H2 Blockers Research Articles

Abstract P252: Duration and Life-stage of Antibiotic Use and Risk of Cardiovascular Disease in Women

Background and Aims: Growing data suggest that antibiotic use, which may alter the gut microbiome, is related to risk of cardiovascular disease (CVD) and mortality. However, evidence from prospective cohort studies is still scarce; and no large prospective study has investigated associations between cumulative antibiotic use during adulthood and risk of CVD. We aimed to examine duration of antibiotic use and risk of CVD among apparently healthy women from the Nurses’ Health Study (NHS). Methods: This study included 36,922 women without history of myocardial infarction (MI), angina pectoris, stroke, or cancer in the NHS and with available data on total days of antibiotics use per year (0 to <15 days, 15 days to <2 months, or 2 months or more) during ages 20-39, 40-59 and after age 60, as reported on the 2004 questionnaire. Incidence of CVD (MI or stroke) over 8 years was assessed. Hazard ratios (HRs) were estimated as categories of duration of use compared with the none to <15 days per year group, using multivariate-adjusted Cox proportional hazards model including traditional risk factors (such as demographic variables, hypertension, diabetes, hypercholesterolemia, smoking, physical activity, Alternative Healthy Eating Index score, body mass index, aspirin, and anti-inflammatory medication), and reasons for antibiotics use (respiratory infection, urinary tract infections, acne or rosacea, chronic bronchitis, or dental), as well as other medications (such as H2 blockers, proton pump inhibitors), and other diseases (such as lung or kidney disease). Results: As compared to women with “none to <15 days per year of use” during age 40-59 y, those with a history of antibiotics use “15 days to < 2 months” or “2 months or more” had a significantly increased risk of CVD with an adjusted hazard ratio (HR [95%CI])_ of 1.19 (1.03, 1.38) and 1.34 (1.08, 1.66), respectively. Reported use of antibiotics for 2 months or more per year after age 60 was also associated with a HR of 1.24 (1.02, 1.51) for CVD. A longer exposure of antibiotics use was more strongly associated with increased risk of stroke than MI Antibiotic use during young adulthood (age 20-39) was not significantly associated with elevated risk of CVD. Conclusions: Our results suggest greater duration of exposure to antibiotics in middle- and older adulthood may be related to an increased risk of future CVD, independent of traditional risk factors.

VENTRICULAR TACHYCARDIA TRIGGERED BY LOPERAMIDE AND FAMOTIDINE ABUSE

A 32-year-old male developed recurrent ventricular tachycardia after taking mega doses of loperamide and famotidine in order to experience an opiate-like euphoric effect. He was taking up to 200 mg of loperamide and multiple doses of famotidine each day. He developed palpitations and syncope. Electrocardiography demonstrated ventricular tachycardia and QT interval prolongation (corrected QT interval was 597 ms). He was diagnosed with loperamide-induced QT prolongation resulting in incessant ventricular tachycardia. Loperamide was discontinued, and he was treated with electrolyte replacement, supportive care, and monitoring. After 5 days, his electrocardiogram (ECG) normalized and he had no more ventricular tachycardia. A Naranjo assessment score of 8 was obtained, indicating a probable relationship between QT prolongation and his use of loperamide. Large doses of loperamide can cause QT interval prolongation and life-threatening arrhythmias. These effects may be accentuated when histamine-2 receptor blockers are also abused.

Correlation between Helicobacter pylori infection and reflux esophagitis: still an ongoing debate

