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Introduction: We aimed to provide a practical and evidence-based guide on the indications, performance and reporting of high-resolution oesophageal manometry (HRM) and ambulatory pH monitoring (PHM) in adult patients in Singapore. Methods: The guideline committee comprised local gastroenterologists from public and private sectors with particular expertise in aspects of HRM and PHM, and it was tasked to produce evidence-based statements on the indications, performance and reporting of these tests. Each committee member performed literature searches to retrieve relevant articles within the context of domains to which they were assigned. Results: Twelve recommendation statements were created and summarised. Conclusion: Standardising key aspects of HRM and PHM is imperative to ensure the delivery of high-quality care. We reported the development of recommendations for the performance and interpretation of HRM and ambulatory reflux monitoring in Singapore. Keywords: Gastro-oesophageal reflux disease, GERD, high-resolution oesophageal manometry, oesophagus, pH testing

Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings. This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated. 58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (p = 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (p

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians. ispartof: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY vol:38 issue:2 pages:197-209 ispartof: location:Australia status: published

INTRODUCTION Decompensation with ascites portends a poor prognosis in cirrhosis. The aim of this study was to compare the outcomes of patients with nonalcoholic steatohepatitis (NASH) with hepatitis B virus (HBV) cirrhosis after decompensation with ascites. METHODS We conducted a retrospective study to evaluate the outcomes of patients with NASH and HBV cirrhosis who were admitted to hospital for first-onset ascites from January 1, 2004, to June 30, 2015. They were followed up until death, liver transplantation, or loss to follow up. RESULTS Patients with NASH had lower median (interquartile range) Model for End-Stage Liver Disease score (11 [9-14] vs 14 [11-17], P < 0.001). Over 60 months, patients with NASH cirrhosis had higher cumulative incidence of dilutional hyponatremia (P < 0.001) and refractory ascites (P = 0.028). They also had higher cumulative incidence of cirrhosis-related deaths and liver transplantation compared with HBV cirrhosis (65.7%; [95% confidence interval (CI) 53.6-75.4] vs 42.5% [95% CI 32.4-55.2], P = 0.008). Multivariable competing risk analysis showed that NASH (subdistribution hazard ratio [sHR] 1.88 [95% CI 1.14-3.11], P = 0.014), non-Chinese ethnicity (sHR 1.63 [95% CI 1.06-2.50], P = 0.027), history of hepatocellular carcinoma (sHR 1.76 [95% CI 1.05-2.95], P = 0.033), estimated glomerular filtration rate

During the Coronavirus Disease 2019 (COVID-19) pandemic, practices of gastrointestinal procedures within the digestive tract require special precautions due to the risk of contraction of severe acute respiratoy syndrome coronavirus-2 (SARS-CoV-2) infection. Many procedures in the gastrointestinal motility laboratory may be considered moderate to high-risk for viral transmission. Healthcare staff working in gastrointestinal motility laboratories are frequently exposed to splashes, air droplets, mucus, or saliva during the procedures. Moreover, some are aerosol-generating and thus have a high risk of viral transmission. There are multiple guidelines on the practices of gastrointestinal endoscopy during this pandemic. However, such guidelines are still lacking and urgently needed for the practice of gastrointestinal motility laboratories. Hence, the Asian Neurogastroenterology and Motility Association had organized a group of gastrointestinal motility experts and infectious disease specialists to produce a position statement paper based-on current available evidence and consensus opinion with aims to provide a clear guidance on the practices of gastrointestinal motility laboratories during the COVID-19 pandemic. This guideline covers a wide range of topics on gastrointestinal motility activities from scheduling a motility test, the precautions at different steps of the procedure to disinfection for the safety and well-being of the patients and the healthcare workers. These practices may vary in different countries depending on the stages of the pandemic, local or institutional policy, and the availability of healthcare resources. This guideline is useful when the transmission rate of SARS-CoV-2 is high. It may change rapidly depending on the situation of the epidemic and when new evidence becomes available.

