World Journal of Gastrointestinal Pharmacology and Therapeutics最新文献

Aim: To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease (CD).

Methods: One hundred seven patients with CD based on standard clinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the Harvey-Bradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and non-responders. Whole peripheral blood was extracted and genotyping was performed by PCR.

Results: One hundred and seven patients were included in the study. Seventy two (67.3%) patients were classified as complete responders, 22 (20.5%) as partial while 13 (12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to anti-TNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.

Conclusion: No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

Gastrointestinal (GI) dysmotility is a common problem in the critically ill population. It can be a reflection and an early sign of patient deterioration or it can be an independent cause of morbidity and mortality. GI dysmotility can be divided for clinical purposes on upper GI dysmotility and lower GI dysmotility. Upper GI dysmotility manifests by nausea, feeding intolerance and vomiting; its implications include aspiration into the airway of abdominal contents and underfeeding. Several strategies to prevent and treat this condition can be tried and they include prokinetics and post-pyloric feeds. It is important to note that upper GI dysmotility should be treated only when there are clinical signs of intolerance (nausea, vomiting) and not based on measurement of gastric residual volumes. Lower GI dysmotility manifests throughout the spectrum of ileus and diarrhea. Ileus can present in the small bowel and the large bowel as well. In both scenarios the initial treatment is correction of electrolyte abnormalities, avoiding drugs that can decrease motility and patient mobilization. When this fails, in the case of small bowel ileus, lactulose and polyethylene glycol solutions can be useful. In the case of colonic pseudo obstruction, neostigmine, endoscopic decompression and cecostomy can be tried when the situation reaches the risk of rupture. Diarrhea is also a common manifestation of GI dysmotility and the most important step is to differentiate between infectious sources and non-infectious sources.

Aim: To determine the tools needed and problems encountered during the transition of inflammatory bowel disease (IBD) patients from pediatric to adult gastroenterologists (GIs) in Québec, Canada.

Methods: We conducted a needs assessment survey of Quebec health care professionals (HCPs). The survey was handed out to 136 Québec HCPs at a local conference in 2013. Additionally, it was emailed to any other HCPs in Quebec involved in caring for IBD patients. The completed surveys were compiled to derive descriptive data. Further specific subgroup analysis was then conducted.

Results: Among the conference attendees and individuals emailed 77 (28.2%) completed the questionnaire. Respondents included adult GIs (61.3%), pediatric GIs (20.8%) and IBD nurses (18.3%). The majority of respondents believed that a standardized structure is important for a successful transition. Adult and pediatric GIs equally felt that patients were inadequately prepared for the transition (P = 0.6). There were significant differences between adult and pediatric GIs when it came to resource availability (55.6% vs 90.9%, P = 0.002) and perceived need of a formal transition clinic (21.7% vs 68.8%, P = 0.0006). Both transition program and medical summaries were identified as the most valuable tools to improve transition.

Conclusion: As described in previous studies, our survey reinforces the importance of a transition program, education for young adult IBD patients and the need to improve communication between adult and pediatric GIs.

Aim: To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency.

Methods: Thirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules.

Results: Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT.

Conclusion: A substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.

Anti-tumor necrosis factor (TNF) biologics are currently amongst the most widely used and efficacious therapies for inflammatory bowel disease (IBD). The development of therapeutic drug monitoring for infliximab and adalimumab has allowed for measurement of drug levels and antidrug antibodies. This information can allow for manipulation of drug therapy and prediction of response. It has been shown that therapeutic anti-TNF drug levels are associated with maintenance of remission, and development of antidrug antibodies is predictive of loss of response. Studies suggest that a low level of drug antibodies, however, can at times be overcome by dose escalation of anti-TNF therapy or addition of an immunomodulator. We describe a retrospective case series of twelve IBD patients treated at the University of California-Irvine, who were on infliximab or adalimumab therapy and were found to have detectable but low-level antidrug antibodies. These patients underwent dose escalation of the drug or addition of an immunomodulator, with subsequent follow-up drug levels obtained. Eight of the twelve patients (75%) demonstrated resolution of antidrug antibodies, and were noted to have improvement in disease activity. Though data regarding overcoming low-level anti-TNF drug antibodies remains somewhat limited, cases described in the literature as well as our own experience suggest that this may be a viable strategy for preserving the use of an anti-TNF drug. Low-level anti-TNF drug antibodies may be overcome by dose escalation and/or addition of an immunomodulator, and can allow for clinical improvement in disease status. Therapeutic drug monitoring is an important tool to guide this strategy.

5-Aminosalicylates are a class of anti-inflammatory agents that have been used for decades in inflammatory bowel disease. Whilst they are first line for induction and an option for maintenance of remission in ulcerative colitis, the picture in Crohn's disease is variable. For maintenance of remission, key Cochrane systematic reviews have found conflicting results between the medical and surgical induced contexts. In this piece, the possible reasons for this are considered. It is proposed that clinicians should consider 5-aminosalicylates agents an option to maintain remission post-surgery. Future primary research is needed in the medical induced remission setting which considers the length of remission on enrolment and endoscopic or histological disease scores. Additionally, secondary research to rank the various treatment options in the post-surgical setting could be achieved through the use of network meta-analysis and will guide policy makers in the future.

Aim: To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis (UC).

Methods: A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin (150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0, 4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario (ITT-WCS).

Results: Of 300 patients with UC, 62 patients (curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients (curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission (31.3% vs 27.3%, P = 0.75), clinical response (20.7% vs 36.4%, P = 0.18), mucosal healing (34.5% vs 30.3%, P = 0.72), and treatment failure (25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.

Conclusion: Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy (CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn's disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment naïve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC's conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

Ingestion of caustic substances and its long-term effect on the gastrointestinal system maintain its place as an important public health issue in spite of the multiple efforts to educate the public and contain its growing number. This is due to the ready availability of caustic agents and the loose regulatory control on its production. Substances with extremes of pH are very corrosive and can create severe injury in the upper gastrointestinal tract. The severity of injury depends on several aspects: Concentration of the substance, amount ingested, length of time of tissue contact, and pH of the agent. Solid materials easily adhere to the mouth and pharynx, causing greatest damage to these regions while liquids pass through the mouth and pharynx more quickly consequently producing its maximum damage in the esophagus and stomach. Esophagogastroduodenoscopy is therefore a highly recommended diagnostic tool in the evaluation of caustic injury. It is considered the cornerstone not only in the diagnosis but also in the prognostication and guide to management of caustic ingestions. The degree of esophageal injury at endoscopy is a predictor of systemic complication and death with a 9-fold increase in morbidity and mortality for every increased injury grade. Because of this high rate of complication, prompt evaluation cannot be overemphasized in order to halt development and prevent progression of complications.