Getting the BS out of Irritable Bowel Syndrome with Diarrhea (IBS-D): Let's Make a Diagnosis.

PURPOSE OF REVIEW: Irritable bowel syndrome with diarrhea (IBS-D) is diagnosed when chronic symptoms of abdominal pain accompany loose stools, and alarm features, such as fever, anemia, rectal bleeding, and weight loss are absent. This combination of symptoms makes structural disorders, such as inflammatory bowel disease or cancer, unlikely, but does not exclude other conditions that cause these symptoms. The question is whether making a "positive diagnosis" of IBS-D based on symptoms alone and instituting therapy based on that diagnosis still makes sense. RECENT FINDINGS: Clinical observations suggest that at least two-thirds of cases of IBS-D can be explained by three mechanisms: a) food intolerances (~ 30-40%), b) bile acid diarrhea (~ 20-30%), and c) disturbed microbial flora (~ 15-20%). Other conditions that are less frequent but can cause IBS symptoms or be confused with IBS include: celiac disease, microscopic colitis, mastocytosis/mast cell activation, and drug side-effects. Many cases of IBS-D have a discoverable, underlying cause that can direct therapy more efficiently.

Tocilizumab use in patients with moderate to severe COVID-19: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) associated cytokine activation can lead to a rapid progression into respiratory failure, shock and multiorgan failure. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that likely contributes to the pathogenesis of cytokine release syndrome. It is hypothesized that modulating IL-6 levels or its effects with tocilizumab, a recombinant humanized anti-IL-6 receptor monoclonal antibody, may alter the course of disease. METHODS: We examined the association between tocilizumab use and intubation or death at a community hospital in New York City. Data were obtained regarding consecutive patients hospitalized with COVID-19. The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received tocilizumab with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS AND DISCUSSION: In this single-centre retrospective cohort study involving 1225 hospitalized patients with SARS-CoV-2 infection, the probability to respiratory failure, which was measured as intubation or death, was less frequent in patients who received tocilizumab. WHAT IS NEW AND CONCLUSION: Tocilizumab and other IL-6 receptor monoclonal antibodies may evolve as a viable option in treating patients with moderate and severe COVID-19.

Maldigestion Versus Malabsorption in the Elderly.

PURPOSE OF REVIEW: To evaluate recently published information about the frequency of maldigestion and malabsorption in older individuals, likely diagnoses causing these problems, and the diagnostic scheme when these diagnoses are being considered. RECENT FINDINGS: Although the prevalence of malnourishment and frank malnutrition may be increasing among older adults admitted to the hospital, this appears to be due to reduced food intake rather than maldigestion or malabsorption. The mechanisms of food digestion and absorption seem to be resilient, even in old age, but concurrent illness may produce malabsorption in older individuals. Illnesses that may be more common among the elderly include small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, enteropathies, vascular disease, diabetes, and certain infections, such as Whipple's disease. In addition, older adults may have had previous surgeries or exposure to medicines which may induce malabsorption. The presentation of maldigestion and malabsorption in the elderly may be different than in younger individuals, and this may contribute to delayed recognition, diagnosis, and treatment. Diagnostic testing for maldigestion and malabsorption generally is similar to that used in younger patients. Maldigestion and malabsorption occur in older individuals and require a high level of suspicion, especially when weight loss, sarcopenia, or nutrient deficiencies are present.

Chronic Diarrhea Evaluation in the Elderly: IBS or Something Else?

PURPOSE OF REVIEW: Chronic diarrhea is a common problem in all age groups but is a particularly challenging diagnostic problem in the elderly, since many different conditions need to be considered. The purpose of this review is to discuss the evaluation of chronic diarrhea in older individuals. It highlights those conditions that seem to occur with increased frequency in the elderly, discusses the diagnostic tests that are of greatest value in sorting out these problems, and presents an approach to evaluation that is both practical and affordable. RECENT FINDINGS: There appears to be little value in distinguishing irritable bowel syndrome with diarrhea (IBS-D) from functional diarrhea in most patients, including older individuals. Both conditions need a thoughtful analysis of potential causes that may lead to more focused treatment. Older individuals may be more at risk of having certain structural disorders, and these need to be considered when constructing a differential diagnosis. In addition, elderly patients may have atypical presentations of specific disorders that require an increased index of suspicion. Diagnostic tests generally seem to perform well in older patients but have not been validated in this cohort of patients. Although the pretest probabilities of certain diseases are different in the elderly, the conventional algorithm for assessment of chronic diarrhea should lead to a diagnosis in most cases. Better studies are needed to adequately quantitate the likelihood of different diagnoses and the operating characteristics of diagnostic tests in older patients with chronic diarrhea. Lacking that information, physicians can still do a good job of making a diagnosis in these patients by adopting a stepwise approach.

