H2 Antagonists Research Articles

PD04 Real-life experience of Scottish patients with idiopathic solar urticaria

Abstract We conducted a retrospective study to characterize our most recent cohort of patients with idiopathic solar urticaria (SU), to compare with our previous findings (Beattie PE, Dawe RS, Ibbotson SH, Ferguson J. Characteristics and prognosis of idiopathic solar urticaria: a cohort of 87 cases. Arch Dermatol 2003; 139:1149–54). We analysed data derived from our in-house database and paper and electronic records of patients with SU seen through the Scottish Photobiology Service between 2003 and 2022. Eighty-four patients with SU were seen in this period, 57 (68%) women and 27 (32%) men. Twenty-nine (35%) had a single consultation/phototesting and 55 (65%) had follow-up assessments. The average age of onset was 37 years, with the average age of diagnosis being 41 years, with delays from symptom onset to diagnosis ranging from 6 months to 24 years. Importantly, 20 (24%) patients self-reported systemic symptoms, most commonly fatigue, dizziness and nausea. Of 61 patients using antihistamines before diagnosis, 31 (51%) reported benefit. Of patients who tried sunscreens, 31 of 65 (48%) reported benefit. On monochromator phototesting, sensitivity predominantly involved the ultraviolet (UV)A waveband (335–400 + 27 nm in 55%), extending into the visible spectrum (> 430 + 27 nm) in 44% and UVB waveband (305 + 5 nm) in 1%, consistent with previous reports of predominant UVA/visible light dependency in SU. On review of follow-up data, we analysed the fold benefit in minimal urticaria dose (MUD) from testing on H1 antihistamines alone, H1 and H2 antihistamines combined and the addition of montelukast. Most (65%) responded with a more than twofold improvement in MUD after a single dose of H1 antihistamine, with only 35% not responding. Increasing the dose of H1 antihistamine did not provide notable additional benefit. There was a suggestion of improved responses by the addition of an H2 antagonist (in 76% vs. 66% with H1 antagonist alone), but this was not statistically significant (P > 0.05). No additional improvement in threshold sensitivity (MUD) was observed by the addition of montelukast. Small numbers of patients used other treatments such as photo(chemo)therapies and systemic immunosuppressants, and these were found to be of limited benefit. Since 2011, we have used omalizumab for patients with treatment-resistant SU. Of the current cohort, 13 received omalizumab, with 62% reporting a good clinical response and a further 15% a partial clinical response. Phototesting in these patients showed complete abolition of photosensitivity or excellent responses (more than fivefold increase in MUD) in 73%, demonstrating the efficacy of omalizumab in recalcitrant SU. Given the systemic features reported by some patients with SU, this supports a management approach, which includes systemic immunomodulation as a potentially effective option.

PPIs and gastric cancer: any causal relationship?

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality. Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.

Epigenetic Histone Methylation of PPARγ and CPT1A Signaling Contributes to Betahistine Preventing Olanzapine-Induced Dyslipidemia.

As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a combination therapy, although the underlying epigenetic mechanisms are still not known. Recent studies have revealed that histone regulation of key genes for lipogenesis and adipogenesis in the liver is one of the crucial mechanisms for olanzapine-induced metabolic disorders. This study investigated the role of epigenetic histone regulation in betahistine co-treatment preventing dyslipidemia and fatty liver caused by chronic olanzapine treatment in a rat model. In addition to abnormal lipid metabolism, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), as well as the downregulation of carnitine palmitoyltransferase 1A (CPT1A) in the liver induced by olanzapine, were significantly attenuated by betahistine co-treatment. In addition, betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of Cpt1a gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A). Betahistine co-treatment also significantly enhanced the global expression of H3K9me and the enrichment of H3K9me binding on the promoter of the Pparg gene, but inhibited the expression of two of its site-specific demethylases, lysine demethylase 4B (KDM4B) and PHD finger protein 2 (PHF2). These results suggest that betahistine attenuates abnormal adipogenesis and lipogenesis triggered by olanzapine through modulating hepatic histone methylation, and thus inhibiting the PPARγ pathway-mediated lipid storage, while at the same time promoting CP1A-mediated fatty acid oxidation.

