Opioid use and misuse in ulcerative colitis

BACKGROUND Patients with ulcerative colitis(UC) may be exposed to opioids over their disease duration. The use of such medications carries significant risk, including intestinal dysmotility and potential for addiction. However, the rates of narcotic use and misuse in patients with UC have not been studied extensively. Functional gastrointestinal disorders(FGID) are prevalent in patients with UC, and have been shown to increase the risk of narcotic use and misuse in patients with Crohn's disease. We hypothesized that patients with UC and a concurrent diagnosis of FGID would have increased rates of both opioid use and misuse in our patient cohort.AIM To evaluate the prevalence of chronic opioid use and misuse in UC.METHODS A retrospective chart review of UC patients seen at the University of Virginia Digestive Health Center was performed on all patients evaluated between 2006 and 2011. Patient demographics, medical, surgical, and medication histories were obtained from the electronic medical record. Concomitant diagnosis of FGID was also noted at the time. The electronic prescription monitoring program was accessed to obtain prescription opioid filling histories. Prescription opioid misuse was defined as opioid prescriptions filled from four or more prescribers and four or more different pharmacies in a 12-mo period.RESULTS A total of 497 patients with UC were included. Patients with UC and FGID were more likely to be female, but no other demographic variables were associated with FGID. Of the UC patients who had FGID, a greater proportion were found to be using opioids chronically(36% with FGID vs 9% without FGID, P < 0.0001)and were misusing prescription opioids(12.8% vs 1.3%, P < 0.001). Multivariate logistic regression demonstrated a significant association with FGID and chronic opioid use(OR = 4.50; 95%CI: 1.91-10.59) and opioid misuse(OR = 5.19; 95%CI1.04-25.76). Tobacco use(OR 2.53; 95%CI: 1.06-6.08) and anxiety(OR 3.17; 95%CI:1.08-9.26) were other variables associated with an increased risk of chronic narcotic use.CONCLUSION FGID was associated with a 4.5-fold increase in chronic opioid use and a 5-fold increased risk of opioid misuse in this patient cohort with UC.

Instructions to authors

GENERAL INFORMATION World Journal of Gastrointestinal Pharmacology and Therapeutics (World J Gastrointest Pharmacol Ther, WJGPT, online ISSN 2150-5349, DOI:

Management of gastric outlet obstruction:Focusing on endoscopic approach

Gastric outlet obstruction(GOO)is a medical condition characterized by epigastric pain and postprandial vomiting due to mechanical obstruction.The obstructions typically involved in GOO can be benign or malignant.Peptic ulcer disease is the most common cause of benign GOO,and malignant causes include gastric cancer,lymphoma,and gastrointestinal stromal tumor.With the eradication of Helicobacter pylori(H.pylori)and the use of proton pump inhibitors,the predominant causes have changed from benign to malignant diseases.Treatment of GOO depends on the underlying cause:Proton pump inhibitors,H.pylori eradication,endoscopic treatments including balloon dilatation or the placement of self-expandable stents,or surgery.

Correlation of rapid point-of-care vs send-out fecal calprotectin monitoring in pediatric inflammatory bowel disease

AIM To assess the correlation between the send-out enzymelinked immuno sorbent assay(ELISA) and the point-ofcare(POC) calprotectin test in pediatric inflammatory bowel disease(IBD) patients.METHODS We prospectively collected stool samples in pediatric IBD patients for concomitant send-out ELISA analysis and POC calprotectin testing using the Quantum Blue?(QB) Extended immunoassay. Continuous results between 17 to 1000 μg/g were considered for comparison. Agreement between the two tests was measured by a Bland-Altman plot and statistical significance was determined using Pitman's test.RESULTS Forty-nine stool samples were collected from 31 pediatric IBD patients. The overall means for the rapid and ELISA tests were 580.5 and 522.87 μg/g respectively. Among the 49 samples, 18(37.5%) had POC calprotectin levelsof ≤ 250 μg/g and 31(62.5%) had levels > 250 μg/g.Calprotectin levels ≤ 250 μg/g show good correlation between the two assays. Less correlation was observed at quantitatively higher calprotectin levels. CONCLUSION In pediatric IBD patients, there is better correlation of between ELISA and POC calprotectin measurements at clinically meaningful, low-range levels. Future adoption of POC calprotectin testing in the United States may have utility for guiding clinical decision making in real time.

