Irritable bowel syndrome: more than abdominal pain and bowel habit abnormalities.

BACKGROUND & AIMS: Although irritable bowel syndrome (IBS) can be defined using few symptoms, principal symptoms alone may be inadequate in monitoring disorder severity. Secondary analysis of a published data set was performed to determine if more inclusive symptom measures would better reflect the burden of this disorder. METHODS: From a prospective naturalistic study of 213 patients meeting Rome II criteria, all the data were used from daily questionnaires recorded for 4 weeks, and repeated again after an interval of 4 weeks. The total number of 11 symptoms and intensity grading score of each symptom were analyzed alongside individual symptom intensities by principal component analysis. RESULTS: The trend accounting for the most variance was explained by the intensity of all symptoms together. The second largest trend was explained by differences between IBS bowel habits (constipation and diarrhea). The 2 constipation and 4 diarrhea symptoms closely correlated within each group, but the category of other symptoms were not correlated directly with either, and represent a separate dimension. Other symptoms (pain/discomfort, abdominal uneasiness, flatulence/distension, incomplete evacuation, pain or burning in the stomach) correlated more highly with disease intensity than either constipation or diarrhea symptoms. The sum of all symptoms and their intensity was consistent over each week, although the relative intensity of individual symptoms was more variable. Investigator measures of disease intensity underestimated that reported by patients. CONCLUSIONS: Non-bowel habit symptoms include more than abdominal pain and discomfort, and contribute to the largest component of the total symptom burden. Thus, more than bowel habits and abdominal pain drive IBS symptom severity.

Recent advances in understanding depression in adults with diabetes.

The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance.

Gastric residual volume and aspiration in critically ill patients receiving gastric feedings.

BACKGROUND: The helpfulness of bedside assessment of gastric residual volume in the prediction of aspiration has been questioned, as has the volume that signals increased risk of aspiration. OBJECTIVE: To describe the association between gastric residual volumes and aspiration of gastric contents. METHODS: In a prospective study of 206 critically ill patients receiving gastric tube feedings for 3 consecutive days, gastric residual volumes were measured with 60-mL syringes every 4 hours. Measured volumes were categorized into 3 overlapping groups: at least 150 mL, at least 200 mL, and at least 250 mL. Patients were categorized as frequent aspirators if 40% or more of their tracheal secretions were positive for pepsin and as infrequent aspirators if less than 40% of their secretions were positive for pepsin. Gastric residual volumes were compared between the 2 aspiration groups. RESULTS: Approximately 39% of the 206 patients had 1 or more gastric residual volumes of at least 150 mL, 27% had 1 or more volumes of at least 200 mL, and 17% had 1 or more volumes of at least 250 mL. Large-bore tubes identified most of the high volumes. Eighty-nine patients were frequent aspirators. Volumes less than 150 mL were common in both aspiration groups. However, the frequent aspirators had a significantly greater frequency of 2 or more volumes of at least 200 mL and 1 or more volumes of at least 250 mL. CONCLUSIONS: No consistent relationship was found between aspiration and gastric residual volumes. Although aspiration occurs without high gastric residual volumes, it occurs significantly more often when volumes are high.

Development of esophageal peristalsis in preterm and term neonates.

BACKGROUND & AIMS: High-resolution manometry demonstrates a chain of 3 sequential pressure segments that represent esophageal peristalsis in children and adults. We performed high-resolution manometry in preterm and term neonates to determine the ontogenesis of esophageal motility with regard to this segmental architecture. METHODS: Sixteen preterm (gestational age 32.9 +/- 2.6 weeks at examination) and 14 term neonates (38.9 +/- 1.6 weeks) underwent manometry with a 9-lumen perfused catheter having recording side holes spaced at 1-cm intervals. Pressure responses to swallows were evaluated for the presence of peristaltic segments on isobaric contour maps by an investigator who was blinded to gestational age. RESULTS: The second segment was well developed in > or =50% of swallows in all preterm and term neonates. In contrast, the first segment was present in > or =50% of swallows in only 2 preterm neonates (12.5%) and 8 term neonates (57.1%; P < .05 for each compared with second segment) with identical findings for the third segment (12.5% preterm and 57.1% term neonates; P < .05 for each). Completed peristalses with intact segmental contraction sequences throughout the esophageal body were present in 26% +/- 6% of swallows in preterm neonates vs 55% +/- 9% in term neonates (P = .01). CONCLUSIONS: The second pressure segment in the midesophagus (proximal smooth-muscle region) is well developed before term. Presence of other segments significantly improves at term, but peristalsis remains incomplete in nearly half of swallows. Control mechanisms for both striated- and smooth-muscle esophageal regions are incompletely developed in neonates, the outcome of which could participate in infant reflux disease.

