Biomedical subjects
Publications and source records attributed to Nicholas J Talley.
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.
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.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
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.
The lack of validated outcome measures is a key limitation for the evaluation of drug efficacy in the treatment of irritable bowel syndrome (IBS). In clinical trials with tegaserod, the Subject's Global Assessment (SGA) of Relief (a global measure that includes overall wellbeing, abdominal pain/discomfort, and bowel function) was used to identify responders. A total of 1680 patients with IBS with constipation were included in two clinical studies comparing tegaserod with placebo. The SGA of Relief was obtained weekly by a single, self-administered question with five possible answers. Responders for the SGA of Relief reported statistically significant (P<.001) and clinically relevant improvements in multiple IBS-related symptoms compared with nonresponders. Response was also associated with a significant improvement in quality of life. The SGA of Relief is reliable as a new outcome measure for assessing response to therapy in IBS patients and has demonstrated responsiveness and reproducibility.
The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents relieve the symptoms of IBS; constipation probably improves. Anticholinergic and antispasmodic agents are of questionable benefit in IBS despite positive meta-analyses of poor quality trials. A meta-analysis concluded that the tricyclic antidepressants were superior to placebo in IBS, although the individual trial results were variable. Selective serotonin reuptake inhibitors are of uncertain benefit. Laxatives are used for constipation but probably poorly control the IBS symptom complex. Loperamide is superior to placebo in improvement of diarrhoea but not abdominal pain in IBS. Tegaserod is a well- tolerated aminoguanidine indole derivative of serotonin that is a partial 5HT4-receptor agonist with prokinetic properties; a therapeutic gain over placebo of 5% to 15% has been observed in constipation-predominant IBS in females. Alosetron is a 5HT3-receptor antagonist that is efficacious in females with diarrhoea-predominant IBS, with a 12% to 17% therapeutic gain; the risk of ischaemic colitis is 1 in 350, with very severe constipation occurring in about 1 in 1000. Optimizing study design remains a challenge in IBS. New visceral analgesic and motility modifying agents, as well as anti-inflammatory agents are in trials, and hopefully additional efficacious therapeutic options for patients with IBS will soon emerge.
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BACKGROUND: Disturbed bowel habit, diarrhoea or constipation is a key manifestation of irritable bowel syndrome (IBS). In some patients, diarrhoea and constipation alternate, giving rise to the so-called alternating subtype. AIMS: To assess IBS subtype breakdown (constipation (C-IBS), diarrhoea (D-IBS) or alternating (A-IBS)) according to the Rome II criteria and patients' self-assessment, the predominance in the alternating subtype (i.e. constipation, diarrhoea or neither), and the medical and personal impact, including health-related quality of life (HRQoL), of the different IBS subtypes. SUBJECTS AND METHODS: Two thousand individuals selected randomly to represent the general population were classified as potential IBS subjects (n = 281) or as non-potential IBS subjects (n = 1719) according to a validated questionnaire. Bowel habit classification was determined using the Rome II IBS supportive symptoms. RESULTS: Among 201 subjects meeting the Rome I criteria, 15% presented with D-IBS, 44% presented with C-IBS, 19% presented with A-IBS, and 22% presented with normal bowel habit. Among the 63 subjects meeting the Rome II criteria, 23% presented with A-IBS. According to the subjects' self-assessment, of those meeting the Rome I criteria, 16% considered themselves to have D-IBS, 66% to have C-IBS and 18% to have A-IBS. In subjects meeting the Rome II criteria, 24% considered themselves to have A-IBS. Among those classified with A-IBS by the Rome II criteria, most considered themselves to be constipated. Regardless of the subtype self-classification, most subjects reported a normal frequency of bowel movements. Clinical manifestations in A-IBS were very similar to those of C-IBS but with the added presence of defecatory urgency. Abdominal discomfort/pain and frequency of visits to physicians were greater in the A-IBS subtype than in the other two IBS subtypes. HRQoL was affected similarly in all IBS subtypes. CONCLUSIONS: Approximately one-quarter of subjects with IBS belong to the A-IBS subtype by the Rome II criteria, although the majority consider themselves to be constipated; indeed, clinical manifestations are more akin to the C-IBS subtype than to the D-IBS subtype. Abdominal discomfort/pain and frequency of visits to physicians are greater in the A-IBS subtype than in the other two IBS subtypes, while HRQoL is impaired similarly.