P19-derived neuronal cells express H1, H2, and H3 histamine receptors: a biopharmaceutical approach to evaluate antihistamine agents

Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase. The exposure of P19 neurons to histamine reduced cell viability to 65% maximally. This effect involves specific histamine receptors, since it was prevented by treatment with desloratadine and cimetidine, respectively, H1 and H2 antagonists, but not by the H3 antagonist ciproxifan. RT-PCR analysis showed that P19 neurons express H1 and H2 receptors, and the H3 receptor, although it seemed not involved in the histamine effect on these cells. The H4 receptor was not expressed. H1 and H2 antagonists as well as vegetal diamine oxidase diminished the intracellular Ca2+ mobilization triggered by histamine. The treatment with vegetal diamine oxidase or catalase protected against mortality and a significant reduction of H2O2 level, generated from the cells under the histamine action, was found upon treatments with desloratadine, cimetidine, vegetal diamine oxidase, or catalase. Overall, the results indicate the expression of functional histamine receptors and open the possibility of using P19 neurons as model system to study the roles of histamine and related drugs in neuronal pathogenesis. This model is less expensive to operate and can be easily implemented by current laboratories of analysis and by Contract Research Organizations.

Histamine receptors in GtoPdb v.2023.1

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [80, 174]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [80]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [174]. Some agonists at the human H3 receptor display significant ligand bias [183]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [174] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [217, 8].

Valproic Acid is an Effective Anti-Emetic Treatment in Alexander Disease (P10-9.010)

<h3>Objective:</h3> To explore safety and effectiveness of anti-emetic strategies in Alexander disease (AxD). <h3>Background:</h3> Emesis is a frequent symptom in AxD and leads to inadequate intake and food avoidance behaviors. As a result, weight loss and failure to thrive are common in AxD. We explored emesis treatment strategies to determine their relative benefits and side effects in clinical practice. <h3>Design/Methods:</h3> Medical records of patients with AxD (&lt;21 years) participating in a natural history cohort study were reviewed for history of emesis, difficulty with weight gain, and medications. Patients were retrospectively evaluated for response to medication, which was defined as a clinically meaningful decrease in emesis. Treatment failure was defined as no improvement, worsened emesis, clinically significant weight loss, or presence of an intolerable side effect. Deceased patients, patients with a Nissen fundoplication, and patients with insufficient longitudinal data were excluded. Fisher’s exact tests were used to compare response rates of valproic acid to those of anti-reflux medications (proton pump inhibitors, H2 antagonists analyzed together) or cyproheptadine. <h3>Results:</h3> Among 59 subjects with vomiting, 34 subjects met inclusion criteria. Emesis was treated with multiple anti-reflux medications (N=24), cyproheptadine (N=19), and valproic acid (VPA, N=22). Overall, 48% of patients responded to multiple anti-reflux medications, 32% responded to cyproheptadine, and 95% responded to VPA. VPA had a higher success rate in reducing emesis compared to multiple reflux medications (p=0.0001) or cyproheptadine (p&lt;0.0001). Adverse effects from VPA included bone fractures (N=1) in a non-ambulatory patient, hyperammonemia (N=2) which resolved with dose lowering, and mild hair loss (N=2). <h3>Conclusions:</h3> Recognizing the limitations of retrospective review, 95% of AxD patients on VPA showed improvements in emesis and weight gain. Response rates to VPA were greater compared to anti-reflux medications or cyproheptadine. VPA is well tolerated overall, although use should be monitored for known adverse effects. <b>Disclosure:</b> Ms. Sergio has nothing to disclose. Miss Gallison has nothing to disclose. Dr. Porcari has nothing to disclose. The institution of Mr. Joung has received research support from Ionis Pharmaceuticals. Mr. Faig has nothing to disclose. An immediate family member of Geraldine Liu has received publishing royalties from a publication relating to health care. Dr. Waldman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio. An immediate family member of Dr. Waldman has stock in Pfizer. The institution of Dr. Waldman has received research support from Ionis Pharmaceuticals. Dr. Waldman has received publishing royalties from a publication relating to health care.