Recent advances in understanding depression in adults with diabetes.

The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance.

Efficacy of sertraline in prevention of depression recurrence in older versus younger adults with diabetes.

OBJECTIVE: Sertraline maintenance therapy effectively delays recurrence of major depressive disorder in adult diabetic patients when data are examined across all age-groups. A secondary analysis was performed to assess this effect in younger and older subsets of patients. RESEARCH DESIGN AND METHODS: Younger (aged <55 years, n = 85) and older (aged > or =55 years, n = 67) subsets were identified from a multicenter, double-blind, placebo-controlled, maintenance treatment trial of sertraline in diabetic participants who achieved depression recovery with open-label sertraline treatment. Cox proportional hazards models were used to determine differences in time to depression recurrence between treatment arms (sertraline or placebo) for each age subset and between age subsets for each treatment. RESULTS: In younger subjects, sertraline conferred significantly greater prophylaxis against depression recurrence than placebo (hazard ratio 0.37 [95% CI 0.20-0.71]; P = 0.003). Benefits of sertraline maintenance therapy were lost in older participants (0.94 [0.39-2.29]; P = 0.89). There was no difference in time to recurrence for sertraline-treated subjects between age subsets (P = 0.65), but older subjects had a significantly longer time to recurrence on placebo than younger subjects (P = 0.03). CONCLUSIONS: While sertraline significantly increased the time to depression recurrence in the younger diabetic participants, there was no treatment effect in those aged > or =55 years because of a high placebo response rate. Further research is necessary to determine the mechanisms responsible for this effect and whether depression maintenance strategies specific for older patients with diabetes should be developed.

Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion.

OBJECTIVE: Depression management in both short- and longer-term treatment studies has been associated with improvement in glycemic control. We used bupropion hydrochloride (Wellbutrin XL) to determine whether this improvement could be attributed to changes in anthropometrics or diabetes self-care. RESEARCH DESIGN AND METHODS: Ninety-three patients with type 2 diabetes and major depressive disorder (MDD) received bupropion hydrochloride in a two-phase, open-label treatment trial. Those who completed the acute phase (10 weeks; n = 75) and whose depression remitted (n = 63) continued bupropion at the remission dose and were followed in the maintenance phase (24 weeks) until attrition (n = 8) or relapse of MDD (n = 0). Self-report scales were used to measure depression symptom severity and diabetes self-care behaviors. Body composition and glycemic control were determined using dual-energy X-ray absorptiometry and serial determinations of A1C. RESULTS: BMI, total fat mass, and A1C decreased and composite diabetes self-care improved over the acute phase (-0.5 kg/m2, -0.7 kg, -0.5%, and +0.4, respectively, P < 0.01 for each), effects that persisted through the maintenance phase for BMI, A1C, and self-care (P < or = 0.01 for each). Reductions in BMI (B = 0.30, P = 0.01) and depression severity (B = 0.04, P = 0.046) independently predicted lower A1C after acute-phase treatment, whereas only reduction in depression severity (B = 0.08, P = 0.001) predicted A1C over the maintenance interval. CONCLUSIONS: In the short term, improvement in glycemic control during bupropion treatment is predicted independently by improvements in mood and body composition. Longer-term improvements in glycemic control are predicted primarily by sustained improvement in mood via mechanisms independent of anthropometric and self-care modifications.

Predictors of premature antidepressant discontinuation in functional gastrointestinal disorders.

