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Biomedical subjects

Nicholas J Talley

Publications and source records attributed to Nicholas J Talley.

At least 19 recordsLinked to original sources
PubMed2004

Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Clinical presentation and personality factors are predictors of the response to treatment in patients with functional dyspepsia; a randomized, double-blind placebo-controlled crossover study.

The role of psychological factors or symptom pattern for the response to treatment in patients with unexplained (functional) dyspepsia is unknown. We hypothesized that patients with reflux- and ulcer-like symptoms would be more likely to respond to acid-lowering therapy, while psychological disturbances would be associated with a less favorable response to treatment. Seventy-eight patients with a diagnosis of functional dyspepsia were recruited and 75 completed the trial. Patients were treated for 4 weeks in a double-blind, placebo-controlled crossover trial starting in random order with either active drug (ranitidine, 150 mg b.d.) or placebo. Every 7 days, medication was switched from active drug to placebo, or vice versa. At entry, patient characteristics were assessed utilizing a semistructured standardized interview and standardized questionnaires, and weekly intensity of symptoms was assessed utilizing a visual analogue scale. Patients with a greater reduction of the symptom score during active treatment and an overall reduction of the global symptom score by more than 50% at the end of the study period were categorized as responders. Logistic regression analysis was utilized to assess the influence of symptom type and presence of psychological disturbances on the treatment response. During treatment the symptom score decreased significantly, from 32.1 +/- 1.44 (SD) to 21.3 +/- 1.9 at the end of the trial (P < 0.001). Twenty of 75 were responders. High scores for somatization (OR, 3.6; 95% Cl, 1.2-11.4), anxiety (OR, 3.3; 95% Cl, 0.9-11.8), and reflux-like symptoms (OR, 5.3; 95% Cl, 1.7-16.7) were associated with response to treatment, while dysmotility-like symptoms were associated with an unfavorable response (OR, 0.3; 95% Cl, 0.1-0.9). Symptom pattern and psychological disturbances are independent predictors of treatment response. Patients with reflux-like symptoms and greater psychological disturbances are more likely to respond to an acid-lowering compound.

Adult↗
PubMed2004

Gastroparesis Cardinal Symptom Index (GCSI): development and validation of a patient reported assessment of severity of gastroparesis symptoms.

BACKGROUND: Patient-rated symptom assessments are needed for evaluating the effectiveness of medical treatments and for monitoring outcomes in gastroparesis. OBJECTIVE: This paper summarizes the development and psychometric evaluation of a new instrument, the Gastroparesis Cardinal Symptom Index (GCSI), for assessing severity of symptoms associated with gastroparesis. METHODS: The GCSI was based on reviews of the medical literature, patient focus groups, and interviews with clinicians. A sample of 169 patients with a documented diagnosis of gastroparesis participated in the psychometric evaluation study. Patients completed the GCSI, the SF-36 Health Survey, and disability days questions at baseline and after 8 weeks. A randomly selected sub-sample of 30 subjects returned at 2 weeks to assess test retest reliability. Clinicians rated severity of symptoms, and both clinicians and patients rated change in gastroparesis-related symptoms over the 8 week study. RESULTS: The GCSI is based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). Internal consistency reliability was 0.84 for the GCSI total score and ranged from 0.83 to 0.85 for the subscale scores. Two week test retest reliability was 0.76 for the total score and ranged from 0.68 to 0.81 for subscale scores. Construct validity was supported, given that we observed significant relationships between clinician assessed symptom severity and GCSI total score, significant differences between gastroparesis and dyspepsia patients (n = 760) on GCSI total (p < 0.0001) and subscale scores (p < 0.03 to p < 0.0001), moderate and significant relationships between GCSI total and SF-36 scores, and significant associations between GCSI total score and reports of restricted activity and bed disability days. Patients with greater symptom severity, as rated by clinicians, reported more symptom severity on GCSI total score. GSCI total scores were responsive to changes in overall gastroparesis symptoms as assessed by clinicians (p < 0.0001) and patients (p = 0.0004). CONCLUSION: The findings of this study indicate that the GCSI is a reliable and valid instrument for measuring symptom severity in patients with gastroparesis.

Adolescent↗
PubMed2004

Splitting irritable bowel syndrome: from original Rome to Rome II criteria.

