Painful Diverticular Disease or Irritable Bowel Syndrome?

Transcription

1 Painful Diverticular Disease or Project ID: Learning Objectives Introduction Upon completion of this activity, the participant will be better The term diverticular disease encompasses a spectrum of conditions (diverticulosis, diverticulitis, diverticular bleeding, etc), which share the underlying pathology of acquired diverticula of the colon. It is believed to occur as a result of outpouching of the mucosa and submucosa through weaknesses in the muscular wall of the colon alongside natural openings where arteries (the vasa recta) penetrate the muscularis layer to reach the mucosa and submucosa.1 Between 10% and 30% of patients with diverticulosis, a purely anatomic diagnosis that describes the presence of 1 diverticula, may develop painful diverticular disease or diverticulitis.2,3 These patients experience a range of acute and chronic symptoms, including abdominal pain, peritonitis, obstruction, bleeding, fistulization, and abscess formation.4 prepared to: Describe the pathophysiology, presentation, clinical features, and treatment of painful diverticular disease Describe the pathophysiology, presentation, and treatment of irritable bowel syndrome () Differentiate between painful diverticular disease and in clinical practice Credit Designation Purdue University College of Pharmacy designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. In some respects, symptomatic diverticular disease shares many of the features of irritable bowel syndrome (). is a chronic complex of gastrointestinal symptoms characterized by significant abdominal pain and disturbed defecation.5 is defined by the Rome III criteria as recurrent abdominal pain or discomfort for 3 days a month in the last 3 months that is associated with at least 2 of the following: 1) improvement with defecation, 2) onset associated with a change in stool form, or 3) onset associated with a change in the frequency of stool. Physician Accreditation Statement This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Purdue University College of Pharmacy and the Gi Health Foundation. Purdue University College of Pharmacy, an equal access/equal opportunity institution, is accredited by the ACCME to provide continuing medical education for physicians. The symptoms associated with symptomatic diverticular disease and overlap significantly; in fact, the concept of symptomatic diverticular disorder has been questioned, with some suggesting that it represents coincident occurrence of in patients who happen to have diverticula.6 More recent evidence suggests that painful diverticular disease may actually be a distinct entity occurring as a result of an interaction between an inflammatory process and neuromuscular function in the colon.6 Disclosure of Conflicts of Interest All faculty and staff involved in the planning or presentation of continuing education activities sponsored/provided by Purdue University College of Pharmacy are required to disclose to the audience any real or apparent commercial financial affiliations related to the content of the presentation or enduring material. Full disclosure of all commercial relationships must be made in writing to the audience prior to the activity. The Gi Health Foundation staff and Purdue University College of Pharmacy staff have no relationships to disclose. However, the approach to management of these diseases differs considerably. It is important to distinguish between these 2 disease states consistently to avoid inappropriate treatment, particularly when surgical treatment for diverticulitis is under consideration. In this monograph, we will explore the epidemiology, etiology, diagnosis, and treatment of diverticular disease and and then examine pathways that help distinguish these 2 disease states. 1

2 Painful Diverticular Disease or DIVERTICULAR DISEASE AND NOMENCLATURE Despite the fact that diverticular disease is one of the most common gastrointestinal diseases in the Western world, much remains to be learned about it; in fact, confusion exists regarding even the naming of the various conditions that fall under the diverticular umbrella. The term diverticulosis indicates the presence of colonic diverticula circumscribed pouches or sacs occurring due to herniation of the mucous membrane of the gastrointestinal tract which may or may not be symptomatic. Diverticular disease, in contrast, is a term that denotes clinically significant and symptomatic diverticulosis. 4 The term symptomatic (or painful) diverticular disease is also in common use. 7 Diverticulitis describes acute or chronic macroscopic inflammation of the colon and may be associated with pain, bleeding, or colonic inflammation or infections. 7 Epidemiology of Diverticular Disease Notably, diverticular disease occurs almost exclusively in developed countries; in fact, it has been called a disease of Western civilization. 