Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use, health-related quality of life, safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP. METHODS: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1 mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS). RESULTS: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p = .0181) or for IBS-D (p = .0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported. CONCLUSIONS: Alosetron 1 mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.

Adderall induced acute liver injury: a rare case and review of the literature.

Adderall (dextroamphetamine/amphetamine) is a widely prescribed medicine for the treatment of attention-deficit/hyperactivity disorder (ADHD) and is considered safe with due precautions. Use of prescribed Adderall without intention to overdose as a cause of acute liver injury is extremely rare, and to our knowledge no cases have been reported in the English literature. Amphetamine is an ingredient of recreational drugs such as Ecstacy and is known to cause hepatotoxicity. We describe here the case of a 55-year-old woman who developed acute liver failure during the treatment of ADHD with Adderall. She presented to the emergency room with worsening abdominal pain, malaise, and jaundice requiring hospitalization. She had a past history of partial hepatic resection secondary to metastasis from colon cancer which was under remission at the time of presentation. She recovered after intensive monitoring and conservative management. Adderall should be used carefully in individuals with underlying liver conditions.

A prospective study evaluating emotional disturbance in subjects undergoing defecating proctography.

AIM: To investigate the prevalence of psychiatric illness in association with functional gastrointestinal disorders using defecating proctography (DP) and validated questionnaires. METHODS: We prospectively evaluated 45 subjects referred for DP using hospital anxiety and depression scale (HADS), state trait anxiety inventory (STAI), patient health questionnaire 15-item somatic symptom severity scale (PHQ-15), validated questionnaires for sexual or physical abuse; post-traumatic stress disorder questionnaire (PTSD) and ROME-III questionnaires for gastrointestinal complaints. DP results were considered negative if levator ani function was normal, rectoceles (if any) were < 4 cm and there was no evidence of intussusception, rectal prolapse, or other anatomic abnormality demonstrated. Subjects were subsequently divided into those with structural defects seen on DP (DP positive group) and those with a normal defecography study (DP negative group). RESULTS: Forty five subjects were included in the study of which 20 subjects were classified as DP negative (44.4%). There was a striking prevalence of a history of sexual abuse in DP negative group compared to the DP positive group (n = 9, 5 respectively; P = 0.036). Further, subjects in the DP negative group scored significantly higher on the HADS anxiety (6.60 ± 1.00 vs 4.72 ± 0.40, P = 0.04) and depression scales (5.72 ± 1.00 vs 3.25 ± 0.46, P = 0.01). This correlated well with significantly higher scores on the STAI state anxiety scale (42.75 ± 3.16 vs 35.6 ± 2.00, P = 0.027), PHQ-15 questionnaire (13.15 ± 0.82 vs 10.76 ± 0.97, P = 0.038) and prevalence of PTSD (20% vs 4%, P = 0.045) among DP negative subjects. There was no difference between the groups in terms of STAI trait anxiety. CONCLUSION: The findings of this prospective study demonstrate a significantly high degree of psychiatric ailments in patients with negative findings on DP who should be appropriately screened for a history of sexual abuse and symptoms of psychosocial distress.

Targeted therapies for diarrhea-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT(3) receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT(3) receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.

What factors are associated with the difficult-to-sedate endoscopy patient?

BACKGROUND: Difficult sedation during endoscopy results in inadequate examinations and aborted procedures. We hypothesized that gender, alcohol abuse, physical/sexual abuse, and anxiety are predictors of difficult-to-sedate endoscopy patients. METHODS: This is a prospective cohort study. At the time of enrollment, subjects completed the following three validated questionnaires: state-trait anxiety inventory, self-report version of alcohol use disorder inventory, and Drossman questionnaire for physical/sexual abuse. Conscious sedation was administered for the endoscopic procedures at the discretion of the endoscopist and was graded in accordance with the Richmond agitation sedation scale (RASS). Subjects' perceptions of sedation were documented on a four-point Likert scale 24 h after their procedure. RESULTS: One-hundred and forty-three (79 %) of the 180 subjects enrolled completed the study. On the basis of the RASS score, 56 (39 %) subjects were found to be difficult to sedate of which only five were dissatisfied with their sedation experience. State (n = 39; p = 0.003) and trait (n = 41; p = 0.008) anxiety and chronic psychotropic use (p = 0.040) were associated with difficult sedation. No association was found between difficult sedation and gender (p = 0.77), alcohol abuse (p = 0.11), sexual abuse (p = 0.15), physical abuse (p = 0.72), chronic opioid use (p = 0.16), or benzodiazepines (BDZ) use (p = 0.10). CONCLUSION: Pre-procedural state or trait anxiety is associated with difficult sedation during endoscopy. In this study neither alcohol abuse nor chronic opiate/BDZ use was associated with difficult sedation.

