Gastrointestinal symptoms associated with enteric-coated sulfasalazine (Azulfidine EN tablets)

Abstract

To investigate both the incidence and the dosage used to treat gastrointestinal (GI) symptoms associated with enteric-coated sulfasalazine (Azulfidine EN, AZL) in patients with rheumatoid arthritis (RA), we studied the clinical history of 153 RA patients, and any available data on GI symptoms that might have been associated with AZL. GI symptoms appeared in 64 (42.5%) of the 153 cases. There were 19 events of nausea, vomiting, or dyspepsia, 14 events each of epigastric discomfort and reduction or loss of appetite, 10 events of epigastric, stomach, or abdominal pain, 9 events of heartburn, 8 events of mouth ulcer, 3 events each of loss of taste and abdominal bloating or borborygmus, 2 events each of diarrhea or loose stools, hematemesis or melanemia, and gastric or esophageal ulcer, and 1 event of stomatitis. These results indicate that GI symptoms associated with AZL are usually mild and treatment can continue, with almost all cases responding to a reduction in dose or drug cessation. In some cases, a histamine receptor-2 blocker or proton pump inhibitor is also required.     

Gastrointestinal symptoms and health related quality of life in patients with arthritis

OBJECTIVE: To evaluate the relationship between gastrointestinal (GI) symptoms and health related quality of life (QOL) in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: A total of 1773 patients with arthritis participating in a longterm outcome study (OA of the hip or knee = 648, RA = 1125) completed mailed surveys that included assessments of GI symptoms and overall GI symptom severity, Short Form-36, the visual analog scale (VAS) for the EuroQol (Health QOL), a VAS global disease severity scale, and measures of disease and psychological status. The overall response rate exceeded 85%. RESULTS: Dyspepsia (heartburn, bloating, or belching) and upper abdominal/epigastric pain were identified as the most important GI contributors to reduction in QOL, and the simultaneous presence of both these symptoms was associated with lower QOL (54.5) compared to those without symptoms (70.9) on the 0-100 Health QOL scale. Similarly, those in the upper tertile of the global GI severity scale had Health QOL scores of 55.7 compared to 76.4 for those in the lower tertile. These differences in GI symptoms and GI severity, however, were reduced substantially when the effects of functional disability, pain, and depression were adjusted for: 62.3 to 68.6 (p = 0.003) and 63.7 to 70.3 (p<0.001) for the GI symptoms and GI severity scales, respectively. CONCLUSION: QOL is significantly impaired among unselected arthritis patients with GI symptoms compared to those without these symptoms. Dyspepsia and upper abdominal/epigastric pain are more strongly related to QOL measures than other GI symptoms, and are common among arthritis patients. It is possible to construct a simple scale of these 2 symptoms or to use the VAS GI severity scale and get a clinically useful idea of the current level of GI distress and alteration of QOL by GI problems. Two components of impairment can be identified, one that is smaller and unrelated to disease or psychological factors, and a second that is larger and includes these factors. Because GI symptoms can alter function, pain, and psychological status, it is likely that the true effect of GI symptoms on QOL is somewhere between the unadjusted and adjusted values cited above.     

The comparative risk and predictors of adverse gastrointestinal events in rheumatoid arthritis and osteoarthritis: a prospective 13 year study of 2131 patients

OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) itself may be a risk factor for adverse gastrointestinal (GI) events, but this hypothesis has not been studied in a large sample, nor has the effect of time on risk factors been studied. We investigated rates and risk factors for GI events in RA and osteoarthritis (OA) and assessed the additional risks conveyed by having RA. METHODS: A prospective study of patients with OA and RA from a single center was undertaken using questionnaires mailed at 6 month intervals. The relationship between drug therapy and GI events was assessed in the same 6 month time frame. Over 13 years of biannual assessments, 2,131 patients were studied for serious GI events and adverse GI symptoms during 9,621 patient-years of observation. RESULTS: The incidence rate (IR) for GI hospitalization was 1.56 and 1.28 per 100 patient-years, and for GI bleeding or perforation was 0.50 and 0.58 for RA and OA, respectively. After controlling for age, sex, nonsteroidal antiinflammatory drug (NSAID) and steroid use, the incidence rate ratio (IRR) for RA versus OA did not differ for hospitalization [IRR 1.07 (95% CI 0.66, 1.74)] or for bleeding or perforation [IRR 0.63 (95% CI 0.29, 1.35)]. In multivariate analyses for both groups combined, the IRR was 2.95 (2.05, 4.24) for prednisone use, 1.41 (1.08, 1.85) for NSAID use, and 1.46 (1.22, 1.74) for every 10 year increase in age. In additional multivariate models, Health Assessment Questionnaire disability was also a significant risk factor. During the study period, the odds of NSAID use decreased 2.94 times per 10 year period, while the odds of prednisone use increased by 1.49. Dysphagia [IRR 1.11 (1.00, 1.24)], anorexia [IRR 1.13 (1.03, 1.23)], nausea [IRR 1.13 (1.04, 1.25)], heartburn [IRR 1.12 (1.05, 1.19)], vomiting [IRR 1.20 (1.02, 1.42)], peptic ulcer symptoms [IRR 1.20 (1.11, 1.29)], and abdominal pain [IRR 1.11 (1.01, 1.22)] were associated with NSAID use, but not with steroids. CONCLUSION: Patients with RA and OA do not differ in the rates and risk factors for GI hospitalizations and symptoms after controlling for age, steroid use, NSAID use, or (for OA) body mass index. Prednisone is a more important risk factor among patients with RA than NSAID.     