OBJECTIVES: Diagnosis of irritable bowel syndrome (IBS) and other functional bowel disorders (FBD) is based on symptom evaluation. Clinical criteria have changed over time, yielding different proportions of subjects fulfilling diagnostic requirements. According to new diagnostic criteria (Rome II), subjects considered some years ago to have IBS no longer do so. The aim of this article is to evaluate how patients diagnosed as having IBS according to original Rome criteria have been split, and to which clinical diagnosis they belong today. METHODS: Two hundred and eleven subjects meeting original Rome IBS diagnostic criteria were studied: 65 also met Rome II criteria while 146 did not. Subjects were extracted from an epidemiological survey, using home-based personal interviews, on 2000 subjects randomly selected as representative of the Spanish population. Clinical complaints, personal well-being, resource utilization, and health-related quality of life (HRQOL) were compared. RESULTS: Of the subjects meeting original Rome but not Rome II criteria, the present diagnosis should be: 40%"minor" IBS (IBS symptoms of less than 12 wk duration), 37% functional constipation, 12% alternating bowel habit, 7% functional diarrhea, 3% functional abdominal bloating, and 1% unspecified functional bowel disorder (FBD). Thus, 52 subjects (36%) should not be diagnosed with IBS because they really had other FBD, 59 (40%) because of symptoms consistent with IBD diagnosis but not the required duration or frequency, and 35 (24%) because of symptoms consistent with some other FBD diagnosis but not meeting the required duration. Clinical complaints, personal well-being, resource utilization, and HRQOL were more severely affected in IBS than in other FBD as a group, and in "major" rather than in "minor" forms. CONCLUSIONS: Many subjects meeting original Rome criteria for IBS do not meet Rome II criteria: approximately one quarter of subjects do not have sufficient symptom duration or frequency to be diagnosed with IBS and almost half are now considered as having other ("major" or "minor") FBD.

Adolescent↗
PubMed2004

G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia.

BACKGROUND & AIMS: In patients with functional dyspepsia, altered alpha-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein beta 3 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein beta 3 subunit genotypes with functional dyspepsia. METHODS: In study A, abdominal symptoms were assessed in 67 patients with unexplained, upper abdominal symptoms and 259 consecutive blood donors with and without abdominal symptoms. In study B, a further 56 patients with functional dyspepsia and 112 age- and sex-matched healthy controls from a blood donor population study were evaluated. Genomic DNA was isolated from buccal swabs and genotyping of the C825T polymorphisms was performed by polymerase chain reaction and restriction analysis. RESULTS: In the blood donors with no abdominal symptoms in study A (controls, n = 161), genotype distribution was 17 TT, 77 TC, and 67 CC. In blood donors and patients with unexplained abdominal symptoms, genotype distribution was 22 TT, 54 TC, and 89 CC (P = 0.007 vs. controls). In study B, the genotype distribution in functional dyspepsia patients was 4 TT, 18 CT, and 34 CC compared with 4 TT, 62 CT, and 46 CC in the controls (P < 0.02). Combining studies A and B, the odds ratio (OR) adjusted for age and sex for upper abdominal symptoms associated with the CC genotype was 2.2 (95% confidence interval [CI]: 1.4-3.3), compared with subjects with TC and TT genotype carrying an allele. CONCLUSIONS: Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms.

Abdominal Pain↗
PubMed2004

Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsia.

Functional dyspepsia (FD) remains a relatively poorly characterized gastrointestinal disorder of unknown etiology that is frequently difficult to manage. A systematic review of the literature relating to food intake and FD is summarized here. Many patients with FD report symptoms after meal ingestion, including fullness, bloating, epigastric pain, nausea, and vomiting, and this has been interpreted as indicative of an underlying "motor disorder of the stomach or small intestine." Such hypotheses are, however, still largely unsubstantiated, and the data that do exist are inconclusive, particularly as few studies have directly examined the temporal relationships between dyspeptic symptoms, meal ingestion, and disordered gastric motility. Moreover, studies attempting to relate symptoms to specific disturbances in gastric motor function have, in most cases, not evaluated symptoms concurrently with the function test, and/or have used suboptimal symptom scoring to quantify symptoms. Furthermore, the term "early satiety" has been used loosely as a symptom, rather than a quantitative measure of food intake. Currently, the most widely accepted mechanism underlying FD is visceral hypersensitivity, which may contribute to both enhanced motor and symptomatic responses to food ingestion. However, the possible contribution of food and dietary habits to the induction and/or exacerbation of dyspeptic symptoms represents a relatively new area-despite frequent reports by patients that their symptoms are often related to food ingestion; this association has not been formally assessed. Dietary assessments have frequently implicated fatty foods in symptom induction, and these findings are supported by laboratory-based studies, particularly the demonstration that FD patients more often experience symptoms after intraduodenal infusions of fat, than glucose. Further studies into the potential role of dietary factors in the induction of dyspeptic symptom are required to establish whether dietary therapies have any place in the management of FD.

Diet↗
PubMed2004

Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study.

