receiving either omeprazole or ranitidine treatment for GERD. HRQL was assessed using the Psychological General Well-Being Index (PGWB) in each of the three clinical trials, and two of the trials also included the Medical Outcomes Study Sleep disturbance scale. Gastrointestinal symptoms were evaluated using either the Gastrointestinal Symptom Rating Scale or a modified version of the scale. Baseline heartburn severity (none/minor, mild, moderate or severe) was defined based on patient-reported symptoms. Analysis of covariance (ANCOVA) models were used to compare mean HRQL scores by baseline level of heartburn symptom severity and whether or not patients experienced complete heartburn resolution. At baseline, PGWB scores were significantly worse (p < 0.05) for patients with more severe heartburn symptoms. There were no statistically significant baseline severity by symptom resolution interactions in any of the ANCOVA models. For all three trials and across all follow-up assessments, mean PGWB scores were statistically significantly higher for patients with completely resolved heartburn symptoms versus those whose symptoms were unresolved (all p-values < 0.05). Few significant effects were observed for sleep disturbance scores. While the severity of heartburn symptoms at the start of medical treatment for GERD is not associated with improvements in HRQL in subsequent weeks of treatment, complete resolution of symptoms is associated with improvements in psychological well-being.

The clinical characteristics and impact of laryngopharyngeal reflux disease on health-related quality of life.

BACKGROUND AND OBJECTIVES: Although it is accepted that reflux of stomach acid causes gastroesophageal reflux disease (GERD), it is less well understood that it also contributes to the clinical signs and symptoms of laryngitis in the form of laryngopharyngeal reflux (LPR). Study objectives were to identify what is known about the impact of LPR on health-related quality of life (HRQL) compared with the impact of GERD on HRQL and to assess whether currently available HRQL instruments adequately measure this impact or if a new disease-specific instrument should be recommended. METHODS: The authors combined a systematic literature review with prospective patient evaluation via focus groups. The review, using MEDLINE, focused on clinical characteristics and HRQL measurement and impact. Focus groups involving a total of 30 patients with LPR provided input on clinical manifestations of the disease and its HRQL impact. RESULTS: Information gleaned from the literature indicates that less than 40% of patients presenting with symptoms of laryngitis directly attributable to reflux also report experiencing the classic symptoms of heartburn and acid regurgitation associated with GERD. Reflux laryngitis is thus a distinct clinical entity from GERD and may have a unique impact on HRQL. Although multiple instruments are available to assess the impact of GERD on HRQL, no specific instruments are available for LPR. Focus group discussions identified voice problems, chronic cough, throat clearing, and swallowing difficulties to be key concerns of patients with LPR. These manifestations negatively impact HRQL as described by the focus group participants, notably in role functioning, physical well-being, and emotional well-being. CONCLUSIONS: A disease-specific instrument to assess the impact of LPR on HRQL would contribute to clinical care and the evaluation of new therapies. This instrument would ideally be sensitive to the variety of LPR's symptomatic presentations.

Improving health-related quality of life in gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) is a common, chronic disorder that can progress to erosive or ulcerative oesophagitis and other complications. Uncomplicated GORD can be defined using criteria that combine symptom assessment and the impact of symptoms on well being or quality of life. The extent of impairment of health-related quality of life (HRQL) in GORD patients has been evaluated using generic HRQL questionnaires, GORD-specific quality of life questionnaires or a combination of the two types of instruments. The impact of GORD on HRQL in affected individuals is proportional to the frequency and severity of heartburn, and is greater than that associated with many other chronic diseases. In the treatment of GORD, the goal should be complete symptom resolution as this has been shown to be associated with a clinically significant improvement in HRQL. Both drug treatment and surgical intervention have been successful in improving HRQL of patients with GORD when complete symptom resolution can be attained.

Willingness to pay for complete symptom relief of gastroesophageal reflux disease.