Impact of gastrointestinal endoscopy on HIV‐infected children

Objective: To evaluate the role of gastrointestinal (GI) endoscopy in human immunodeficiency virus (HIV)‐infected children with GI problems. Methods: From 1998 to 2002, we retrospectively reviewed all cases of HIV‐infected children presenting with GI problems in which an upper or lower GI endoscopy was indicated. The initial diagnostic endoscopic examination and any repeat endoscopic session leading to a new diagnosis were used in the data analysis. Tissue biopsies were obtained from all abnormal lesions and representative sites of normal‐appearancing GI mucosa. Results: Fourteen patients (median age: 22.5 months) underwent 23 sessions of GI endoscopy, including 10 esophagogastroduodenoscopy, nine colonoscopy and four flexible sigmoidoscopy. Chronic diarrhea was the most common indication, followed by lower GI bleeding, abdominal/retrosternal pain, dysphagia/odynophagia, and upper GI bleeding. Gross endoscopic abnormalities were observed in 78.3%; whereas histological inflammation and opportunistic pathogens were identified in 87% and 43.5%, respectively. Cytomegalovirus was the most common identified pathogen. Abnormal gross findings were significantly associated with histological inflammation and identification of pathogens (P = 0.006 and 0.046, respectively). Specific changes in medical management were made in 50% of cases as a result of endoscopic investigation. Conclusion: If non‐invasive investigations for HIV‐infected children with GI symptoms fail to establish a diagnosis, gastrointestinal endoscopy should be performed and often yields a positive result leading to changes in medical management.     

The importance of gastrointestinal (GI) symptom severity in rheumatoid and osteoarthritis: symptom rates and risk for GI hospitalization

OBJECTIVE: To determine the prevalence and stability of gastrointestinal (GI) symptoms in outpatients with rheumatoid arthritis (RA) and osteoarthritis (OA); to determine the specific symptoms that contribute to severity; and to determine the predictive value of GI symptoms and GI severity on the risk of future GI hospitalization. METHODS: A questionnaire survey was mailed to 1221 patients with RA and OA on a continuing 6 month schedule. Patients completed an average of 4.4 questionnaires (n = 5,047). Questionnaires included a visual analog scale GI severity scale, and questions regarding GI hospitalizations and specific GI symptoms. Hospitalizations that were reported as relating to the GI system were audited by checking hospital records. RESULTS: We found 57.5%, 40.2%, and 25.5% of patients had at least one assessment in which they had a GI symptom severity of 0.25-0.99, 1.00-1.99, and 2.00 or greater, respectively. Overall 74.9% had at least one score of 0.25 or greater, and 73.6% had one score of < 0.25, the cutoff for GI symptoms. By contrast, 6.45% had a GI hospitalization, and in only 0.75% of the questionnaire assessments were hospitalizations noted. Pyrosis and peptic ulcer symptoms were common, and were found in 62.5% and 42.4% of patients and 28.2% and 12.9% of observations, respectively. Among patients reporting GI severity scores between 2 and 3, roughly 60% and 45% reported the presence of pyrosis and peptic ulcer symptoms, respectively. The presence of a GI severity score > or = 0.25 was associated with 2.8-3.0-fold increase in the risk of hospitalization over the following 6 months. CONCLUSION: These data suggest that symptoms have an importance of their own that relates to quality of life, regardless of the risk of serious GI events like hospitalization, and that more attention should be placed on symptoms and symptom severity in future research. In spite of the statistical predictive value of GI symptom severity on future hospitalizations, it is important to recognize that rate of GI hospitalization increases from 0.92 per 100 patient-years to only 2.90 per 100 patient-years when the GI symptom scale goes from approximately zero to positive values. Thus, in spite of its statistical predictive ability, GI symptom severity is a poor clinical predictor of the hospitalizations that occur in patients with rheumatic diseases. Instead, GI symptom severity and specific GI symptoms have a separate importance to patients.     