BACKGROUND: It is widely accepted based on volunteer studies that levels of psychological distress are similar in those with functional gastrointestinal (GI) disorders and health in the community, while increased psychological distress in outpatients is largely explained by health-care seeking. AIMS: To determine if psychological distress, life event stress, or social support is associated with functional GI disorders in a population-based study. METHODS: A nested case-control study was performed by first mailing a self-report bowel disease questionnaire to a random sample of Olmsted County, Minnesota, aged 20-50 yr. All persons who reported symptoms of nonulcer dyspepsia (NUD) or irritable bowel syndrome (IBS) (cases), or an absence of GI symptoms (controls), were invited to complete a series of validated questionnaires designed to measure psychological distress, life event stress, social support, current symptoms, and physician visits. RESULTS: 103 subjects with functional GI disorders and 119 controls participated (85% of eligible). Functional GI disorders were more likely to be reported by those with higher scores on each of the nine SCL-90-R scales used to measure psychological distress (except phobic anxiety), and those with more negative and total life event stress. In a multiple logistic regression model (including age and gender), somatization, interpersonal sensitivity, and total life event stress were independently associated with functional GI disorders. Findings were similar when subjects with the IBS and NUD were analyzed separately compared to controls. CONCLUSIONS: Contrary to current dogma, psychosocial factors were significantly associated with functional GI disorders in this community sample. This suggests that these factors may be involved in the etiopathogenesis rather than just driving health-care utilization.

Adult↗
PubMed2004

Antidepressants in IBS: are we deluding ourselves?

The benefit of selective serotonin reuptake inhibitors (SSRIs) in the irritable bowel syndrome (IBS) has not been clear. In the latest randomized trial published this month in the Journal, paroxetine was superior to placebo in terms of improving well-being, but not abdominal pain or bloating. Based on the results of the most recent studies, both tricyclic antidepressants and SSRIs may improve patient satisfaction or quality-of-life without relieving most of the primary gastrointestinal symptoms. This suggests that antidepressant therapy represents at best only a "band-aid" approach to management. Optimizing the use of antidepressants in IBS is a challenge, and these issues are explored in this Editorial.

Antidepressive Agents↗
PubMed2004

Celiac disease serology in irritable bowel syndrome and dyspepsia: a population-based case-control study.

OBJECTIVE: To determine whether undiagnosed celiac disease is associated with irritable bowel syndrome (IBS) or dyspepsia in the community. SUBJECTS AND METHODS: A self-report bowel disease questionnaire was mailed to a random sample of Olmsted County, Minnesota, residents aged 20 to 50 years. All respondents who reported symptoms of dyspepsia or IBS (cases) and all respondents without notable gastrointestinal symptoms (controls) were invited to participate (260 eligible subjects; 150 [58%] were studied). Each respondent was examined by a physician, and the medical records of each were reviewed (3 subjects did not meet the criteria for dyspepsia or IBS at the time of the physician interview). Serum was obtained to measure antiendomysial antibodies and tissue transglutaminase (TTg) IgA antibodies using validated assays. RESULTS: A total of 34 subjects had dyspepsia (20 had ulcerlike dyspepsia), 50 had IBS (19 had diarrhea-predominant IBS), and 15 met criteria for both dyspepsia and IBS; 78 were asymptomatic healthy controls. The overall prevalence of positive TTg serology was 4% (95% confidence interval [CI], 1.5%-8.5%). The number of subjects who were seropositive for TTg was 2 of 34 (5.9%) with dyspepsia (95% CI, 0.7%-19.7%), 2 of 50 (4.0%) with IBS (95% CI, 0.5%-13.7%), and 2 of 78 (2.6%) of asymptomatic controls (95% CI, 03%-9.0%) (P = .64 IBS vs controls; P = .58 dyspepsia vs controls). No subjects had positive antiendomysial antibodies. CONCLUSION: In this community, celiac disease did not explain the presence of either IBS or dyspepsia.

Adult↗
PubMed2004

Enterochromaffin cells and 5-HT signaling in the pathophysiology of disorders of gastrointestinal function.

Disorders of gastrointestinal function are common and significantly reduce quality-of-life, as well as negatively impacting healthcare costs. Consequently, there is much interest in understanding the pathogenesis of these disorders. Increasing, albeit as yet limited, evidence has implicated alterations in 5-hydroxytryptamine (5-HT) release, and the subsequent interaction of 5-HT with specific 5-HT receptor subtypes, in the altered gut function of patients with irritable bowel syndrome (IBS) and other functional bowel diseases. Alterations to enterochromaffin cells and/or 5-HT signaling can result in gastrointestinal dysmotility, visceral hypersensitivity and secretomotor abnormalities in the gut. Evidence is beginning to link disturbed 5-HT physiology with the pathophysiology of diarrhea and constipation in IBS, and with slow-transit constipation. This review discusses the current evidence on the pathobiology of these systems.

Constipation↗
PubMed2004

Management of chronic constipation.