OBJECTIVES: To identify factors responsible for premature antidepressant discontinuation that would assist in designing management strategies for patients with functional gastrointestinal disorders. Antidepressants are being used increasingly to manage patients with functional gastrointestinal disorders; poor patient adherence to treatment regimens, particularly in the period shortly after antidepressant initiation, is common and interferes with success. METHODS: Clinical records were reviewed from 172 outpatients who attended a university-based practice and who had been prescribed antidepressants to manage their functional gastrointestinal symptoms. Survival analysis methods were used to determine independent predictors of premature antidepressant discontinuation (within 6 months of initiation). Logistic regression analyses were used to see if the same predictors were responsible for side effects or poor treatment response. RESULTS: Premature antidepressant discontinuation occurred in 41 (23.8%) subjects. Somatization features (state or trait) and history of depression or an anxiety disorder were the most significant predictors of premature discontinuation (p < or = .01 for each). Advancing age and female sex also were independent predictors (p < .05 for each). Somatization features and psychiatric illness were each linked to poor treatment response, whereas somatization features most consistently were associated with antidepressant side effects. CONCLUSIONS: Failure to maintain treatment occurs in nearly a quarter of outpatients given antidepressants for functional gastrointestinal disorders. Somatization features and history of depression or anxiety most significantly interfered with treatment by predicting side effects, poor treatment response, and premature antidepressant discontinuation. Management algorithms should include specific strategies targeted at patients with these risk factors for poor treatment adherence.

Complications related to feeding tube placement.

PURPOSE OF REVIEW: Blind placement of a feeding tube can result in serious complications. Given the widespread use of tube feedings, even a small percentage of such problems can affect a significant number of people. The purpose of this review is to describe recent reports of feeding tube placement problems and to examine possible solutions. RECENT FINDINGS: Multiple case reports of complications of malpositioned feeding tubes continue to surface; most are due to inadvertent placement in the respiratory tract. A tube with feeding ports in the esophagus significantly increases risk for aspiration, as does the displacement of a small bowel tube into the stomach of a patient with significantly slowed gastric motility. Isolated reports of a nasally placed tube entering the brain following head injury continue to occur, as do reports of esophageal and gastric perforation in neonates. A recent study showed that malpositioned tubes are not routinely recorded in risk management databases; it further demonstrated that a comprehensive intervention to reduce complications from small-bore nasogastric feeding tubes was effective. SUMMARY: Complications related to malpositioned feeding tubes are usually preventable. Poor reporting of feeding tube placement errors hinders the adoption of effective protocols to prevent such errors.

High somatic symptom burdens and functional gastrointestinal disorders.

BACKGROUND & AIMS: Unexplained, multi-system somatic symptoms and syndromes, the hallmark features of somatization, are prevalent in patients with functional gastrointestinal disorders (FGIDs). We studied outpatients attending a gastroenterology clinic to see whether current somatic symptom burdens (a somatization state measure) or number of prior functional diagnoses (a somatization trait measure) could predict the presence of an FGID over structural gastrointestinal disease, and whether the predictive value was dependent on comorbid depression or anxiety disorders. METHODS: Clinical data from 327 consecutive new referrals to an outpatient gastroenterology practice were reviewed, 187 with an FGID and 140 with a structural illness. Somatization state and trait were measured by using self-reported current symptoms and functional diagnoses recorded in the medical history, respectively. Psychiatric comorbidity (depression or anxiety disorders) was extracted from chart review. RESULTS: FGID subjects endorsed more somatization state symptoms, had more somatization trait diagnoses, and had greater likelihood of psychiatric comorbidity (P < .001 for each). Logistic regression analysis adjusting for age and sex differences showed that each of these features independently predicted the likelihood of an FGID over structural disease (P < .05 for each). When high ratings on the somatization measures were present together with psychiatric comorbidity, the positive predictive value exceeded 0.95. CONCLUSIONS: Higher burdens of either current somatic symptoms or functional diagnoses in the medical history are strong predictors of an FGID in outpatients presenting with gastrointestinal complaints. The mechanism is not solely dependent on a relationship with affective disorders, which independently predicts FGID, at least in part, through another path.

Tricyclic antidepressants for chronic vomiting in diabetic patients.