Comparison of gastroduodenal,renal and abdominal fat biopsies for diagnosing amyloidosis in rheumatoid arthritis

The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidisis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis. Received: 6 June 2001 / Accepted: 10 September 2001     

Celecoxib,a cyclooxygenase-2 inhibitor,improved upper gastrointestinal lesions in rheumatoid arthritis patients as assessed by endoscopic evaluation

Abstract

We prospectively evaluated the effects of celecoxib (CEL) on the gastrointestinal (GI) tract of rheumatoid arthritis (RA) patients with endoscopically identified GI mucosal injury after therapeutic switching from the long-term use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Upper GI endoscopy was performed on RA patients who had been treated with NSAIDs for ≥3 months. GI mucosal injury was evaluated according to the modified LANZA score. Patients with mucosal injury without ulcers were switched from NSAIDs to CEL, while those with ulcers were switched to CEL with famotidine after ulcer healing. At week 16 of treatment, GI mucosal injury was endoscopically revaluated. An efficacy analysis was performed before therapeutic switching and at 8 and 16 weeks post-switching. Endoscopic analysis revealed GI mucosal injury, including six ulcers, in 45 of the 82 patients (54.9%). Sixteen weeks after switching to CEL, LANZA scores were significantly improved [2.1 ± 0.8 (pre-switching) vs. 1.6 ± 1.3, P = 0.0073] in patients with LANZA scores of 1, 2, or 3 (n = 35). The Disease Activity Score using 28 joint counts (DAS28) [erythrocyte sedimentation rate item score (ESR4) (P = 0.0257) and C-reactive protein item score (CRP4) (P = 0.0031)] was also significantly improved by week 16. Based on these results, we conclude that preexisting NSAID-induced upper GI injury is improved following therapeutic switching to CEL without any reduction in analgesic efficacy.     

Upper gastrointestinal problems in inhalational ketamine abusers

OBJECTIVE: To study the association between upper gastrointestinal (GI) problems and inhalational ketamine abuse. METHODS: This is a retrospective study of 64 ketamine abusers treated from 2001 to 2008. Variables studied included clinical presentations, findings of upper GI endoscopy, abstinence from ketamine and relief of epigastric pain. RESULTS: The following patients with (i) a previous history of upper GI problem; (ii) a history of non-steroidal anti-inflammatory drug (NSAID), aspirin or other substance abuse; and (iii) a known history of Helicobacter pylori (H. pylori) infection were excluded. The study group thus consisted of 37 ketamine abusers, of whom 28 had upper GI symptoms. Overall 14 of these patients had an upper endoscopy performed. The endoscopic diagnoses were: 12 (85.7%) with gastritis, one (7.1%) with gastroduodenitis, and one (7.1%) normal finding. Test for H. pylori, infection was negative. Abstinence from ketamine was found to be associated significantly with relief of symptoms (P= 0.027). Logistic regression showed the odds ratio of symptomatic relief for abstinence versus continued use of ketamine is 12.5 (95% CI[1.20, 130.6], P= 0.035). In patients whom an upper GI endoscopy was performed, H. pylori negative gastritis was the commonest histopathological finding (78.6%). Despite the use of medications, symptoms are commonly not relieved and that is associated with the continued abuse of ketamine. CONCLUSION: Ketamine abusers frequently presented with upper GI symptoms, the commonest of which is epigastric pain (73% of abusers). Abstinence from ketamine abuse can lead to the relief of symptoms, which is an important message for ketamine abusers.     

