Switching from intravenous to subcutaneous vedolizumab maintenance treatment in patients with inflammatory bowel disease followed by therapeutic drug monitoring.

OBJECTIVE: Vedolizumab (VDZ) for subcutaneous (SC) administration has recently become available. We aimed to assess feasibility, safety and clinical outcome when switching from intravenous (IV) to SC VDZ maintenance treatment in a real world cohort of patients with inflammatory bowel disease (IBD) followed by therapeutic drug monitoring (TDM). METHODS: Eligible IBD patients were switched from IV to SC treatment and assessed six months prior to switch, at baseline and six, twelve and twenty-six weeks after switch. Primary outcome was proportion of patients on SC treatment after 26 weeks. Secondary outcomes included adverse events (AEs), clinical disease activity, biochemical markers, treatment interval, serum-VDZ (s-VDZ), preferred route of administration and health-related quality of life. RESULTS: In total, 108 patients were switched. After 26 weeks, 100 patients (92.6%) were still on SC treatment and median s-VDZ was 47.6 mg/L (IQR 41.3 - 54.6). The most frequent AE was injection site reaction (ISR), reported by 20 patients (18.5%). There were no clinically significant changes in disease activity, biochemical markers and quality of life. The proportion of patients preferring SC administration increased from 28.0% before switch to 59.4% after 26 weeks (p < 0.001). CONCLUSIONS: Nine out of ten patients still received SC treatment after 26 weeks. No change in disease activity occurred, and levels of serum VDZ increased. Although almost one fifth of patients experienced ISRs, a higher proportion favored SC administration at 26 weeks. This study demonstrates that SC maintenance treatment is a safe and feasible alternative to IV treatment.

De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation.

BACKGROUND: Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation. METHODS: This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids. RESULTS: In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017. CONCLUSION: De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.

The incidence of psoriasis among smokers and/or former smokers inflammatory bowel diseases patients treated with tumor necrosis factor antagonist: A systematic review and meta-analysis.

BACKGROUND: Infliximab (IFX) and adalimumab (ADA) refer to the classic drugs to treat moderate-severe inflammatory bowel disease (IBD), which have been proven to be effective to control IBD. However, the side effects exerted by IFX and ADA should be monitored in therapies, especially the paradoxical reaction of the skin system (e.g., psoriasis). Psoriasis is recognized as the most common skin lesion, capable of significantly affecting the quality of patients' life. METHODS: This study searched literatures published in English language with the qualifications on PubMed, Embase, Web of Science, Google, and Geenmedical databases. Over 2 co-authors assessed the quality of the articles and extracted the data independently. The data acquired were statistically analyzed with the statistical software of Revman and Stata. RESULTS: The ADA Group achieved a higher incidence of psoriasis (odds ratio [OR] = 0.658, 95% confidence interval [CI] [0.471-0.919]); Females achieved a higher incidence of psoriasis than males (OR = 1.941, 95%CI [1.326-2.843], P < .05); Smoking up-regulated the incidence of psoriasis (OR = 1.679, 95%CI [1.237-2.279], P < .05); The interval of medication was over 1 year, and the interval of medication applying IFX was longer than that of the ADA Group; most cases could be relieved by using local hormone, phototherapy, or systemic hormone therapy under the strategy of biological agents. CONCLUSIONS: The frequency of reported in IBD exceeds those of other autoimmune diseases, and the ADA treatment for IBD is safer than IFX. Psoriasis is more common in females than in males. Smoking refers to one of risk factors of psoriasis.

Medical Management of Inoperable Malignant Bowel Obstruction.