Review article: An analysis of the pharmacological rationale for selecting drugs to inhibit vomiting or increase gastric emptying during treatment of gastroparesis.

Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms. Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another? Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use. Vomiting: Rationale for 5-HT3 , D2 , H1 or muscarinic antagonists, and mirtazapine, amitriptyline, nortriptyline, are poor. Arguments for inhibiting central consequences of vagal afferent transmission by NK1 antagonism are complicated by doubts over effects on nausea. Gastric emptying: Confusion emerges because of side-effects of drugs increasing gastric emptying: Metoclopramide (5-HT4 agonist, D2 and 5-HT3 antagonist; also blocks some emetic stimuli and causes tardive dyskinesia) and Erythromycin (high-efficacy motilin agonist, requiring low doses to minimise side-effects). Limited trials with selective 5-HT4 agonists indicate variable efficacy. Several drug classes inhibiting vomiting have no scientific rationale. NK1 antagonism has rationale but complicated by limited efficacy against nausea. Studies must resolve variable efficacy of selective 5-HT4 agonists and apparent superiority over motilin agonists. Overall, lack of robust activity indicates a need for novel approaches targeting nausea (e.g., modulating gastric pacemaker or vagal activity, use of receptor agonists or new targets such as GDF15) and objective assessments of nausea.

Histamine and its H1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors.

Many structures of the central nervous system recruit different neurotransmitters in pain processing. This study focused on the contribution of histamine and its H1 receptors in the ventral pallidum (VP) in mediating pain-triggered behaviors. Intra-VP microinjection of histamine and 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist) at the same doses of 0.5 and 1 µg/200 nl reduced both the first and second phases of licking/biting duration as well as flinching number induced by intra-plantar (ipl) injection of formalin (2.5%, 50 µl). Premicroinjection of mepyramine (a histamine H1 antagonist, 2 µg/200 nl) into the VP antagonized the suppressive effects of 1 µg/200 nl histamine and 2-PEA on licking/biting and flinching behaviors. The possible mechanisms of the above-mentioned pain-reducing effects were followed by intra-VP and intrathecal administration of naloxone (an opioid receptor antagonist). Naloxone (2 µg/200 nl) preadministration into the VP inhibited attenuating effects of histamine and 2-PEA on both the licking/biting and flinching behaviors, whereas intrathecal injection of naloxone only inhibited their suppressing effects on flinching behavior. None of the treatments used in this study altered the animal's motor activity. The obtained results may reveal the role of histamine and its activated H1 receptor in the VP in suppressing the pain behaviors caused by formalin. Opioid receptors in the VP and spinal cord may contribute to these functions.

644 - Proton pump inhibitors versus H2 antagonists for prevention of COVID-19 complications

644 - Proton pump inhibitors versus H2 antagonists for prevention of COVID-19 complications

Vertigo and H4 Antagonist Effect on Vestibular Symptoms

Vertigo and H4 Antagonist Effect on Vestibular Symptoms

Correlation between Medications Used during COVID Infection and Post-conditions after the Acute Phase of Infection: A Cross-sectional Study