Clinical and genetic characteristics of upper gastrointestinal disease in rheumatoid arthritis

Clinical and genetic studies were analyzed in 47 patients with rheumatoid arthritis (RA) who had upper gastrointestinal (GI) endoscopies. Fifty-three percent of patients with RA had peptic ulcers and/or erosions. Sixty percent of patients with ulcers and/or erosions had a history of peptic ulcer disease. Although a greater number of patients with ulcers and/or erosions was taking regular aspirin or indomethacin, comparable numbers of patients with abnormal and normal endoscopies were using nonsteroidal antiinflammatory drugs. Nineteen of the 25 patients (76%) with ulcers and/or erosions had type O blood. Patients with abnormal and normal endoscopies had similar frequencies of GI complaints and fecal blood loss. GI symptoms and occult fecal blood loss, therefore, are not prominent features of upper GI disease in RA. ABO screening may be helpful in determining which patients with RA are at risk for developing peptic ulcers and/or erosions.     

Gastrointestinal symptoms related to the irritable bowel syndrome – a longitudinal population-based register study

Objective Functional gastrointestinal (GI) symptoms can develop into persistent states often categorised as the irritable bowel syndrome (IBS). In the severe end of the GI symptom continuum, other coexisting symptoms are common. We aimed to investigate the GI symptom continuum in relation to mortality and development of GI diseases, and to examine if coexisting symptoms had an influence on the outcomes. Material and methods A longitudinal population-based study comprising two 5-year follow-up studies: Dan-Monica1 (1982–1987) and Inter99 (1999–2004). IBS was defined according to a population-based IBS definition. The pooled cohort (n?=?7278) was followed until December 2013 in Central Registries. Results Fifty-one percent had no GI symptoms, 39% had GI symptoms but never fulfilled the IBS definition, 8% had fluctuating IBS and 2% had persisting IBS. There was no significant association between symptom groups and mortality (p?=?0.47). IBS and GI symptoms with abdominal pain were significantly associated with development of GI diseases. Only GI symptoms with abdominal pain were associated with development of severe GI diseases (HR: 1.38; 95% CI: [1.06–1.79]). There were no statistically significant interactions between symptom groups and coexisting symptoms in relation to the two outcomes. Conclusions GI diseases were seen more frequently, but IBS was not associated with severe GI diseases or increased mortality. Clinicians should be more aware when patients do not fulfil the IBS definition, but continue to report frequent abdominal pain. Coexisting symptoms did not influence mortality and development of GI diseases.     

Initial validation of a bowel symptom questionnaire* and measurement of chronic gastrointestinal symptoms in Australians

Background: Chronic gastrointestinal (GI) symptoms are believed to be common in the general population, but Australian data are lacking. A valid instrument is required to assess GI symptoms adequately and determine their prevalence in the community. Aims: To test the feasibility, reliability and concurrent validity of a self-report Bowel Symptom Questionnaire (BSQ) as a measure of GI symptoms, and obtain preliminary data on the prevalence of symptoms in an Australian population-based sample. Methods: Outpatients (n= 63), volunteers (n= 163) and a random sample (n= 99) of the Penrith population, Sydney, completed the BSQ. Feasibility was evaluated in 264 subjects. Reliability was measured by a test-retest procedure (n= 43), while concurrent validity was documented by comparing self-report data with an independent interview (n= 20). The response rate in the population mail survey was 68%. Prevalence data on bowel symptoms in the community sample (n= 99) were age and gender standardised to the Australian population. Results: The majority of subjects found the BSQ easy to complete (97%) and understand (97%); 90% completed the questionnaire in half an hour or less. Reliability (median kappa 0.70, interquartile range 0.20) and concurrent validity (median kappa 0.79, interquartile range 0.26) of GI symptoms were both very acceptable. The internal consistency of all GI symptom scales was good (Cronbach's Alpha range 0.51-0.74). The prevalence of the irritable bowel syndrome (defined as abdominal pain and disturbed defaecation based on two or more of the Manning criteria) was 17.2% (95% CI: 10–25%). Conclusions: The BSQ was well accepted and easy to understand; it provided reliable and valid data on GI symptoms and should prove useful in large scale epidemiological studies in Australia. (Aust NZ J Med 1995; 25: 302–308.)     

The clinical application of etanercept in Chinese patients with rheumatic diseases