ContextThe vast majority of pathologies in the oesophagus, stomach and duodenum are related to either H. pylori infection or gastro-oesophageal reflux disease (GERD). Both conditions affect a large proportion of the population and they may occur either independently or concomitantly. The question of whether the two conditions are mutually exclusive, synergistic, or simply independent is an issue that was raised several years ago and is a matter of ongoing debate.AimWe aimed to determine the correlation between gastric Helicobacter colonization and grossly and histologically proven reflux esophagitis.Settings and designThis work was designed as a descriptive cross-sectional study.Patients and methodsThe study was conducted on 50 patients, five women and 45 men, aged 19–79 years (mean: 35.3 years). The inclusion criterion was having a history of symptoms suggestive of GERD.The cases were chosen from among outpatients and inpatients undergoing diagnostic endoscopic study at the endoscopy unit. The main presenting complaints were GERD symptoms, dyspepsia and postprandial epigastric pain. All cases were subjected to thorough history taking regarding the details and nature of the presenting complaint, special habits including caffeine consumption, smoking, and intake of medications such as antacids and H2 blockers, complete physical examination and upper endoscopy.Detailed description of upper endoscopic examination was reported, including the grade of esophagitis according to Savary–Miller classification.Three groups of biopsies were taken from each case: the first set from the lower end of the oesophagus and the two other sets from the gastric antrum. The oesophageal biopsies and one set of gastric biopsies were examined histologically after being processed.The second gastric biopsy set was used for direct detection of H. pylori using the rapid urease test (Campylobacter-like organism test). The rapid urease test offers a sensitivity of 80–99% and a specificity of 92–100% in untreated patients when compared with histology as the gold standard in the diagnosis of H. pylori infection.Statistical analysisData were statistically described in terms of frequencies (number of cases) and percentages and compared using the χ2-test. The exact test was used when the expected frequency was less than 5.ResultsOn using the rapid urease enzyme test there were 44 (88%) positive cases and six (12%) negative cases for H. pylori.By direct histopathologic examination there were 32 (64%) positive cases and 18 (36%) negative cases for H. pylori.There was no statistically significant correlation between gastric colonization with H. pylori and reflux esophagitis diagnosed grossly and histopathologically.ConclusionThe study showed no statistically significant correlation between H. pylori infection and the presence of reflux esophagitis.

Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury

Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60ml/min/1.73m2, incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy.

Are gastric hyperplastic polyps an additional manifestation in celiac disease?: Results from a retrospective study.

Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.

Using Probiotics Instead of Pharmaceuticals to Treat Gastrointestinal Disorders

Gastrointestinal disorders affect the majority of the population. While many people can go to the store and buy an antacid to alleviate their symptoms, millions of people each month seek out treatment from a physician and are prescribed H2 blockers and proton pump inhibitors (PPIs) to treat their digestive discomfort. Antacids used for a short period of time do not typically exhibit any negative side effects. If used properly, H2 blockers present very few side effects or negative health outcomes. PPIs on the other hand, are being linked to a myriad of serious side effects and permanent long-term health complications. Now that H2 blockers and PPIs are available for purchase without a prescription, it is virtually impossible to track the symptoms or disorders that are being treated with these medications. Probiotics are natural, healthy bacteria that offer the consumer health benefits from consumption. Probiotics are being studied for their role in positive health outcomes as well as treatment options for a variety of disease states including gastrointestinal disorders. Many strains of probiotics have been shown to alleviate symptoms of digestive tract discomfort as well as enhancing the microbiome. Given the severity of long-term use of antacids, H2 blockers, and PPIs, more research needs to be put into using probiotics to treat gastrointestinal disorders. Physicians and patients need to explore the possibility of using probiotics to treat gastrointestinal disorders in place of using pharmaceuticals that can have very serious, and potentially deadly, side effects.

Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H1-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H2-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%–70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3–10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine.

Low Re-infection Rate of Helicobacter pylori after Successful Eradication in Thailand: A 2 Years Study

