Jessica Ching

Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding: A Randomized Trial

BACKGROUND It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin. OBJECTIVE To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases. DESIGN A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725) SETTING A tertiary endoscopy center. PATIENTS Low-dose aspirin recipients with peptic ulcer bleeding. INTERVENTION 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up. MEASUREMENTS The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks. RESULTS 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, -3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]). LIMITATIONS The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy. CONCLUSION Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial

BACKGROUND Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. METHODS 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313. FINDINGS Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. INTERPRETATION Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases

BACKGROUND Anticoagulants and antiplatelet agents commonly are used to treat patients with cardiovascular and cerebrovascular diseases. Data on the safety of the use of these drugs before colonoscopic polypectomy are scanty. METHODS An audit was conducted for a 2-year period of consecutive patients undergoing colonoscopy and polypectomy. Patient demographics, site and size of polyps, and the use of anticoagulants and antiplatelet agents were documented from a hospital on-line database. Bleeding episodes were classified as immediate or delayed and were graded as mild, moderate, or severe. Risk factors associated with postendoscopy bleeding were analyzed by multivariate logistic regression analysis. RESULTS A total of 5593 cases were reviewed. Polypectomy was performed in 1657 patients. There were 37 cases of polypectomy-associated bleeding (2.2%); bleeding was immediate in 32 and delayed in 5. Multivariate analysis showed that warfarin use, after adjustment for the effects of each of the other factors, was an independent risk factor for bleeding, with an odds ratio 13.37: 95% CI[4.10, 43.65]. Age; the location and size of polyp; and the use of aspirin, non-steroidal anti-inflammatory drugs, and other antiplatelet agents were not associated with a higher risk of polypectomy-associated bleeding. CONCLUSIONS The use of antiplatelet agents during polypectomy was not associated with an increase in post-polypectomy bleeding. In contrast, treatment with warfarin should be discontinued, because this was associated with a significant increase in post-polypectomy bleeding.

The Asia-Pacific Colorectal Screening score: a validated tool that stratifies risk for colorectal advanced neoplasia in asymptomatic Asian subjects

Objective To develop and validate a clinical risk score predictive of risk for colorectal advanced neoplasia for Asia. Methods A prospective, cross-sectional and multicentre study was carried out in tertiary hospitals in 11 Asian cities. The subjects comprise 2752 asymptomatic patients undergoing screening colonoscopy. From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors for advanced colorectal neoplasia defined as invasive carcinoma or advanced adenoma. The ORs for significant risk factors were utilised to develop a risk score ranging from 0 to 7 (Asia-Pacific Colorectal Screening (APCS) score). Three tiers of risk were arbitrarily defined: 0–1 ‘average risk’ (AR); 2–3 ‘moderate risk’ (MR); and 4–7 ‘high risk’ (HR). Subjects undergoing screening colonoscopy between July 2006 and December 2007 were prospectively enrolled to form an independent validation group. Each subject had a personal APCS score calculated by summing the points attributed from the presence of risk factors in the individuals. The performance of the APCS score in predicting risk of advanced neoplasia was evaluated. Results There were 860 subjects in the derivation set and 1892 subjects in the validation set, with a baseline prevalence of advanced neoplasia of 4.5% and 3%, respectively. Applying the APCS stratification in the validation set, 559 subjects (29.5%) were in the AR tier, 966 subjects (51.1%) in the MR tier and 367 (19.4%) subjects in the HR tier. The prevalence of advanced neoplasia in the AR, MR and HR groups was 1.3, 3.2 and 5.2%, respectively. The subjects in the MR and HR tiers had 2.6-fold (95% CI 1.1 to 6.0) and 4.3-fold (95% CI 1.8 to 10.3) increased prevalence of advanced neoplasia, respectively, than those in the AR tier. Conclusions The APCS score based on age, gender, family history and smoking is useful in selecting asymptomatic Asian subjects for priority of colorectal screening.

Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection.

OBJECTIVES:We aimed to study the relationship between the hepatitis B virus (HBV) genotypes, core promoter/precore stop codon mutations, and histological liver damage among hepatitis B e antigen (HBeAg)-negative patients.METHODS:Liver biopsy specimens of 55 HBeAg-negative chronic HBV-infected patients were studied. A histological activity index was scored for degree of necroinflammation (HAI-NI) and fibrosis (HAI-F) as described by Knodell et al. HBV DNA was determined by a cross-linking assay and polymerase chain reaction (PCR) at the core promoter/precore region and the S region. PCR-positive samples were directly sequenced for core promoter and precore mutations and examined by restriction fragment length polymorphism for genotyping.RESULTS:Forty-one males and 14 females at a median age of 43 were studied. HBV DNA was detectable in 32 (58%) and 37 (67%) patients by the cross-linking assay and PCR, respectively, at the time of liver biopsy. The median (range) HAI-NI and HAI-F scores were 5 (1–10) and 2 (0–4), respectively. HBV DNA detectable by either the cross-linking assay or PCR was associated with a higher HAI-NI score. Eleven and 31 patients had genotypes B and C HBV, respectively. Genotype C HBV was associated with higher HAI-NI than genotype B HBV. Core promoter mutations and precore stop codon mutation were detected in 74% and 40% patients, respectively, but they were not associated with higher HAI-NI or HAI-F scores.CONCLUSIONS:Detectable HBV DNA and genotype C HBV, but not core promoter or precore stop codon mutations, are associated with more severe liver damage in HBeAg-negative patients.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening

Objective Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Design Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Results Age range for CRC screening is defined as 50–75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Conclusions Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding

BACKGROUND AND STUDY AIMS Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated. PATIENTS AND METHODS In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed. RESULTS 20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up. CONCLUSION These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

Objective The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. Design 442 incident cases (186 Crohns disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. Results In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. Conclusions This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Efficacy of Cap-Assisted Colonoscopy in Comparison With Regular Colonoscopy: A Randomized Controlled Trial

OBJECTIVES:Colonoscopy cannot be completed in up to 10% of cases. We postulate that cap-assisted colonoscopy (CAC), by fitting a mucosectomy cap to the tip of a colonoscope, could improve the outcome.METHODS:We conducted a prospective randomized controlled trial in two regional endoscopy centers. All colonoscopies were performed by experienced colonoscopists. Patients 18 years or older undergoing their first colonoscopy were recruited. Patients were randomized to the CAC group or to the regular colonoscopy (RC) group. The first successful cecal intubation rate, rescue cecal intubation rate, cecal intubation and total colonoscopy times, and polyp detection rate were compared.RESULTS:One thousand patients were enrolled (mean age 52.6 years, 46% men). There was no statistically significant difference in the first successful cecal intubation rate between CAC and RC groups (96.2% vs. 94.6%, P=0.23). The cecal intubation and total colonoscopy times were shorter in the CAC group than in the RC group (6.0±4.0 min vs. 7.2±4.8 min, P<0.001; 14.7±8.6 min vs. 16.7±10.3 min, P=0.001). The adenoma detection rate was significantly lower in the CAC group than in the RC group (30.5% vs. 37.5%, P=0.018), but there was no significant difference in the detection of advanced lesions. In case of failing cecal intubation, use of CAC as a rescue method could achieve a higher success rate than RC (66.7% vs. 21.1%, P=0.003).CONCLUSIONS:Among experienced colonoscopists, CAC did not improve the initial cecal intubation rate and had a lower adenoma detection rate. However, it shortened the cecal intubation time and performed better as a rescue method. Its utilization should be reserved for selected cases, especially when initial cecal intubation fails.

Obstacles to Colorectal Cancer Screening in Chinese: A Study Based on the Health Belief Model

BACKGROUND:Colorectal cancer (CRC) has emerged as the second most common cancer in Asia. This study uses the Health Belief Model (HBM) to examine the factors associated with the uptake of CRC testing.METHODS:A population-based telephone survey in which 1,004 randomly selected Chinese residents of Hong Kong aged between 30 and 65 yr were interviewed in 2006. Instruments were developed to measure the variables pertinent to the HBM, including perceived susceptibility, severity, benefit, barriers, and cues to action. The relationships of these predictors with CRC testing were examined using bivariate and multiple logistic regression analyses.RESULTS:Ten percent of the respondents had undertaken a CRC screening test. In the multiple logistic regression analyses, knowledge factors that were positively associated with CRC testing included knowledge of CRC symptoms (adjusted odds ratio [aOR] 3.33, 95% confidence interval [CI] 1.21–9.11) and knowledge of CRC risk factors (aOR 2.61, 95% CI 1.16–5.88). Five of the variables pertaining to the HBM were significant correlates of CRC testing—perceived severity of CRC (aOR 0.28, 95% CI 0.13–0.65), perceived health and psychological barriers to CRC testing (aOR 0.42, 95% CI 0.21–0.84, 95% CI 0.21–0.85), perceived access barriers to CRC testing (aOR 0.22, 95% CI 0.05–0.85), physicians recommendation (indicator of cues to action) (aOR 23.50, 95% CI 10.66–51.80), and having health insurance (indicator of cues to action) (aOR 2.06, 95% CI 1.01–4.19).CONCLUSIONS:CRC testing compliance among this Asian population is low. Knowledge of CRC symptoms and risk factors are low. Perceived health, psychological, and access barriers to CRC testing are high. The physicians recommendation and having health insurance coverage significantly increase testing, but physicians mainly recommend patients with a family history of CRC for testing, and only around one-third of the population has health insurance.