Background/Aims The relationship between animal exposure and irritable bowel syndrome (IBS) is debated. Epidemiological studies have shown that atopy is more prevalent in IBS patients and vice versa. We set out to examine the association between animal danders sensitization and IBS-like symptoms in atopic patients. Methods We recruited 69 consecutive atopic patients from the allergy clinic of a tertiary hospital. Subjects completed validated bowel questionnaires, underwent skin prick test, blood was collected for serum total immunoglobulin E, and ImmunoCAP immune solid-phase allergen chip (ISAC) IgE multiplex assay. Results Twenty-eight (41.0%) atopic patients fulfilled the Rome III IBS criteria (atopy-IBS). There were no differences in gender, age, pet ownership, total serum IgE, or food allergen sensitization between atopy-IBS group and atopy-non-IBS group. We found that atopy- IBS group had significantly higher number of positive skin prick test for cat dander (64.3% vs 24.4%, P < 0.001), dog dander (64.3% vs 41.5%, P = 0.015) and weed pollens (32.1% vs 14.6%, P = 0.050) compared to atopy-non-IBS group. Out of 112 components from 51 allergen sources (both aeroallergen and food allergens), only Fel d1 (a major cat dander antigen) IgE is significantly higher in atopy-IBS group than atopy-non-IBS group (21.4% vs 2.4%, P = 0.029). Majority of atopy-IBS patients had mixed-type IBS. Conclusions We demonstrated an association between animal danders sensitization, in particular cat dander sensitization, and IBS-like symptoms in atopic patients. Future studies are needed to explore the relationship between aeroallergen and functional gastrointestinal disorders. Sensitization may be related to the pathophysiology of IBS or it could be that we are missing aeroallergen-induced gut allergy. (J Neurogastroenterol Motil 2020;26:267-273)

Background: Epidemiology data of gastroesophageal junction (GEJ) cancers in Asia are extremely scarce. It is hardly registered by any cancer registry in the region, and only a few reports are available. Based on existing literature works, the overall trend indicates similar or gradually increasing GEJ cancers in Asia but comparably less than the West. The increasing trend in Asia is likely a result of rising risk factors, especially of gastroesophageal reflux disease and obesity. Summary: However, epidemiology data may be misleading due to several contentious diagnostic issues. The diagnostic conundrums are due to inherent complexity of the GEJ as a functional and pathological unit. Challenging diagnostic issues in Asia include the following: nonstandardized landmark of the GEJ, misclassification of Barrett esophagus, targeted versus nontargeted tissue sampling, histopathology disagreement and challenges in screening or surveillance of dysplastic BE and early GEJ cancer. The recent Asian-Pacific survey led by the Asian Barrett Consortium (ABC) has provided useful insights into these contentious issues. A key learning point from these diagnostic limitations is that the awareness of the disease and adherence to existing recommendations or guidelines are poor in the region. Key Messages: Standardization in diagnostic methodology is vital for accurate epidemiology data, and this can only come from better awareness and adherence through educational and international efforts. Last, surveillance strategy may need a paradigm shift from a purely diagnostic approach to a combined targeted surveillance and treatment approach using novel endoscopic techniques.

Background Irritable bowel syndrome (IBS) is a prevalent and debilitating gastrointestinal condition. Research has reported persistent, low-grade mucosal inflammation and significant overlaps between patients with IBS and those with dyspepsia, suggesting a possible pathogenic role of Helicobacter pylori (H. pylori) in IBS. This study therefore aimed to provide the first systematic review and meta-analysis on the association between H. pylori infection and IBS. Aim To investigate the association between H. pylori infection and IBS. Methods Using the keywords "H. pylori OR Helicobacter OR Helicobacter pylori OR infection" AND "irritable bowel syndrome OR IBS", a preliminary search of PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Web of Science, Google Scholar and WanFang databases yielded 2924 papers published in English between 1 January 1960 and 1 June 2018. Attempts were also made to search grey literature. Results A total of 13 clinical studies were systematically reviewed and nine studies were included in the final meta-analysis. Random-effects meta-analysis found a slight increased likelihood of H. pylori infection in patients with IBS, albeit this was not statistically significant (pooled odds ratio 1.47, 95% confidence interval: 0.90-2.40, P = 0.123). It must also be acknowledged that all of the available studies reported only crude odd ratios. H. pylori eradication therapy also does not appear to improve IBS symptoms. Although publication bias was not observed in the funnel plot, there was a high degree of heterogeneity amongst the studies included in the meta-analysis (I 2 = 87.38%). Conclusion Overall, current evidence does not support an association between IBS and H. pylori infection. Further rigorous and detailed studies with larger sample sizes and after H. pylori eradication therapy are warranted.