Background:H. pylori is an important cause of chronic gastritis, peptic ulcers and gastric cancer. Re-infection rates after successful eradication vary in different regions of the world but only limited studies have been performed in ASEAN Countries to clarify this important issue. The present study was designed to evaluate the H. pylori re-infection rate and predictors of re-infection in Thailand.Methods:We recruited patients with chronic gastritis after 1 and 2 years successful H. pylori eradication from Thammasat University Hospital, Pathumthani (Central urban area) and Maesod district, Tak (Northern rural area), Thailand. 13C-UBT was performed to evaluate re-infection status after cessation of PPI, H2 blocker and antibiotics for at least 4 weeks. Statistical analysis was performed using SPSS for Windows Version 22.0 (IBM Corp., Armonk, NY).Results:A total of 105 subjects were enrolled (40 M and 65F with a mean age of 53.1 years). The overall re-infection rate was 6/105 (5.7%). The 1-year and 2-year H. pylori re-infection rates after successful eradication were only 5.1% (2/39) and 6.1% (4/66). 1-year and 2-year reinfection rates in urban areas were 2/39 (5.1%) and 1/26 (3.8%), while the 2-year reinfection rate in rural areas was 3/40 (7.5%). Location (urban vs rural area) and sex did not show any association with either 1-year or 2-year H. pylori re-infection. With 2-year reinfection, the mean age of H. pylori re-infected patients was significantly higher than those who remained cured (63.0 years vs. 51.6 years, p-value = 0.01). The annual H. pylori infection rate was 2.9%.Conclusions:1-year and 2-year H. pylori re-infection rates after successful eradication in Thailand appear low in both rural and urban areas. H. pylori eradication for prevention of significant upper GI disease should be recommended and confirmation of successful eradication should be the aim. Patients at higher risk such as the elderly should be monitored for possible risk of H. pylori re-infection.

Prevalence and Impact of Anemia Among Elderly Population in Qatar: A Cross Sectional Study

Background: Anemia is a most common condition in the older population, and the prevalence of anemia increases with advanced age. The present study is conducted to estimate the prevalence of anemia in elderly population and to identify the potential predictive factors associated with the etiology and disease progression. Methods: A retrospective chart review was conducted to include all geriatric patients (≥60 years) with anemia admitted at the geriatrics facilities (Rumailah hospital, skilled nursing facility and home healthcare services) in the state of Qatar between January 2013 and December 2013. Data include demographics, principle diagnosis, laboratory findings hemoglobin, hematocrit value, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), reticulocyte count, iron profile, serum folate, serum Creatinine other co-morbidities, medication, and assessment. Charlson’s comorbidity index, activity of daily living (ADL) and Bergs Balance Scoring level was compared with severity of anemia. Analysis was also performed for gender based on different age groups. Results: Prevalence of anemia was analysed according to severity. A total of 522 elderly patients were found to be anemic with mean age of 78.2 ± 8.6 years; of which 66.7% were females. The majority of patients were Qatari nationals (79.7%). The mean index hemoglobin level was 11.04 ± 1.6 and lowest hemoglobin level was 9.7 g/dl ± 1.6 g/dl. The severity of anemia was classified as mild deficiency (17.4%), moderate (60.3%) and severe anemia (21.8%). The severity in the hemogram values among patients showed significant difference for hematocrit (p=0.001), serum Iron (p=0.001) and serum Ferritin (p=0.001). Co-morbidities such as chronic kidney disease (p=0.001), and Gastrointestinal bleeding (p=0.03) were also were higher in severe group. There was significant negative correlation between hemoglobin level and creatinine level (p=0.001) among elderly patients. Patients with severe anemia were more likely to receive clopidogril (p=0.01), H2 blocker (p=0.04) and calcium (p=0.01). Severe anemia was observed more in patients with advanced age (≥ 80 years) while, elderly <80 years suffered frequently with mild-to-moderate anemia. The common type of anemia was diagnosed as normocytic normochromic anemia (73.6%) than microcytic anemia (26.8%). Conclusion: The present study identified a high prevalence of anemia among geriatric population in Qatar, with a higher frequency of comorbidities such as diabetes mellitus, hypertension and chronic kidney disease. An appropriate clinical approach is essential to treat anemia in elderly that can improve the quality of life and minimize the needs and costs of long-term healthcare facilities.

THU-129 - Chronic treatment with over-the-counter H1 or H2 histamine receptor blockers decreases cholangiocarcinoma xenograft tumor growth, angiogenesis and EMT

THU-129 - Chronic treatment with over-the-counter H1 or H2 histamine receptor blockers decreases cholangiocarcinoma xenograft tumor growth, angiogenesis and EMT

Evaluation of the central and peripheral effects of doxepin on carrageenan-induced inflammatory paw edema in rat.