8 The incidence of diverticular disease generally increases with age; estimates suggest a prevalence of <5% of people aged 40 years, increasing to approximately 65% in people aged 65 years. In general, approximately 80% of people who present with diverticulitis are aged 50 years, although recent trends suggest a rising prevalence in younger individuals. 9 Diverticula are less common among vegetarians and others who consume large amounts of dietary fiber. Right-sided disease is significantly more common among Asians and patients aged 60 years. 5 While diverticulosis is very commonly seen in Western countries, only 10% to 30% of patients with diverticular disease experience an episode of overt diverticulitis, 3 of whom a smaller percentage will develop significant complications, including abscess formation, fistulas, and hemorrhage. 10 Mortality and morbidity from painful diverticular disease is significant. In a study conducted in England, more than 500,000 hospital admissions were recorded over a 10- year period; the majority of these admissions were for emergencies. 11 Thirty-day mortality was 5% and 1-year mortality was 20% in this population. Recent estimates suggest that the hospitalization rates for diverticulitis are increasing, particularly among younger people. 11 Pathophysiology of Diverticular Disease Diverticula are simply small mucosal herniations that protrude through the intestinal layers and the smooth muscle, most commonly in the sigmoid colon (potentially because of increased intraluminal pressure in this region), although they can be found throughout the large bowel. In most patients, multiple diverticula are present, 1 generally ranging from 5 to 10 mm in diameter, although occasionally exceeding 20 mm. These herniations create small pouches lined by the mucosa. The relationship between age and the prevalence of diverticula can be explained by age-related degeneration of the mucosal wall as well as segmental increases in colon pressure that result in bulging at weak points, typically at the insertion of the vasa recta. 4 It is unknown why only a small percentage of patients with diverticulosis develop symptomatic diverticular disease. Obstruction of the junction between the lumen of the diverticulum and the intestine proper by fecaliths or poorly absorbed food components may prompt bacterial overgrowth, inflammation, mucosal abrasion, barotrauma, and even microperforations. 4 No connection has been observed between symptomatic disease and smoking, caffeine, or alcohol intake, although a lack of exercise may play an indirect role. 1 There is an inverse relationship between dietary fiber intake and the development of symptomatic disease; 12 in fact, some authors consider diverticulitis a disease of deficiency like scurvy, in that it is largely avoidable by increasing fiber intake. 8 Painful or symptomatic diverticular disease may also be associated with fundamental physiologic factors, including increased motility index and increased intraluminal pressure. 13 Recent evidence suggests that painful diverticular disease may be associated with ongoing inflammatory changes that affect neuromuscular function in the colon In fact, resected tissues from the sigmoid colon of patients with smouldering diverticular disease show chronic inflammatory changes. Moreover, some patients have a symptomatic response to anti-inflammatory agents such as mesalazine Both acute and subtle chronic changes in the colonic microbiota have also been implicated in the pathogenesis of diverticular disease. 22 Presentation and Diagnosis of Symptomatic Diverticular Disease Symptomatic diverticular disease is, like, a diagnosis of exclusion. Symptomatic diverticular disease is characterized by acute attacks of localized abdominal pain. 9 In general, patients present with colicky pain, although the pain may sometimes be steady (Box 1). Pain may be precipitated by eating and is often relieved by passing flatus or having a bowel movement. 7 Bloating and changes in stool form, particularly constipation, may be observed in some patients. Patients may also have fullness or tenderness in the left lower quadrant or a tender loop of the sigmoid colon, reflecting the propensity of the disease to occur in the sigmoid colon, 8 although as noted previously, Asian patients have predominantly right-sided diverticula and may manifest rightsided pain. Anorexia, nausea, and vomiting may occur. 8 Bowel sounds are often suppressed but may be normal in mild cases. Many of these symptoms overlap with the Rome III criteria for, particularly with constipation (-C) (Box 2). 2