Diagnostic approach to chronic constipation in adults.

Constipation is traditionally defined as three or fewer bowel movements per week. Risk factors for constipation include female sex, older age, inactivity, low caloric intake, low-fiber diet, low income, low educational level, and taking a large number of medications. Chronic constipation is classified as functional (primary) or secondary. Functional constipation can be divided into normal transit, slow transit, or outlet constipation. Possible causes of secondary chronic constipation include medication use, as well as medical conditions, such as hypothyroidism or irritable bowel syndrome. Frail older patients may present with nonspecific symptoms of constipation, such as delirium, anorexia, and functional decline. The evaluation of constipation includes a history and physical examination to rule out alarm signs and symptoms. These include evidence of bleeding, unintended weight loss, iron deficiency anemia, acute onset constipation in older patients, and rectal prolapse. Patients with one or more alarm signs or symptoms require prompt evaluation. Referral to a subspecialist for additional evaluation and diagnostic testing may be warranted.

Hepatic failure and death due to new onset T cell lymphoma.

INTRODUCTION: Liver involvement is commonly seen in disseminated T cell lymphoma; however, it is rarely the presenting organ. Here, we describe a case of T cell lymphoma presenting as acute hepatobiliary disease leading to hepatic failure and death. DISCUSSION: Forty-seven-year-old male with history of cirrhosis (etiology undetermined), diabetes mellitus, and pancytopenia was admitted to ICU for hypotension and failure to thrive. He had icterus, minimal ascitis, and hepatosplenomegaly on physical examination. No lymphadenopathy was noted. Laboratory workup on admission showed elevated total bilirubin (10.1 mg/dl) and liver enzymes. Serology for acute viral hepatitis, human immunodeficiency virus, Epstein-Barr virus, and autoimmune hepatitis was negative. CT abdomen showed cirrhotic liver with heterogeneous arterial enhancement of the liver without definite mass lesions. Hospital course was complicated by progressively worsening hypotension, respiratory failure, profound acidosis, disseminated intravascular coagulation, and multi-organ system failure leading to death on hospital day 12. Autopsy of the liver showed cirrhotic changes with infiltration with atypical small lymphocytes confined to septa which were CD3 and CD5 positive (CD4 weakly positive, CD8, CD20, CD57, CD56, CD30, Alk-1, granzyme B, TIA1, and S100 negative). Unusual clinical/histological features include (1) initial clinical presentation of hepatic dysfunction without obvious physical signs of lymphoma, (2) negative workup for viral, toxic, autoimmune, and metabolic liver disease, (3) involvement of the entire liver, observed as heterogeneous enhancement of liver without any focal mass lesion as seen on CT scan, (4) an aggressive nature of disease, and (5) autopsy of liver with T cell infiltration confined to septa. Initial diagnosis was challenging due to unusual clinical presentation suggesting inflammatory hepatobiliary disease and the absence of enlarged lymph nodes. CONCLUSION: In conclusion, early suspicion of this aggressive lymphoma is important and should be considered in the evaluation of a patient whose course is atypical for hepatitis. Even in the absence of a mass lesion or lymphadenopathy, hepatosplenic T cell lymphoma should be included in the differential diagnosis of acute hepatic dysfunction in a patient who has no evidence of viral, toxic, autoimmune, or metabolic liver disease.

Carcinosarcoma of the colon: a rare cause of colovesical fistula.

Carcinosarcomas are relatively rare tumors composed of both carcinomatous and sarcomatous components. The most common sites involved by this tumor are the head and neck, respiratory tract, uterus, ovaries, and fallopian tubes. Within the gastrointestinal tract this tumor most often occurs in the esophagus, followed by the stomach. Carcinosarcomas are very aggressive tumors associated with a poor prognosis. The first case of carcinosarcoma of the colon was reported in 1986. The case reported here is the only one involving an associated colovesical fistula.