The anti-inflammatory effects of anti-depressants have been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), has some special properties in comparison with the other members of its family. It has some H1, H2, alpha-1 adrenergic and muscarinic receptor blocking effects. It revealed also anti-nociceptive and relatively potent sedative effects. This study was aimed to evaluate its possible anti-inflammatory effect in a well-established animal model. Male Wistar rats weighing 200-250 g were used in carrageenan-induced inflammatory paw edema model. The test and control drugs were injected by intraperitoneal (i.p.) and intracerebral (i.c.v.) routes. The anti-inflammatory activity of doxepin (15, 30 and 60 mg/kg, i.p. and 50 and 100 μg/rat, i.c.v.) and the reference drug, dexamethasone (2 mg/kg, i.p.) were evaluated by determination and comparison of some involved biological markers including the paw volume, cytokine levels (interleukin 6 (IL-6), IL-1β, tumor necrosis factor α (TNFα)), myeloperoxidase (MPO) activity and histopathological parameters. All i.p. doses of doxepin showed significant anti-inflammatory effect. It also significantly reduced MPO activity and cytokine levels and improved histopathologic parameters of carrageenan-injected paw tissues. I.c.v. administration of the drug did not show any significant reduction of carrageenan-induced paw edema. Although the exact mechanism of the anti-inflammatory effect of doxepin is not clear, it seems that reduced leukocyte migration and pro-inflammatory cytokines play important role in its anti-inflammatory effect. Also central sites are not involved in the anti-inflammatory effect of the drug.

Two Cases of PFAPA Syndrome Treated with Tonsillectomy

PFAPA syndrome is characterized by five features: Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis, occurring in children under 5 years of age. Periodic fever, the main symptom, persists for about 3–6 days, accompanied by aphthous stomatitis, pharyngitis, neck lymphadenitis. We reviewed the data of two patients with PFAPA syndrome treated by tonsillectomy. In one patient, no improvement of the symptonms was obtained in response to treatment with a steroid and H2 blocker prescribed by a pediatrician, and tonsillectomy was performed; the patient has had no symptoms since this treatment.

Kinetic Studies of Ranitidine Hydrochloride Film Coated Tablets Available in Bangladesh: In vitro Study Reflection on in vivo

Background: This study deals with the comparative in vitro dissolution and in vitro disintegration characteristics of different brands of ranitidine hydrochloride film coated tablets most commonly available in Bangladesh which reflects the in vivo study. The objective of this present study was to evaluate the in vitro kinetic studies of ranitidine hydrochloride film coated tablets available in Bangladesh. Ranitidine hydrochloride is a potent H2 blocker recommended for hyperacidity related disorders and most common OTC drugs that frequently used by the common people in the world. Methods: Twenty one brands of ranitidine hydrochloride film coated tablets available in Bangladesh drug market were assayed spectrophotometrically and their various kinetics (Zero Order, First Order, Higuchi and Hixson-Crowell) studies were performed to predict in vivo analysis. Results: In Bangladesh, commercially available twenty one brands of ranitidine hydrochloride film coated tablets were studied. The media of the study was distilled water (pH 7.5) due to identify complete organoleptic properties of Ranitidine Hydrochloride. Nine brands (RH-3, RH-5, RH-6, RH-10, RH-11, RH-12, RH-13, RH-14 and RH-17) showed delayed disintegration time instead of quick release formulation, which often claimed by those manufacturer. Other twelve brands (RH-1, RH-2, RH-4, RH-7, RH-8, RH-9, RH-15, RH-16, RH-18, RH-19, RH-20 and RH-21) showed the moderate disintegration time. The tablets were studied for in vitro dissolution behavior for 1 h in distilled water using USP reference dissolution apparatus. The in vitro dissolution profiles of the thirteen brands (RH-1, RH-2, RH-4, RH- 7, RH-8, RH-9, RH-13, RH-15, RH-16, RH-18, RH-19, RH-20 and RH-21) were fulfilled the USP in vitro dissolution specification of 80% drug release within 45 min. On the other hand, five of the total selected brands (RH-3, RH-5, RH-10, RH-12 and RH-17) were failed to fulfill the USP in vitro dissolution specification. Rest three brands (RH-6, RH-11 and RH-14) exhibited very poor release pattern among the selected brands and their drug release rate were 23%, 11% and 19% respectively after one hour study. The drug potency, multiple coefficient (from zero order, first order, Higuchi and Hixson-Crowell cube root law), similarity and dissimilarity factors were determined in this study. The predicted steady state plasma concentration determined by comparing the in vivo pharmacokinetic data of reference brand (Zantac) using superposition principle of steady state plasma levels determination. Conclusion: Most of the brands meet the official requirements, which are very essential parameters for the prediction of in vivo drug release by oral route. As a result the patients will get the proper therapeutic effect to combat against hyperacidity problems while they use those brands of ranitidine hydrochloride film coated tablets.