3 Painful Diverticular Disease or Box 1. Signs and Symptoms of symptomatic diverticular disease 7 Localized abdominal pain in the absence of inflammation (eg, fever, leukocytosis, peritoneal signs on examination) Pain is usually colicky (although may be steady in some patients) Pain may be precipitated by eating Pain may be relieved by passing flatus or having a bowel movement Bloating may be present Changes in stool form may occur (usually constipation) Fullness or tenderness in left lower quadrant may be present A tender loop of the sigmoid colon may be present Anorexia, nausea, and vomiting may occur Bowel sounds are typically depressed Dysuria and urinary frequency may be reported by some patients Box 1: Signs and symptoms of symptomatic diverticular disease 7 Box 2. Rome III criteria for : Recurrent abdominal pain/discomfort 3 days/month for the past 3 months, associated with 2 of the following: - Improvement with defecation - Onset associated with change in stool frequency - Onset associated with change in stool form Subtyped by predominant stool pattern - -C: hard or lumpy stools 25% of defecations; loose or watery stools <25% of defecations Box 2: Rome III criteria for Laboratory studies and imaging may be appropriate in some cases to distinguish symptomatic diverticular disease from other conditions that mimic its symptoms. Common differential diagnoses are listed in box 3. 1 White blood cell count may be elevated with a predominance of polymorphonuclear cells. 1 An abdominal radiograph series should be obtained in patients with abdominal pain to examine whether macro-perforations have occurred. Computerized tomography (CT) with intravenous and oral contrast is the gold standard to confirm a suspected diagnosis of diverticulitis. 10 Contrast enema examinations are useful as a complement to CT scanning. 3 Ultrasonography may also be performed. 3 Endoscopy should be avoided in initial evaluations because of the risk for perforation. 3 Refer to the treatment guidelines for a complete discussion of diagnostic modalities. 3 Box 3. Differential diagnoses of symptomatic diverticular disease and diverticulitis. Adapted from Salzman Acute appendicitis Colorectal cancer Complicated ulcer disease Crohn s disease Cystitis Ectopic pregnancy Gallbladder disease Incarcerated hernia Irritable bowel syndrome Ischemic colitis Mesenteric infarction Ovarian cyst, abscess, or neoplasm Ovarian torsion Pancreatic disease Pelvic inflammatory disease Peritonitis Pseudomembranous colitis Renal disease Small bowel obstruction Ulcerative colitis Box 3: Differential diagnoses of symptomatic diverticular disease and diverticulitis. Adapted from Salzman Recurrence is common among patients who suffer a symptomatic episode of diverticular disease; furthermore, increasing evidence suggests that an acute episode may be followed by chronic symptoms, possibly as a result of inflammatory changes around diverticula, although exact incidence is unclear. 23 Treatment of Symptomatic Diverticular Disease High-fiber diets are usually recommended to patients with asymptomatic disease in an effort to prevent symptomatic diverticular disease; however, there are no well-designed, randomized, controlled clinical trials to support this strategy. 2,10 Acutely, in patients with significant pain, tenderness, or fever, outpatient treatment should be initiated with broad-spectrum antibiotics; common choices include metronidazole plus a quinolone, metronidazole plus trimethoprimsulfamethoxazole, or amoxicillin-clavulanic acid, all for 7 to 10 days. 3 Patients should follow a clear liquid diet for 24 to 72 hours, after which the diet may cautiously include solids. If the patient is hospitalized, he or she should be placed on bowel rest and treated with intravenous fluids and intravenous antibiotics. 3 Between 15% and 20% of patients may require surgery during hospital admission due to a lack of response to conservative medical treatment, particularly among patients who have been hospitalized previously for 1 episodes or because of complications of diverticulitis. 1,10 As noted previously, symptomatic diverticular disease may be related to inflammatory changes in the colon affecting neuromuscular function. 24 These data suggest that anti-inflammatory agents may have a clinical role in the management of symptomatic diverticular disease. A systematic review of the literature evaluated the efficacy of 5- aminosalicylic acid (5-ASA) in patients with colonic diverticular disease. 21 A total of 6 randomized, controlled clinical trials were identified, which enrolled a total of 818 patients (3 in patients with uncomplicated diverticulitis and 3 in patients with symptomatic uncomplicated diverticular disease). The results of these studies showed that patients treated with 5-ASA had significantly better outcomes and that daily mesalazine was superior to cyclic administration to prevent relapse of diverticular disease. Given the efficacy of both oral and intravenous antibiotics in the management of symptomatic diverticular disease, it is clear that the colonic microbiota play a role in the pathogenesis and symptomatology of disease. Nonabsorbable antibiotics such as rifaximin may be a useful treatment in diverticular disease. 18,19 Indeed, several studies have examined the combination of acute rifaximin with long-term mesalazine. In one study of 90 consecutive patients with symptomatic uncomplicated diverticular disease, patients were treated with rifaximin 800 mg/d plus mesalazine 2.4 grams/d for 10 days, followed by mesalazine 1.6 grams/d for 8 weeks. 18 Patients were assessed for constipation, diarrhea, abdominal pain, rectal bleeding, and mucus with stools. Total symptom scores decreased from 1439 to 44 (P<.001). The majority of patients were completely asymptomatic after 8 weeks of treatment. 3

