An exploration of the barriers to the confident diagnosis of irritable bowel syndrome: A survey among general practitioners, gastroenterologists and experts in five European countries.

BACKGROUND: The diagnostic processes for chronic abdominal conditions are challenging. Despite their tendency for diagnostic tests in patients with irritable bowel syndrome (IBS) symptoms, clinicians are encouraged to make a positive diagnosis based on symptom criteria without alarm signs. We explored how European physicians diagnose and manage patients suffering from IBS. METHODS: We conducted a vignette-based survey to evaluate the diagnostic approaches in four standardized patients with IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), inflammatory bowel disease (IBD) and chronic constipation (CC). General practitioners (GP, n = 104), gastroenterologists (GE, n = 100) and IBS experts (n = 25) from five European countries participated. RESULTS: Experts showed the highest rates of correct diagnoses (88%-92%) for all cases except CC (only 60%) and were more prone to a positive diagnosis (64%/68% in IBS-C/CC), whereas GEs and GPs tended toward a diagnosis by exclusion (63%/63% and 62%/60% in IBS-C/CC). In the CC vignette, conducting tests was more frequent than prescribing treatment among 44% experts, 63% GEs and 36% GPs. The diagnosis of IBD presented little difficulty for any of the participants. CONCLUSIONS: This study highlights the difficulties in confidently diagnosing chronic functional bowel conditions, especially for non-experts, whereas IBD caused little difficulty. Differentiating between IBS-C and CC seemed particularly challenging, even for experts.

Burden of constipation-predominant irritable bowel syndrome (IBS-C) in France, Italy, and the United Kingdom.

BACKGROUND: Several studies have examined the effect of irritable bowel syndrome (IBS) on health outcomes in Western Europe, but less research has focused on the constipation subtype (IBS-C). The current study addresses this gap by comparing patients with IBS-C and matched controls for health status, work productivity, and resource utilization. METHODS: Data were obtained from the 2010 5EU National Health and Wellness Survey (NHWS), which includes respondents from France, Germany, Italy, Spain, and the UK. Only participants from France (n = 15,051), Italy (n = 7580), and the UK (n = 15,065) were included in the analyses. Respondents who reported a physician diagnosis of IBS and reported only constipation symptoms were compared with respondents who did not report being diagnosed with IBS using a propensity score-matching methodology (matching on sociodemographics, health behaviors, and comorbidities). Differences between patients with IBS-C and matched controls were examined on health status (Short Form Survey Instrument version 2), work productivity (Work Productivity and Activity Impairment questionnaire), and health care resource use in the past 6 months. RESULTS: A total of 83 (0.55%), 109 (1.44%), and 204 (1.35%) respondents reported a diagnosis of IBS with only constipation symptoms in France, Italy, and the UK, respectively. Within each country, patients with IBS-C reported significantly worse health status compared with matched controls (all P < 0.05) and significantly more physician visits (all P < 0.05). More hospitalizations were also observed in the UK (P < 0.05). Among those who were employed, patients with IBS-C in France and the UK also reported significantly more presenteeism than matched controls (all P < 0.05). CONCLUSION: These findings highlight the pervasive influence of IBS-C on the day-to-day functioning of sufferers, their ability to be productive at work, and their influence on the wider health care system. Significant unmet needs remain, and improved management of this condition could result in significant and clinically meaningful gains in health status as well as alleviating a societal cost burden.

Patient assessment of onset of action and overall satisfaction with ebastine fast-dissolving tablets in allergic rhinitis.

AIM: To evaluate patient perception of the onset of action and overall satisfaction with a fast-dissolving tablet (FDT) formulation of ebastine in patients with intermittent or persistent allergic rhinitis. PATIENTS AND METHODS: This was a cross-sectional, multicenter, pharmacy-based survey involving adult patients (>18 years) with allergic rhinitis who presented with a prescription for ebastine FDT. Via a telephone interview, patients were asked to evaluate the characteristics of ebastine FDT in comparison with their previous experience with other antihistamines. RESULTS: 100 patients with allergic rhinitis were included in the study (41 had intermittent disease, 57 persistent disease and two with unknown disease states). Patients rated ebastine FDT very highly (mean scores: 4.5-4.7 out of a possible 5) for all characteristics related to convenience, such as easy to take, easy to carry around in a bag or pocket, suitable for taking anytime/anywhere, and convenient to use. A total of 85% of patients perceived ebastine FDTs onset of action to be fast or very fast, and 77% indicated that it acted faster than their usual antihistamine. A total of 96% were satisfied or very satisfied with ebastine FDT and 98% were interested in using the drug again. CONCLUSIONS: Patients with rhinitis rate ebastine FDT very highly in terms of its formulation, convenience of use and its rapid onset of action. These characteristics resulted in a high level of individual satisfaction with the new formulation and a clear preference by the majority of patients to use ebastine FDT in the future.