The role of pH in symptomatic relief and effective treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a condition in which gastroduodenal contents pass into the oesophagus and cause troublesome symptoms and complications. The aetiopathogenesis of gastroesophageal reflux disease is complex and multifactorial. Acid reflux plays an important role in the GERD pathogenesis, both in erosive and non-erosive reflux disease. Reduction of GERD symptoms and mucosal healing correlates with the number of hours that intragastric acid is suppressed to a pH > 4.0. Mucosal healing was achieved in most of patients who received different types of proton pump inhibitors, but only in 50% of those who received H2 blockers. These findings seem to be best accounted for by differences in the duration and degree of acid suppression achieved by different classes of drugs and perhaps between agents within those classes.

Systemic Mastocytosis Patient Experience from Mast Cell Connect, the First Patient-Reported Registry for Mastocytosis

Background:Systemic mastocytosis (SM) is a rare mast cell disorder associated with a range of debilitating symptoms and a shortage of effective treatment options. Little is known about the impact of the disease from the patients' perspective. Systematically characterizing the natural history of SM and its impact on patients will facilitate the development of new therapies. Registries that engage patients have proven valuable in other rare diseases by expanding knowledge of current treatment approaches, evaluating disease burden and accelerating clinical trials.Methods:Mast Cell Connect (NCT02620254, www.mastcellconnect.org) is an observational database that captures demographic, socioeconomic and disease information from patients with mastocytosis. It is the first patient-reported registry for mastocytosis to our knowledge. Key objectives are to improve collective understanding of the disease burden on patients and to facilitate development of new therapies by increasing participation in clinical trials. Enrollment is "site-agnostic" as participants register and take surveys on a secure online portal. Since many US patients are seen outside large clinical centers, this enables broader participation and collection of real-world data. Inclusion criteria are a diagnosis of SM or cutaneous mastocytosis (CM). Diagnoses are self-reported and participants are asked to provide medical reports that will be used to confirm diagnoses in the future. Informed consent is required to join this IRB-approved study.Results:Mast Cell Connect opened on December 1, 2015. As of May 31, 2016, 166 participants had registered, of whom 157 had responded to the online survey. Of the 153 participants who reported their diagnosis, 107 had SM and 38 had CM. Those who reported a diagnosis of SM were categorized as SM participants if they also reported other diagnoses. The current analyses are based on data provided by the 107 SM participants.Of the 107 SM participants, 60 (56%) had Indolent SM (ISM), 8 (7%) had Smoldering SM (SSM), 10 (9%) had Advanced SM (AdvSM, defined as aggressive SM, SM with an associated hematological neoplasm, and Mast Cell Leukemia) and 29 (27%) did not know their subtype. Median age was 50 years (range 4-77). More females participated (74%) than males (26%). Median time from symptom-onset to diagnosis was 7 years. Participants saw a median of 3 specialists prior to diagnosis, most frequently dermatology (67%), allergy/immunology (67%), hematology/oncology (63%) and general practitioner/internal medicine (63%). Specialists diagnosing SM most often included dermatology (36%), allergy/immunology (25%) and hematology/oncology (23%). AdvSM participants were typically diagnosed by hematology/oncology (70%).The medications taken most often at the time of survey were anti-histamines (85% H1 blockers, 72% H2 blockers), leukotriene inhibitors (38%) and cromolyn sodium (33%). Agents to reduce mast cell burden were taken less often (imatinib: 7%, interferon-α: 