INSTRUCTIONS TO AUTHORS

GENERAL INFORMATION World Journal of Gastrointestinal Pharmacology and Therapeutics(World J Gastrointest Pharmacol Ther,WJGPT,online ISSN 2150-5349,DOI:10.4292),is a bimonthly,open-access(OA),peer-reviewed journal supported by an editorial board of 188 experts in gastrointestinal pharmacology and therapeutics from 36

Response of irritable bowel syndrome with constipation patients administered a combined quebracho/conker tree/M. balsamea Willd extract

The aim of this case series was to retrospectively examine the symptom response of irritable bowel syndrome with constipation(IBS-C) patients administered an herbal extract in a real-world setting. Twenty-four IBS-C patients in a community office practice were provided a combination over-the-counter dietary supplement composed of quebracho(150 mg), conker tree(470 mg) and M. balsamea Willd(0.2 mL) extracts(Atrantil?) and chose to take the formulation for a minimum of 2 wk in an attempt to manage their symptoms. Patient responses to the supplement were assessed by visual analogue scale(VAS) for abdominal pain, constipation and bloating at baseline and at 2 wk as part of standard-of-care. Patient scores from VAS assessments recorded in medical chart data were retrospectively compiled and assessed for the effects of the combined extract on symptoms. Sign tests were used to compare changes from baseline to 2 wk of taking the extract. Significance was defined as P < 0.05. Twenty-one of 24 patients(88%) responded to the dietary supplement as measured by individual improvements in VAS scores for abdominal pain, bloating and constipation symptoms comparing scores prior to administration of the extract against those reported after 2 wk. There were also significant improvements in individual as well as mean VAS scores after 2 wk of administration of the combinedextract compared to baseline for abdominal pain [8.0(6.5, 9.0) vs 2.0(1.0, 3.0), P < 0.001], bloating [8.0(7.0, 9.0) vs 1.0(1.0, 2.0), P < 0.001] and constipation [6.0(3.0, 8.0) vs 2.0(1.0, 3.0), P < 0.001], respectively. In addition, 21 of 24 patients expressed improved quality of life while taking the formulation. There were no reported side effects to administration of the dietary supplement in this practice population suggesting excellent tolerance of the formulation. This pilot retrospective analysis of symptom scores from patients before and after consuming a quebracho/conker tree/M. balsamea Wil d extract may support the formulation's use in IBS-C.

Clinical utility of quantitative multi-antibody Polycheck immunoassays in the diagnosis of coeliac disease

AIM:To evaluate the clinical utility of multi-antibody strategies in the diagnosis of coeliac disease(CD),the new quantitative Polycheck immunoassays were analysed.METHODS:Polycheck Celiac Panels(PCPs)are immunoenzyme screening assays for the quantitative measurement of coeliac-specific immunoglobulin class G(Ig G)or class A(Ig A)in serum.Lines of relevant antigens are coated together with five Ig G or Ig A standard lines used for the standard curve as positive control.PCP IgA consists of human recombinant human tissue transglutaminase(t TG)and deamidated gliadin peptides(DGP)as targets to detect Ig A antibodies.PCP IgG consists of t TG,DGP and IF(intrinsic factor)antigens to detect antibodies in Ig G class.PCPs were performed on 50 CD patients,including 6 cases with selective Ig A deficiency,and 50 non-coeliac controls.CD diagnosis was performed according to the ESPGHAN recommendations:The presence of specific anti-t TG-Ig A or anti-DGP-Ig G(in the case of Ig A deficiency)antibodies,typical histopathological changes in duodenal mucosa described in Marsh-Oberhüber classification as at least grade 2.The diagnosis of the majority of the control subjects was functional gastrointestinal disorders.The PCP results were compared with reference EliA Celikey.RESULTS:The usage of PCPs led to the correct identification of all CD patients.In our study,PCPs showed 100%agreement with the histopathological results.PCP IgA test showed a 98%concordance and correlated positively(R=0.651,P=0.0014)with Eli A Celikey test.The highest specificity and positive predictive value(both 100%)were observed for the detection of Polycheck anti-t TG-Ig A antibodies.The highest sensitivity and negative predictive value(both 100%)were achieved by Polycheck anti-DGPIg G antibody detection.The best performance(98%sensitivity and negative predictive value,100%specificity and positive predictive value,diagnostic accuracy-AU ROC 99%)was observed for the strategy of using both PCP IgA and IgG and determining positive outcomes of the test with two or more coeliac-specific antibodies detected.The majority of coeliac patients had multiple antibodies.All four antibodies were detected in 7(14%)cases,19 children(38%)were positive for three antibodies and 23(46%)were positive for two antibodies.CONCLUSION:The present study showed that detection of coeliac-specific antibodies with multi-antibody PCPs is effective and efficacious in the diagnosis of CD.