Background: During the COVID-19 pandemic, off-label medication prescribing and utilizing herbal products and multiple vitamins in the treatment, prevention, and symptom management of COVID-19 was an urgently needed practice to halt the SARS-CoV-2 infection crisis and progression. Objectives: This study aimed to determine the correlation between medications used during the pandemic and SARS-CoV-2 infection post-recovery symptoms. Methods: A cross-sectional questionnaire-based study was conducted on recovered COVID-19 patients. There were 20 multiple-choice questions, including patient demographics, treatment, and post-recovery symptoms. Chi-square and Fisher’s exact tests were used to investigate significant relationships. In addition, Binary logistic regression was performed to determine confounders. Data were analyzed using SPSS version 22. Results: Medications and supplements varied in their therapeutic effects on SARS-CoV-2 post-recovery symptoms. Patients who took vitamin D and calcium experienced increased symptom frequency, and patients taking ACE inhibitors experienced more headaches and coughs. Furthermore, patients receiving azithromycin were asymptomatic after recovery. Patients who took H2 antagonists reported persistent headaches and muscle pain. Conclusion: Patients infected with SARS-CoV-2 have responded differently to medications, multivitamins, and herbal supplements. Patients reported resolution of some symptoms and persistence of others post-recovery. Therefore, expert opinion should be considered in COVID-19 management until randomized controlled trials answer many questions and determine medications' safety and efficacy in prevention, treatment strategies, and symptoms of SARS-CoV-2 infection post-recovery.

Correlation between Medications Used During Covid Infection and Post-Conditions after the Acute Phase of Infection: A Cross-Sectional Study

Background During the COVID-19 pandemic, off-label medication prescribing and utilizing herbal products and multiple vitamins in the treatment, prevention, and symptom management of COVID-19 was an urgently needed practice to halt the SARS-Cov2 infection crisis and progression. Objectives This study aimed to determine the correlation between medications used during the pandemic and SARS-CoV-2 infection post-recovery symptoms. Methods A cross-sectional questionnaire-based study was conducted on recovered COVID-19 patients. There were 20 multiple-choice questions, including patient demographics, treatment, and post-recovery symptoms. Chi-square and Fisher’s exact tests were used to investigate significant relationships. In addition, Binary logistic regression was performed to determine confounders. Data were analyzed using SPSS version 22. Results Medications and supplements varied in their therapeutic effects on SARS-CoV-2 post-recovery symptoms. Patients who took vitamin D and calcium experienced increased symptom frequency, and patients taking ACE inhibitors experienced more headaches and coughs. Furthermore, more patients receiving azithromycin were asymptomatic after recovery. Patients who took H2 antagonists reported persistent headaches and muscle pain. Conclusion Patients infected with SARS-CoV-2 have responded differently to medications, multivitamins, and herbal supplements. Patients reported resolution of some symptoms and persistence of others post-recovery. Therefore, expert opinion should be considered in covid-19 management until randomized controlled trials answer many questions and determine medications' safety and efficacy in prevention, treatment strategies, and symptoms of SARS-Cov-2 Infection post-recovery.

PD29 Systematic Review With Meta-analysis Of Pharmacokinetic Parameters Of Tyrosine Kinase Inhibitors Used In Chronic Myeloid Leukemia

IntroductionTherapeutic drug monitoring (TDM) is a cost-effective tool to increase treatments’ efficacy and safety. Analyses of pharmacokinetics proprieties of tyrosine kinase inhibitors (TKI) used for chronic myeloid leukemia (CML) can contribute towards effective TDM, development of tailored treatments and new dosing regimens. We aimed to synthesize the available evidence on pharmacokinetic parameters of imatinib, nilotinib, bosutinib, ponatinib in healthy individuals vs. CML patients.MethodsSystematic searches were conducted in PubMed, Scopus and Web of Science. We included in vivo studies addressing TKIs’ pharmacokinetics, including maximum observed concentration (Cmax), time of maximum observed concentration (Tmax) and half-life (t1/2). Meta-analyses of event rates (mixed-effect models) were performed for the parameters of interest: area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and from time zero to infinity (AUC 0-∞). Results were presented as event rates with 95 percent confidence intervals. Heterogeneity was assessed using chi-square and I2 statistical tests and considered significant when p&lt;0.05 and high when I2&gt;75 percent (Comprehensive Meta-Analysis v.2 Biostat-Englewood, NJ).ResultsOverall, 50 articles were included for analyses (n=26 imatinib, n=11 nilotinib, n=8 bosutinib, n=5 ponatinib). Most studies were performed in the United States (46.0%), designed as open-label trials (70.0%). Several significant interactions between TKI with enzyme inhibitors (ketoconazole, midazolam, aprepitant, metoprolol, grapefruit juice), proton pump inhibitors (esomeprazole, lanzoprazole, omeprazole), antacids, H2 antagonists (famotidine) and enzyme inducers (St. John’s, rifampicin) were found (p&lt;0.001). Given the significant increase in AUC and Cmax in patients with hepatic/liver impairments currently using TKI, strict therapeutic monitoring is paramount to maintain safety. The between study heterogeneity was rated as moderate to high (I2=75-90%) due the limited number of trials for some drugs, different study design, and populations.ConclusionsThe co-administration of TKI with hepatic enzyme inducers or inhibitors, proton pump inhibitors, antacids, H2 antagonists, as well as in patients with hepatic/liver failures requires caution and additional monitoring. Further well-designed trials are needed to strengthen this evidence for some TKIs, namely bosutinib and ponatinib.