Comparison of inhibition of cutaneous histamine reaction of ebastine fast-dissolving tablet (20 mg) versus desloratadine capsule (5 mg): a randomized, double-blind, double-dummy, placebo-controlled, three-period crossover study in healthy, nonatopic adults.

BACKGROUND: Ebastine is a long-acting, second-generation, selective histamine H1-receptor antagonist. A fast-dissolving tablet formulation of ebastine has been developed at 10- and 20-mg doses, with the intention of facilitating administration to patients experiencing problems with swallowing, including those confined to bed and elderly people, as well as those who may need to use ebastine when they do not have easy access to water to aid swallowing a tablet. OBJECTIVES: This study was conducted to assess the pharmacodynamic effects (ie, inhibition of wheal response to cutaneous histamine challenge, and subjective assessments of itching, flare, and pain) and tolerability of the fast-dissolving 20-mg ebastine tablet formulation compared with desloratadine 5-mg capsule and placebo. Acceptability and convenience of the fast-dissolving tablet were also evaluated. METHODS: This double-blind, double-dummy, randomized, placebo-controlled, 3-period crossover study was conducted at the Drug Research Centre, Department of Clinical Pharmacology, the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Healthy, nonatopic, white adults aged 18 to 40 years were randomly assigned to 1 of 6 study sequences: ABC, ACB, BAC, BCA, CBA, or CAB, where A was the ebastine fast-dissolving 20-mg tablet, B was the desloratadine 5-mg capsule, and C was placebo. All study drugs were given orally once daily (8-9 AM) on days 1 to 5 of each study period. Study periods were separated by a washout period of 7 to 10 days. Histamine skin-prick test (SPT) challenge was performed before study drug administration on day 1 of each period (baseline), and then every 20 minutes for 2 hours after administration and again after 24 hours. The final SPT was 24 hours after the day-5 dose was administered. The primary end point was inhibition o f the histamine response, defined as the percentage reduction from baseline wheal area 24 hours after 5 days of administration. Subjective symptoms (itching, flare, and pain) were assessed by subjects using visual analog scales every 20 minutes for 2 hours after administration on day 1. At study end, acceptability (taste, convenience, and overall preference) of the fast-dissolving tablet and capsule formulations were assessed using a questionnaire completed by subjects. Tolerability was assessed using physical examination, laboratory analysis, physician questioning, and spontaneous reporting. RESULTS: Thirty-six people were randomized (22 women, 14 men; mean [SD] age, 24.7 [4.1] years; mean [SD] weight, 63.2 [9.9] kg); 35 completed the study (1 subject was lost to follow-up after the second study period). Unadjusted mean (SD) wheal areas 24 hours after dose administration on day 5 were 72.9 (29.5), 115.0 (32.1), and 146.7 (32.2) mm(2), for ebastine, desloratadine, and placebo, respectively. Mean differences in reduction from baseline in wheal area were 29.0% for ebastine versus desloratadine and 43.7% for ebastine versus placebo (both, P < 0.001). Corresponding unadjusted mean (SD) wheal areas 24 hours after administration of the first dose on day 1 were 76.5 (22.5), 128.9 (24.0), and 140.5 (33.1) mm(2). Mean itching, flare, and pain ratings were not significantly different between study drugs. Results from the preference questionnaire indicated that the majority (80%) preferred the ebastine fast-dissolving tablet to the desloratadine capsule (and hypothetically also to tablets and oral solution, which were not tested in this study). Ninety-seven percent of subjects were of the opinion that compliance in the home setting would be facilitated by the fas-tdissolving tablet formulation. Fourteen adverse events (AEs) were reported in 9 (25%) volunteers; all AEs were of mild or moderate intensity. Five occurred with ebastine 20 mg (intermittent somnolence, back pain, pharyngolaryngeal pain, pyrexia, and oral pain [1 patient each]), 5 occurred with desloratadine 5 mg (asthenia [2 patients] and dry mouth, somnolence, and back pain [1 patient each]), and 4 occurred with placebo (diarrhea [2 patients] and somnolence and headache [1 patient each]). The relationship with the study drugs was considered unlikely in 6 cases and possible in the remaining 8 cases. An additional AE (back pain) occurred during a washout period. CONCLUSIONS: In this small study in healthy, nonatopic white subjects, inhibition of the response to histamine injection was significantly greater with the ebastine 20-mg fast-dissolving tablet compared with desloratadine 5-mg capsule and placebo after 1 and 5 days of administration. Most participants expressed an overall preference for the fast-dissolving tablet formulation over capsules. All study drugs were well tolerated.