BACKGROUND: Over $6 billion per year is spent on prescription medication for gastroesophageal reflux disease (GERD). This study is an economic analysis of patients' willingness to pay for a prescription medication that offers complete relief of GERD symptoms. METHODS: The study was a cross-sectional, nonrandomized design recruiting patients from 5 clinical sites. A computer-administered discrete-choice questionnaire was used to explore patients' willingness to pay for various attributes (time to relief, amount of relief, side effects, and out-of-pocket cost) associated with GERD treatment. Patients chose between 2 different combinations of attributes by indicating which scenario they preferred. Data were gathered on health status, health-related quality of life, and sociodemographic characteristics. RESULTS: Two hundred five patients completed the discrete-choice questionnaire with a consistency rate of 99.5%. All attributes were relevant to patient decision making. Respondents were willing to pay up to $182 to obtain complete relief in a short period of time without side effects. Patients with less severe GERD symptoms were willing to pay more to avoid side effects ($58.25 vs $38.43). Older patients were less willing to pay for better relief than younger patients. CONCLUSIONS: Results demonstrate that patients are willing to pay more per month for a medication that provides more complete and faster relief from GERD symptoms. This information can guide clinicians and formulary committees in evaluating optimal treatment for GERD.

Identification of frequent cytogenetic aberrations in hepatocellular carcinoma using gene-expression microarray data.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Frequent cytogenetic abnormalities that occur in HCC suggest that tumor-modifying genes (oncogenes or tumor suppressors) may be driving selection for amplification or deletion of these particular genetic regions. In many cases, however, the gene(s) that drive the selection are unknown. Although techniques such as comparative genomic hybridization (CGH) have traditionally been used to identify cytogenetic aberrations, it might also be possible to identify them indirectly from gene-expression studies. A technique we have called comparative genomic microarray analysis (CGMA) predicts regions of cytogenetic change by searching for regional gene-expression biases. CGMA was applied to HCC gene-expression profiles to identify regions of frequent cytogenetic change and to identify genes whose expression is misregulated within these regions. RESULTS: Using CGMA, 104 HCC gene-expression microarray profiles were analyzed. CGMA identified 13 regions of frequent cytogenetic change in the HCC samples. Ten of these regions have been detected in previous CGH studies (+lq, -4q, +6p, -8p, +8q, -13q, -16q, -17p, +17q, +20q). CGMA identified three additional regions that have not been previously identified by CGH (+5q, +12q, +19p). Genes located in regions of frequent cytogenetic change were examined for changed expression in the HCC samples. CONCLUSIONS: Our results suggest that CGMA predictions using gene-expression microarray datasets are a practical alternative to CGH profiling. In addition, CGMA might be useful for identifying candidate genes within cytogenetically abnormal regions.

Large-Scale Postmarketing Surveillance of Hypertensive Patients Treated with Verapamil.

BACKGROUND: In general clinical practice, physicians prescribe calcium channel blockers to a wide range of patients with differing demographic characteristics and hypertension history. This study was undertaken to investigate the effectiveness and safety of sustained-release verapamil (Verelan((R)), verapamil HCl) in patients with essential hypertension, studied under "usual use" conditions. METHODS: In this prospective, open-label, postmarketing surveillance study, 25 089 patients with hypertension received once-daily verapamil therapy for 4 weeks, during which they were evaluated by 8106 physicians at baseline and at two follow-up visits (weeks 2 and 4). In this study, hypertension was defined as an average sitting diastolic blood pressure (DBP) of greater-than-or-equal 90 mm Hg at baseline. Previously diagnosed hypertensive patients with a sitting DBP <90 mm Hg but experiencing untoward effects requiring discontinuation of current antihypertensive therapy were also included. RESULTS: Eighty-five percent (n = 21 446) of the total patients enrolled at baseline completed this office-based trial. Nearly 24% of patients were newly diagnosed hypertensives. At baseline, the mean systolic blood pressure (SBP) and diastolic blood pressure were 161 and 96 mm Hg, respectively. In evaluable patients with mild, moderate, and severe hypertension, as stratified by baseline measurements, treatment with verapamil produced DBP reductions of 12, 19, and 29 mm Hg, respectively. Verapamil treatment produced clinically similar SBP, DBP, and HR (heart rate) reductions across gender and racial groups studied (white, black, Hispanic, and Asian). Only 6.1% of patients failed to complete the study because of any reported adverse experiences (4.5% of patients discontinued because of adverse experiences considered drug related). Constipation (5.0%) and headache (1.1%) were the most commonly reported adverse events. CONCLUSION: In general clinical practice, verapamil is well tolerated and effective in a broad range of hypertensive patients.