2%, hydroxyurea: 1% and investigational agents: 1%). Symptoms reported as moderately to severely bothersome included: fatigue (69%), difficulty concentrating (63%), abdominal pain (55%), pain in other locations (53%), difficulty sleeping (53%), itching (46%), diarrhea (45%), bloating (43%), nausea (42%), headache (40%), skin changes (40%), anxiety (39%) and flushing (37%). Participants reported being limited in work or other daily activities "quite a bit" to "very much" in 47% of ISM, 43% of SSM, and 70% of AdvSM cases. Participants’ physical condition or medical treatment interfered with their family life "quite a bit" or "very much" in 59% of ISM, 43% of SSM, and 80% of AdvSM cases.Conclusions:Over 160 participants joined Mast Cell Connect in the first 6 months, indicating the mastocytosis community, including The Mastocytosis Society, is highly motivated to participate in research. SM participants reported a diagnostic odyssey, seeing multiple specialists over a median of 7 years prior to diagnosis. Despite frequent use of symptom-directed medications, symptom burden remains substantial and considerably impacts quality of life. Novel therapies targeting the underlying disease are needed. Establishing US centers of excellence may hasten the time to diagnosis. Continued collaboration between researchers, patient advocates and industry is needed to advance the care of patients with SM. DisclosuresLee:Blueprint Medicines: Employment, Equity Ownership. George:Allakos: Research Funding; Novartis: Consultancy; Blueprint Medicines: Consultancy; Allakos: Research Funding; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy; GLG: Consultancy; Wiley Blackwell: Consultancy; American Registry of Pathology: Patents & Royalties; Wolters Kluwer: Patents & Royalties; UpToDate: Patents & Royalties. Shi:Blueprint Medicines: Employment, Equity Ownership. Evans:Blueprint Medicines: Employment, Equity Ownership. Singh:Blueprint Medicines: Employment, Equity Ownership. Boral:Blueprint Medicines: Employment, Equity Ownership. Rangel Miller:PatientCrossroads: Employment, Equity Ownership.

Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema

The B2 receptor antagonist icatibant is approved for treatment of attacks of hereditary angioedema. Icatibant has been reported to decrease time-to-resolution of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema in 1 study of European patients. We sought to test the hypothesis that a bradykinin B2 receptor antagonist would shorten time-to-resolution from ACE inhibitor-associated angioedema. Patients with ACE inhibitor-associated angioedema (defined as swelling of lips, tongue, pharynx, or face during ACE inhibitor use and no swelling in the absence of ACE inhibitor use) were enrolled at Vanderbilt University Medical Center from October 2007 through September 2015 and at Massachusetts General Hospital in 2012. C1 inhibitor deficiency and patients with bowel edema only were excluded. Patients were randomized within 6hours of presentation to subcutaneous icatibant 30mg or placebo at 0 and 6hours later. Patients assessed severity of swelling using a visual analog scale serially following study drug administration or until discharge. Thirty-three patients were randomized and 31 received treatment, with 13 receiving icatibant and 18 receiving placebo. One patient randomized to icatibant did not complete the visual analog scale and was excluded from analyses. Two-thirds of patients were black and two-thirds were women. Time-to-resolution of symptoms was similar in placebo and icatibant treatment groups (P=.19 for the primary symptom and P>.16 for individual symptoms of face, lip, tongue, or eyelid swelling). Frequency of administration of H1 and H2 blockers, corticosteroids, and epinephrine was similar in the 2 treatment groups. Time-to-resolution of symptoms was similar in black and white patients. This study does not support clinical efficacy of a bradykinin B2 receptor antagonist in ACE inhibitor-associated angioedema.