4 Painful Diverticular Disease or Probiotics, with and without 5-ASA, have been examined in the prevention of symptomatic diverticular disease recurrence. 25 In a multicenter, prospective, randomized, controlled study, Tursi and colleagues treated patients with symptomatic uncomplicated diverticular disease to remission with rifaximin 800 mg/d plus mesalazine 2.4 grams/d for 10 days, followed by mesalazine 1.6 grams/d for 8 weeks. Patients were subsequently randomized to long-term treatment with mesalazine 1.6 grams/d, Lactobacillus casei probiotic, or the combination of the 2 treatments. Notably, 76.7% of the monotherapy groups and 96% of the combination therapy group remained recurrence-free at 12 months. is a chronic complex of gastrointestinal symptoms characterized by significant abdominal pain and disturbed defecation. is defined by the Rome criteria as recurrent abdominal pain or discomfort for 3 days a month in the last 3 months that is associated with at least 2 of the following: 1) improvement with defecation, 2) onset associated with a change in stool form, or 3) onset associated with a change in the frequency of stool (Box 2). 5 It is most commonly classified into 3 subtypes depending on predominant stool form: with constipation (-C), with diarrhea (-D), and with both diarrhea and constipation (-M). Other subtypes used in the literature include -A (alternating diarrheal/constipation pattern) and -U, which describes without a predominant stool form or pattern. As noted above, there is considerable overlap between the symptoms of symptomatic diverticular disease and (particularly -C). Given that the appropriate management paradigms for these 2 disease states differ, particularly with regard to surgical approaches to treatment, it is critical to distinguish them consistently. Epidemiology of represents a major burden in terms of patient quality of life, work productivity, and health care costs. 26 In North America, is common, with prevalence estimates ranging from 1% to over 20%; 27 when defined using the most stringent criteria, pooled analyses indicate that between 7% and 10% of people have worldwide Notably, the actual number of patients suffering from is likely to be greater than the reported prevalence, as most patients fail to seek medical attention is one of the most commonly diagnosed gastrointestinal conditions in clinical practice and has historically been the primary motivating factor in between 25% and 50% of all referrals to gastroenterologists. 33 also accounts for a significant number of visits to primary care physicians. On the individual level, has a tremendous impact on the patient in terms of physical and psychological wellbeing, the ability to interact socially, and the ability to work. In fact, studies consistently demonstrate that health-related quality of life is consistently lower among patients with than among those with depression or gastroesophageal reflux disease and similar to that seen in patients with diabetes. 24,34 is associated with significant incremental health care costs, with some studies suggesting annual direct and indirect costs of up to $30 billion, 22 much of which arises from sequential diagnostic tests, invasive procedures, and abdominal operations, despite data suggesting that symptoms almost invariably persist following surgery. 35 Pathophysiology of The precise cause(s) of is (are) not known; however, it is likely that there are multiple underlying etiologies (eg, altered gastrointestinal motility, visceral hypersensitivity, infection and inflammation, stress, bile acid modulation) that ultimately result in similar symptoms. Of particular note, recent data suggest a role of immune activation and/or low-grade inflammatory processes in the pathogenesis of. 36 For these reasons, remains an area of very active clinical research. Diagnosis of -C Like diverticular disease, is largely a disease of exclusion. Although the exact definition of remains controversial, is currently defined by abdominal pain or discomfort that occurs in association with altered bowel habits over a period of at least 3 months. 