Chronic vomiting in diabetic patients often is unresponsive to prokinetic agents and poorly explained by delayed gastric emptying or neuropathy. This retrospective study examines clinical response to tricyclic antidepressants, a treatment of reported benefit in nondiabetic patients with unexplained vomiting syndromes. Outcomes were studied in 24 diabetic outpatients who had been treated with tricyclic antidepressants specifically for nausea and vomiting after an unsatisfactory response to prokinetic therapy. Symptom patterns and treatment response were determined from chart review and telephone interview. Ten patients (42%) had recurrent, stereotypical vomiting episodes with symptom-free intervals suggesting cyclic vomiting syndrome; 14 (58%) had persistent symptoms. By chart review, at least moderate symptom response to tricyclic antidepressant treatment (median dosage, 50 mg/day) occurred in 88% of subjects, with complete or nearly complete resolution of symptoms in one-third. At follow-up interview, 77% self-reported at least moderate symptom improvement during therapy and 68% rated tricyclic antidepressants the most effective treatment received. Duration of diabetes, presence of neuropathy, and psychiatric status were not predictive of treatment outcome in multivariate analysis, but a cyclical symptom pattern attenuated antidepressant response (P< 0.05). In this retrospective review, the majority of diabetic patients with chronic vomiting and incomplete response to prokinetic therapy benefited from tricyclic antidepressants in low-dose, open-label regimens and rated them the most effective treatment received. This therapeutic option should be further studied in diabetic patients considering the morbidity of chronic vomiting in this population.

Zonisamide or levetiracetam for adults with cyclic vomiting syndrome: a case series.

BACKGROUND & AIMS: Management of cyclic vomiting syndrome in adults is limited by the small number of effective medications for maintenance therapy. The clinical response to treatment with 2 newer antiepileptic drugs was evaluated retrospectively to see whether they might have a prophylactic role in this syndrome. METHODS: Outpatient records from 20 adult patients with cyclic vomiting syndrome attending a university-based practice were reviewed. Each had received zonisamide (median dose, 400 mg/d) or levetiracetam (median dose, 1000 mg/d) because tricyclic antidepressants alone were unsatisfactory as maintenance medications. Outcome was graded from chart review and directed interview; characteristics of the vomiting episodes were compared before and after initiation of antiepileptic drug therapy. RESULTS: At least moderate clinical response was described by 15 (75.0%) subjects, and 4 of these (20.0% of the total) reported symptomatic remission during 9.5 +/- 1.8 months of follow-up. Rate of vomiting episodes decreased from 1.3 +/- 0.3 to 0.5 +/- 0.2 per month (P = .01). Tricyclic antidepressants were discontinued in 11 (61.1%) of the 18 subjects who were still taking the medications when antiepileptic drug therapy was initiated. Moderate or severe side effects were reported by 45.0%, but by switching drugs, intolerance to antiepileptic drug therapy occurred in only 1 subject. CONCLUSIONS: Newer antiepileptic drugs, specifically zonisamide and levetiracetam, appeared beneficial as maintenance medications for nearly three fourths of adults with cyclic vomiting syndrome in this uncontrolled clinical experience. Although side effects occur in a large proportion of subjects, newer antiepileptic drugs might offer an alternative for patients who fail conventional treatment.

Endoscopic removal of the wireless pH monitoring capsule in patients with severe discomfort.

BACKGROUND: Few patients have significant symptoms during wireless esophageal pH monitoring, and the capsule typically sloughs spontaneously. Severe discomfort during monitoring can occur that requires endoscopic dislodgement of the capsule. OBJECTIVE: To determine the frequency with which endoscopic capsule dislodgement is required and the outcomes of the intervention. DESIGN: Chart review. SETTING: University-based outpatient endoscopy facility. PATIENTS: A total of 452 consecutive patients undergoing wireless pH monitoring over a 3.5-year period. INTERVENTIONS: Endoscopic dislodgement of the capsule by using nudging with the endoscope tip and cold snare techniques. RESULTS: Eight subjects (1.8%) required endoscopic capsule dislodgement because of severe chest pain or odynophagia (n = 7) or severe foreign-body sensation (n = 1). Chest pain was the initial indication for pH monitoring in 5 (62.5%) of the subjects. Initial nudging with the endoscope tip successfully dislodged 2 capsules; continued nudging produced mucosal stripping in 3 subjects, which required hemostasis in 1. A cold snare was used successfully, without complication, to separate the capsule from stripped mucosa and as a primary removal method in the remainder of subjects. Capsule removal uniformly resulted in marked improvement of discomfort. CONCLUSIONS: Endoscopic removal of the capsule was required in <2% of subjects who underwent wireless pH monitoring. Separation of the capsule from the mucosa with a cold snare may be the preferred method of accomplishing uncomplicated removal.

