Burden of upper gastrointestinal symptoms in patients receiving low-dose acetylsalicylic acid for cardiovascular risk management: a prospective observational study.

BACKGROUND: Continuous low-dose acetylsalicylic acid (aspirin; ASA) is a mainstay of cardiovascular (CV) risk management. It is well established, however, that troublesome upper gastrointestinal (GI) symptoms are commonly experienced among low-dose ASA users. OBJECTIVE: The objective of this study was to investigate the occurrence of upper GI symptoms, and their impact on well-being, among patients taking low-dose ASA for CV risk management. STUDY DESIGN: This was a multicenter, non-interventional, 12-week study carried out in primary-care, cardiology, and practice group centers in the USA, Canada, and France. PATIENTS: Eligible patients were adults (age ≥18 years) at risk of or with confirmed CV disease, with physician-prescribed/-recommended low-dose ASA (75-325 mg) use. MAIN OUTCOME MEASURES: An electronic device (eDiary) was used to collect patient-reported outcome data three times per day (morning, afternoon, and evening; regular reports), including upper GI (gastroesophageal disease [GERD]-like or dyspepsia-like) symptoms and the impact of such symptoms on sleep quality, perceived stress, and emotions. In addition to regular reports, patients were able to self-initiate a report of upper GI symptoms (spontaneous reports). RESULTS: Overall, 81,282 eDiary reports (including 4,407 spontaneous reports of upper GI symptoms) were collected from 340 patients. Upper GI symptoms (most commonly GERD-like) were commonly blamed on food/drink (39 %), and around one-third of patients (37 %) used medication to relieve their symptoms. Analysis showed that upper GI symptoms had a negative impact on sleep quality, perceived stress, and emotions (all p < 0.01). Overall, GI medication use was infrequent, but was more common among low-dose ASA-experienced patients (41 % vs. 12 % of evening reports in patients naïve to low-dose ASA at baseline; p < 0.01); adherence to prescribed daily proton pump inhibitors (PPIs) was poor (47 %). CONCLUSION: Upper GI symptoms impact negatively on well-being among low-dose ASA users, in terms of decreased quality of sleep, increases in perceived stress, and negative impact on emotions. Despite this, patients may not necessarily associate these symptoms with their low-dose ASA therapy and do not readily take steps to manage such symptoms, which extends to poor adherence to prescribed daily PPIs.

Partial response to proton pump inhibitor therapy for GERD: observational study of patient characteristics, burden of disease, and costs in the USA.

BACKGROUND: Disease burden and associated costs are not well understood among patients with gastroesophageal reflux disease (GERD) who have persistent symptoms despite optimized proton pump inhibitor (PPI) therapy. The aim of this study was to investigate disease burden and costs of GERD in partial responders to PPI therapy. METHODS: The Partial Response to PPI treatment: the Cost to Society and the Burden to the Patient in the US (REMAIN US) study was a 12-month, multicenter, noninterventional, observational study of 552 partial PPI responders in the USA. Participating sites were comprised of family practice (n = 30), internal medicine (n = 8), and specialist (gastroenterologist) centers (n = 15). GERD symptoms, health-related quality of life (HRQL), and impact on productivity were evaluated from patient-reported outcome instruments. Resource utilization data were also collected. RESULTS: Patients had a high symptom burden, impaired HRQL, and reduced productivity while at work and in daily activities, despite optimized PPI therapy. Mean annual GERD-related costs were US$9944 per patient, comprising total direct costs and mean productivity loss costs of US$4068 and US$5876 per patient, respectively. CONCLUSION: Patients with GERD and a partial response to PPI therapy have considerable direct and indirect costs, along with substantial impairments in HRQL and productivity.

Impact of gastrointestinal problems on adherence to low-dose acetylsalicylic Acid: a quantitative study in patients with cardiovascular risk.