Evaluation of chronic diarrhea and irritable bowel syndrome with diarrhea in adults in the era of precision medicine.

Chronic diarrhea is a common clinical problem, affecting roughly 5% of the population in any given year. Evaluation and management of these patients can be difficult due to the extensive differential diagnosis of this symptom. Many patients with chronic diarrhea have structural problems, such as inflammatory bowel disease or celiac disease, that can be readily identified. Others do not, and often are given a diagnosis of irritable bowel syndrome with diarrhea (IBS-D). When based on generally accepted clinical criteria, a diagnosis of IBS-D identifies a group of patients who are unlikely to have disorders producing anatomical changes in the gut. It is less clear that a diagnosis of IBS-D identifies a specific pathophysiology or leads to better management of symptoms. Disorders such as small intestinal bacterial overgrowth, bile acid malabsorption, food intolerance, and motility disorders may account for symptoms in patients with IBS-D. More effective tests are being developed to identify the clinical problems underlying IBS-D and may lead to more specific diagnoses that may improve the results of therapy. Application of the principles of precision medicine (identifying a specific mechanism for disease and applying treatments that work on that mechanism) should lead to more expeditious diagnosis and treatment for patients with chronic diarrhea including IBS-D, but currently is limited by the availability of sufficiently sensitive and specific tests for underlying mechanisms that can predict response to treatment.

Chronic Diarrhea: Diagnosis and Management.

Chronic diarrhea is a common problem affecting up to 5% of the population at a given time. Patients vary in their definition of diarrhea, citing loose stool consistency, increased frequency, urgency of bowel movements, or incontinence as key symptoms. Physicians have used increased frequency of defecation or increased stool weight as major criteria and distinguish acute diarrhea, often due to self-limited, acute infections, from chronic diarrhea, which has a broader differential diagnosis, by duration of symptoms; 4 weeks is a frequently used cutoff. Symptom clusters and settings can be used to assess the likelihood of particular causes of diarrhea. Irritable bowel syndrome can be distinguished from some other causes of chronic diarrhea by the presence of pain that peaks before defecation, is relieved by defecation, and is associated with changes in stool form or frequency (Rome criteria). Patients with chronic diarrhea usually need some evaluation, but history and physical examination may be sufficient to direct therapy in some. For example, diet, medications, and surgery or radiation therapy can be important causes of chronic diarrhea that can be suspected on the basis of history alone. Testing is indicated when alarm features are present, when there is no obvious cause evident, or the differential diagnosis needs further delineation. Testing of blood and stool, endoscopy, imaging studies, histology, and physiological testing all have roles to play but are not all needed in every patient. Categorizing patients after limited testing may allow more directed testing and more rapid diagnosis. Empiric antidiarrheal therapy can be used to mitigate symptoms in most patients for whom a specific treatment is not available.

Antidiarrheal Drug Therapy.

INTRODUCTION: Acute diarrhea often runs a self-limited course and little by way of treatment is needed except for oral rehydration therapy. Chronic diarrhea poses a longer-term problem. If not treatable with specific therapy aimed at the underlying pathophysiology, chronic diarrhea often needs long-term symptomatic therapy. PURPOSE OF REVIEW: This paper aims to examine the options for symptomatic, nonspecific treatment of diarrhea. RECENT FINDINGS: The most frequently used therapies are opiate antidiarrheal drugs. These drugs are effective for a wide variety of diarrheal conditions and generally can be used safely if monitored closely. They work by slowing motility and allowing more time for absorption. They vary in potency and in addictive liability. In recent years, a variety of other drugs have been developed, which provide more targeted therapy that can mitigate diarrhea in specific situations. These drugs work on other regulatory pathways in the gut or on mucosal absorptive mechanisms. There is evidence for efficacy for both traditional and newer agents used for the symptomatic management of diarrhea. Opiates are used most often for this indication. Other agents may benefit individuals, but further research is needed to establish indications and best practices.

Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis.

OBJECTIVES: Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. RESULTS: The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. CONCLUSIONS: Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.

The effect of fiber supplementation on irritable bowel syndrome: a systematic review and meta-analysis.

