Jeffrey S. Baggish

Episodic Nature of Symptoms in Irritable Bowel Syndrome

OBJECTIVES:The objectives of this study were to determine whether the symptoms of diarrhea (defined as loose or watery stools), constipation (hard or lumpy stools), abdominal pain, and bloating occur in episodes rather than sporadically in patients with irritable bowel syndrome (IBS); to identify rules for defining the onset and termination of symptom episodes; and to assess the overlap of these episodes.METHODS:IBS patients kept a symptom log in which they rated the consistency of each bowel movement (BM) on the Bristol Stool Scale for 3 months. Each night they transferred these data to an internet website and also rated abdominal pain and bloating for that day. Data were analyzed for 124 patients who completed at least 21 consecutive diary days (mean of 73 days) without taking laxative, antidiarrheal, or IBS-specific medications. For each symptom in each patient, we computed the correlation between consecutive observations (autocorrelations) in the diary to determine whether the symptom tended to occur in clusters of several instances, as would happen in episodes vs. happening randomly. Next, we compared different patterns by which diarrhea and nondiarrhea stools alternate to identify episode definitions that captured at least 75% of loose/watery stools. A similar pattern analysis was performed for constipation. Pain and bloating episodes were defined as days with an intensity rating >3 on a 0–10 scale. These patterns were converted into rules for defining the onset and termination of symptom episodes. Last, we used these episode definitions to examine the overlap of pain with episodes of diarrhea, constipation, and pain.RESULTS:Significant (P<0.05) autocorrelations were found in the Bristol Stool Scale ratings of 69.4% of patients and in the daily abdominal pain and bloating ratings of 52.4% and 68.5% of patients, respectively. Defining a diarrhea episode as two or more loose/watery stools never separated by >1 nonloose/watery stool or by a day without a BM captured 76% of all loose/water stools. Defining constipation episodes as two or more hard/lumpy stools never separated by >1 nonhard/lumpy stool captured 80% of hard/lumpy stools. Sequences of 3 or more days without a BM were also defined as constipation episodes because they were strongly associated with hard stools. Average episode durations were 2.1 days for diarrhea, 4.5 days for constipation, 3.1 days for pain, and 3.5 days for bloating. Overlap analysis showed that only 41.6% of constipation episode days and 67.0% of diarrhea episode days were pain episode days. Bloating and pain coexisted on 59.1% of days on which either type occurred.CONCLUSIONS:Loose/watery stools and hard/lumpy stools occur in well-defined episodes. Pain and bloating also occur in episodes, but contrary to the Rome criteria more than half of the pain episodes occur outside episodes of abnormal stool consistency.

Patients with primary immunodeficiency receiving subcutaneous immune globulin Hizentra maintain health‐related quality of life and treatment satisfaction in a multicentre extension study of efficacy, tolerability and safety

Objective  The purpose of the study was to evaluate the maintenance and sustainability of health‐related quality of life (HRQoL) in patients being treated long‐term for primary immunodeficiency (PID) with subcutaneous infusions of Hizentra, a new human immunoglobulin G containing proline.

Safety of L-proline as a stabilizer for immunoglobulin products

Privigen® (immune globulin intravenous [human], 10% liquid) and Hizentra® (immune globulin subcutaneous [human], 20% liquid) are stabilized by proline. The clinical implications of administering proline-containing immunoglobulin products to patients with defects of proline metabolism have not been addressed; Privigen and Hizentra are contraindicated in these patients. Some patients with chromosome 22q11.2 deletion syndrome have elevated proline levels; however, only 3–4% of patients also have an immunodeficiency that requires IgG therapy. This review summarizes the evidence related to the safety and pharmacokinetics of proline assessed in Privigen and Hizentra preclinical and clinical studies, and subsequent implications for patients with defects in proline metabolism. Clinical data indicate that proline does not accumulate after Privigen or Hizentra treatment and is not associated with adverse events. There is no evidence to suggest that patients with defects of proline metabolism would be affected by transient elevations in plasma proline following Privigen and/or Hizentra treatment.

M1332 Anticipating Diarrhea: Triggers, Warnings, and Prevention

Aim: To explore triggers and warning sensations that precede diarrhea and how individuals make use of these. Methods: 579 individuals (68.6% female; ages 19-71, mean=30.5) with recurring diarrhea completed an internet survey including the Rome III diagnostic functional bowel disorders modules and a detailed questionnaire asking about diarrhea history, triggers, warning sensations and self-management. Individuals with inflammatory bowel disease, celiac disease, lactose intolerance or GI surgery history were excluded. Results: Most respondents (90.7%) had diarrhea at least 2-3 times per month. 23.7% had consulted health care providers about diarrhea. 70.5% met Rome III irritable bowel syndrome criteria but only 0.3% met functional diarrhea criteria. Diarrhea was self-defined by survey respondents, and typically considered to be characterized by loose/watery stools (92.5%), urgency (56.4%), pain/ discomfort (40.2%) and frequent stools (35.3%). 79.8% of subjects reported specific diarrhea triggers (i.e., actions or experiences they knew might result in diarrhea), and 44.0% stated that diarrhea resulted half or more of the times that these triggers occurred. Most common triggers were specific foods or drinks (72.3% of subjects), especially high-fat or spicy foods or caffeine beverages; stress/anxiety (49.7%); and large meals (25.2%). 83% of subjects with triggers rated stress/anxiety as the most frequent trigger. Nearly all subjects (95.6%) reported one or more types of physical warning sensations in advance of diarrhea, usually the same in nature for each subject and generally first occurring 10-25 minutes before diarrhea. The earliest warnings were typically either pain/discomfort (44.6%) or rumbling/bowel sounds (29.1%). 84.9% reported doing nothing to prevent or diminish diarrhea after warning sensations, but 15.1% used anti-diarrheal or antispasmodic drugs to counter the anticipated diarrhea. 74.4% used no medication once diarrhea started, 9.9% took medication early after onset, and 13.3% only later if it did not stop on its own. Warning sensations preceded at least half of all diarrhea bowel movements for 84.5% of subjects. Conclusions: Recognizable triggers and warning sensations precede diarrhea in most individuals, but few make efforts to prevent anticipated diarrhea. [Supported by McNeil Consumer Healthcare and R24 DK067674]