37 Individual symptoms have limited accuracy for diagnosing, and therefore, the disorder should be considered a symptom complex. Alarm features (eg, anemia, weight loss, family history of colorectal cancer, inflammatory bowel disease, celiac sprue), offer little discriminative value in separating patients with from those with organic diseases. For this reason, in patients who fulfill symptombased criteria for in the absence of alarm features are usually considered to have. 37 Routine diagnostic testing with a complete blood count, serum chemistries, thyroid function studies, stool for ova and parasites, and abdominal imaging is generally not recommended for patients with typical symptoms and no alarm features because of a low likelihood of uncovering organic disease. Routine screening for celiac sprue should be considered in patients with -D or -M but not in those with -C, and lactulose breath testing should be considered in patients in whom lactose maldigestion remains a concern despite dietary modification. The value of breath testing for small bowel bacterial overgrowth remains an area of considerable controversy, although recent meta-analyses suggest that this test has diagnostic value. 38 Managing -C Although the symptoms of diverticular disease and -C can overlap significantly, the pharmacologic management paradigm, aside from increasing fiber intake, differs significantly. Often, the symptomatic overlap between these 2 disease states can be a source of considerable frustration for both health care providers and patients. Fiber, laxatives, antidepressants, lubiprostone, and linaclotide all offer pharmacologic options for the management of ; probiotics and diet have also been shown to be effective. In general, fiber is effective for relieving global symptoms, but 4

5 Painful Diverticular Disease or there is little evidence that it is effective for relief of abdominal pain. Soluble and insoluble fiber had different effects on global symptoms. Soluble fiber (eg, psyllium, ispaghula, calcium polycarbophil) has been associated with significant improvements in global symptoms (relative risk of symptoms not improving, 1.55; 95% CI, ). In contrast, insoluble fiber (eg, corn, wheat bran) was no better than placebo (relative risk, 0.89; 95% CI, ) and, in fact, may be associated with worse outcomes. A systematic review conducted for the ACG guidelines identified 12 randomized, controlled trials evaluating fiber in patients with, most of which were old, had suboptimal design, or failed to differentiate between -C and -D patients. 39 Overall, the relative risk of symptoms not improving with wheat bran was 1.02 (95% CI, ). In contrast, global symptoms were improved in 4 of 6 studies with psyllium. The relative risk of symptoms not improving with psyllium was 0.78 (95% CI, ) and the number needed to treat was 6 (95% CI, 3-50). Thus, fiber probably provides only marginal benefits in patients with. As importantly, these data suggest that the various available fiber supplements should not be considered a homogenous class; indeed, if fiber is used at all in -C, it should be soluble. Few well-designed clinical trials have evaluated the overall efficacy of osmotic laxatives (eg, lactulose, PEG-3350, magnesium hydroxide, milk of magnesia) in patients with, although they are commonly used. Three randomized, double-blind, placebo-controlled studies compared lactulose with placebo in patients with chronic constipation; lactulose was superior to placebo in improving stool consistency and the number of bowel movements per day in all 3 studies. 40 A single, small, sequential study in patients with -C compared symptoms before and after PEG treatment in adolescents with -C. 41 In this study, PEG resulted in a significant improvement in the frequency of bowel movements (P<.05) but was not associated with a significant improvement in pain. Stimulant laxatives (eg, senna, bisacodyl, cascara) are another option for the management of constipation in patients with. Two recent randomized trials have been conducted evaluating these agents for chronic constipation. In the first, 42 patients with chronic constipation, as defined by Rome III criteria, were randomly allocated to treatment with 10 mg bisacodyl (n=247) or placebo (n=121) once daily for 4 weeks; the primary endpoint was the number of complete spontaneous bowel movements (CSBMs) per week during the treatment period. The mean number of CSBMs increased from 1.1 ± 0.1 in both groups to 5.2 ± 0.3 in the bisacodyl group and 1.1 ± 0.1 in the placebo group (P<.0001). All secondary endpoints evaluated in this trial (number of CSBMs/week, number of spontaneous bowel movements (SBMs), and constipation-associated symptoms) improved significantly with bisacodyl. A separate study 43 evaluated the effects of sodium picosulfate in patients with chronic constipation. In this study (n=367), the mean number of CSBMs/week increased from 0.9 ± 0.1 to 3.4 ± 0.2 in the sodium picosulfate group and from 1.1 ± 0.1 to 1.7 ± 0.1 in the placebo group (P<.0001). Antidepressants are another option for the management of -C, particularly among those who fail to respond to peripherally acting 5 agents and those in whom abdominal pain is a prominent symptom. While individual clinical trials of antidepressants have failed to show a prominent benefit, meta-analysis suggests that these agents can be effective in patients with. 44 A meta-analysis of 13 randomized, controlled trials that evaluated either TCAs or SSRIs (N=789) found that global symptoms were significantly more likely to improve in patients taking an antidepressant, regardless of type (relative risk of symptoms not improving, 0.66; 95% CI, ). Among those taking TCAs (9 trials; N=575), the relative risk of not improving was 0.68 (95% CI, ; NNT=4.0); among those taking SSRIs (5 trials; n=230) the relative risk of not improving was 0.62 (95% CI, ; NNT=3.5). Lubiprostone is a locally acting, bicyclic functional fatty acid derived from prostaglandin E1 that acts by specifically activating CIC-2 chloride channels on the apical aspect of gastrointestinal cells, eliciting a chloride-rich fluid secretion. 