BACKGROUND: Low-dose acetylsalicylic acid (ASA; 75-325 mg) is a mainstay of therapy for patients at high risk of cardiovascular (CV) events. However, in some patients, such treatment is associated with upper gastrointestinal (GI) adverse effects, e.g. dyspeptic symptoms, peptic ulceration, and GI bleeding, that may interfere with adequate adherence to, and continuation of, low-dose ASA for CV protection. OBJECTIVE: The objective of this study was to explore the extent of, and drivers for, poor adherence to, and discontinuation of, low-dose ASA treatment for CV protection among a representative sample of patients in the US with GI problems. METHODS: An online questionnaire was completed by eligible US adult patients (aged ≥20 years) who had been recommended low-dose ASA by a healthcare professional for secondary CV prevention or high-risk primary CV prevention (defined as diabetes mellitus or three or more risk factors for CV disease) and had experience of upper GI problems. Participants were asked questions about their demographic profile, general health, and attitudes towards low-dose ASA use. Patients were classified as 'lapsers' if they reported no longer regularly taking low-dose ASA; patients were also asked if they ever took deliberate, short-term breaks from their low-dose ASA regimen ('breakers'). Statistical analysis was descriptive. RESULTS: From 56 296 invitation emails that were sent out, 1007 questionnaires were completed in full and were eligible for the analysis. The main reason for ineligible responses was unread emails. Respondents had a mean age of 52 years and 59% were women. Some 57% of patients were categorized as being at high primary CV risk and 43% were categorized as secondary CV prevention patients. A total of 67% of all patients used ASA at a daily dose of 81 mg. Overall, 28% of patients were considered to be poorly adherent through lapsing and/or taking deliberate, short-term breaks, and those receiving low-dose ASA for secondary CV prevention were more likely to be poorly adherent than were high-risk primary CV prevention patients (32% vs 25%). Of the overall population, 15% were lapsers (12% of secondary and 18% of high-risk primary CV prevention patients). The most common spontaneously reported reasons for lapse of low-dose ASA therapy were contraindicated combinations of medications and 'stomach problems'. Deliberate, short-term breaks from treatment were reported by 19% of all patients (24% of secondary and 15% of high-risk primary CV prevention). The most common spontaneously reported reasons for breaks were 'stomach problems' and preparation for surgery. Overall, 88% of patients reported experiencing heartburn or acid reflux symptoms. Self-reported rates of GI problems were greater in secondary than in high-risk primary CV prevention patients. CONCLUSION: Among the US cohort studied (i.e. low-dose ASA users with experience of upper GI problems), poor adherence to low-dose ASA treatment for both secondary and high-risk primary CV prevention was common.

The impact of upper gastrointestinal symptoms on nonadherence to, and discontinuation of, low-dose acetylsalicylic acid in patients with cardiovascular risk.

