Tenapanor for constipation-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is among the most common gastrointestinal disorders encountered in primary and secondary care and is associated with impaired quality of life, increased healthcare utilization, and significant costs to patients and society. There are three primary phenotypes of IBS, categorized according to stool pattern: IBS with diarrhea (IBS-D), IBS with constipation (IBS-C) and IBS with a mixed bowel pattern (IBS-M). The treatment approach to all forms of IBS is typically hierarchal, with initial therapies consisting of dietary and lifestyle modifications. When these interventions are impractical or ineffective, pharmacotherapy with over-the-counter and prescription therapies is often employed. Tenapanor is a locally acting, minimally absorbed, selective small-molecule inhibitor of the intestinal sodium/hydrogen exchanger 3 (NHE3) that was approved in September 2019 by the U.S. Food and Drug Administration (FDA) for IBS-C. This agent works by increasing the sodium level in the intestinal lumen and promoting the efflux of fluid into the gut lumen to maintain osmotic balance in addition to having an antinociceptive effect. Tenapanor has been shown to improve bowel movement frequency/form and abdominal pain in patients with IBS-C. This article will elaborate on the clinical development program for tenapanor for this indication.

Online symptom checker diagnostic and triage accuracy for HIV and hepatitis C.

We sought to address the prior limitations of symptom checker accuracy by analysing the diagnostic and triage feasibility of online symptom checkers using a consecutive series of real-life emergency department (ED) patient encounters, and addressing a complex patient population - those with hepatitis C or HIV. We aimed to study the diagnostic and triage accuracy of these symptom checkers in relation to an emergency room physician-determined diagnosis. An ED retrospective analysis was performed on 8363 consecutive adult patients. Eligible patients included: 90 HIV, 67 hepatitis C, 11 both HIV and hepatitis C. Five online symptom checkers were utilised for diagnosis (Mayo Clinic, WebMD, Symptomate, Symcat, Isabel), three with triage capabilities. Symptom checker output was compared with ED physician-determined diagnosis data in regards to diagnostic accuracy and differential diagnosis listing, along with triage advice. All symptom checkers, whether for combined HIV and hepatitis C, HIV alone or hepatitis C alone had poor diagnostic accuracy in regards to Top1 (<20%), Top3 (<35%), Top10 (<40%), Listed at All (<45%). Significant variations existed for each individual symptom checker, as some appeared more accurate for listing the diagnosis in the top of the differential, vs. others more apt to list the diagnosis at all. In regards to ED triage data, a significantly higher percentage of hepatitis C patients (59.7%; 40/67) were found to have an initial diagnosis with emergent criteria than HIV patients (35.6%; 32/90). Symptom checker diagnostic capabilities are quite inferior to physician diagnostic capabilities. Complex patients such as those with HIV or hepatitis C may carry a more specific differential diagnosis, warranting symptom checkers to have diagnostic algorithms accounting for such complexity. Symptom checkers carry the potential for real-time epidemiologic monitoring of patient symptoms, as symptom entries and subsequent symptom checker diagnosis could allow health officials a means to track illnesses in specific patient populations and geographic regions. In order to do this, accurate and reliable symptom checkers are warranted.

Repeat Rifaximin for Irritable Bowel Syndrome: No Clinically Significant Changes in Stool Microbial Antibiotic Sensitivity.

BACKGROUND: Rifaximin has demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM: To determine the rifaximin repeat treatment effect on fecal bacterial antibiotic susceptibility. METHODS: Patients with IBS in Trial 3 (TARGET 3) study who responded to open-label rifaximin 550 mg three times daily for 2 weeks, with symptom recurrence within 18 weeks, were randomized to double-blind treatment: two 2-week repeat courses of rifaximin or placebo, separated by 10 weeks. Prospective stool sample collection occurred before and after open-label rifaximin, before and after the first repeat course, and at the end of the study. Susceptibility testing was performed with 11 antibiotics, including rifaximin and rifampin, using broth microdilution or agar dilution methods. RESULTS: Of 103 patients receiving open-label rifaximin, 73 received double-blind rifaximin (n = 37) or placebo (n = 36). A total of 1429 bacterial and yeast isolates were identified, of which Bacteroidaceae (36.7%) and Enterobacteriaceae (33.9%) were the most common. In the double-blind phase, Clostridium difficile was highly susceptible to rifaximin [minimum inhibitory concentration (MIC) range 0.008-1 µg/mL] and rifampin (MIC range 0.004-0.25 µg/mL). Following double-blind rifaximin treatment, Staphylococcus isolates remained susceptible to rifaximin at all visits (MIC50 range ≤0.06-32 µg/mL). Rifaximin exposure was not associated with long-term cross-resistance of Bacteroidaceae, Enterobacteriaceae, and Enterococcaceae to rifampin or nonrifamycin antibiotics tested. CONCLUSIONS: In this study, short-term repeat treatment with rifaximin has no apparent long-term effect on stool microbial susceptibility to rifaximin, rifampin, and nonrifamycin antibiotics. CLINICALTRIALS. GOV IDENTIFIER: NCT01543178.