Urticaria: Etiology, pathogenesis, diagnosis, and treatment

Urticaria is the most common skin disease, it may be chronic or acute. Infections, medicines, psychogenic factors, food, and respiratory allergens such factors are accused of etiology. But sometimes it may be idiopathic. H1 antihistamines and short-term systemic corticosteroids are taken for the treatment. H2 antagonists may be preferred during resistant cases. Cyclosporine, omalizumab, and leukotriene receptor antagonists are other treatment options considered during missed events.

Green Solvents for Eco-Friendly Synthesis of Dimethindene: A Forward-Looking Approach.

Dimethindene is a selective histamine H1 antagonist and is commercially available as a racemate. Upon analyzing the synthetic pathways currently available for the industrial preparation of dimethindene, we set up a sustainable approach for the synthesis of this drug, switching from petroleum-based volatile organic compounds (VOCs) to eco-friendly solvents, such as 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) belonging to classes 3 and 2, respectively. Beyond decreasing the environmental impact of the synthesis (E-factor: 24.1-54.9 with VOCs; 12.2-22.1 with 2-MeTHF or CPME), this switch also improved the overall yield of the process (from 10% with VOCs to 21-22% with 2-MeTHF or CPME) and remarkably simplified the manual operations, working under milder conditions. Typical metrics applied at the first and second pass, according to the CHEM21 metrics toolkit, were also calculated for the whole synthetic procedure of dimethindene, and the results were compared with those of the classical procedure.

Pharmacological interventions for prevention of weight gain in people with schizophrenia.