BACKGROUND: While low-dose acetylsalicylic acid (ASA [aspirin]; 75-325 mg) is a mainstay of cardiovascular (CV) protection in patients at high risk of CV events, such protection may be compromised due to poor adherence (or discontinuation) resulting from gastrointestinal (GI) adverse events. To date, however, the link between GI adverse events and nonadherence to, and discontinuation of, low-dose ASA is not well established in the literature. OBJECTIVE: The aim of this study was to characterize the real-world impact of upper GI symptoms on low-dose ASA nonadherence and discontinuation in patients with CV risk taking low-dose ASA for CV protection. STUDY DESIGN: Multicenter, observational, noninterventional study. SETTING: Primary-care, cardiology, and practice group centers in the US, Canada, and France. PATIENTS: Subjects aged ≥18 years at risk of, or with confirmed, CV disease, and who had been prescribed or recommended low-dose ASA (75-325 mg daily) by a physician. MAIN OUTCOME MEASURE: Adherence to low-dose ASA was assessed using 3 months of data prospectively collected using an electronic diary (completed at least three times/day). Adherence was defined as low-dose ASA intake of ≥75% over the 3-month eDiary phase. Discontinuation was defined as no reported low-dose ASA intake for ≥7 continuous days. The odds of daily adherence were calculated using a mixed-model analysis for repeated measures, and a Cox-proportional hazard model was used to assess the association between upper GI symptoms and time to discontinuation of low-dose ASA. RESULTS: Overall, 340 patients (mean age 50 years; 59% women) participated in the analysis. Most patients (75%) were low-dose ASA naïve at inclusion, and had not experienced upper GI symptoms within the previous 14 days. Among these patients, the onset of upper GI symptoms was rapid; symptoms were reported by 19% of patients on the first day of the study, rising to 46% of patients at the end of the first week. Over the 3-month study period, 18% of patients were nonadherent to low-dose ASA treatment. The occurrence of upper GI symptoms negatively affected low-dose ASA adherence, in both the overall patient population (odds ratio [OR] = 0.84; 95% CI 0.70, 1.0) and among patients who were low-dose ASA naïve at baseline (OR = 0.76; 95% CI 0.57, 1.0). A total of 13% of patients discontinued low-dose ASA therapy. For the overall cohort and for the low-dose ASA-naïve patients at baseline, more than three episodes of upper GI symptoms during the previous week was associated with an increased risk of low-dose ASA discontinuation compared with no episodes of upper GI symptoms during the previous week (hazard ratio [HR] = 2.60; 95% CI 1.00, 6.80, and HR = 7.52; 95% CI 2.57, 22.04, respectively). CONCLUSIONS: Upper GI symptoms can lead to nonadherence to, and discontinuation of, low-dose ASA CV-protective therapy. Patients who initiate low-dose ASA may experience an early onset of upper GI symptoms. ( TRIAL REGISTRATION NUMBER: NCT00681759 [ClinicalTrials.gov Identifier]; AstraZeneca study code: D961FC00004).

Low-dose aspirin therapy for cardiovascular prevention: quantification and consequences of poor compliance or discontinuation.

Long-term therapy with low-dose aspirin (acetylsalicylic acid; ASA), 75-325 mg, is highly effective for the secondary prevention of cardiovascular (CV) events. For high-CV-risk patients to attain the full benefits of this therapy, it is important that treatment is continuous and that good compliance is maintained over the long term. We aimed to quantify the level of, and investigate the reasons for, patient-driven non-compliance and treatment discontinuation among patients taking low-dose ASA for the prevention of CV events. We therefore performed a systematic search of the PubMed, Embase, and Cochrane databases using the terms 'aspirin' AND 'patient compliance' OR 'withdrawal', with no restrictions on the start date and up to July 2008. A total of 32 studies, summarizing >144 800 patients, were selected from over 400 results for inclusion. Poor compliance (defined differently among the studies included) with low-dose ASA therapy ranged from approximately 10% to over 50%, and patient-initiated discontinuation of therapy occurred in up to 30% of patients. Common predictors of both non-compliance and treatment discontinuation were lower education level, female sex, or a history of depression, diabetes mellitus, or cigarette smoking. Adverse events were cited as the reason for low-dose ASA discontinuation in almost 50% of patients. The findings of this review suggest that poor compliance is common among patients receiving low-dose ASA therapy, placing them at substantial risk of CV events. By addressing barriers to compliance with low-dose ASA therapy, healthcare professionals can improve CV risk management for such patients.

Gastroduodenal toxicity of low-dose acetylsalicylic acid: a comparison with non-steroidal anti-inflammatory drugs.

BACKGROUND: Low-dose acetylsalicylic acid (ASA; aspirin; 75-325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events. OBJECTIVES AND SCOPE: To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is 'safe' from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review. FINDINGS: Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among 'at-risk' low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation. CONCLUSION: Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.

Esomeprazole for the management of upper gastrointestinal symptoms in patients who require NSAIDs: a review of the NASA and SPACE double-blind, placebo-controlled studies.