Systematic review of the relationship between bladder and bowel function: implications for patient management.

BACKGROUND: The complex relationship between bladder and bowel function has implications for treating pelvic disorders. In this systematic review, we discuss the relationship between bladder and bowel function and its implications for managing coexisting constipation and overactive bladder (OAB) symptoms. METHODS: Multiple PubMed searches of articles published in English from January 1990 through March 2011 were conducted using combinations of terms including bladder, bowel, crosstalk, lower urinary tract symptoms, OAB, incontinence, constipation, hypermotility, pathophysiology, prevalence, management and quality of life. Articles were selected for inclusion in the review based on their relevance to the topic. RESULTS: Animal studies and clinical data support bladder-bowel cross-sensitization, or crosstalk. In the rat, convergent neurons in the bladder and bowel as well as some superficial and deeper lumbosacral spinal neurons receive afferent signals from both bladder and bowel. On a functional level, in animals and humans, bowel distention affects bladder activity and vice versa. Clinically, the bladder-bowel relationship is evident through the presence of urinary symptoms in patients with irritable bowel syndrome and bowel symptoms in patients with acute cystitis. Functional gastrointestinal disorders, such as constipation, can contribute to the development of lower urinary tract symptoms, including OAB symptoms, and treatment of OAB with antimuscarinics can worsen constipation, a common antimuscarinic adverse effect. The initial approach to treating coexisting constipation and OAB should be to relieve constipation, which may resolve urinary symptoms. CONCLUSIONS: The relationship between bladder and bowel function should be considered when treating patients with urinary symptoms, bowel symptoms, or both.

The utility of flexible sigmoidoscopy after a computerized tomographic colonography revealing only rectosigmoid lesions.

BACKGROUND: Identifying polyps by computerized tomographic colonography typically prompts colonoscopy, increasing its cost, risk and inconvenience. Many polyps are confined to the rectosigmoid and theoretically amenable to resection via flexible sigmoidoscopy. AIM: To determine the prevalence of advanced proximal colonic neoplasia when computerized tomographic colonography reveals only rectosigmoid polyps, and characterize the yield of polypectomy via flexible sigmoidoscopy in such patients. METHODS: Subjects underwent computerized tomographic colonography and colonoscopy with segmental unblinding. Patients with only rectosigmoid findings by computerized tomographic colonography were identified retrospectively. Flexible sigmoidoscopy findings were estimated by including lesions distal to the descending/sigmoid colon junction during colonoscopy. Proximal lesions were also reviewed. Advanced lesions were defined as: adenocarcinoma, tubular adenoma >1 cm, > or =3 tubular adenomas, tubulovillous histology or high-grade dysplasia. RESULTS: By computerized tomographic colonography, 15% (203 of 1372) had only rectosigmoid polyps. Concomitant lesions in the proximal colon were seen in 32% (64 of 203) during colonoscopy. Advanced proximal neoplasia occurred in 2% (three of 203) with only rectosigmoid polyps on computerized tomographic colonography. CONCLUSIONS: Using flexible sigmoidoscopy to follow-up computerized tomographic colonography demonstrating only rectosigmoid polyps would eliminate 15% of subsequent colonoscopies. This strategy carries a small risk of missed proximal advanced neoplasia. This miss rate appears comparable to that of colonoscopy alone. Further study on the cost-effectiveness of this approach is warranted.

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

BACKGROUND: The concept of augmenting the management of irritable bowel syndrome with antibiotics is evolving, and many questions remain regarding this therapy relative to known and hypothesized irritable bowel syndrome pathophysiology. The clinical evidence of small intestinal bacterial overgrowth as an important aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms of bacterial overgrowth and irritable bowel syndrome are similar; however, a definitive cause-and-effect relationship remains unproven. It is unclear whether motility dysfunction causes bacterial overgrowth or gas products of enteric bacteria affect intestinal motility in irritable bowel syndrome. AIM: To discusses the efficacy and tolerability of current symptom-directed pharmacotherapies and of antibiotics in the treatment of irritable bowel syndrome. METHODS: A computerized search of PubMed was performed with search terms "IBS", "pharmacotherapy" and "antibiotics". Relevant articles were selected, and the reference list of selected articles was reviewed to identify additional references. RESULTS: Antibiotic treatment benefits a subset of irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a favourable safety and tolerability profile compared with systemic antibiotics and demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel syndrome pharmacotherapies. CONCLUSION: Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in irritable bowel syndrome patients in a placebo-controlled trial. Whether antibiotics can improve quality of life in patients with irritable bowel syndrome warrants further research.