OBJECTIVES: GI symptoms form distinct symptom clusters in community samples when factor and cluster analysis is applied. However, this has not been studied in diabetic populations, despite clear evidence that GI complaints are common in patients with diabetes mellitus (DM). This study aimed to describe clustering of GI symptoms among individuals with and without diabetes mellitus, and to describe associations of symptom clustering in diabetes mellitus, with self-reported glucose control and treatment. METHODS: A large population survey (n = 15,000) was used to identify a cohort with diabetes mellitus. Items assessing therapy and quality of glycemic control were included, as were those assessing 16 common GI symptoms. Latent GI symptom factors were extracted by factor analysis and used in a k-means cluster analysis. The latter serves to group individuals according to commonalities in symptom profiles. The association of cluster group membership to glycemic control and diabetic treatment was described by logistic regression. RESULTS: Factor analysis identified four latent symptom factors, which accounted for 69.3% of the total variance. These were labeled Upper GI/Dysmotility, Diarrhea, Constipation, and Vomiting/Nausea. The k-means analysis produced a five-cluster solution, which included a "health" group and four "diseased" groups, each identified by a predominant symptom: Upper GI/Dysmotility symptoms, Nausea/Vomiting, Diarrhea, and Constipation. After adjustment for age and gender, poor glycemic control predicted membership in all disease clusters, when compared separately with the health group. Oral hypoglycemic drugs predicted membership in the Nausea/Vomiting cluster (OR = 5.13) when used alone, and membership in the Nausea/Vomiting (OR = 10.12) and Upper GI/Dysmotility cluster (OR = 10.12) when used in combination with insulin. CONCLUSION: Diabetes can be grouped according to common GI symptoms. Glycemic control and treatment for DM predict membership of symptom clusters.
The treatment of diabetic gastropathy, which here refers to a clinical syndrome of upper GI tract symptoms suggestive of an upper motility disturbance in diabetes whether or not there is delayed gastric emptying, remains suboptimal. New prokinetics and other motility-modifying agents may prove useful, but adequate clinical trials will be required to establish a role for them. However, diabetic gastropathy seems to represent a heterogenous syndrome in terms of pathophysiology, which potentially complicates the design of new randomized, controlled trials. This review aims to provide guidelines for future trials in this field. The evidence that delayed gastric emptying is a cause of symptoms in diabetic gastropathy is critically evaluated. The trial evidence supporting the short and long term efficacy of prokinetics is reviewed. Based on the available literature, it is concluded that improvement in gastric emptying does not equate with symptom relief in diabetic gastropathy. It is suggested that although gastric emptying should still be measured in clinical trials, it should not represent the primary outcome. The withdrawal treatment design applied in studies of diabetic gastropathy might be suboptimal. Double blind, parallel group studies remain the trial design of choice, but incorporation of validated outcome assessments and measurement of potential confounders of treatment response need attention in future trials.
The management of the irritable bowel syndrome (IBS) remains unsatisfactory. For abdominal pain, antispasmodics are, at best, of only modest efficacy. Tricyclic antidepressants in low dose are useful (with the number needed to treat being three), but side effects and patient concerns regarding use of a centrally acting agent for depression remain limitations. Selective serotonin reuptake inhibitors are of uncertain efficacy in IBS. Opioid agonists, especially loperamide, are useful for diarrhea but not for pain in IBS; rebound constipation also remains a problem. Bile salt sequestering agents are not of established value in IBS but seem to be useful clinically in a small group of IBS patients with diarrhea. Aloestron, a 5HT(3) antagonist, should be reserved, if available, for women with severe diarrhea predominant IBS who have failed to respond to conventional therapy, and started at a low dose. Fiber and bulking agents may help constipation in some trials, but the evidence that they are efficacious in IBS is equivocal; they are frequently prescribed as first-line drugs for IBS regardless of the primary bowel disturbance but often increase bloating, gas, and pain. Laxatives are not of established value in IBS but are often taken by patients with constipation predominant IBS. Tegaserod, a partial 5HT(4) agonist, is now available in the United States and other countries for use in women with IBS whose primary bowel symptom is constipation; its efficacy in men and in those with alternating bowel habits is unknown. Probiotics are of uncertain efficacy. Chinese herbal medicine data are insufficient. Other new drugs in development include the cholecystokinin antagonists and novel visceral analgesics. Both current and potential therapies for IBS are reviewed in this article.