Background Depression is a growing public health problem that affects over 350 million people globally and accounts for approximately 7.5% of healthy years lost due to disability. Escitalopram, one of the first-line medications for the treatment of depression, is a selective serotonin reuptake inhibitor and one of the most commonly prescribed antidepressant medications worldwide. Although thought to be generally safe and with minimal drug-drug interactions, we herein present an unusual case of cholestatic liver injury, likely secondary to escitalopram initiation. Case summary A 56-year-old Chinese lady presented with fever and cholestatic liver injury two weeks after initiation of escitalopram for the treatment of psychotic depression. Physical examination was unremarkable. Further investigations, including a computed tomography scan of the abdomen and pelvis and tests for hepatitis A, B and C and for autoimmune liver disease were unyielding. Hence, a diagnosis of escitalopram-induced liver injury was made. Upon stopping escitalopram, repeat liver function tests showed downtrending liver enzymes with eventual normalization of serum aspartate aminotransferase and alanine aminotransferase one-week post-discharge. Conclusion Clinicians should be aware of the possibility of escitalopram-induced liver injury when initiating depressed patients on antidepressant treatment. This requires extra vigilance as most patients may remain asymptomatic. Measurement of liver function tests could be considered after initiation of antidepressant treatment, especially in patients with pre-existing liver disease.

BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus (BE), making standardization challenging. AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists. METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE. RESULTS Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSION Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

Background While many studies have found an association between irritable bowel syndrome (IBS) and obesity, many others did not. Hence, this systematic review with meta-analysis aims to evaluate the relationship between obesity and IBS, and determine whether obesity correlates differently with the various IBS endotypes. Methods A systematic review of published literature was conducted in concordance with the PRISMA guidelines and followed by a meta-analysis of relevant studies using the random-effects model. The 34 included studies assessed obesity among non-IBS controls and IBS subjects, either as continuous or dichotomous outcomes, using body mass index (BMI) and waist circumference (WC). The standardized mean difference (SMD) and 95% confidence interval (CI); and the odds ratio (OR) and 95% CI were obtained for continuous and dichotomous outcomes respectively. Meta-regression was performed to identify sources of heterogeneity. Results We found a weak association between IBS and obesity, but this was not statistically significant. For BMI, the overall SMD was +0.227 (95% CI: –0.093 to 0.547, p = 0.164) and OR was 1.312 (95% CI: 0.974 to 1.767, p = 0.074). For WC, the overall SMD was +1.020 cm (95% CI: –1.768 to 3.807, p = 0.473). However, subgroup analysis revealed significantly higher BMI among IBS-diarrhoea (IBS-D) subjects compared to controls (SMD = +1.940; 95% CI: 0.679 to 3.200, p = 0.003) and significantly lower BMI among IBS-constipation (IBS-C) subjects compared to IBS-D subjects (SMD = –1.720; 95% CI: –2.489 to –0.950, p Conclusions In conclusion, our systematic review with meta-analysis showed that obesity is positively associated with diarrhoea-predominant IBS, but not IBS in general. Our findings support the exploration of shared pathophysiology between IBS-D and obesity.

Background and aim Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients. Methods A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed. Results Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies. Conclusions There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.

Background: Derangements of the gut microbiome have been linked to increased systemic inflammation and central nervous system disorders, including schizophrenia. This systematic review thus aimed to investigate the hypothesis that probiotic supplementation improves schizophrenia symptoms. Methods: By using the keywords (probiotic OR gut OR microbiota OR microbiome OR yogurt OR yoghurt OR lactobacillus OR bifidobacterium) AND (schizophrenia OR psychosis), a preliminary search of the PubMed, Medline, Embase, Google Scholar, ClinicalTrials.gov, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine databases yielded 329 papers published in English between January 1, 1960 and May 1, 2018. Attempts were made to search grey literature as well. Results: Three clinical studies were reviewed, comparing the use of probiotics to placebo controls. Applying per-protocol analysis and a fixed-effects model, there was no significant difference in schizophrenia symptoms between the group that received probiotic supplementation and the placebo group post-intervention as the standardized mean difference was –0.0884 (95% CI –0.380 to 0.204, p = 0.551). Separate analyses were performed to investigate the effect of probiotic supplementation on positive or negative symptoms of schizophrenia alone. In both instances, no significant difference was observed as well. Conclusion: Based on current evidence, limited inferences can be made regarding the efficacy of probiotics in schizophrenia. Although probiotics may have other benefits, for example to regulate bowel movement and ameliorate the metabolic effects of antipsychotic medications, the clinical utility of probiotics in the treatment of schizophrenia patients remains to be validated by future clinical studies.