45 Lubiprostone was assessed in an analysis of 1171 patients with -C;46 the primary efficacy endpoint was the percentage of overall responders (moderate or significant relief for at least 2 of the 3 months of the study). The percentage of overall responders with the lubiprostone group was 17.9% vs 10.1% in the placebo group (P=.001). The mean improvement from baseline in abdominal discomfort and pain was also significantly greater among patients who received lubiprostone compared with placebo-treated patients (-0.43 vs -0.35; P=.039). Linaclotide is approved for chronic constipation and -C A randomized, double-blind, placebo-controlled Phase 3 trial examined the efficacy and safety of linaclotide at a once daily dosage of 290 μg (n=407) versus placebo (n=397) for 12 weeks. 49 In this study, -C patients with an average of <3 CSBMs/week, 5 SBMs/week, and abdominal pain 3 (0-10 scale) during a 2-week baseline period were randomized to linaclotide 290 μg or placebo for 12 weeks. Significantly more linaclotide patients met the 4 primary and 10 secondary endpoints over the 12-week duration of the trial. In a second study of approximately 800 patients, improvements among linaclotide patients were sustained through 26 weeks of treatment. 50 Overall, linaclotide demonstrated statistically significant improvement compared with placebo at each of the 26 weeks of treatment for abdominal pain as well as for abdominal discomfort, bloating, straining, stool consistency, CSBMs, and SBMs. 50 Diarrhea was the most common adverse event, resulting in the discontinuation of 4% of linaclotide and 0.2% of placebo patients. 49,50 CONCLUSIONS As shown in this monograph, there is considerable overlap between diverticular disease and and there are few objective methods for distinguishing among the 2 disease states in clinical practice. In general, is more often seen in younger patients and women, whereas diverticular disease should be more strongly suspected in older male or female patients. Diverticular disease is usually episodic, short-lived, and often responds to treatment with fiber, laxatives, antibiotics, or surgical removal of the diverticular segment. In contrast, is usually chronic and recurrent.

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Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation. Am J Gastroenterol. 2010;105: Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and metaanalysis. Gut. 2009;58: Camilleri M, Bharucha AE, Ueno R, et al. Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2006;290:G Drossman DA, Chey WD, Johanson JF, et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebocontrolled studies. Aliment Pharmacol Ther. 2009;29: Lembo AJ, Kurtz CB, Macdougall JE, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010;138: Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365: Rao S, Lembo A, Shiff SJ. Efficacy and safety of once daily linaclotide in patients with irritable bowel syndrome with constipation: a 12-week, randomized, double-blind, placebo-controlled Phase 3 trial followed by a 4-week randomized withdrawal period. Gastroenterology. 2011;140:S Chey WD, Lembo A, MacDougall JE. Efficacy and safety of once-daily linaclotide administered orally for 26 weeks in patients with -C: results from a randomized, double-blind, placebo-controlled Phase 3 trial. Gastroenterology. 2011;140:S135. 6

7 Project ID: The term diverticulitis describes: a. The presence of colonic diverticula b. Clinically significant and symptomatic disease c. Acute or chronic macroscopic inflammation of the colon d. Segmental colitis Post Test Painful Diverticular Disease or If you wish to receive acknowledgement of participation for this activity, please complete the post test, evaluation form, and request for credit and fax pages 7-11 to Please select the one best answer by circling the appropriate letter. 2. Which of the following has been hypothesized to be a mechanism for symptomatic diverticular disease? a. Increased production of flatus b. Chronic inflammatory changes c. Functional constipation d. Functional diarrhea 3. The relationship between diverticular disease and fiber intake is: a. Inverse b. Direct c. Direct in patients aged <50; inverse in patients aged 50 d. Diverticular disease is unaffected by fiber intake 4. Which of the following is the only demographic factor that has been shown to be related to the development of diverticular disease? a. Smoking b. Alcohol c. Lack of exercise d. Caffeine 5. What percentage of patients with diverticulosis develop diverticulitis? a. 10% to 30% b. 20% to 40% c. 30% to 50% d. 40% to 60% 6. The term diverticulosis refers to: a. The presence of colonic diverticula b. Clinically significant and symptomatic disease c. Acute or chronic macroscopic inflammation of the colon d. Segmental colitis 7