OBJECTIVE: Little is known about the natural history of functional GI symptoms, including what factors influence GI symptom patterns and health care seeking for them over the long term. We aimed to determine whether psychological factors play a role in the development and long-term course of these symptoms. METHODS: A random sample of community subjects (n = 361) who reported having unexplained abdominal pain for > or =1 month in a previous population survey were included in the study. Controls (n = 120) were defined as not having abdominal pain for > or =1 month from this initial survey. Subjects were prospectively followed up via a questionnaire every 4 months over a 12-month period. The questionnaire asked about the presence of GI symptoms over the past week and psychological distress over the past 3 wk (psychological caseness being defined as a score of > or=2 of 12 on the General Health Questionnaire). The number of visits made to a physician or medical specialist over the past 4 months was evaluated. RESULTS: GI symptoms were common among community controls and subjects with abdominal pain. Similar onset and disappearance rates were observed for the majority of GI symptom categories, accounting for the stability of the prevalence rates over a 1-yr period. Changes in a state measure of psychological distress were not significantly associated with changes in GI symptom status between the 4- and 8-month (r = 0.14, p = 0.08) and 8- and 12-month (r = 0.02, p = 0.77) follow-ups. Baseline psychological distress, however, was an independent predictor of having persistent GI symptoms, including abdominal pain, bloating, and constipation, and frequently seeking health care for GI symptoms over 1 yr. CONCLUSIONS: Psychological distress levels do not seem to be important in explaining GI symptom change over a 1-yr period. Psychological distress, however, is linked to having persistent GI symptoms and frequently seeking health care for them over time. Clinicians should consider psychological factors in the treatment of this subset of irritable bowel syndrome patients.
OBJECTIVES: Many factors have been associated with the occurrence of constipation, particularly poor diet and lack of exercise. However, the importance of medications and general medical illnesses in constipation remains more uncertain. We aimed to identify risk factors for constipation from among patient clinical, therapeutic, and demographic characteristics. METHODS: The sample was composed of patients explicitly diagnosed with chronic constipation (n = 7251), those diagnosed with constipation of unspecified chronicity (n = 6441), and a sample of controls (n = 7103). All were drawn from a general practice research database representing more than 10 yr of data collection. RESULTS: A large number of clinical and therapeutic factors were independently associated with chronic constipation over and above age and gender. Primary neurological diseases were strongly associated with constipation but accounted for few cases. Opioids (OR = 1.6, population attributable risk [PAR] = 2.6%), diuretics (OR = 1.7, PAR = 5.6%), antidepressants (OR = 1.9, PAR = 8.2%), antihistamines (OR = 1.8, PAR = 9.2%), antispasmodics (OR = 3.3, PAR = 11.6%), anticonvulsants (OR = 2.8, PAR = 2.5%) and aluminum antacids (OR = 1.7, PAR = 3.0%) were associated with the highest risk among medications. CONCLUSIONS: Constipation is common in primary care, and multiple medications seem to be an important contributing factor. Concurrent diseases are also associated but at most are only contributing to a minority of cases.
OBJECTIVES: Distinguishing between irritable bowel syndrome (IBS) and functional dyspepsia can be challenging because of the variations in symptom patterns, which commonly overlap. However, the overlap is poorly quantified, and it is equally uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed to determine and to compare the distribution of GI symptoms, both, upper and lower, among IBS-C and IBS-D patients. METHODS: A total of 121 consecutive patients presenting with a diagnosis of IBS were grouped according to primary bowel symptoms as IBS-C (58 women and 18 men, mean age 47 +/- 17 yr) or IBS-D (26 women and 19 men, mean age 47 +/- 15 yr). The Hopkins Bowel Symptom Questionnaire, which includes a brief Quality of Life assessment, and the Hopkins Symptom Checklist 90-Revised were completed by all patients at intake. RESULTS: IBS-C patients reported significantly more overall GI symptoms when compared to patients with IBS-D (6.67 vs 4.62, respectively, p<0.001). Abdominal pain patterns differed in patients with IBS-C versus IBS-D (lower abdominal pain: 40.8% vs 24.4% p=0.05 and upper abdominal pain: 36.8% vs 24.4%, respectively). Bloating was substantially more common in IBS-C patients (75%) than in IBS-D (40.9%). There were no significant differences in personality subscales by IBS subgroup; however, somatization was positively associated with multiple symptom reports and was negatively correlated with quality of life. CONCLUSIONS: Upper GI symptoms consistent with functional dyspepsia were more frequent in IBS-C. Although there was considerable overlap of upper and lower GI symptoms in patients with IBS-C and IBS-D, the former had more frequent lower abdominal pain and bloating.