Akbar K. Waljee

Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis

Background  A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis.

A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. RESULTS A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Threefold increased risk of infertility: a meta-analysis of infertility after ileal pouch anal anastomosis in ulcerative colitis

Background: Increased infertility in women has been reported after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis but reported infertility rates vary substantially. Aims: (1) To perform a systematic review and meta-analysis of the relative risk of infertility post-IPAA compared with medical management; (2) to estimate the rate of infertility post-IPAA; and (3) to identify modifiable risk factors which contribute to infertility. Methods: Medline, EMBASE, Current Contents, meeting abstracts, and bibliographies were searched independently by two investigators. The titles and abstracts of 189 potentially relevant studies were reviewed; eight met the criteria and all data were extracted independently. Consensus was achieved on each data point, and fixed effects meta-analyses, a funnel plot, and sensitivity analyses were performed. Results: The initial meta-analysis of eight studies had significant heterogeneity (p = 0.004) due to one study with very high preoperative infertility (38%). When this study was omitted, the relative risk of infertility after IPAA was 3.17 (2.41–4.18), with non-significant heterogeneity. The weighted average infertility rate in medically treated ulcerative colitis was 15% for all seven studies, and the weighted average infertility rate was 48% after IPAA (50% if all eight studies are included). We were unable to identify any procedural factors that consistently affected the risk of infertility. Conclusions: IPAA increases the risk of infertility in women with ulcerative colitis by approximately threefold. Infertility, defined as achieving pregnancy in 12 months of attempting conception, increased from 15% to 48% in women post-IPAA for ulcerative colitis. This provides a basis for counselling patients considering colectomy with IPAA. Further studies of modifiable risk factors are needed.

A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis

Background: Several pharmacological agents for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been studied. Clinical trials evaluating the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. Aim: To perform a meta-analysis of studies evaluating the effect of prophylactic rectal NSAIDs on PEP. Methods: By searching Medline, Embase, meeting abstracts and bibliographies, two independent reviewers systematically identified prospective randomised controlled trials (RCTs) examining the effect of rectally administered prophylactic NSAIDs on the incidence of PEP pancreatitis. A meta-analysis of these clinical trials was performed. Results: Four RCTs, enrolling a total of 912 patients, have been published. Meta-analysis of these studies demonstrates a pooled relative risk for PEP after prophylactic administration of NSAIDs of 0.36 (95% CI 0.22 to 0.60); patients who received NSAIDs in the periprocedural period were 64% less likely to develop pancreatitis and 90% less likely to develop moderate to severe pancreatitis. The pooled number needed to treat with NSAIDs to prevent one episode of pancreatitis is 15 patients. No adverse events attributable to the use of NSAIDs were reported in any of the clinical trials. Conclusion: In this meta-analysis, prophylactic NSAIDs were effective in preventing PEP. Widespread prophylactic administration of these agents may significantly reduce the incidence of PEP, resulting in major clinical and economic benefit. Given current scepticism regarding the efficacy of any prophylactic medication for ERCP, additional multicentre studies are needed for confirmation prior to widespread adoption of this strategy.

A Primer on Effectiveness and Efficacy Trials

Although efficacy and effectiveness studies are both important when evaluating interventions, they serve distinct purposes and have different study designs. Unfortunately, the distinction between these two types of trials is often poorly understood. In this primer, we highlight several differences between these two types of trials including study design, patient populations, intervention design, data analysis, and result reporting.

The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: A meta-analysis

Objectives:The PNPLA3 rs738409 single-nucleotide polymorphism is known to promote nonalcoholic steatohepatitis (NASH), but its association with fibrosis severity and hepatocellular carcinoma (HCC) risk is less well-defined. The objectives of this study were to determine the association between PNPLA3 and liver fibrosis severity, HCC risk, and HCC prognosis among patients with liver disease.Methods:We performed a systematic literature review using the Medline, PubMed, Scopus, and Embase databases through May 2013 and a manual search of national meeting abstracts from 2010 to 2012. Two investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios (ORs), according to PNPLA3 genotype, were calculated using the DerSimonian and Laird method for a random effects model.Results:Among 24 studies, with 9,915 patients, PNPLA3 was associated with fibrosis severity (OR 1.32, 95% confidence interval (CI) 1.20–1.45), with a consistent increased risk across liver disease etiologies. Among nine studies, with 2,937 patients, PNPLA3 was associated with increased risk of HCC in patients with cirrhosis (OR 1.40, 95% CI 1.12–1.75). On subgroup analysis, increased risk of HCC was demonstrated in patients with NASH or alcohol-related cirrhosis (OR 1.67, 95% CI 1.27–2.21) but not in those with other etiologies of cirrhosis (OR 1.33, 95% CI 0.96–1.82). Three studies, with 463 patients, do not support an association between PNPLA3 and HCC prognosis but are limited by heterogeneous outcome measures. For all outcomes, most studies were conducted in homogenous Caucasian populations, and studies among racially diverse cohorts are needed.Conclusions:PNPLA3 is associated with an increased risk of advanced fibrosis among patients with a variety of liver diseases and is an independent risk factor for HCC among patients with nonalcoholic steatohepatitis or alcohol-related cirrhosis.

Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A systematic review and meta-analysis of randomized trials conducted by B. Joseph Elmunzer and colleagues reports that that flexible sigmoidoscopy-based screening reduces the incidence of colorectal cancer in average-risk patients, as compared to usual care or no screening.

Systematic review with network meta‐analysis: the efficacy of anti‐tumour necrosis factor‐alpha agents for the treatment of ulcerative colitis

Antibodies against tumour necrosis factor‐alpha (anti‐TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown.

Systematic review with network meta-analysis: the efficacy of anti-TNF agents for the treatment of Crohn's disease

Anti‐tumour necrosis factor‐alpha agents (anti‐TNF) are effective therapies for the treatment of Crohns disease (CD), but their comparative efficacy is unknown.

Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study

Objective To determine the frequency of prescriptions for short term use of oral corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures) associated with their use. Design Retrospective cohort study and self controlled case series. Setting Nationwide dataset of private insurance claims. Participants Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014. Main outcome measures Rates of short term use of oral corticosteroids defined as less than 30 days duration. Incidence rates of adverse events in corticosteroid users and non-users. Incidence rate ratios for adverse events within 30 day and 31-90 day risk periods after drug initiation. Results Of 1 548 945 adults, 327 452 (21.1%) received at least one outpatient prescription for short term use of oral corticosteroids over the three year period. Use was more frequent among older patients, women, and white adults, with significant regional variation (all P<0.001). The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Prescriptions were provided by a diverse range of specialties. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P<0.001). Conclusion One in five American adults in a commercially insured plan were given prescriptions for short term use of oral corticosteroids during a three year period, with an associated increased risk of adverse events.