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication:A randomized study in Japan

AIM:To find the way to improve the eradication rate of first-line therapy in Japanese patients.METHODS:We prospectively compared the effectiveness of 7-d quadruple therapy to standard 7 d triple therapy in Japanese patients infected with Helicobacter pylori(H.pylori).One hundred and nineteen patients were randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,amoxicillin,clarithromycin and metronidazole(LACM7) or 7-d triple therapy with lansoprazole,amoxicillin and clarithromycin(LAC7).After three months,H.pylori status was analyzed by 13C-urea breath test.Incidence rates of adverse events were evaluated by use of questionnaires.RESULTS:By intention-to-treat(ITT) analysis,the eradication rate in the LACM7 group was 94.9%,which was significantly higher than the LAC7 group(68.3%,P < 0.001).Per protocol analysis also showed a significantly higher eradication rate in the LACM7 group(98.3%) than the LAC7 group(73.2%,P < 0.001).Nevertheless,the incidence of serious adverse events did not differ between the two groups(RR:1.10,95% CI:0.70-1.73,P = 0.67).CONCLUSION:Seven day non-bismuth quadruple therapy(LACM7) was superior to standard 7-d triple therapy(LAC7) for first-line eradication.

Increase in colonic diverticular hemorrhage and confounding factors

AIM: To classify changes over time in causes of lower gastrointestinal bleeding(LGIB) and to identify factors associated with changes in the incidence and characteristics of diverticular hemorrhage(DH).METHODS: A total of 1803 patients underwent colonoscopy for overt LGIB at our hospital from 1995 to 2013. Patients were divided into an early group(EG, 1995-2006, n = 828) and a late group(LG, 2007-2013, n = 975), and specific diseases were compared between groups. In addition, antithrombotic drug(ATD) use and nonsteroidal anti-inflammatory drug(NSAID) use were comparedbetween patients with and without DH. RESULTS: Older patients(≥ 70 years old) and those with colonic DH were more frequent in LG than in EG(P < 0.01). Patients using ATDs as well as NSAIDs, male sex, obesity(body mass index ≥ 25 kg/m2), smoking, alcohol drinking, and arteriosclerotic diseases were more frequent in patients with DH than in those without. CONCLUSION: Incidence of colonic DH seems to increase with aging of the population, and factors involved include use of ATDs and NSAIDs, male sex, obesity, smoking, alcohol drinking, and arteriosclerotic disease. These factors are of value in handling DH patients.

Is there any progress in the treatment of non-alcoholic fatty liver disease?

Despite the fact that non-alcoholic fatty liver disease(NAFLD) and its severe clinical form,non-alcoholic steatohepatitis,are becoming increasingly prevalent in the industrialised countries,there are no licensed pharmacological treatments for them.Weight loss and life modifications,antioxidant therapies and insulin-sensitising agents are the current treatment strategies and have all been tested with inconclusive results.Low sample numbers,inadequate treatment duration and invalid surrogate markers for treatment response might all account for these results.As NAFLD is a systemic rather than a liver disease,future trials should address the patient as a whole and also address cardiovascular risk factors.

