548 Colchicine in patients with coronary artery disease: a meta-analysis of randomized trials

Aims The aim of this study was to provide a systematic appraisal of the effects of colchicine treatment on cardiovascular outcomes, adverse events, and mortality in patients with coronary artery disease. Methods and results We performed a meta-analysis of randomized controlled trials (RCTs) that compared add-on colchicine to standard treatment vs. standard treatment in patients with coronary artery disease. Mixed-effects Poisson regression model with random intervention effects was used to estimate the pooled incidence rate ratios (IRR) with 95% confidence intervals (CI). The number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH) were calculated. Prespecified subgroup analyses according to colchicine dose (e.g. <1 mg/daily or ≥ 1 mg/daily) and the type of clinical syndrome [e.g. acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] were performed. Ten RCTs were identified, including 12 819 participants with a median follow-up of 6 months. Add-on colchicine, compared to standard treatment, was associated with a lower risk of major adverse cardiovascular events (IRR: 0.69, 95% CI: 0.60–0.79, NNTB = 28), myocardial infarction (IRR: 0.77, 95% CI: 0.64–0.93, NNTB = 95), and ischaemic stroke (IRR: 0.48, 95% CI: 0.30–0.76, NNTB = 155), while it was associated with a higher risk of gastrointestinal adverse events (IRR: 1.69, 95% CI: 1.12–2.54, NNTH = 10). Colchicine use did not affect all-cause death (IRR: 1.09, 95% CI: 0.85–1.40), or cardiovascular death (IRR: 0.75, 95% CI: 0.51–1.12), while it was associated with a higher risk of non-cardiovascular death (IRR: 1.45, 95% CI: 1.04–2.02, NNTH = 396). In the subgroup analysis of colchicine dose, a significant interaction was found with the risk of gastrointestinal adverse events (IRR: 1.03, 95% CI: 0.91–1.15, in patients receiving colchicine <1 mg/daily; IRR: 2.91, 95% CI: 1.91–4.44, in patients receiving colchicine ≥1 mg/daily, p for interaction <0.0001), while there was no evidence for a modification of treatment effect for the remaining endpoints. In the subgroup analysis of the clinical syndrome, there was little evidence for an interaction with the risk of myocardial infarction (IRR: 0.91, 95% CI: 0.71–1.18, in patients presenting with ACS; IRR: 0.65, 95% CI: 0.50–0.84, in patients presenting with CCS, p for interaction = 0.07), while there was no evidence for a modification of treatment effect for the remaining endpoints. Conclusions This meta-analysis of RCT provides evidence for a significant clinical benefit of add-on colchicine in terms of risk reduction of cardiovascular events in patients with coronary artery disease, that largely outweigh a potential harmful effect of colchicine on the risk of non-cardiovascular death. Colchicine is associated with a higher risk of gastrointestinal adverse effects that can be prevented by using a low-dose regimen (e.g. <1 mg daily).

Auricular acupressure for adverse events following immunization related to COVID-19 vaccine injection: study protocol for a multicenter, three-arm, blinded randomized controlled trial

Background Some pain, fatigue, and gastrointestinal adverse events were observed in potential association with injection of COVID-19 vaccines, while there was no preventive intervention for it. We aim to investigate the efficacy of auricular acupressure (AA) therapy in preventing and relieving AEFI after injection of COVID-19 vaccine. Methods The study design is a randomized, multicentre, three-arm controlled, single-blind trial. Participants meeting the inclusion criteria will be advertised and enrolled and assigned in the medical institutions randomly for post-injection observation. No less than 360 participants will be randomized into one of three groups: auricular acupressure group, sham auricular acupressure group, and wait-list group. Interventions will be performed immediately and will happen 4 to 5 times per day for 5 days. The primary clinical outcomes will be quality and quantity evaluation among participants who reported any AEFI and who reported local pain at injection site. Secondary outcomes will concern headache, muscle and (or) joint pain, fatigue, nausea, vomiting, diarrhoea, and other potential events. All the outcomes will be assessed at baseline and 1, 3, 5, 7, and 14 days after the injection. Both intention-to-treat and per-protocol analyses will be performed, with significance level determined as 5%. Discussion Results of this trial will help to clarify the value of auricular acupressure therapy in preventing and relieving overall and certain adverse events following immunization after injection of COVID-19 vaccine. Trial registration China Clinical Trial Registry (ChiCTR) (ChiCTR2100043210). Registered on 8 February, 2021.