OBJECTIVE: To review medical management of inoperable malignant bowel obstruction. DATA SOURCES: A literature review using PubMed and MEDLINE databases searching malignant bowel obstruction, etiology, types, pathophysiology, medical, antisecretory, anti-inflammatory, antiemetic drugs, analgesics, promotion of emptying, prevention of infection, anticholinergics, somatostatin analogs, gastric antisecretory drugs, prokinetic agents, glucocorticoid, opioid analgesics, antibiotics, enema, and adverse effects. STUDY SELECTION AND DATA EXTRACTION: Randomized or observational studies, cohorts, case reports, or reviews written in English between 1983 and November 2020 were evaluated. DATA SYNTHESIS: Malignant bowel obstruction (MBO) commonly occurs in patients with advanced or recurrent malignancies and severely affects the quality of life and survival of patients. Its management remains complex and variable. Medical management is the cornerstone of MBO treatment, with the goal of reducing distressing symptoms and optimizing quality of life. Until now, there has been neither a standard clinical approach nor registered medications to treat patients with inoperable MBO. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides information on the etiology, type and pathophysiology, and medical treatment of MBO and related adverse reactions of the drugs commonly used, which can greatly assist clinicians in making clinical decisions when treating MBO. CONCLUSIONS: Published research shows that medical management of MBO mainly consists of antisecretory, anti-inflammatory strategies, controlling vomiting and pain, promoting emptying, preventing infection, and combination therapy. Being knowledgeable about the most current treatment options, the related adverse effects, and the evidence supporting different practices is critical for clinicians to provide individualized medical therapy for MBO patients.

Combination of Panax notoginseng saponins and aspirin potentiates platelet inhibition with alleviated gastric injury via modulating arachidonic acid metabolism.

High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment are associated with poor compliance and an increased risk of cardiovascular events. Panax notoginseng saponins (PNS) have been widely used for the treatment of coronary heart disease (CHD) in addition to antiplatelet drugs in China; however, the joint effect and possible mechanism of PNS in addition to ASA on platelet activation and gastric injury remain unclear. This study was designed to investigate the combinational effects of PNS with ASA, and to explore the underlying mechanism via arachidonic acid (AA) metabolism pathway using lipidomic analysis. In a randomized, assessor-blinded trial, 42 patients with stable coronary heart disease (SCHD) and chronic gastritis were randomly assigned to receive ASA (n = 21) or PNS + ASA (n = 21) for 2 months. Compared with ASA alone, PNS + ASA further inhibited CD62p expression, GPIIb-IIIa activation and platelet aggregation and led to increased platelet inhibition rate. PNS + ASA suppressed the activity of platelet cyclooxygenase (COX)-1, and decreased the production of TXB2, PGD2, PGE2, 11-HETE, the downstream oxylipids of AA/COX-1 pathway in platelets, compared with ASA alone. The severity of dyspepsia assessment (SODA) results showed that patients in PNS + ASA group exhibited relieved dyspeptic symptoms as compared with those in ASA group, which might be associated with enhanced secretion of gastrin and motilin. In vivo study of myocardial infarction rats demonstrated that PNS attenuated ASA-induced gastric mucosal injury, which was related to markedly boosted gastric level of 6,15-diketo-13,14-dihydro-prostaglandin (PG)F1α, 13,14-dihydro-15-keto-PGE2 and PGE2 from AA/PG pathway in response to PNS + ASA compared with ASA alone. In summary, our study demonstrated that the combination of PNS and ASA potentiated the antiplatelet effect of ASA via AA/COX-1/TXB2 pathway in platelets, and mitigated ASA-related gastric injury via AA/PG pathway in gastric mucosa.

Targeting gut barrier dysfunction with phytotherapies: Effective strategy against chronic diseases.

The intestinal epithelial layer serves as a physical and functional barrier between the microbe-rich lumen and immunologically active submucosa; it prevents systemic translocation of microbial pyrogenic products (e.g. endotoxin) that elicits immune activation upon translocation to the systemic circulation. Loss of barrier function has been associated with chronic 'low-grade' systemic inflammation which underlies pathogenesis of numerous no-communicable chronic inflammatory disease. Thus, targeting gut barrier dysfunction is an effective strategy for the prevention and/or treatment of chronic disease. This review intends to emphasize on the beneficial effects of herbal formulations, phytochemicals and traditional phytomedicines in attenuating intestinal barrier dysfunction. It also aims to provide a comprehensive understanding of intestinal-level events leading to a 'leaky-gut' and systemic complications mediated by endotoxemia. Additionally, a variety of detectable markers and diagnostic criteria utilized to evaluate barrier improving capacities of experimental therapeutics has been discussed. Collectively, this review provides rationale for targeting gut barrier dysfunction by phytotherapies for treating chronic diseases that are associated with endotoxemia-induced systemic inflammation.