Antipsychotic-induced weight gain is an extremely common problem in people with schizophrenia and is associated with increased morbidity and mortality. Adjunctive pharmacological interventions may be necessary to help manage antipsychotic-induced weight gain. This review splits and updates a previous Cochrane Review that focused on both pharmacological and behavioural approaches to this problem. To determine the effectiveness of pharmacological interventions for preventing antipsychotic-induced weight gain in people with schizophrenia. The Cochrane Schizophrenia Information Specialist searched Cochrane Schizophrenia's Register of Trials on 10 February 2021. There are no language, date, document type, or publication status limitations for inclusion of records in the register. We included all randomised controlled trials (RCTs) that examined any adjunctive pharmacological intervention for preventing weight gain in people with schizophrenia or schizophrenia-like illnesses who use antipsychotic medications. At least two review authors independently extracted data and assessed the quality of included studies. For continuous outcomes, we combined mean differences (MD) in endpoint and change data in the analysis. For dichotomous outcomes, we calculated risk ratios (RR). We assessed risk of bias for included studies and used GRADE to judge certainty of evidence and create summary of findings tables. The primary outcomes for this review were clinically important change in weight, clinically important change in body mass index (BMI), leaving the study early, compliance with treatment, and frequency of nausea. The included studies rarely reported these outcomes, so, post hoc, we added two new outcomes, average endpoint/change in weight and average endpoint/change in BMI. Seventeen RCTs, with a total of 1388 participants, met the inclusion criteria for the review. Five studies investigated metformin, three topiramate, three H2 antagonists, three monoamine modulators, and one each investigated monoamine modulators plus betahistine, melatonin and samidorphan. The comparator in all studies was placebo or no treatment (i.e. standard care alone). We synthesised all studies in a quantitative meta-analysis. Most studies inadequately reported their methods of allocation concealment and blinding of participants and personnel. The resulting risk of bias and often small sample sizes limited the overall certainty of the evidence. Only one reboxetine study reported the primary outcome, number of participants with clinically important change in weight. Fewer people in the treatment condition experienced weight gains of more than 5% and more than 7% of their bodyweight than those in the placebo group (> 5% weight gain RR 0.27, 95% confidence interval (CI) 0.11 to 0.65; 1 study, 43 participants; > 7% weight gain RR 0.24, 95% CI 0.07 to 0.83; 1 study, 43 participants; very low-certainty evidence). No studies reported the primary outcomes, 'clinically important change in BMI', or 'compliance with treatment'. However, several studies reported 'average endpoint/change in body weight' or 'average endpoint/change in BMI'. Metformin may be effective in preventing weight gain (MD -4.03 kg, 95% CI -5.78 to -2.28; 4 studies, 131 participants; low-certainty evidence); and BMI increase (MD -1.63 kg/m2, 95% CI -2.96 to -0.29; 5 studies, 227 participants; low-certainty evidence). Other agents that may be slightly effective in preventing weight gain include H2 antagonists such as nizatidine, famotidine and ranitidine (MD -1.32 kg, 95% CI -2.09 to -0.56; 3 studies, 248 participants; low-certainty evidence) and monoamine modulators such as reboxetine and fluoxetine (weight: MD -1.89 kg, 95% CI -3.31 to -0.47; 3 studies, 103 participants; low-certainty evidence; BMI: MD -0.66 kg/m2, 95% CI -1.05 to -0.26; 3 studies, 103 participants; low-certainty evidence). Topiramate did not appear effective in preventing weight gain (MD -4.82 kg, 95% CI -9.99 to 0.35; 3 studies, 168 participants; very low-certainty evidence). For all agents, there was no difference between groups in terms of individuals leaving the study or reports of nausea. However, the results of these outcomes are uncertain given the very low-certainty evidence. There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain.

S223 Factors Related to Fecal Microbiota Transplant Failure in the Treatment of Recurrent C. difficile - A Single Center Retrospective Cohort Study