OBJECTIVES: Fiber has been used for many years to treat irritable bowel syndrome (IBS). This approach had fallen out of favor until a recent resurgence, which was based on new randomized controlled trial (RCT) data that suggested it might be effective. We have previously conducted a systematic review of fiber in IBS, but new RCT data for fiber therapy necessitate a new analysis; thus, we have conducted a systematic review of this intervention. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched up to December 2013. Trials recruiting adults with IBS, which compared fiber supplements with placebo, control therapy, or "usual management", were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy as well as number needed to treat (NNT) with a 95% confidence interval (CI). RESULTS: We identified 14 RCTs involving 906 patients that had evaluated fiber in IBS. There was a significant benefit of fiber in IBS (RR=0.86; 95% CI 0.80-0.94 with an NNT=10; 95% CI=6-33). There was no significant heterogeneity between results (I(2)=0%, Cochran Q=13.85 (d.f.=14), P=0.46). The benefit was only seen in RCTs on soluble fiber (RR=0.83; 95% CI 0.73-0.94 with an NNT=7; 95% CI 4-25) with no effect seen with bran (RR=0.90; 95% CI 0.79-1.03). CONCLUSIONS: Soluble fiber is effective in treating IBS. Bran did not appear to be of benefit, although we did not uncover any evidence of harm from this intervention, as others have speculated from uncontrolled data.

Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate. METHODS: We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS: The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial. CONCLUSIONS: Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea: definition, classification, diagnosis.

Diarrhea is best defined as passage of loose stools often with more frequent bowel movements. For clinical purposes, the Bristol Stool Form Scale works well to distinguish stool form and to identify loose stools. Laboratory testing of stool consistency has lagged behind. Acute diarrhea is likely to be due to infection and to be self-limited. As diarrhea becomes chronic, it is less likely to be due to infection; duration of 1 month seems to work well as a cut-off for chronic diarrhea, but detailed scientific knowledge is missing about the utility of this definition. In addition to duration of diarrhea, classifications by presenting scenario, by pathophysiology, and by stool characteristics (e.g. watery, fatty, or inflammatory) may help the canny clinician refine the differential diagnosis of chronic diarrhea. In this regard, a careful history remains the essential part of the evaluation of a patient with diarrhea. Imaging the intestine with endoscopy and radiographic techniques is useful, and biopsy of the small intestine and colon for histological assessment provides key diagnostic information. Endomicroscopy and molecular pathology are only now being explored for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is increasing; aside from a handful of well-described infections because of pathogens, little is known about alterations in the microbiome in chronic diarrhea. Serological tests have well-defined roles in the diagnosis of celiac disease but have less clearly defined application in autoimmune enteropathies and inflammatory bowel disease. Measurement of peptide hormones is of value in the diagnosis and management of endocrine tumors causing diarrhea, but these are so rare that these tests are of little value in screening because there will be many more false-positives than true-positive results. Chemical analysis of stools is of use in classifying chronic diarrhea and may limit the differential diagnosis that must be considered, but interpretation of the results is still evolving. Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial overgrowth, and intestinal transit are fraught with technical limitations that decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption have had limited utility beyond empirical trials of bile acid sequestrants.

A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome.

Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.

Ileostomy diarrhea: Pathophysiology and management.

Ileostomy is a common component of surgical treatments for various gastrointestinal conditions. Loss of the fluid absorptive capacity of the colon results in increased fluid and electrolyte losses, which causes a state of relative fluid depletion. These losses can be offset in part by increased oral intake, but the remaining small intestine also compensates by increasing the efficiency of fluid and electrolyte absorption, a process termed adaptation, which occurs within weeks to months of ileostomy creation. Some patients fail to adapt adequately and have high ileostomy outputs from the time of surgery. Others with a previously well-adapted ileostomy may encounter periods of sustained high output when some additional process causes diarrhea. Many patients experience periods of high output after ileostomy creation and often require hospital readmission for this reason. Any patient with an ileostomy is at great risk of dehydration and electrolyte depletion should output rise dramatically. Prompt attention should be given to rehydration and identification of the underlying cause so that directed therapies may be implemented. This review discusses the alteration of normal intestinal fluid balance from colectomy with ileostomy, proposed mechanisms for adaptation, the differential diagnosis of ileostomy diarrhea, the evaluation of ileostomy diarrhea, and current treatment options.

Chronic constipation: new insights, better outcomes?

Constipation is a symptom that affects around 11-20% of the adult population yearly. Most physicians consider infrequency of defecation as a hallmark of constipation. However, most patients view excessive straining as the biggest component of constipation and only a minority of patients with constipation have infrequent bowel movements. Constipation might be due to many different medical conditions or occur as a side-effect of drug therapy. When these medical conditions or drug therapies are not present, a diagnosis of functional constipation, chronic idiopathic constipation, or irritable bowel syndrome with constipation is often made. In all patients with constipation, rectal outlet dysfunction should be excluded by physical examination because this condition occurs in approximately 25% of patients diagnosed with idiopathic constipation and can be improved with different therapeutic approaches than administration of laxatives. Because of the availability of over-the-counter laxatives, most patients consider themselves able to self-manage constipation, and patients have often tried many different treatments before seeking professional help. The physician must carefully assess these previous efforts of self-treatment, optimise them, and strategically use the increasing list of prescription medications for management.