Review article: The role of serotonergic agents in the treatment of patients with primary chronic constipation.

Chronic constipation is a highly prevalent disorder that is associated with significant direct and indirect costs and has substantial impact on patient quality of life. It is more common among women and non-white populations and is evenly distributed across adult age groups. Constipation is a heterogeneous disorder associated with multiple symptoms and aetiologies. Recent research has increased our understanding of the pathogenesis of this disorder and the central role of the neurotransmitter serotonin in mediating gastrointestinal motility, secretion and sensation. Abnormal serotonin signalling and reuptake appear to play central roles in the symptoms of a subset of patients with chronic constipation. This observation provides a rationale for the use of targeted serotonergic agents for the treatment of chronic constipation. As the role of serotonin in gastrointestinal function is further elucidated and additional candidate drugs are developed, it is likely that serotonergic agents will afford additional treatment options for patients with chronic constipation. This article provides a concise review of the evidence supporting a role for serotonin in the pathogenesis of chronic constipation and a summary of the currently available evidence supporting the use of serotonergic agents for this disorder.

Irritable bowel syndrome - an evidence-based approach to diagnosis.

Irritable bowel syndrome (IBS) represents one of the most common reasons for primary care visits and consultation with a gastroenterologist. It is characterized by abdominal discomfort, bloating and disturbed defecation in the absence of any identifiable physical, radiologic or laboratory abnormalities indicative of organic gastrointestinal disease. IBS is a costly disorder, responsible for significant direct and indirect costs to patients and society. Much of the cost attributed to IBS arises from the time and resources used to establish the diagnosis. Historically IBS has been viewed by many as a diagnosis of exclusion rather than as a primary diagnosis, and many patients with typical symptoms will undergo an extensive array of diagnostic tests and procedures prior to the eventual diagnosis of IBS. Recent reviews addressing the management of such patients have cast doubt on the necessity for this degree of testing. Current best evidence does not support the routine use of blood tests, stool studies, breath tests, abdominal imaging or lower endoscopy in order to exclude organic gastrointestinal disease in patients with typical IBS symptoms without alarm features. Serological testing for celiac sprue in this population may eventually prove useful but validation of studies indicating an increased prevalence of this disease in patients with suspected IBS is needed. The development and refinement of symptom-based criteria defining the clinical syndrome of IBS has greatly facilitated the diagnosis of this condition, which can be confidently diagnosed through the identification of typical symptoms, normal physical examination and the exclusion of alarm features. The presence of alarm features or persistent non-response to symptom-directed therapies should prompt a more detailed diagnostic evaluation dictated by the patient's predominant symptoms.

Historical perspective of achalasia.

This article provides an overview of the historic background of achalasia. It describes how achalasia was first chronicled in the 17th century. Prevalent theories of etiology from the original description to present day constructs are examined. Important individuals and their contributions to the concepts of achalasia are reviewed and various nonsurgical and surgical therapeutic techniques from antiquity to today are presented.

Licensure, use, and training of paramedical personnel to perform screening flexible sigmoidoscopy.

BACKGROUND: The purpose of this study was to assess the state board of nursing guidelines about the performance of flexible sigmoidoscopy by nurses and to determine the current use and training of paramedical personnel in flexible sigmoidoscopy at gastroenterology fellowship programs in the United States. METHODS: Separate one-page questionnaires were sent to state boards of nursing and directors of endoscopy at gastroenterology fellowship programs in the United States. RESULTS: Twenty percent (10 of 50) of state boards of nursing explicitly approve the performance of sigmoidoscopy by registered nurses, and 50% (25 of 50) explicitly approve the practice by nurse practitioners. Forty-six percent (23 of 50) of state boards of nursing have no written policy but allow nurses to use a "decision making model" to determine whether the performance of sigmoidoscopy is allowed. Fifteen percent (24 of 164) of gastroenterology fellowship programs in the United States use paramedical personnel to perform flexible sigmoidoscopy. Sixty-three percent (15 of 24) of these programs started since 1995, and 67% (16 of 24) require that the paramedical personnel perform 50 or more supervised sigmoidoscopies during their training. Forty-five percent (5 of 11) of programs with physician assistants/nurse practitioners use these personnel to perform colonoscopy or endoscopy. CONCLUSIONS: Nurses are allowed to perform flexible sigmoidoscopy in most states based on current state board of nursing guidelines. The use of paramedical personnel to perform endoscopic procedures is increasing rapidly.