Introduction: Fecal Microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridioides difficile infection (CDI) with reported success rates of 80-90%. There are limited data on factors contributing FMT failure, particularly in the outpatient setting. Our objective was to describe FMT failure rates within one year and to evaluate factors associated with FMT failure. Methods: We conducted a retrospective cohort study of consecutive patients who had outpatient FMT at Baystate Medical Center, Springfield, MA from 12/14 through 9/18. We collected patient data including demographics, CDI related factors, comorbid conditions, medications and FMT route. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. diff toxin or PCR. IRB approval was obtained. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Due to low power, we present possible associations with p-values < 0.2. Results: 92 patients were included with a mean age of 64y. CDI severity (per IDSA guidelines) was mild/moderate in 73% and severe or fulminant in 27%. 69% of patients had been previously hospitalized for CDI and the most common FMT indication was recurrent CDI in 76%. FMT failure occurred in 25 of 92 (27%) of which half occurred within 21 days. Factors associated with FMT failure were immunosuppression (RR=2.90); current or previous malignancy (RR=2.50); prior hospitalizations (RR=2.42); and receipt of non-CDI antibiotics within 6 months of FMT (RR=2.80). None of the following factors were associated with risk of FMT failure: age, indication, CDI severity, history of colectomy, diabetes, prior radiation, history of appendectomy, probiotics prior to FMT, H2 antagonists or PPIs, ICU admission, inflammatory bowel disease, or route of FMT delivery (oral, NGT, colonoscopy). (Table) Conclusion: We have identified four factors associated with FMT failure for outpatients with recurrent CDI: immunosuppression, current or previous malignancy, prior CDI hospitalizations and non-CDI antibiotics within 6 months prior to FMT. Knowledge of the above factors may help inform treatment options for patients with recurrent or refractory CDI. Table 1. - Univariable analysis of associations between factors associated with FMT failure within one year Overall FMT FailureNo FMT FailureYes p- value Relative Risk N=92 N=67 N=25 (95% CI) Age at transplant (yrs) 63.9 65.1 60.7 0.319 0.92 (0.77 to 1.10) Male n=20 (21.7%) Female n=72 (78.3%) FMT Indication Recurrent CDI 70 (76.1%) 54 (77.1%) 16 (22.9%) 0.062 n/a Severe CDI 3 (3.3%) 3 (100.0%) 0 (0.0%) Fulminant Colitis 2 (2.2%) 2 (100.0%) 0 (0.0%) Recurrent and Severe CDI 17 (18.5%) 8 (47.1%) 9 (52.9%) CDI Severity Mild/Moderate 67 (72.8%) 51 (76.1%) 16 (23.9%) 0.415 Referent Severe 15 (16.3%) 10 (66.7%) 5 (33.3%) 1.40 (0.61 to 3.21) Fulminant Colitis 10 (10.9%) 6 (60.0%) 4 (40.0%) 1.67 (0.70 to 4.00) Prior Hospitalization Due to C. Diff No 29 (31.5%) 25 (86.2%) 4 (13.8%) 0.076 Referent Yes 63 (68.5%) 42 (66.7%) 21 (33.3%) 2.42 (0.91 to 6.40) Immunosuppression No 57 (62.0%) 48 (84.2%) 9 (15.8%) 0.003 Referent Yes 35 (38.0%) 19 (54.3%) 16 (45.7%) 2.90 (1.44 to 5.83) Current or Previous Malignancy No 70 (76.1%) 56 (80.0%) 14 (20.0%) Referent Yes 22 (23.9%) 11 (50.0%) 11 (50.0%) 0.012 2.50 (1.33 to 4.68) Antibiotics (6 mos. prior to cdiff; not treating c.diff.) No 32 (34.8%) 28 (87.5%) 4 (12.5%) 0.027 Referent Yes 60 (65.2%) 39 (65.0%) 21 (35.0%) 2.80 (1.05 to 7.46)

S2303 Endoscopic Balloon Dilation of Recurrent Peptic Stricture in a Patient With Portal Hypertension

Introduction: Variceal hemorrhage is a devastating complication and a major cause of mortality in patients with portal hypertension. Unfortunately, one third of patients with varices develop bleeding in their lifetime. This case depicts a rarely reported intervention that physicians may be hesitant to pursue. Case Description/Methods: A 61-year-old male with history significant for atrial fibrillation (afib), alcoholic cirrhosis complicated by gastric and esophageal varices, and GERD presented with dysphagia. He previously underwent endoscopic variceal band ligation (EVL) in 2009 for primary prevention of esophageal varices and placed on daily nadolol. His GERD was controlled with twice daily PPI and as-needed H2 antagonist. Despite this, he developed strictures secondary to severe erosive esophagitis. He was then started on apixaban for afib and transitioned from nadolol to carvedilol. His MELD-Na is 8 and had a reported distant history of hepatic encephalopathy. He presented to the esophageal motility clinic with progressive dysphagia to both solids and liquids. An EGD was scheduled which revealed a partially obstructive ulcerative stricture spanning 29 - 34 cm from incisors. The stricture was injected with 4 ml of triamcinolone acetonide distributed in 1 cm increments across 4 quadrants. Then the stricture was dilated with a 10-12 mm cre balloon under fluoroscopic guidance. Dilation caused shallow mucosal tears with scant blood but otherwise no significant bleeding or complication. The scope was traversed into the stomach with retroflexion revealing moderate gastric varices in the cardia. After the procedure was completed, the patient had complete resolvent of symptoms and tolerated oral nutrition (Figure). Discussion: This case describes a cirrhotic patient with portal hypertension requiring frequent endoscopic balloon dilations for severe dysphagia secondary to recurrent peptic strictures. Extensive literature review did not reveal any documented cases describing this scenario. The presence of gastric varices in this patient is indicative of active portal hypertension. This in combination with the patient’s anticoagulation places a theoretical high risk of bleeding during the procedure. Although this case demonstrates that it is safe to perform serial dilations in patients with portal hypertension if they have undergone EVL and do not have active esophageal varices.Figure 1.: A) EGD showed ulcerative peptic stricture located in the mid-esophagus. (B) There was scant bleeding after dilation, otherwise no significant bleeding or complication. (C) Retroflexion was performed in the stomach and revealed moderate gastric varies in the cardia.