Abstract

Over a 2-year period, to evaluate the efficacy and safety of biologic agents, etanercept (25?mg twice per week, s.c.) was used to treat 57 rheumatoid arthritis (RA) patients, 9 ankylosing spondylitis (AS) patients, 6 psoriatic arthritis (PSA) patients, and 4 juvenile rheumatoid arthritis (JRA) patients. In addition to inflammatory arthritis, I have used this tumor necrosis factor (TNF) blocker in other rheumatic diseases including idiopathic thrombocytopenic purpura (ITP), Behçet's disease with intractable oral ulcer, fibromyalgia syndrome, and systemic lupus erythematosis with intractable pleural effusion and acute lumbar disc herniation. For RA, after 6 months of etanercept treatment, all the parameters including number of swollen joints, number of tender joints, disease activity score, erythrocyte sedimentation rate, C-reactive protein, and global health status were rapidly improved (P < 0.001 or P < 0.0001). The anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor also significantly declined. For spondyloarthropathy, it also gave a similar effect as to RA. Both Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index also improved. One of the two cases with Behçet's disease with intractable oral ulcer had a long-term remission after etanercept. The other Behçet's disease patient with oral ulcer and another with ITP obtained a good response temporarily. The short-term use of etanercept (<3 months) did not bring a significant effect for cases of fibromyalgia syndrome, pleural effusion, and lumbar disc herniation. In conclusion, a dramatic and rapid clinical response in different kinds of arthritis patients can be achieved by etanercept. Moreover, the TNF-α inhibitor also can treat other severe rheumatic-related symptoms. In general, except for a few cases with infection and two cases with malignancy, etanercept was safe in our arthritis patients. We need to study a larger number of patients in order to better understand the efficacy and safety of etanercept.     

Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus

OBJECTIVE: Gastrointestinal (GI) symptoms are common in patients with long-standing diabetes mellitus, but the pathogenesis is controversial. We aimed to determine if GI symptoms are linked to psychological distress in diabetes. METHODS: A consecutive sample of outpatients with diabetes mellitus (n = 209) and a random sample of community diabetics (n = 892) completed a validated questionnaire measuring GI symptoms, the Hospital Anxiety and Depression (HAD) Scale for anxiety and depression, and the Eysenck short neuroticism scale. RESULTS: Overall, 42% reported one or more GI symptoms: bloating, abdominal pain, loose stools, and urgency were most common. The mean HAD and neuroticism scores were significantly higher for most GI symptoms (11 of 14, all p < 0.05), and a dose-response relationship was observed. GI symptoms were, in general, approximately twice as frequent in cases with anxiety or depression (HAD > or = 11). Anxiety, depression, and neuroticism were each independently associated with the number of GI symptoms, adjusting for age, gender, duration and type of diabetes, and self-reported glycemic control. CONCLUSIONS: Increased levels of state anxiety and depression and neuroticism are associated with upper and lower GI symptoms in diabetes mellitus. It is uncertain whether psychological distress is causally linked to symptoms, or whether GI symptoms per se increase levels of anxiety and depression.     

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan

Abstract

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58–0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori?/NSAID? group, 1.24% in the H. pylori?/NSAID+ group, 1.06% in the H. pylori+/NSAID? group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19–7.38) and 4.31 (95% CI: 0.57–32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.     

NSAID-induced ulcers

Opinion statement Nonselective nonsteroidal antiinflammatory drugs (NSAIDs) are used chronically by approximately 13 million to 15 million Americans annually for the treatment of painful and inflammatory conditions. While all these agents are quite effective in reducing inflammation and pain, they are also associated with UGI symptoms and mucosal injury. These include abdominal pain/dyspepsia in the absence of ulcer disease; symptomatic and asymptomatic gastric and duodenal ulcers; and clinically significant upper GI events such as bleeding, gastric outlet obstruction, and perforation. The clinically relevant treatments related to NSAID-associated symptoms and mucosal injury fall into three major categories: symptomatic treatment of dyspepsia while using NSAIDs; treatment of acute endoscopically proven ulcers and ulcer complications in those using these medications; and prevention (prophylaxis) of ulcer and ulcer complications in patients at high risk for ulcer complications. The new COX-2 selective inhibitors are likely to be associated with different short- and long-term safety profiles as compared to traditional NSAIDs; the literature and post-marketing data regarding these agents (celecoxib, rofecoxib) are evolving. As such, this article primarily focuses on the approach to patients using traditional, nonselective, nonsteroidal agents.     