Depression, anxiety, and nonalcoholic steatohepatitis.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a morbid liver disease with limited treatment. Depression and anxiety have been associated recently with insulin resistance and inflammatory states, factors that are relevant to the development of NASH. We hypothesized that depression and anxiety would be more prevalent in NASH patients and predict more severe histological findings on liver biopsy. METHODS: Histories of major depressive disorder (MDD) and generalized anxiety disorder (GAD) were determined using a structured interview and DSM-IV criteria in 36 NASH subjects and 36 matched controls without liver disease who had undergone cholecystectomy. Histological changes on liver biopsy in NASH subjects were age-adjusted and compared in subjects with and without psychiatric disorders. A multivariate model incorporating other potential risk factors for NASH (female sex, body mass index, waist-to-hip ratio, and presence of diabetes) was used to determine independent effects of MDD and GAD on severity of histological findings. RESULTS: NASH subjects had significantly increased lifetime rates of MDD (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.4-10.2; p = .018) and GAD (OR 5.0, 95% CI, 1.7-14.9; p = .005). The onset of psychiatric illness preceded diagnosis of liver disease by 18 to 20 years. Each psychiatric disorder was associated with more severe histological features (p < .05 for each), the effect of GAD on fibrosis stage persisting in the multivariate model. CONCLUSIONS: MDD and GAD are overrepresented in NASH subjects and are associated with more advanced liver histological abnormalities. Additional investigation will be required to determine if depression and anxiety affect the development or progression of NASH and serve as modifiable risk factors.

Functional esophageal disorders.

Functional esophageal disorders represent processes accompanied by typical esophageal symptoms (heartburn, chest pain, dysphagia, globus) that are not explained by structural disorders, histopathology-based motor disturbances, or gastroesophageal reflux disease. Gastroesophageal reflux disease is the preferred diagnosis when reflux esophagitis or excessive esophageal acid exposure is present or when symptoms are closely related to acid reflux events or respond to antireflux therapy. A singular, well-defined pathogenetic mechanism is unavailable for any of these disorders; combinations of sensory and motor abnormalities involving both central and peripheral neural dysfunction have been invoked for some. Treatments remain empirical, although the efficacy of several interventions has been established in the case of functional chest pain. Management approaches that modulate central symptom perception or amplification often are required once local provoking factors (eg, noxious esophageal stimuli) have been eliminated. Future research directions include further determination of fundamental mechanisms responsible for symptoms, development of novel management strategies, and definition of the most cost-effective diagnostic and treatment approaches.

Functional abdominal pain syndrome.

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogeneous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

CONTEXT: In patients with diabetes mellitus, depression is a prevalent and recurrent problem that adversely affects the medical prognosis. OBJECTIVE: To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes. DESIGN: A randomized, double-blind, placebo-controlled, maintenance treatment trial. Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline (n = 79) or placebo (n = 73) and were followed up for up to 52 weeks or until depression recurred. SETTING: Outpatient clinics at Washington University, St Louis, MO, the University of Washington, Seattle, and the University of Arizona, Tucson. PATIENTS: One hundred fifty-two patients with diabetes (mean age, 52.8 years; 59.9% female; 82.9% with type 2 diabetes) who recovered from major depression (43.3% of those initially assigned) during 16 weeks of open-label treatment with sertraline (mean dose, 117.9 mg/d). INTERVENTION: Sertraline continued at recovery dose or identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was length of time (measured as the number of days after randomization) to recurrence of major depression as defined in DSM-IV. The secondary outcome was glycemic control, which was assessed via serial determinations of glycosylated hemoglobin levels. RESULTS: Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo (hazard ratio = 0.51; 95% confidence interval, 0.31-0.85; P = .02). Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline. Glycosylated hemoglobin levels decreased during the open treatment phase (mean +/- SD glycosylated hemoglobin level reduction, -0.4% +/- 1.4%; P = .002). Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance (P = .002) and did not differ between treatment groups (P = .90). CONCLUSIONS: In patients with diabetes, maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression. Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year.