Pancreatic plasmacytoma presenting as variceal hemorrhage: life threatening complication of a rare entity.

CONTEXT: Pancreatic plasmacytoma is a rare entity and presents with features of mass lesion of pancreas. CASE REPORT: We present an interesting case of pancreatic plasmacytoma with life threatening gastrointestinal bleeding secondary to isolated gastric varices. CONCLUSION: This case highlights the importance of considering it in differential diagnosis of patients with anemia, recurrent pancreatitis or jaundice and isolated gastric varices, prompting a CT scan to evaluate for any pancreatic mass lesions.

Isolated tuberculosis of the pancreas: a case report.

CONTEXT: Pancreatic tuberculosis is a rare entity. Only a few cases have been reported in the medical literature. We hereby describe a case of pancreatic tuberculosis in an immunocompromized individual. CASE REPORT: A fifty-year-old African-American gentleman with history of HIV non-compliant on anti-retroviral therapy presented with epigastric pain for five weeks duration. CT scan of abdomen showed large necrotic node on the posterior aspect of the head of pancreas and multiple cystic masses adjacent to the pancreas. Acid fast bacilli were found on staining of CT guided biopsy of the node. Cultures grew Mycobacterium tuberculosis. Anti-tubercular therapy was initiated and resulted in gradual resolution of symptoms. CONCLUSION: Pancreatic tuberculosis is rare and is frequently confused with pancreatic cancer on clinical presentation as well as on imaging studies. Since it is a curable disease, accurate diagnosis is paramount CT or ultrasound guided biopsy is cornerstone of diagnosis. Endoscopic ultrasound is now increasingly being used for obtaining tissue for diagnosis. Anti-tubercular therapy is curative in majority of the cases.

Fecal incontinence in an inpatient population: a not uncommon finding.

The prevalence of fecal incontinence (FI) in hospitalized patients was determined, as well as the frequency with which physicians query about FI. Using a standardized questionnaire, subjects admitted to general medicine services at three university hospitals were questioned about FI. Investigators also reviewed the subjects' charts to determine if presence or absence of FI was documented. One hundred ninety-nine patients were enrolled, and 46% (92/199) reported ongoing FI. Advanced age, looser stools, symptoms of fecal urgency, urinary incontinence, and history of forceps delivery were found to be potential predictors of FI. Only 6% (6/92) with FI had documentation of FI in the medical chart and only 3% (6/199) of the entire sample were queried about FI. Fecal incontinence is an extremely common condition in hospitalized patients. Physician history-taking is severely deficient in this area. Methods to improve FI detection in the hospitalized patient population need to be developed.

Cyclic vomiting and compulsive bathing with chronic cannabis abuse.

Cannabis is commonly recognized for its antiemetic properties. However, chronic cannabis use can lead to paroxysmal vomiting. In some patients this vomiting can take on a pattern identical to cyclic vomiting syndrome. Interestingly cyclic vomiting syndrome has been associated with compulsive bathing which patients report can relieve their intense feelings of nausea and lessen their vomiting intensity. We report a case of a patient with chronic cannabis use who developed symptoms similar to cyclic vomiting syndrome who also engaged in compulsive bathing behavior as observed by members of the medical and nursing staff. The patient reported that frequent hot showers would prevent him from vomiting and also relieve his concomitant abdominal pain. Previous hospitalizations at our hospital for the same complaint also noted similar showering behavior. During the hospital stay, the patient agreed to engage in a outpatient drug rehabilitation program which he subsequently completed. Abstinence from cannabis use caused the patients vomiting symptoms and abdominal pain to disappear completely. Likewise, his compulsive showering behavior also ceased. Other investigators have reported similar findings in patients with cyclic vomiting syndrome who initially used cannabis to treat their vomiting episodes but subsequently found that it contributed to their vomiting. Our patient has lead us to conclude that in patients seen for chronic severe vomiting and abdominal pain which has no obvious structural or chemical etiology and which is accompanied by compulsive showering and/or bathing behavior a diagnosis of cyclic vomiting syndrome with concomitant cannabis abuse needs to be considered.

Ischemic duodenal ulcer, an unusual presentation of sickle cell disease.

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.