Assessment of Body Weight Changes in Patients with Inflammatory Bowel Diseases Initiating Biologic Therapy: A Prospective Cohort Study.

BACKGROUND: Prior studies have inconsistently suggested that biologic therapy may be associated with weight gain in inflammatory bowel disease patients (IBD). Our aim was to compare weight gain across different biologic therapy classes with distinct mechanisms of action. METHODS: This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab, or ustekinumab. Weight measurements were performed at weeks 0, 14, 30, and 54. Changes in weight between baseline and each of the follow-up visits were modeled as a continuous variable, and multivariate regression assessed the independent effect of therapeutic class on this outcome. RESULTS: Our study enrolled 269 patients (163 CD, 106 UC) initiating biologic therapy [99 anti-TNF (37%), 122 vedolizumab (45%), 48 ustekinumab (18%)]. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg (± 3.8 kg, p = 0.004) and continued to increase compared to baseline with 0.96 kg (± 3.9 kg, p < 0.001) and 1.29 kg (± 4.2 kg, p < 0.001) at week 30 and 54, respectively. On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain were seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at wk 14, wk 30, and wk 54, respectively). None of the disease activity parameters showed any statistical association with weight gain. CONCLUSION: There was no difference in weight gain among the different biologic therapeutic classes.

Tumor Necrosis Factor Inhibitor-Induced Psoriasis in a Pediatric Crohn's Disease Patient Successfully Treated with Ustekinumab.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors are widely used in pediatric patients with inflammatory bowel disease, as well as psoriasis. However, there is growing evidence that these medications can also paradoxically induce a psoriasiform skin reaction in a subset of patients. GOALS: We seek to share our experience in treating severe TNF inhibitor-induced psoriasis in a pediatric patient with Crohn’s disease. STUDY: We report a case of a 10-year-old female with Crohn’s disease, who developed psoriasis after twelve months of infliximab therapy. Her skin disease was recalcitrant to topical therapies, methotrexate, and phototherapy. RESULTS: The patient was transitioned to ustekinumab with significant improvement in her symptoms and maintenance of remission of her bowel disease. CONCLUSION: This is the first reported case of a school-age pediatric patient with TNF inhibitor-induced psoriasis treated with ustekinumab. Controlled trials are warranted to fully assess the safety and efficacy of ustekinumab for treating TNF inhibitor-induced psoriasis in the pediatric population.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.2106.

AGA Clinical Practice Update on Functional Heartburn: Expert Review.

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

Longitudinal Trajectory of Fatigue With Initiation of Biologic Therapy in Inflammatory Bowel Diseases: A Prospective Cohort Study.

BACKGROUNDS AND AIMS: Fatigue is prevalent in patients with inflammatory bowel diseases [IBD]. Biologic therapy is effective in achieving symptomatic and endoscopic remission, but its impact on fatigue is less well established. Our aim is to define the longitudinal trajectory of fatigue over 1 year in patients initiating biologic therapy. METHODS: This prospective cohort enrolled patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] initiating biologic therapy with infliximab, adalimumab, ustekinumab, or vedolizumab. Fatigue was quantified using the seven-point fatigue question in the Short Inflammatory Bowel Disease Questionnaire [SIBDQ]. A score of ≤4 for this question was used to define fatigue. Multivariable regression models adjusting for relevant confounders examined the independent association between attaining clinical remission and resolution of fatigue. RESULTS: Our study included 326 patients [206 CD, 120 UC] initiating biologic therapy [144 anti-tumour necrosis factor, 129 vedolizumab, 63 ustekinumab]. A total of 61% of the included patients reported significant fatigue at baseline. This was associated with female gender, depressive symptoms, active disease, and disturbed sleep [p < 0.001]. Among the 198 patients who were fatigued at therapy initiation, 86 [70%], 55 [63%], and 44 [61%] remained fatigued at Week 14, 30, and 54, respectively. At each of these time points, achieving clinical remission was associated with lower likelihood of persistent fatigue. However, despite achieving remission, 35%, 30%, and 28% of patients experienced persistent fatigue at Week 14, 30, and 54, respectively. CONCLUSIONS: Fatigue is common in IBD. Though biologic therapy improves fatigue parallel symptomatic improvement, a significant proportion continue to experience persistent fatigue up to 1 year.