A comparison of ebastine 10 mg fast-dissolving tablet with oral desloratadine and placebo in inhibiting the cutaneous reaction to histamine in healthy adults.

BACKGROUND AND OBJECTIVE: Ebastine is a long-acting, second-generation selective histamine H(1) receptor antagonist. The pharmacodynamics of a new 10mg fast-dissolving tablet (FDT) oral lyophilisate tablet formulation of ebastine were compared with those of desloratadine and placebo following histamine skin intradermal test challenge. The acceptability of the FDT was also assessed. METHODS: This was a double-blind, double-dummy, placebo-controlled, randomised, crossover, three-period study in 36 healthy adults. The histamine skin intradermal test (0.05 mL of 100 microg/mL solution) was administered into volunteers' forearms, and wheal area was measured 15 minutes later. Ebastine 10 mg FDT, desloratadine 5mg capsule or placebo were given on days 1-5. On day 1, a skin intradermal test was performed at baseline, then every 20 minutes for 2 hours after administration and at 24 hours. The final skin intradermal test was on day 6, 24 hours after the last drug dose. Subjective symptoms (itching, heat and pain) were assessed on day 1 for 2 hours following the first drug dose. There was a washout period of 7-10 days between treatments. At study end, the acceptability of the new ebastine formulation was evaluated using a questionnaire. RESULTS: Ebastine 10mg inhibited the wheal response to histamine significantly more than desloratadine 5 mg or placebo 24 hours after 5 days' treatment (mean difference between treatments in wheal area reduction from baseline: 26.7%, p < 0.0001; 46.9%, p < 0.0001, respectively), and after 24 hours on day 1 (mean difference: 16.2%, p = 0.0082; 34.2%, p < 0.0001, respectively). The results with desloratadine were also significantly different from placebo on day 1 and after 5 days, but less than with ebastine after 5 days (difference, desloratadine vs placebo: 20.2%, p = 0.0001). No differences in itching, heat and pain were observed between the treatments. Most participants (70%) preferred the FDT, and all reported that it made adherence easier. CONCLUSION: Ebastine 10 mg FDT demonstrated significantly superior antihistamine activity compared with desloratadine and placebo.

Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom.

The objective was to compare the incidence of adverse reactions reported with three nonsteroidal anti-inflammatory drugs with different cyclo-oxygenase (COX)-2 selectivity. All spontaneous adverse reaction notifications in the pharmacovigilance database of the World Health Organisation Collaborating Centre for International Drug Monitoring with aceclofenac, meloxicam, and rofecoxib that were recorded during the first year of marketing were included. The incidence rate (adverse reactions/10(6) defined daily dose) and 95% confidence interval for total adverse reactions was 8.7 (6.1-12.0) for aceclofenac, 24.8 (23.1-26.6) for meloxicam, and 52.6 (49.9-55.4) for rofecoxib. Aceclofenac had a lower incidence of gastrointestinal bleeding, abdominal pain, and arterial hypertension than meloxicam and a lower incidence of gastrointestinal bleeding, abdominal pain, liver toxicity, thromboembolic cardiovascular events, arterial hypertension, and edema than rofecoxib. The incidence of total and gastrointestinal adverse reactions was significantly lower with aceclofenac than with meloxicam or rofecoxib, thus raising doubts about the hypothetical advantage of COX-2 selective inhibitors.

The efficacy and safety of aceclofenac versus placebo and naproxen in women with primary dysmenorrhoea.

OBJECTIVE: To determine the analgesic efficacy and safety of a single oral dose of aceclofenac 100 mg and compare that with placebo and naproxen 500 mg in women with primary dysmenorrhoea. STUDY DESIGN: In this double-blind, prospective, multicentre, randomised, three-way, crossover study, women were randomly assigned to receive one of six treatment sequences, comprising single oral doses of aceclofenac 100 mg, naproxen 500 mg or placebo, when menstrual pain reached a predetermined level of severity. A single dose of the assigned study medication was taken on three menstrual periods; a different medication was taken on each treatment day. Analgesic efficacy was determined by self-reported analgesia scoring and participants' and investigators' global evaluation of treatment effectiveness. Measurements also included physical examination and adverse events. RESULTS: Total pain relief scores were not statistically significantly different for aceclofenac and naproxen, and both were statistically significantly more effective than placebo (p = 0.019 and 0.002, respectively). This finding was supported by secondary endpoints including sum of pain intensity differences (SPID/8), peak analgesia (peak pain intensity and peak pain relief), and participants' and investigators' overall evaluation of effectiveness. Both aceclofenac and naproxen were well tolerated. CONCLUSIONS: Aceclofenac (100 mg) and naproxen (500 mg) effectively treated the pain associated with primary dysmenorrhoea, and both were more effective than placebo at easing menstrual pain assessed by various pain relief criteria.