8 Project ID: Post Test 7. What percentage of patients who present with diverticulitis are aged 50 years? a. 40% b. 50% c. 70% d. 80% 8. True or false: daily 5-ASA is superior to cyclic administration of 5-ASA to prevent relapse of diverticular disease? a. True b. False 9. Rifaximin treatment resulted in asymptomatic disease in the majority of patients with diverticular disease after weeks of treatment. a. 2 b. 4 c. 6 d What is the relative risk of symptoms not improving in patients with who receive soluble fiber? a b c d

9 Project ID: Evaluation Painful Diverticular Disease or Purdue University College of Pharmacy respects and appreciates your opinions. To assist us in evaluating the effectiveness of this activity and to make recommendations for future educational offerings, please take a few minutes to complete this evaluation form. How well did this activity meet the following learning objectives? Describe the pathophysiology, presentation, clinical features, and treatment of painful diverticular disease Describe the pathophysiology, presentation, and treatment of irritable bowel syndrome () Differentiate between painful diverticular disease and in clinical practice This learning objective did (or will) increase/ improve my: High Impact Knowledge... q Competence... q Performance... q Patient Outcomes... q Knowledge... q Competence... q Performance... q Patient Outcomes... q Knowledge... q Competence... q Performance... q Patient Outcomes... q Moderate Impact No Impact Not Applicable Impact of the Activity Please indicate which of the following American Board of Medical Specialties/Institute of Medicine core competencies were addressed by this educational activity (select all that apply): q Patient care or patient-centered care q Practice-based learning and improvement q Interpersonal and communication skills q Employ evidence-based practice q Interdisciplinary teams q Professionalism q Quality improvement q Medical knowledge q System-based practice q Utilize informatics q None of the above The content of this activity matched my current (or potential) scope of practice. q No q Yes, please explain Was this activity scientifically sound and free of commercial bias* or influence? q Yes q No, please explain * Commercial bias is defined as a personal judgment in favor of a specific product or service of a commercial interest. 9

10 Project ID: Evaluation Painful Diverticular Disease or Strongly Agree The educational activity has enhanced my professional effectiveness in treating patients Agree Disagree Strongly Disagree Not Applicable q q The educational activity will result in a change in my practice behavior q q How will you change your practice as a result of participating in this activity (select all that apply)? q Create/revise protocols, policies, and/or procedures q Change the management and/or treatment of my patients q This activity validated my current practice q I will not make any changes to my practice q Other, please specify: What new information did you learn during this activity? Please indicate any barriers you perceive in implementing these changes. q Lack of experience q Lack of resources (equipment) q Lack of time to assess/counsel patients q Lack of consensus of professional guidelines q Lack of opportunity (patients) q Lack of administrative support q Reimbursement/insurance issues q Patient compliance issues q No barriers q Cost q Other If you indicated any barriers, how will you address these barriers in order to implement changes in your knowledge, competency, performance, and/or patients outcomes? Comments to help improve this activity? Recommendations for future CME/CPE topics. To assist with future planning, please attest to time spent on activity: I spent hours on this program. 10

11 REQUEST FOR CREDIT If you wish to receive acknowledgement of participation for this activity, please complete this request for credit and fax to Please do not use abbreviations. We need current and complete information to assure delivery of participation acknowledgement. Degree (please mark appropriate box and circle appropriate degree): q MD/DO q PharmD/RPh q NP q PA q RN q Other Full Name (please print clearly) Last Name: First Name: Middle Initial: Street Address: City: State or Province: Postal Code: Phone: Ext: Fax: Specialty: Address: Signature is required to receive statement of credit. Signature: Date: Attestation to time spent on activity is required. Purdue University College of Pharmacy designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. q I participated in the entire activity and claim 1.0 AMA PRA Category 1 Credit(s). q I participated in only part of the activity and claim credits. 11