Current US Food and Drug Administration-Approved Pharmacologic Therapies for the Treatment of Irritable Bowel Syndrome with Diarrhea.

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alterations in stool form and/or frequency, leading to reduced quality of life. Pharmacologic agents currently approved by the US Food and Drug Administration for treatment of IBS with diarrhea (IBS-D) in adults are the nonsystemic antibiotic rifaximin, the mixed µ- and κ-opioid receptor agonist/δ-opioid antagonist eluxadoline, and the selective serotonin 5-HT3 antagonist alosetron (the last of which is indicated only in women with severe IBS-D refractory to conventional therapy). Both eluxadoline and alosetron are administered as chronic daily therapies; rifaximin is given as a 2-week course of treatment with repeat courses administered as needed for symptom recurrence. Presumed mechanisms of action of rifaximin include modulation of the gut microbiota, anti-inflammatory activity, normalization of visceral hypersensitivity, and reduction in intestinal permeability. Eluxadoline targets opioid receptors in the gastrointestinal (GI) tract, resulting in decreased GI motility, fluid secretion, and visceral pain perception. Alosetron antagonizes serotonergic afferent neural signals and also slows GI motility. The efficacy and safety of these agents have been investigated in several rigorous clinical trials, and it has been demonstrated that they improve global and individual IBS symptoms. This review highlights the pivotal efficacy and safety data of the three pharmacologic agents currently indicated in the USA for the management of IBS-D in adults.Funding: Salix Pharmaceuticals.

Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.

Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear. Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence). Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation (a probiotic formulation) participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