Constipation is a common problem in the United States. Although most individuals do not seek health care for its symptoms, there are still more than 2 million visits to physicians annually for treatment. In this article, the author presents an overview of current diagnostic tools and treatment options for chronic constipation.

Cathartics↗
PubMed2004

Definitions, epidemiology, and impact of chronic constipation.

Constipation, however it is defined, is a common problem in the community. The exact prevalence of constipation depends on the definition used; prevalence estimates range from 2% to 28%. The prevalence of constipation has been stable because the onset and disappearance rates over time are similar, but accurate data on the incidence of constipation are lacking. Approximately one third of those individuals with constipation seek health care; this is an expensive fraction due to investigational and medication costs. The evidence that life-style factors are causally linked to constipation is weak, although nonsteroidal anti-inflammatory drug use and the use of other constipation-inducing medications are important risk factors. Constipation is not of clinical importance until it causes physical risks or impairs quality of life. There is accumulating evidence that self-reported constipation and functional constipation as defined by the Rome Criteria lead to significant impairment of quality of life, with the implication that this is a serious condition in the majority of people afflicted. Constipation may have other serious consequences; an increased risk of colon cancer has been reported but could be explained by confounding. Although hemorrhoids have been attributed to constipation, this association has been questioned. The costs of testing in patients presenting with constipation has been conservatively estimated to be 6.9 billion dollars annually in the United States; treatment costs add substantially to the health care burden.

Chronic Disease↗
PubMed2003

Dyspepsia.

Explore the source record for details and available documents.

Abdominal Pain↗
PubMed2003

Can symptoms predict endoscopic findings in GERD?

BACKGROUND: It is difficult to decide which patients with reflux symptoms require endoscopy. The aim of this study was to develop a scoring system to predict esophageal findings at endoscopy. METHODS: A consecutive sample of 1011 adult patients scheduled for upper endoscopy were asked to complete a validated symptom questionnaire. The endoscopy reports were abstracted. Individual logistic regression models were developed to predict esophagitis, Barrett's esophagus (long and short segment) and esophageal stricture, including Schatzki's ring. RESULTS: Reflux esophagitis was independently associated with heartburn frequency (p<0.0001) but not severity or duration (p>0.05). Barrett's esophagus was associated with the duration of acid regurgitation (p<0.005) but not with frequency or severity (p>0.05). Strictures were associated with dysphagia severity (p<0.0001) and duration (p<0.0001) but not frequency (p>0.05). At a sensitivity of 80%, the models had a specificity of 49% for esophagitis, 57% for Barrett's esophagus, and 68% for strictures. At a specificity of 80%, the sensitivities were 51% for esophagitis, 62% for Barrett's esophagus and 71% for strictures. CONCLUSIONS: Endoscopic findings were associated with distinct attributes of reflux symptoms. Symptoms are only modestly predictive of findings at endoscopy.

Barrett Esophagus↗
PubMed2003

Relationship between abdominal pain subgroups in the community and psychiatric diagnosis and personality. A birth cohort study.

INTRODUCTION: It is unclear if there is a causal link between psychiatric disorders and unexplained chronic gastrointestinal (GI) symptomatology. The role of personality is also in dispute. We aimed to assess the association of these factors with functional GI symptoms in a birth cohort study. METHODS: The Dunedin birth cohort is well characterised and has been followed-up prospectively to age 26 (n=980). Measured were upper and lower GI symptoms over the prior year at age 26 using a validated questionnaire, psychiatric diagnoses at ages 18 and 21 by standardised interview applying DSM-III-R criteria, and personality at age 18 using the Multidimensional Personality Questionnaire (MPQ). Natural symptom groupings were identified using factor analysis and k-means clustering. The association of these clusters and psychiatric diagnoses or personality was assessed by logistic regression. RESULTS: The k-means analysis produced a six-cluster solution, which was made up of a health group, and five "disease" clusters defined by higher than average scores on a single symptom. A diagnosis of depression at age 18 or 21 years was associated with increases in the odds of 1.69 (95% CI: 1.27-2.25) for all GI, of 2.16 (95% CI: 1.12-4.16) for dysmotility and of 2.07 (95% CI: 1.13-3.80) for constipation, but not with the other clusters. Similar results were observed with respect to anxiety disorders for the odds of GI overall (OR=1.42, 95% CI: 1.01-1.99) and constipation (OR=2.11, 95% CI: 1.17-3.79). The personality subscales were not strongly linked; membership of "any" diseased cluster was associated with a reduced odds of being in the fourth quartile for the well-being scale (OR=0.64, 95% CI: 0.46-0.88) but increased odds of being in the fourth quartile for the social potency scale (OR=1.64, 95% CI: 1.18-2.28). CONCLUSIONS: In a young adult community sample, unexplained GI symptoms appear to be linked to psychiatric disorders but personality differences were minimal.

Abdominal Pain↗