Solubility Enhancement of Ebastine by Formulating Microemulsion Using D-Optimal Mixture Design: Optimization and Characterization.

Ebastine, a histamine H1 antagonist, nonsedating, belonging to BCS class II is used in the treatment of allergic rhinitis and chronic idiopathic urticaria. The current study was intended in augmenting the aqueous solubility and dissolution rate of ebastine, by formulating a microemulsion system using oleic acid, Transcutol® HP, and Tween®80 as oily phase, cosurfactant, and surfactant, respectively, by the phase titration method. A custom mixture design with optimality D was used to design the formulation by using the Design Expert® Software (Version 11; Stat-Ease, Inc., Minneapolis, MN, USA). Optimization of formulation was performed using the numerical optimization technique, where optimization is based upon the desirability. The optimized formulation was evaluated for transmittance, viscosity, globule size, polydispersity index, zeta potential, drug content, morphological studies, and in vitro studies. The optimized formulation displayed percent cumulative drug release, ranging from 82.9% to 90.6% obtained after dissolution studies and the percent cumulative drug release after diffusion studies ranged from 83.3% to 100%. The in vitro release data were subjected to kinetic treatment. The zero-order and first-order plots were linear and showed the highest values for R2, which indicated mixed-order release. The Higuchi plot was linear, indicating diffusion as the mechanism of release. From Peppas plot, it was further confirmed that the release for dissolution studies was anomalous and for diffusion studies it was zero order. Thus, the studies concluded that the microemulsion technique is a very good approach for enhancing the solubility and dissolution rate of the BCS class II drug ebastine.

Effect of proton pump inhibitors and H2 antagonists on gastric wall uptake in myocardial perfusion scan with 99mTc-sestamibi

BackgroundProton pump inhibitors (PPIs) have been speculated to cause gastric wall uptake (GWU) in MPI scans. However, the uptake mechanism and prevention methods are less studied. In this prospective trial we aimed to evaluate the impact of gastroprotective medications on GWU and its solutions. Methods351 consecutive patients, scheduled for 2-day rest/stress 99mTc-MIBI scan, were distributed into 5 groups. 3-7 days following the baseline rest scan, the stress scan was acquired after intervention in the trial group, consisting of patients with history of PPI intake, randomly assigned to 3 subgroups: discontinuing PPIs(A), replacement with H2 blockers (B), and continuing PPIs (C). Patients receiving H2 blockers, continued it as before (D) and the remaining patients were the control group (E). GWU was graded compared to the myocardial uptake. ResultsIn the rest phase, all groups had significantly higher GWU compared to the control group. In the stress phase, group A had less GWU than group B (P-value < 0.05) and both of them had significantly less GWU compared to group C (P-value < 0.001). There was no significant difference between PPI discontinuation periods of 3-5 days versus 5-7 days. There was a significant association between duration of oral PPI intake, but not IV PPIs, and GWU. GWU was significantly lower with oral compared to IV PPI administration. ConclusionPPIs significantly increase GWU and discontinuing them for at least 3-5 days significantly reduces GWU. H2 antagonists are a good alternative in patients who cannot tolerate dyspepsia symptoms.