Abstract 11677: Associations Between Proton Pump Inhibitors and Low Cardiac Mortality in Patients With Heart Failure

Background: It has been recently reported that use of histamine H 2 receptor blocker (H2RA) is associated with the blockade of right and left ventricular remodeling and reduces risk of incident heart failure (HF) in cohort of participants without cardiovascular diseases. However, the association between acid suppressive therapy such as H2RA or proton pump inhibitor (PPI) and cardiac mortality in HF patients is still unclear. Therefore, we examined impacts of the acid suppressive therapy on cardiac mortality in HF patients. Methods and Results: We analyzed consecutive 1191 HF patients. These patients were divided into 3 groups: no acid suppressive therapy group (None, n = 363), H2RA group (n = 164) and PPI group (n = 664). Although presence of male gender, diabetes, atrial fibrillation and reduced left ventricular ejection fraction did not differ among the three groups, prevalence of ischemic etiology, dyslipidemia, chronic kidney disease, anemia and past history of peptic ulcer was higher in PPI group than in H2RA and no acid suppressive therapy groups (ischemic etiology 32.2% vs. 27.4% and 15.7%, p&lt;0.001; dyslipidemia 79.2% vs. 77.4% and 70.5%, p=0.007; chronic kidney disease 62.8% vs. 57.3% and 53.2%, p=0.010; anemia 64.0% vs. 54.3% and 46.0%, p&lt;0.001; peptic ulcer 15.1% vs. 7.9% and 6.3%, p&lt;0.001). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly lower in PPI group than in H2RA and no acid suppressive therapy groups (11.0% vs. 21.3% and 16.8%, respectively, p&lt;0.05). In the multivariable Cox proportional hazard analysis after adjusting for other potential confounding factors, use of PPI, but not H2RA, was an independent predictor of cardiac mortality in HF patients (PPI, HR 0.475, P&lt;0.001 and H2RA, HR 0.968, P=0.881). Conclusion: Proton pump inhibitors may be associated with better outcome in patients with heart failure.

Effect of Gastric Acid Suppressant Prophylaxis on Incidence of Gastrointestinal Bleeding in Pediatric Intensive Care Unit

Background: Critically ill children admitted to pediatric intensive care unit (PICU) are at increased risk of gastrointestinal bleeding due to stress related mucosal injury. Reducing gastric acid by acid suppressant medication is the accepted prophylaxis treatment, but there is not any definitive guideline for using prophylaxis in PICU patients. The present study aimed to assess the effect of Proton Pump Inhibitor (PPI) and H2 Blocker (H2B) prophylaxis on gastrointestinal bleeding in admitted patients of PICU, Mashhad- Iran.Materials and Methods: In this study, 100 patients admitted in PICU divided into two equal groups on the first day of admission. They received ranitidine or pantoprazole as prophylaxis of stress ulcer. Those patients who had history of gastrointestinal bleeding or coagulation disorder were excluded. 100 PICU patients who had not received prophylaxis during last 6 months retrospectively evaluated as control of the study. Data were collected as demographic characteristics, admission reason, definitive diagnosis, receiving corticosteroid and mechanical ventilation in each patient. Gastrointestinal bleeding (hematemesis, coffee ground aspirate, and melena) and clinically significant gastrointestinal bleeding were daily monitored. Data analyzed through descriptive statistical tests, Chi-square, logistic regression, t-test and using SPSS-16 software.Results: Among 204 patients (control group=105 and case group=99), incidence of gastrointestinal bleeding (GB) was 13.2% in which 6.9% of cases presented with clinically significant gastrointestinal bleeding (CSGB). Loss of consciousness and respiratory distress were the main reason of admission. There was no significant differences between the incidence of (GB) and (CSGB) in experimental and control groups (P>0.05) as well as ranitidine and pantoprazole prophylaxis (P>0.05). Significant risk factors of (GB) were mechanical ventilation and loss of consciousness and corticosteroid therapy.Conclusion: There is ambiguity about probable benefits of gastrointestinal bleeding prophylaxis in critically ill children. We proposed that prophylaxis should prescribe in patients with two or more risk factors of gastrointestinal bleeding.