Editorial Board

2010-2013 The World Journal of Gastrointestinal Pharmacology and Therapeutics Editorial Board consists of 188 members,representing a team of worldwide experts in gastrointestinal pharmacology and therapeutics research.They are from 36 countries, including Australia(6),Austria(2)。

Tongue thickness in health vs cirrhosis of the liver:Prospective observational study

BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.

Understanding and treating refractory constipation

Chronic constipation is a frequently encountered disorder in clinical practice. Most constipated patients benefit from standard medical approaches. However, current therapies may fail in a proportion of patients. These patients deserve better evaluation and thorough investigations before their labeling as refractory to treatment. Indeed, several cases of apparent refractoriness are actually due to misconceptions about constipation, poor basal evaluation (inability to recognize secondary causes of constipation, use of constipating drugs) or inadequate therapeutic regimens. After a careful reevaluation that takes into account the above factors, a certain percentage of patients can be defined as being actually resistant to first-line medical treatments. These subjects should firstly undergo specific diagnostic examination to ascertain the subtype of constipation. The subsequent therapeutic approach should be then tailored according to their underlying dysfunction. Slow transit patients could benefit from a more robust medical treatment, based on stimulant laxatives (or their combination with osmotic laxatives, particularly over the short-term), enterokinetics (such as prucalopride) or secretagogues (such as lubiprostone or linaclotide). Patients complaining of obstructed defecation are less likely to show a response to medical treatment and might benefit from biofeedback, when available. When all medical treatments prove to be unsatisfactory, other approaches may be attempted in selected patients (sacral neuromodulation, local injection of botulinum toxin, anterograde continence enemas), although with largely unpredictable outcomes. A further although irreversible step is surgery (subtotal colectomy with ileorectal anastomosis or stapled transanal rectal resection), which may confer some benefit to a few patients with refractoriness to medical treatments.

Editorial Board

2010-2013 The World Journal of Gastrointestinal Pharmacology and Therapeutics Editorial Board consists of 188 members,representing a team of worldwide experts in gastrointestinal pharmacology and therapeutics research. They are

Neuroimaging the brain-gut axis in patients with irritable bowel syndrome

AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.

Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.

Use of acid suppressive therapy in hospitalized non-critically ill patients

AIM: To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS: In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g. , gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS: Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that sup-ports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication. CONCLUSION: AST is overused in hospitalized noncritically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.

Editorial Board

2010-2013The World Journal of Gastrointestinal Pharmacology and Therapeutics Editorial Board consists of188members, representing a team of worldwide experts in gastrointestinal

Colorectal cancer screening use among insured adults: Is out-of-pocket cost a barrier to routine screening?

AIM To describe the characteristics of adults who needed to see a doctor in the past year but could not due to the extra cost and assess the impact of limited financial resources on the receipt of routine fecal occult blood test, sigmoidoscopy, or colonoscopy for colon cancer screening among insured patients. METHODS Data obtained from the 2012 Behavioral Risk Factor Surveillance System included 215436 insured adults age 50-75 years. We computed frequencies, adjusted odds ratios(a ORs), and 95%CIs using SAS v9.3 software. RESULTS Nine percent of the study population needed to see a doctor in the past year but could not because of cost. The numbers were significantly higher among those aged 50-64(P < 0.0001), Non-Hispanic Whites(P < 0.0001), and those with a primary care physician(P < 0.0001) among other factors. Adjusting for possible confounders, a ORs for not seeing the doctor in the past year because of cost were: stool occult blood test within last year a OR = 0.88; 95%CI: 0.76-1.02, sigmoidoscopy within last year a OR = 0.72; 95%CI: 0.48-1.07, colonoscopy within the last year a OR = 0.91; 95%CI: 0.81-1.02. CONCLUSION We found that the limited financial resources within the past 12 mo were significantly associated with colorectal cancer(CRC) non-screening. Patients with risk factors identified in this study should adhere to CRC guidelines and should receive financial help if needed.

Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

The practice of phage therapy, which uses bacterial viruses(phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage-or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infection. Although much about phages and human health is still being discovered, the time to take phage therapy serious again seems to be rapidly approaching.