Irritable bowel syndrome (IBS) is a complex, functional gastrointestinal disorder characterized by chronic abdominal pain or discomfort and altered bowel habits. Despite the global prevalence and disease burden of IBS, its underlying pathophysiology remains unclear. Inflammation may play a pathogenic role in IBS. Studies have highlighted the persistence of mucosal inflammation at the microscopic and molecular level in IBS, with increased recruitment of enteroendocrine cells. Substantial overlaps between IBS and inflammatory bowel disease have also been reported. This review thus aimed to discuss the body of evidence pertaining to the presence of mucosal inflammation in IBS, its putative role in the disease process of IBS, and its clinical relevance. Increased mast cell density and activity in the gut may correlate with symptoms of visceral hypersensitivity. As evidenced by patients who develop postinfectious IBS, infective gastroenteritis could cause systemic inflammation and altered microbiome diversity, which in turn perpetuates a cycle of chronic, low-grade, subclinical inflammation. Apart from mucosal inflammation, neuroinflammation is probably involved in the pathophysiology of IBS via the "gut-brain" axis, resulting in altered neuroendocrine pathways and glucocorticoid receptor genes. This gives rise to an overall proinflammatory phenotype and dysregulated hypothalamic-pituitary-adrenal axis and serotonergic (5-HT) functioning, which could, at least in part, account for the symptoms of IBS. Although a definite and reproducible pattern of immune response has yet to be recognized, further research into anti-inflammatories may be of clinical value.

Clostridium difficile infection (CDI) is an increasingly common occurrence in the hospital setting, and it is associated with significant morbidity and mortality. In vitro studies have found that rifaximin, a nonabsorbable rifamycin antibiotic, displays potent antimicrobial activity against C. difficile. This systematic review thus aimed to examine the clinical role of rifaximin in CDI. Using the keywords [clostridium OR difficile OR colitis] AND [rifaximin OR xifaxan OR rifagut], a preliminary search on the PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases yielded 6210 papers published in English between 1-Jan-1988 and 1-Jul-2018. A total of eight clinical trials were systematically reviewed. Of these, only two were randomized, controlled trials. In the treatment of mild-moderate CDI, rifaximin is a viable alternative to existing therapies (metronidazole or vancomycin). More importantly, rifaximin has a potential role in conjunction with other therapies, showing to be efficacious in reducing the rate of CDI recurrence. However, clinical studies have reported a resistance rate in the range of 29.1–48.9%, with a geographical variance in the distribution of rifaximin-resistant C. difficile strains. With its unique eubiotic properties and positive modulation of the gut flora, rifaximin has a potential therapeutic role in the management of CDI, especially in CDI recurrences. As there is a paucity of randomized, controlled trials to support its use, studies with larger and more diverse populations should be conducted before the efficacy of rifaximin can be conclusively stated. Rifaximin is also a relatively expensive antimicrobial, further studies should include cost-benefit analyses.

Irritable bowel syndrome (IBS) remains a prevalent and difficult-to-manage gastrointestinal condition. There is growing interest in the use of traditional medicine to manage IBS. In particular, curcumin, a biologically active phytochemical, has demonstrated anti-inflammatory and anti-oxidant properties and mucosal protective effects in rat models of colitis. This meta-analysis thus aimed to investigate the hypothesis that curcumin improves IBS symptoms. Using the keywords (curcumin OR turmeric OR Indian saffron OR diferuloylmethane OR curcuminoid) AND (irritable bowel syndrome OR IBS), a preliminary search on the PubMed, Medline, Embase, PsychINFO, Web of Science, and Google Scholar databases yielded 1080 papers published in English between 1 January 1988 and 1 May 2018. Five randomized, controlled trials were systematically reviewed and 3 were included in the final meta-analysis. Random-effects meta-analysis based on three studies and 326 patients found curcumin to have a beneficial albeit not statistically significant effect on IBS symptoms (pooled standardized mean difference from baseline IBS severity rating &minus, 0.466, 95% CI: &minus, 1.113 to 0.182, p = 0.158). This is the first meta-analysis to examine the use of curcumin in IBS. With its unique anti-oxidant and anti-inflammatory activities and ability to modulate gut microbiota, curcumin is a potentially useful addition to our armamentarium of agents for IBS. It also appears safe and well-tolerated, with no adverse events reported in the available trials. However, current findings are based on a considerably limited evidence base with marked heterogeneity. More robust clinical trials involving a standardized curcumin preparation and larger sample sizes should be encouraged.