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain in rheumatic disorders and chronic pain syndromes. Their use is, however, limited by gastrointestinal (GI) toxicity, including upper GI symptoms, ulcers and related complications. Using data from the NASA/SPACE studies, we have reviewed the efficacy and tolerability of esomeprazole (20 or 40 mg once daily) in the management (i.e. short-term resolution plus long-term prevention of relapse) of upper GI symptoms in users of continuous daily NSAIDs. METHODS: The NASA/SPACE programme comprised four double-blind, placebo-controlled studies in NSAID users. Two studies evaluated the efficacy of esomeprazole for upper GI symptom relief over 4 weeks. Those patients with symptom relief were then enrolled into a further two studies that assessed efficacy over 6 months. RESULTS: In the 4-week studies, more patients in the esomeprazole groups achieved relief from upper GI symptoms at week 4 compared with placebo (p<0.05). The proportion of patients with symptom relapse at 6 months was lower with esomeprazole 20 mg and 40 mg than with placebo (p

Upper Gastrointestinal Symptoms Experienced by Users of Low-Dose Aspirin (Acetylsalicylic Acid) [75-325 mg/day] for Primary and Secondary Coronary Artery Disease Prevention: Perspectives from Patient Focus Groups.

BACKGROUND AND OBJECTIVE: : As upper gastrointestinal (GI) symptoms are common with the use of low-dose aspirin (low-dose acetylsalicylic acid [LDASA]; 75-325 mg/day), this exploratory qualitative study evaluated the upper GI symptom experience and attribution of symptoms among patients taking LDASA for coronary artery disease (CAD) or known CAD risk factors. METHODS: : Focus groups were conducted among patients aged ≥40 years with CAD or known CAD risk factors currently taking daily LDASA. Patients were recruited from primary-care clinical sites, and all had experienced upper GI symptoms the week before inclusion (including heartburn, acid reflux, and stomach or abdominal pain). The focus group discussions were designed to explore the participants' experience with upper GI symptoms, LDASA use, potential adverse effects of treatment, and physician interactions. Content analysis and descriptive statistics were used to analyze the data. RESULTS: : Thirty-three men and women participated in four focus group sessions in France and in the US. All participants recognized the cardioprotective benefits of LDASA and reported a high level of compliance with therapy. Although participants regarded LDASA as a necessary and valuable treatment, many participants had concerns about LDASA use, primarily because of the bleeding risk. Many participants were aware that LDASA may cause GI symptoms. Participants experienced a range of upper GI symptoms, including heartburn, regurgitation, and nausea. Almost half of the participants believed that their GI symptoms were solely due to lifestyle issues such as stress and eating spicy food rather than being caused by medication, where others reported that they were directly related to LDASA use. The GI symptoms experienced by LDASA users were cited as troublesome, causing the participants to change eating habits, avoid stress or employ stress-reduction techniques, change physical activities, and take more medication to treat the symptoms. CONCLUSION: : Participants were well aware of the potential adverse effects of LDASA use and reported that GI symptoms had a high impact on several areas of their lives. To maintain the cardioprotective benefits of LDASA, participants used several strategies to deal with their upper GI symptoms, including changing their eating habits, avoiding stress, changing their physical activities, and taking medication.

Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.