Attrition of methylnaltrexone treatment-emergent adverse events in patients with chronic noncancer pain and opioid-induced constipation: a post hoc pooled analysis of two clinical trials

Background: Opioids prescribed for the management of chronic noncancer pain are associated with nausea, vomiting, and constipation. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, has demonstrated robust efficacy and was well-tolerated in treating opioid-induced constipation without affecting central analgesia. Our objective was to assess changes in the frequency of adverse events after the first or second dose of methylnaltrexone or placebo. Methods: This post hoc analysis pooled data from two randomized, placebo-controlled clinical trials assessing methylnaltrexone for opioid-induced constipation in the outpatient setting. Patients received subcutaneous methylnaltrexone (12 mg once daily or 12 mg once every other day), oral methylnaltrexone (150, 300, or 450 mg daily), or placebo. Adverse events, opioid withdrawal symptoms, pain intensity, and rescue-free bowel movements (RFBMs) within 4 hours of the first dose (i.e., RFBM responders) were assessed. Associations between adverse event frequencies and RFBM response were also evaluated. Results: The analysis included 1263 adult patients with chronic noncancer pain. Treatment-emergent adverse event rates declined from treatment day 1 to 2 (methylnaltrexone: 16.2%–5.3%; placebo: 6.6%−5.4%). Among methylnaltrexone-treated patients, significantly greater proportions of RFBM responders versus nonresponders reported gastrointestinal adverse events on day 1. No associations between RFBM response and the frequency of adverse events were observed in the placebo group. No meaningful changes in opioid withdrawal symptoms or pain intensity were observed. Conclusions: Early-onset adverse events following methylnaltrexone treatment, particularly gastrointestinal adverse events, are at least partially due to laxation. Methylnaltrexone treatment effectively relieves opioid-induced constipation without affecting the central analgesic effects of opioids.

Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

A Convolutional Neural Network Deep Learning Model Trained on CD Ulcers Images Accurately Identifies NSAID Ulcers

Background and Study Aims: Deep learning (DL) for video capsule endoscopy (VCE) is an emerging research field. It has shown high accuracy for the detection of Crohn's disease (CD) ulcers. Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications. In the small bowel, NSAIDs may cause a variety of gastrointestinal adverse events including NSAID-induced ulcers. These ulcers are the most important differential diagnosis for small bowel ulcers in patients evaluated for suspected CD. We evaluated a DL network that was trained using CD VCE ulcer images and evaluated its performance for NSAID ulcers.Patients and Methods: The network was trained using CD ulcers and normal mucosa from a large image bank created from VCE of diagnosed CD patients. NSAIDs-induced enteropathy images were extracted from the prospective Bifidobacterium breve (BIf95) trial dataset. All images were acquired from studies performed using PillCam SBIII. The area under the receiver operating curve (AUC) was used as a metric. We compared the network's AUC for detecting NSAID ulcers to that of detecting CD ulcers.Results: Overall, the CD training dataset included 17,640 CE images. The NSAIDs testing dataset included 1,605 CE images. The DL network exhibited an AUC of 0.97 (95% CI 0.97–0.98) for identifying images with NSAID mucosal ulcers. The diagnostic accuracy was similar to that obtained for CD related ulcers (AUC 0.94–0.99).Conclusions: A network trained on VCE CD ulcers similarly identified NSAID findings. As deep learning is transforming gastrointestinal endoscopy, this result should be taken into consideration in the future design and analysis of VCE deep learning applications.