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by symptoms of hyperarousal and hypervigilance. Increasing research on the "gut-brain" axis (bidirectional signaling between the gut and the brain) has drawn links between PTSD and irritable bowel syndrome (IBS), an exceedingly common yet incompletely understood gastrointestinal condition. This meta-analysis thus aimed to examine the body of evidence and extent of association of PTSD with IBS.Using the keywords [early abuse OR childhood abuse OR violence OR trauma OR PTSD] AND [irritable bowel syndrome or IBS], a preliminary search on the PubMed, Medline, Embase, ScienceDirect, PsychINFO, Web of Science, and Google Scholar databases yielded 11,257 papers published in English between January 1, 1988, and May 1, 2018. Of these, only eight studies were included in the final meta-analysis.The eight studies (four cross-sectional and four cohort) contained a total of 648,375 subjects. Most studies were from the USA and conducted on army veterans. The funnel plot revealed a roughly symmetrical distribution of studies, and Egger test was not significant for publication bias (P = 0.583). Random-effects meta-analysis found PTSD to be a significant risk factor for IBS (pooled odds ratio 2.80, 95% confidence interval: 2.06 to 3.54, P 0.001).Overall, PTSD is associated with an increased likelihood of IBS. This is the first meta-analysis to specifically examine the association between PTSD and IBS, and it provides insights into the probable (patho)physiology and management of IBS, supporting a holistic consideration of the psychosocial aspects of IBS and further research into effective multi-modal therapeutics.

What is known and objective Irritable bowel syndrome (IBS) is a complex and chronic, relapsing gastrointestinal condition that affects more than 10% of the population worldwide. There is a pressing need for new therapeutic strategies in the management of IBS. Increasing research has shed light on the modulatory functions of melatonin on pain, local inflammation and motility in the gastrointestinal tract. However, melatonin's effects are limited by its extensive first-pass metabolism and short half-life. Comment Agomelatine, a naphthalene analog of melatonin, is a novel melatonergic drug with a longer half-life and a comparatively greater affinity for MT1 and MT2 melatonin receptors than melatonin itself. Agomelatine also shows serotonin 5-HT3 receptor antagonist activity, which is theoretically of benefit for patients with IBS with diarrhoea (IBS-D) as it regulates gastrointestinal motility and visceral sensory mechanisms. Although only one clinical study of agomelatine use in patients with IBS exists, we believe that agomelatine is a safe and efficacious multimodal agent with untapped potential in the management of IBS. What is new and conclusion Numerous comorbidities are associated with IBS, including chronic pain syndromes and psychiatric disorders. Coupled with its antidepressant actions, agomelatine could serve as an effective adjunct therapeutic. Agomelatine should be considered in our therapeutic armamentarium for IBS management.

Surgery and other non-pharmacological treatments such as sacral nerve stimulation are used for the treatment of difficult-to-treat chronic constipation. Novel pharmacological therapeutic agents are also being introduced. To evaluate the efficacy of these treatments, it is imperative to have a consistent definition of pharmacologically refractory constipation. A systematic review of studies on refractory, difficult-to-treat or surgically treated constipation was carried out to determine the criteria that various authors used to define this group of patients.A systematic review was performed for literature published from June 2005 to June 2015 using PubMed, Cochrane, and Scopus databases, as well as manual searches. Studies on patients with refractory or intractable constipation were extracted. Criteria used for defining refractory constipation, as well as pharmacological agents tried including dosage, frequency, and duration, were reviewed.Sixty-one studies were included in this review. Forty-eight involved surgical treatment of constipation, while 13 examined non-surgical therapies for refractory constipation. There is no generally accepted definition of refractory constipation. Authors consider constipation to be refractory when response to management is suboptimal, but there is no consensus on the choice of drug, order of usage, and dosage or treatment duration. Prior medical therapy was not mentioned at all in five studies.There is need for a detailed definition of pharmacologically refractory constipation before submitting patients to invasive treatments and to evaluate new pharmacological agents.

Chronic hepatitis B (CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferon-based therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future.