ANTECEDENTES: La reservoritis ocurre en aproximadamente el 50% de los pacientes después de la anastomosis entre la bolsa ileal y el ano (IPAA, por sus siglas en inglés) para la colitis ulcerosa crónica (CU). OBJETIVOS: El objetivo primario fue determinar la eficacia y la seguridad de los tratamientos médicos para la prevención o el tratamiento de la reservoritis aguda o crónica. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en MEDLINE, Embase y en CENTRAL, desde su inicio hasta el 25 julio 2018. También se buscó en las listas de referencias, registros de ensayos en curso y actas de congresos. CRITERIOS DE SELECCIÓN: Se consideraron para inclusión los ensayos controlados aleatorios de prevención o tratamiento de la reservoritis aguda o crónica en adultos a los que se les realiza IPAA para la CU. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron la elegibilidad de los estudios, extrajeron los datos y analizaron el riesgo de sesgo. La calidad de la evidencia se evaluó mediante los criterios GRADE. El resultado primario la mejoría clínica o remisión en los pacientes con reservoritis aguda o crónica, o la proporción de pacientes sin episodios de reservoritis después de IPAA. Se incluyeron los eventos adversos como resultado secundario. Se calculó el cociente de riesgos (CR) y el intervalo de confianza (IC) del 95% correspondiente para los resultados dicotómicos. RESULTADOS PRINCIPALES: Se incluyeron 15 estudios (547 participantes). Cuatro estudios evaluaron el tratamiento de la reservoritis aguda. Cinco estudios evaluaron el tratamiento de la reservoritis crónica. Seis estudios evaluaron la prevención de la reservoritis. Tres estudios presentaban bajo de riesgo de sesgo. En tres estudios el riesgo fue alto y en los otros estudios fue poco claro. reservoritis aguda: Todos los pacientes que recibieron ciprofloxacina (7/7) lograron la remisión a las dos semanas en comparación con el 33% (3/9) de los pacientes que recibieron metronidazol (CR 2,68; IC del 95%: 1,13 a 6,35) (evidencia de certeza muy baja). Ninguno de los participantes que recibieron ciprofloxacina (0/7) presentó eventos adversos en comparación con el 33% (3/9) de los participantes que recibieron metronidazol (CR0,18; IC del 95%: 0,01 a 2,98; evidencia de certeza muy baja). Los eventos adversos incluyeron vómitos, disgeusia o neuropatía periférica transitoria. El 40% (6/14) de los participantes que recibieron metronidazol lograron la remisión a las 6 semanas en comparación con el 50% (6/12) de los participantes que recibieron enema de budesonida (CR 0,86; IC del 95%: 0,37 a 1,96; evidencia de certeza muy baja). El 50% (7/14) de los participantes del grupo de metronidazol mejoraron clínicamente a las 6 semanas en comparación con el 58% (7/12) de los participantes que recibieron enema de budesonida (CR 0,86; IC del 95%: 0,42 a 1,74; evidencia de certeza muy baja). El 57% (8/14) de los participantes del grupo de metronidazol presentaron eventos adversos en comparación con el 25% (3/12) de los participantes que recibieron enema de budesonida (CR 2,29; IC del 95%: 0,78 a 6,73; evidencia de certeza muy baja). Los eventos adversos incluyeron anorexia, náuseas, cefalea, astenia, sabor metálico, vómitos, parestesia y depresión. El 25% (2/8) de los participantes que recibieron rifaximina lograron la remisión a las 4semanas en comparación con el 0% (0/10) de los participantes que recibieron placebo (CR 6,11; IC del 95%: 0,33 a 111,71; evidencia de certeza muy baja). El 38% (3/8) de los participantes del grupo de rifaximina mejoraron clínicamente a las 4 semanas en comparación con el 30% (3/10) de los participantes que recibieron placebo (CR 1,25; IC del 95%: 0,34 a 4,60; evidencia de certeza muy baja). El 75% (6/8) de los participantes del grupo de rifaximina presentaron un evento adverso en comparación con el 50% (5/10) de los participantes que recibieron placebo (CR 1,50; IC del 95%: 0,72 a 3,14; evidencia de certeza muy baja). Los eventos adversos incluyeron diarrea, flatulencias, náuseas, proctalgia, vómitos, sed, cándida, infección de las vías respiratorias superiores, aumento de las enzimas hepáticas y cefalea en racimos. El 10% (1/10) de los participantes del grupo de Lactobacillus GGmejoraron clínicamente a las 12 semanas en comparación con el 0% (0/10) de los participantes que recibieron placebo (CR 3,00; IC del 95%: 0,14 a 65,90; evidencia de certeza muy baja). Reservoritis crónica: El 85% (34/40) de los pacientes que recibieron la formulación De Simone mantuvieron la remisión de nueve a 12 meses en comparación con el 3% (1/36) de los participantes que recibieron placebo (CR 20,24; IC del 95%: 4,28 a 95,81; dos estudios; evidencia de certeza baja). El 2% (1/40) de los participantes que recibieron la fórmula De Simone presentaron un evento adverso, en comparación con el 0% (0/36) de los participantes que recibieron placebo (CR 2,43; IC del 95%: 0,11 a 55,89; evidencia de certeza baja). Los efectos secundarios incluyeron cólicos abdominales, vómitos y diarrea. Cuarenta y tres por ciento (3/6) de los pacientes en el grupo de adalimumab lograron una mejoría clínica a las 4 semanas en comparación con un 43 (3/7) de los pacientes del grupo de placebo (CR 1,17, IC del 95%: 0,36 a 3,76; evidencia de certeza baja). El 60% (6/10) de los participantes del grupo de glutamina mantuvieron la remisión a las 3 semanas en comparación con el 33% (3/9) de los participantes que recibieron placebo (CR 1,80; IC del 95%: 0,63 a 5,16; evidencia de certeza muy baja). El 45% (9/20) de los participantes del grupo de enema de espuma de carbómero de bismuto mejoraron clínicamente a las 3 semanas en comparación con el 45% (9/20) de los participantes que recibieron placebo (CR 1,00; IC del 95%: 0,50 a 1,98; evidencia de certeza muy baja). El 25% (5/20) de los participantes del grupo de aceite de cannabis presentaron un evento adverso en comparación con el 35% (7/20) de los participantes que recibieron placebo (CR 0,71; IC del 95%: 0,27 a 1,88; evidencia de certeza muy baja). Los eventos adversos incluyeron diarrea, síntomas de empeoramiento, cólicos, sinusitis y dolor abdominal. Prevención: A los 12 meses, el 90% (18/20) de los pacientes que recibieron la formulación De Simone no presentaron episodios de reservoritis aguda en comparación con el 60% (12/20) de los pacientes que recibieron placebo (CR 1,50: IC del 95%: 1,02 a 2,21; evidencia de certeza baja). Otro estudio halló que el 100% (16/16) de los participantes que recibieron la fórmula De Simone no presentaron episodios de reservoritis aguda a los 12 meses en comparación con el 92% (11/12) de los pacientes del grupo control sin tratamiento (CR 1,10: IC del 95%: 0,89 a 1,36; evidencia de certeza muy baja). El 86% (6/7) de los participantes del grupo de Bifidobacterium longum no presentaron episodios de reservoritis aguda a los 6 meses en comparación con el 60% (3/5) de los participantes que recibieron placebo (CR 1,43; IC del 95%: 0,66 a 3,11; evidencia de certeza muy baja). El 11% (1/9) de los participantes del grupo de Clostridium butyricum MIYAIRI no presentaron episodios de reservoritis aguda a los 24 meses en comparación con el 50% (4/8) de los participantes que recibieron placebo (CR 0,22; IC del 95%: 0,03 a 1,60; evidencia de certeza muy baja). El 46% (43/94) de los participantes del grupo de alopurinol no presentaron episodios de reservoritis a los 24 meses en comparación con el 43% (39/90) de los participantes que recibieron placebo (CR1,06; IC del 95%: 0,76 a 1,46; evidencia de certeza baja). El 81% (21/26) de los participantes del grupo de tinidazol no presentaron episodios de reservoritis a los 12 meses en comparación con el 58% (7/12) de los participantes que recibieron placebo (CR 1,38; IC del 95%: 0,83 a 2,31; evidencia de certeza muy baja). CONCLUSIONES DE LOS AUTORES: No se conocen los efectos de los antibióticos, probióticos y otras intervenciones para el tratamiento y la prevención de la reservoritis. Se necesitan estudios bien diseñados con poder estadístico suficiente para determinar la forma óptima de tratamiento y prevención de la reservoritis.

