Rectal nonsteroidal anti-inflammatory drugs, glyceryl trinitrate, or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: A network meta-analysis.

BACKGROUND: Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are more beneficial in preventing post-ERCP pancreatitis (PEP). Randomized controlled trials (RCTs) have also demonstrated the efficacy of glyceryl trinitrate (GTN). We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. AIM: To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. METHODS: A systematic search was done for full-text RCTs of PEP in PubMed, Embase, Science Citation Index, and the Cochrane Controlled Trials database. Inclusion and exclusion criteria were used to screen for eligible RCTs. The major data were extracted by two independent reviewers. The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: Twenty-four eligible RCTs were selected, evaluating seven preventive strategies in 9416 patients. Rectal indomethacin 100 mg plus sublingual GTN (OR: 0.21, 95%CI: 0.09-0.50), rectal diclofenac 100 mg (0.34, 0.18-0.65), sublingual GTN (0.34, 0.12-0.97), and rectal indomethacin 100 mg (0.49, 0.33-0.73) were all more efficacious than placebo in preventing PEP. The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves (SUCRA) probability of (92.2%) and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of (89.2%). CONCLUSION: Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.

Long Short-Term Memory Network for Development and Simulation of Warfarin Dosing Model Based on Time Series Anticoagulant Data.

Background: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index, and dosage can differ tremendously among individuals. The study aimed to develop an individualized international normalized ratio (INR) model based on time series anticoagulant data and simulate individualized warfarin dosing. Methods: We used a long short-term memory (LSTM) network to develop an individualized INR model based on data from 4,578 follow-up visits, including clinical and genetic factors from 624 patients whom we enrolled in our previous randomized controlled trial. The data of 158 patients who underwent valvular surgery and were included in a prospective registry study were used for external validation in the real world. Results: The prediction accuracy of LSTM_INR was 70.0%, which was much higher than that of MAPB_INR (maximum posterior Bayesian, 53.9%). Temporal variables were significant for LSTM_INR performance (51.7 vs. 70.0%, P < 0.05). Genetic factors played an important role in predicting INR at the onset of therapy, while after 15 days of treatment, we found that it might unnecessary to detect genotypes for warfarin dosing. Using LSTM_INR, we successfully simulated individualized warfarin dosing and developed an application (AI-WAR) for individualized warfarin therapy. Conclusion: The results indicate that temporal variables are necessary to be considered in warfarin therapy, except for clinical factors and genetic factors. LSTM network may have great potential for long-term drug individualized therapy. Trial Registration: NCT02211326; www.chictr.org.cn:ChiCTR2100052089.

Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial.

This study aimed to analyze the influence of renal insufficiency on the anticoagulant effects and safety of warfarin in Chinese patients. Data on the creatinine levels of participants enrolled in a randomized controlled study were screened and divided into the non-renal insufficiency group, mild renal insufficiency group, and moderate renal insufficiency group, according to the creatinine clearance rate. The primary outcome measures were stable dose and average daily dose of warfarin. Secondary outcome measures were percentage of time in the therapeutic international normalized ratio (INR) (%TTR), and the first time to reach the therapeutic INR. Adverse events included bleeding events, thromboembolic events, and mortality. All participants with renal function test results and a baseline INR of less than 1.5 were included in the primary and secondary outcome analysis. The SPSS Statistics 21.0 software was used for statistical analysis. The randomized controlled trial was registered in Clinicaltrials.gov (NCT02211326). A total of 571 patients were included in this analysis. Multiple regression analysis showed that the renal function was correlated with stable dose, average daily dose, and the first time to reach therapeutic INR after adjusting for confounding factors. However, no correlation was noted between kidney function and %TTR. No significant differences were observed across the various safety parameters among the three groups. Renal function is an important consideration in patients using warfarin.

Design of an Optimally-Diagnostic Skin Test for Diagnosis of Sensitivity to Eight Allergens: A First-in-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects.

BACKGROUND: Eight extracts from common native allergens, Artemisia annua pollen, Platanus pollen, Humulus pollen, Betula platyphylla pollen, Ambrosia artemisiifolia pollen, Blattella germanica, cat dander and dog dander were developed for skin prick test (SPT). Since standardization and composition alone cannot guarantee that the allergen extracts are within the concentration range that give the best chance of a true diagnosis, it is necessary to explore the optimal diagnostic concentration (ODC) of allergens in SPT. OBJECTIVE: To identify the optimal diagnostic concentration of eight allergen extracts in SPT and assess the safety of simultaneous administration. PATIENTS AND METHODS: Patients with a history of allergic disease were enrolled in this two-part open-label, parallel study. In Study 1, 92 patients were enrolled into eight groups according to their disease-causing allergens and were given three increasing concentrations of the corresponding allergen. In Study 2, 20 patients were divided into two concentration groups and were given all of the eight allergens. Safety and sensitivity were evaluated to determine the optimal diagnostic concentration. RESULTS: In Study 1, the sensitivity of seven allergen extracts was >80% at middle and high concentrations, except for Ambrosia artemisiifolia pollen. The optimal diagnostic concentration (in DU/mL) for eight allergens was 33,333, 12,000, 8667, 50,000, 40,000, 3333, 7000, and 5000. In Study 2, the prevalence of adverse events in the two groups was 70% and 80%, respectively. A total of 10 wheals of 8 patients did not subside <24 h after SPTs. CONCLUSION: The eight allergens showed high sensitivity and safety at a certain concentration, which was defined as optimal diagnostic concentration. The results support further clinical research of investigated allergens and our study offers a scheme to determine the ODC of allergens in SPT.

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a meta-analysis.

AIM: To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: PubMed, Embase, Science Citation Index, and Cochrane Controlled Trials Register were searched to identify relevant trials published in English. Inclusion and exclusion criteria were used to screen for suitable studies. Two reviewers independently judged the study eligibility while screening the citations. The methodological quality of the included trials was assessed using the Jadad scoring system. All results were expressed as OR and 95%CI. Data were analyzed using Stata12.0 software. RESULTS: Ten eligible randomized controlled trials were selected, including 1176 patients. A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of post-ERCP pancreatitis (PEP) in high-risk patients (OR = 0.25; 95%CI: 0.17-0.38; P < 0.001). Pancreatic stents also alleviated the severity of PEP (mild pancreatitis after ERCP: OR = 0.33; 95%CI: 0.21-0.54; P < 0.001; moderate pancreatitis after ERCP: OR = 0.30; 95%CI: 0.13-0.67; P = 0.004). The result of severe pancreatitis after ERCP was handled more rigorously (OR = 0.24; 95%CI: 0.05-1.16; P = 0.077). Serum amylase levels were not different between patients with pancreatic stents and control patients (OR = 1.08; 95%CI: 0.82-1.41; P = 0.586). CONCLUSION: Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.