Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). METHODS: Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk-benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained. RESULTS: According to NMA, the risk-benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective. CONCLUSION: ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.

Efficacy and safety of celecoxib on the incidence of recurrent colorectal adenomas: a systematic review and meta-analysis.

BACKGROUND: Celecoxib has previously been shown to be effective in reducing recurrent colorectal adenomas, but its long-term effects are unknown. In addition, safety issues are of major concern. Therefore, we examined the efficacy and safety of celecoxib as a chemopreventive agent along with its posttreatment effect. METHODS: We performed a meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing celecoxib at various doses (400 mg once daily, 200 mg twice daily, and 400 mg twice daily) vs placebo in persons with history of colorectal adenomas. Several databases were searched from inception up to April 2018. Long-term follow-ups of RCTs were also included to evaluate posttreatment effect. Primary outcome was the incidence of recurrent colorectal adenomas. Various safety outcomes were evaluated, especially cardiovascular (CV) events. Risk-benefit integrated analyses were also performed. RESULTS: A total of three RCTs (4,420 patients) and three post-trial studies (2,159 patients) were included in the analysis. Use of celecoxib at any dose for 1-3 years significantly reduced the incidence of recurrent advanced adenomas (risk ratio, 0.42 [95% CI, 0.34-0.53]) and any adenomas (0.67 [95% CI, 0.62-0.72]) compared with placebo. Subgroup analysis on different dosing suggested a greater effect with 400 mg twice daily. However, celecoxib 400 mg twice daily significantly increased the risk of serious adverse (1.2 [95% CI, 1.0-1.5]) and CV events (3.42 [95% CI, 1.56-7.46]), while celecoxib at 400 mg/day, especially with once daily dosing, did not increase CV risk (1.01 [95% CI, 0.70-1.46]). Analysis of post-trial studies indicated that the treatment effect disappeared (1.15 [95% CI, 0.88-1.49]) after discontinuing celecoxib for >2 years. CONCLUSION: Celecoxib 400 mg once daily dosing could potentially be considered as a viable chemopreventive option in patients with high risk of adenomas but with low CV risk. Long-term trials on celecoxib at a dose of ≤400 mg either once or twice daily are warranted.

Elevate ALT and AST in an asymptomatic person. What the primary care doctor should do?

ABSTRACT • Abnormal liver function test with raised alanine aminotransferase (ALT) and raised aspartate aminotransferase (AST) are commonly seen in primary care setting. • Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH) and chronic viral hepatitis are common causes associated with raised ALT and AST. • In chronic viral hepatitis, the elevation of liver enzyme may not correlate well with the degree of liver damage. • Non-hepatic causes of raised ALT and AST include polymyositis, acute muscles injury, acute myocardial infarction and hypothyroidism. • In the primary care setting, the doctor should obtain a complete history regarding the risk factors for viral hepatitis, substance abuse and request investigations accordingly. • Suspected chronic viral hepatitis and liver cirrhosis are best referred to hepatologist for further management.

A painful gum.

CASE STUDY: This middle aged Malaysian man presented complaining of painful gums for a few months. He is known to have had epilepsy since childhood.