Incidence,risk and protective factors of symptoms after colonoscopy

BackgroundFew studies focused on minor adverse events which may develop after colonoscopy.AimsTo investigate the incidence and factors associated to post-colonoscopy symptoms.MethodsThis is a prospective study conducted in 10 Italian hospitals. The main outcome was a cumulative score combining 10 gastrointestinal (GI) symptoms occurring the week following colonoscopy. The analyses were conducted via multivariate logistic regression.ResultsOf 793 subjects included in the analysis, 361 (45.5%) complained the new onset of at least one GI symptom after the exam; one symptom was reported by 202 (25.5%), two or more symptoms by 159 (20.1%). Newly developed symptoms more frequently reported were epigastric/abdominal bloating (32.2%), pain (17.3%), and dyspeptic symptoms (17.9%). Symptoms were associated with female sex (odds ratio [OR]=2.54), increasing number of symptoms developed during bowel preparation intake (OR=1.35) and somatic symptoms (OR=1.27). An inverse association was observed with better mood (OR=0.74). A high-risk profile was identified, represented by women with bad mood and somatic symptoms (OR=8.81).ConclusionAbout half of the patients develop de novo GI symptoms following colonoscopy. Improving bowel preparation tolerability may reduce the incidence of post-colonoscopy symptoms, especially in more vulnerable patients.     

Relationship between clinical factors and severity of esophageal candidiasis according to Kodsi's classification

Severe Candida esophagitis (CE) may lead to development of strictures, hemorrhage, esophagotracheal fistula, and a consequent decrease in quality of life. Although the severity of CE has been classified based on macroscopic findings on endoscopy, the clinical significance remains unknown. The aim of the study was to elucidate the predictive clinical factors for endoscopic severity of CE. Patients who underwent upper endoscopy and answered questionnaires were prospectively enrolled. Smoking, alcohol, human immunodeficiency virus (HIV) infection, diabetes mellitus, chronic renal failure, liver cirrhosis, systemic steroids use, proton pump inhibitor use, H2 blocker use, and gastrointestinal (GI) symptoms were assessed on the same day of endoscopy. GI symptoms including epigastric pain, heartburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia were assessed on a 7‐point Likert scale. Endoscopic severity was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of 1855 patients, 71 (3.8%) were diagnosed with CE (mild, n = 48; severe, n = 23). In the CE patients, 50.0% (24/48) in the mild group and 23.1% (6/23) in the severe group did not have any GI symptoms. In HIV‐infected patients (n = 17), a significant correlation was found between endoscopic severity and declining CD4 cell count (Spearman's rho = ?0.90; P < 0.01). Multivariate analysis revealed that GI symptoms (odds ratio [OR], 3.32) and HIV infection (OR, 3.81) were independently associated with severe CE. Patients in the severe group experienced more epigastric pain (P = 0.02), reflux symptoms (P = 0.04), dysphagia (P = 0.05), and odynophagia (P < 0.01) than those in the mild group. Of the GI symptoms, odynophagia was independently associated with severe CE (OR 9.62, P = 0.02). In conclusion, the prevalence of CE in adults who underwent endoscopy was 3.8%. Silent CE was found in both mild and severe cases. Endoscopic severity was associated with characteristic GI symptoms and comorbidity of HIV infection. A decline in immune function correlated with CE disease progression.     

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.     

Unique mode of binding between angiotensin II type 1 receptor and its blockers

ABSTRACT

BACKGROUND: We hypothesized that the 5-oxo-1,2,4-oxadiazole moiety of azilsartan (AZL), which represents a small difference in the molecular structures of AZL and candesartan (CAN) [angiotensin II type 1 receptor (AT₁R) blockers], may be responsible for the molecular effects of AZL. METHODS: We examined the binding affinities of AZL and CAN to AT₁R, along with their ability to block receptor activity. A competition binding study, inositol phosphate (IP) production assay and extracellular signal-regulated kinase (ERK) assay were performed using wild-type (WT) and mutants AT₁R-transfected cells. RESULTS: The binding affinities of CAN and AZL were reduced by > 5-fold for Y35F, W84F, R167K, K199Q and I288A compared with WT. In addition, AZL showed a > 5-fold reduction in its binding affinity to V108A. CAN and AZL exhibited > 20-fold and > 100-fold reductions in binding affinity to R167K, respectively. The loss of binding affinity of AZL to R167K was greater than that of CAN. CAN-7H exhibited a > 10-fold reduction in binding affinity to R167K compared with CAN. On the other hand, the binding affinity of AZL-7H to R167K was comparable to that of AZL. While 10^-6M CAN and CAN-7H partly blocked Ang II-induced IP production in R167K, 10^-6M AZL and AZL-7H did not. In addition, 10^-6M CAN, but not 10^-6M AZL, partly blocked Ang II-induced ERK activation in R167K. CONCLUSIONS: The interaction between 5-oxo-1,2,4-oxadiazole in AZL and Arg¹⁶⁷ in the AT1R appears to be more important than the interaction between the tetrazole ring in CAN and Arg¹⁶⁷.