OBJECTIVES: To investigate the efficacy and safety of the 5-hydroxytrypamine 1A (5-HT(1A)) receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate), termed AZD7371 here, in patients with irritable bowel syndrome (IBS). METHODS: Patients meeting the Rome II criteria for IBS (N = 402) were randomized to treatment with AZD7371 20 mg or 5 mg or matching placebo tablets twice daily for 12 wk. The patients completed daily and weekly diary assessments, reporting abdominal discomfort or pain and description of bowel movements. They also completed validated symptom and quality-of-life questionnaires. RESULTS: Neither AZD7371 regimen was significantly more effective than placebo in providing adequate relief from IBS symptoms in at least 2 out of 4 wk per month over the 12 wk of treatment. There was also no significant difference between the treatment groups and placebo in the change in score in the validated symptom and quality-of-life questionnaires. Overall, 22.1% of patients experienced adverse events (AEs) attributed to the study medication: 44 of 133 (33.1%) in the 20 mg AZD7371 group, 27 of 131 (20.6%) in the 5 mg AZD7371 group, and 17 of 134 (12.7%) in the placebo group. Also, 31 of 57 (54%) of AEs leading to discontinuation were central nervous system-related. Hallucinations or hallucination-like AEs were reported by eight patients taking AZD7371, and by none of the patients in the placebo group. After these events led to discontinuation in six patients, the study was prematurely terminated. CONCLUSIONS: In view of the AE profile and lack of efficacy in IBS, the clinical development of AZD7371 has been stopped.

Maintenance treatment with esomeprazole following initial relief of non-steroidal anti-inflammatory drug-associated upper gastrointestinal symptoms: the NASA2 and SPACE2 studies.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal (GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or 40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology, gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months. Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3 days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%) (p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in patients taking continuous NSAIDs, including selective COX-2 inhibitors.

Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes.

OBJECTIVES: Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls. METHODS: Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N=15), constipation-predominant IBS (N=15), and healthy controls (N=15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N=15) and the other without such a history (nonpostinfectious) (N=15) both compared with healthy controls (N=12). RESULTS: Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12-0.23]) in contrast to constipated IBS (0.085 [0.043-0.13]) and controls (0.07 [0.035-0.19]) (p=0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p=0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69-1.49]) compared with postinfectious IBS (0.43 [0.29-0.63], p=0.028) or controls (0.27 [0.2-0.39]), p=0.001). CONCLUSIONS: Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.

OBJECTIVES: Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use. METHODS: We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months. RESULTS: In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo. CONCLUSIONS: For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.

NSAID-associated adverse effects and acid control aids to prevent them: a review of current treatment options.

NSAIDs are central to the clinical management of a wide range of conditions. However, NSAIDs in combination with gastric acid, which has been shown to play a central role in upper gastrointestinal (GI) events, can damage the gastroduodenal mucosa and result in dyspeptic symptoms and peptic lesions such as ulceration.NSAID-associated GI mucosal injury is an important clinical problem. Gastroduodenal ulcers or ulcer complications occur in up to 25% of patients receiving NSAIDs. However, these toxicities are often not preceded by indicative symptoms. Data obtained from the Arthritis, Rheumatism, and Aging Medical Information System have shown that 50-60% of NSAID-associated peptic ulcer cases can remain clinically silent and do not present until complications occur. Therefore, prophylactic treatment to prevent GI complications may be necessary in a substantial proportion of NSAID users, especially those in groups associated with a high risk of developing these complications. Use of cyclo-oxygenase (COX)-2 selective NSAIDs, also known as 'coxibs', substantially reduces the incidence of upper GI toxicities seen with non-selective NSAIDs. However, there are concerns regarding the cardiovascular safety of coxibs. For this reason, the US FDA recommends minimal use of coxibs and only when strictly necessary. Additionally, rofecoxib has been removed from the US market and sales of valdecoxib have been suspended. Furthermore, upper GI toxicities still occur in patients receiving coxibs. Therefore, cotherapies are required to prevent and/or heal upper GI effects associated with NSAID use. Effective prophylactic and treatment strategies include misoprostol, histamine H(2) receptor antagonists and proton pump inhibitors (PPIs). The key role that gastric acid plays in upper GI adverse events among NSAID users suggests that it is important to choose the most effective agent for acid control to alleviate symptoms, heal mucosal erosions and improve the reduced quality of life in this patient population. PPIs provide effective acid suppression, which is essential to avoid GI mucosal injury, and they are, therefore, capable of dramatically decreasing the morbidity and mortality associated with this disorder. Since many serious GI complications are not heralded by any previous symptoms, physicians need to be aware of risk factor profiles that predispose patients to serious GI problems. Physicians also need to initiate the appropriate preventative acid suppressive therapy to minimise the burden of NSAID-associated GI adverse effects.

Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors.

OBJECTIVES: Upper gastrointestinal (GI) symptoms are common in patients using non-steroidal antiinflammatory drugs (NSAIDs) including selective cyclooxygenase (COX)-2 inhibitors and may be acid related. We therefore assessed esomeprazole treatment for upper GI symptoms in these patients. METHODS: A total of 794 and 848 continuous NSAID users, free of gastroduodenal ulcers, erosive esophagitis, and Helicobacter pylori, were enrolled into two identical, multinational, multicenter double-blind studies (NASA1, SPACE1). Moreover, 608 and 556 patients were randomized to receive 4 wk esomeprazole 20 mg, or 40 mg, or placebo once daily. The primary variable was the patient-reported change in the upper GI symptom (pain, discomfort, or burning in the upper abdomen) score on a 7-graded severity scale (0-6) from the 7 days prior to treatment to the last 7 days in the study. RESULTS: Esomeprazole was associated with highly significant symptom improvement compared to placebo. Symptom improvements were 2.30 mean [SD 1.63] on esomeprazole 20 mg and 2.03 [1.56] on esomeprazole 40 mg versus 1.64 [1.57] on placebo in NASA1 and 2.17 [1.34] and 2.12 [1.48]versus 1.56 [1.26], respectively, in SPACE1 (all placebo comparisons at least p < 0.001). Esomeprazole-improved symptoms in patients taking selective COX-2 inhibitors, with changes of 2.21 [1.46] and 1.92 [1.38]versus 1.64 [1.46] in NASA1 and 2.20 [1.26] and 2.24 [1.62]versus 1.58 [1.37] in SPACE1 (all placebo comparisons at least p < 0.05), as well as those on non-selective NSAIDs. Esomeprazole was well tolerated and associated with significant improvements in HRQL. CONCLUSION: Esomeprazole 20 mg and 40 mg improve upper GI symptoms associated with continuous, daily NSAID therapy, including selective COX-2 inhibitors.

Impact of irritable bowel syndrome on patients' lives: development and psychometric documentation of a disease-specific measure for use in clinical trials.

OBJECTIVE: To develop a disease-specific questionnaire to capture the impact of irritable bowel syndrome (IBS) and its treatment on patients' lives, the Irritable Bowel Syndrome Impact Scale (IBS-IS). PATIENTS AND METHODS: One hundred and fifty-five IBS patients participated (126 (81%) female; age (mean+/-SD) 45.5+/-12.4 years). We developed the initial 39 items from the literature, available IBS-specific instruments and input from physicians, nurses and patients. We deleted IBS-IS items with a high ceiling effect, items that measured a different construct and items showing a high correlation (r>0.90) with another item and with Rasch analysis, leaving 26 items. We then applied exploratory factor analysis to examine domain groupings. Subjects completed the IBS-IS instrument, the Gastrointestinal Symptom Rating Scale for IBS (GSRS-IBS), Short Form-36 (SF-36), Visceral Sensitivity Index (VSI), and Hospital Anxiety and Depression (HAD) scale. Internal consistency, construct validity and discriminate validity were assessed. RESULTS: The 26 items represented five domains: fatigue, impact on daily activities, sleep disturbance, emotional distress and eating habits. The internal consistency reliability for the domains was 0.87 to 0.96. Most associations between similar constructs in the IBS-IS, GSRS-IBS, SF-36, VSI, and HAD were >0.40. Each IBS-IS domain score decreased with increasing IBS symptom severity (P<0.05), and the patients scored >5 score units lower than a US general population scored on all eight SF-36 dimensions. CONCLUSION: The IBS-IS is a short, user-friendly instrument with excellent psychometric properties that has potential usefulness for clinical trials.