Long-term follow-up of composite bladder augmentation incorporating stomach in a multi-institutional cohort of patients with cloacal exstrophy

Composite bladder augmentation, incorporating gastric and bowel segments, has the theoretical advantage of metabolic neutrality while potentially avoiding the morbidities of gastrocystoplasty, such as hematuria-dysuria syndrome. The most common indication for this operation is a paucity of bowel, such as in cloacal exstrophy. Despite several early descriptive studies of this technique, there are no reports, to date, of long-term follow-up in this population. To describe the outcomes of composite bladder augmentation utilizing stomach in a cohort of cloacal exstrophy patients. A retrospective review of cloacal exstrophy patients who underwent composite bladder augmentation from 1984 to 2006at two institutions was performed. The incidence of mortality and morbidities related to augmentation was evaluated. Eleven patients with cloacal exstrophy underwent composite bladder augmentation. Median age at initial augmentation was 6.4 years (interquartile range (IQR) 4.4-9.1). Median follow-up was 13.2 years (IQR 11.2-24.6). The Summary table describes the types of composite bladder augmentations. Of the three patients with pre-operative metabolic acidosis, two improved with composite bladder augmentation and one developed metabolic alkalosis. Three developed hematuria-dysuria syndrome: one improved with staged ileocystoplasty, and two had persistent symptoms successfully treated with H2 receptor blockers. Two of 11 developed symptomatic bladder stones. There were no reported bladder perforations, bladder malignancies, conversions to incontinent urinary diversions, or deaths. With long-term follow-up, very few patients developed metabolic acidosis/alkalosis after composite bladder augmentation. The composite bladder augmentation will continue to be used in patients with cloacal exstrophy, in order to minimize the impact on the pre-existing short gut in these patients.

Insulin Autoimmune Syndrome: a rare cause of postprandial hypoglycemia.

SummaryA 65-year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels. She did not have any evidence for the use of oral antidiabetic medications, insulin, herbal substances, performing strenuous exercise or history of bariatric surgery. Fingerstick blood glucose readings revealed blood sugar of 35 mg/dL and 48 mg/dL, when she had these symptoms. Her medical history was significant for morbid obesity, hypothyroidism and gastro esophageal reflux disease. Her home medications included levothyroxine, propranolol and omeprazole. A blood sample obtained during the symptoms revealed the following: fingerstick blood sugar 38 mg/dL, venous blood glucose 60 mg/dL (normal (n): 70–99 mg/dL), serum insulin 202 IU/mL (n: <21), proinsulin 31.3 pmol/L (n: <28.9), C-peptide 8 ng/mL (n: 0.9–7), beta-hydroxybutyrate 0.12 mmol/L (n: 0.02–0.27) anti-insulin antibody >45.4 U/mL (n: <0.4). The result obtained while screening for serum sulfonylurea and meglitinides was negative. The repeated episodes of postprandial hypoglycemia associated with significantly elevated anti-insulin antibodies led to a diagnosis of insulin antibody syndrome (IAS). Significant improvement of hypoglycemic symptoms and lower anti-insulin antibody levels (33 U/mL) was noted on nutritional management during the following 6 months. Based on a report of pantoprazole-related IAS cases, her omeprazole was switched to a H2 receptor blocker. She reported only two episodes of hypoglycemia, and anti-insulin antibody levels were significantly lower at 10 U/mL after the following 12-month follow-up.Learning points:Initial assessment of the Whipple criteria is critical to establish the clinical diagnosis of hypoglycemia accurately.Blood sugar monitoring with fingerstick blood glucose method can provide important information during hypoglycemia workup.Autoimmune hypoglycemia is a rare cause of hypoglycemia, which can be diagnosed on high index of clinical suspicion and systematic evaluation.