Maneuvering Clinical Pathways for Ulcerative Colitis.

PURPOSE OF REVIEW: Recent years have brought about several advances in the treatment of patients with ulcerative colitis (UC). Here, we discuss salient recommendations of recent treatment guidelines; review the efficacy, safety, and real-world data of vedolizumab and tofacitinib; appraise their place vis-à-vis established agents; and consider the newly proposed approaches of risk-stratified and treat-to-target therapy. RECENT FINDINGS: Once daily oral mesalamine dosing is equivalent to split dosing in mild-moderate UC. Real-world data are accumulating on the effectiveness and safety of vedolizumab for moderate to severe UC, while there are few such data on the most recently approved agent, tofacitinib. High-dose infliximab is being investigated for severe UC. New approaches are challenging the established paradigm of selecting therapy based on current disease activity. The risk-stratified approach incorporates long-term risk as well as the current burden of inflammation. The treat-to-target approach aims at improved long-term outcomes by adjusting therapy to resolve intestinal inflammation. The therapeutic options for UC are continually expanding. Risk-stratified therapy and the treat-to-target approach represent paradigm shifts in UC management. Optimal disease control requires an individualized approach that takes into consideration current inflammatory burden, long-term risk, patient preferences, and ongoing assessment of response to treatment.

Efficacy and safety of a novel topical agent for gallstone dissolution: 2-methoxy-6-methylpyridine.

BACKGROUND: Although methyl-tertiary butyl ether (MTBE) is the only clinical topical agent for gallstone dissolution, its use is limited by its side effects mostly arising from a relatively low boiling point (55 °C). In this study, we developed the gallstone-dissolving compound containing an aromatic moiety, named 2-methoxy-6-methylpyridine (MMP) with higher boiling point (156 °C), and compared its effectiveness and toxicities with MTBE. METHODS: The dissolubility of MTBE and MMP in vitro was determined by placing human gallstones in glass containers with either solvent and, then, measuring their dry weights. Their dissolubility in vivo was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after directly injecting each solvent into the gallbladder in hamster models with cholesterol and pigmented gallstones. RESULTS: In the in vitro dissolution test, MMP demonstrated statistically higher dissolubility than did MTBE for cholesterol and pigmented gallstones (88.2% vs. 65.7%, 50.8% vs. 29.0%, respectively; P < 0.05). In the in vivo experiments, MMP exhibited 59.0% and 54.3% dissolubility for cholesterol and pigmented gallstones, respectively, which were significantly higher than those of MTBE (50.0% and 32.0%, respectively; P < 0.05). The immunohistochemical stains of gallbladder specimens obtained from the MMP-treated hamsters demonstrated that MMP did not significantly increase the expression of cleaved caspase 9 or significantly decrease the expression of proliferation cell nuclear antigen. CONCLUSIONS: This study demonstrated that MMP has better potential than does MTBE in dissolving gallstones, especially pigmented gallstones, while resulting in lesser toxicities.

Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey.

BACKGROUND: Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose-effect on AEs. METHODS: A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. RESULTS: Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose-effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. CONCLUSIONS: IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

A curious association of chronic homeopathic arsenic ingestion with nonspecific symptoms in a Swiss teenager.

Arsenic is a toxicant that has no dose threshold below which exposures are not harmful. Here I report a curious association of chronic homeopathic arsenic ingestion with nonspecific symptoms in a Swiss teenager. For about 4 years she had taken globules of a freely purchasable homeopathic remedy containing inorganic arsenic (iAs), infinitesimally diluted to D6 (average arsenic content per single globule: 0.85 ± 0.08 ng). In the previous 7 months she had taken 20 to 50 globules daily (average 30 ng arsenic daily). She complained of nausea, stomach and abdominal cramps, diarrhoea and flatulence, headache, dizziness, anxiety, difficulty concentrating, insomnia, snoring, leg cramps and fatigue, loss of appetite, increased thirst and sweating, reduced diuresis, weight gain, paleness and coolness of both hands with a furry feeling of the hands, eczema of the hands, arms and legs, conjunctivitis and irregular menstruation. The physical and laboratory examinations showed a body mass index of 30 kg/m2, acne vulgaris, bilateral spotted leukonychia, eczema of hands, arms and legs, non-pitting oedema of the legs, elevated plasma alkaline phosphatase activity, folate deficiency and severe vitamin D3 insufficiency. The arsenic concentration in her blood was <0.013 µmol/l, and arsenic was undetectable in her scalp hair. The total iAs concentration was 116 nmol/l in the morning urine and 47 nmol/l in the afternoon urine. The urinary arsenic concentration decreased and the patient’s complaints improved upon interruption of the arsenic globules, vitamin D3, thiamine and folic acid supplementation, and symptomatic therapy. It is concluded that an avoidable toxicant such as inorganic arsenic, for which no scientific safe dose threshold exists, should be avoided and not be found in over-the-counter medications.

Impact of Peppermint Therapy on Dysphagia and Non-cardiac Chest Pain: A Pilot Study.

BACKGROUND: Due to its smooth muscle relaxing properties, peppermint oil (PO) may relieve dysphagia and chest pain due to esophageal motility disorders. AIM: To explore the impact of PO on dysphagia and/or chest pain in patients referred for motility testing. METHODS: Patients initiated on PO for dysphagia and/or chest pain from 2013 to 2016 were identified. We excluded patients with obstructing esophageal lesions, patients lost to follow-up, and those with preexisting cardiac conditions. Concentrated PO was given as commercially available dissolvable peppermint tablets; two tablets before meals were prescribed to patients with dysphagia and on an as-needed basis for patients with chest pain. Patient-reported symptom response was assessed using a modified five-point Likert scale. RESULTS: Thirty-eight patients were included. Twenty-four patients (63%) reported improvement; 12 were much better and 12 were slightly better. Fourteen experienced no change and none reported feeling worse. Based on pre-treatment HRM, patients with distal esophageal spasm (DES) (n = 10) and esophagogastric junction outflow obstruction (EGJOO) (n = 8) appeared to demonstrate the best subjective improvement (83% and 100%, respectively) (P < 0.05). CONCLUSION: PO appears to provide symptomatic relief in some patients with dysphagia and CP. Presence of a well-defined manometric disorder, particularly DES or EGJOO, appeared to predict response.

Postprandial distress syndrome: stratification and management.

INTRODUCTION: Functional dyspepsia (FD), defined by the Rome consensus as the presence of functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review on the current state of knowledge regarding PDS. Areas covered: Epidemiological studies support PDS as a separate entity and the biggest FD subgroup. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function as well as low grade duodenal inflammation have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high quality studies of new therapeutic approaches.