No abstract

Backgrounds: The potential therapeutic effects of protease inhibitors (PIs), such as lopinavir/ritonavir and darunavir, on COVID-19 are being tested in clinical trials. Although acute pancreatitis (AP) has been reported in patients treated with PIs, there have been few real-world studies comparing the occurrence and characteristics of AP after different PI regimens. Methods: Disproportionality analysis and Bayesian analysis were utilized for data mining of the Food and Drug Administration's Adverse Event Reporting System (FAERS) database for suspected adverse events involving AP after PI from January 2004 to December 2019. The times to onset and fatality rates of AP following different PI regimens were also compared. Results: Based on 33,832 reports related to PIs, 285 cases (0.84% of total adverse drug reactions, ADRs) were associated with AP; in these reports, the number of AP cases reported for the top five PIs was as follows: ritonavir/dasabuvir/ombitasvir/paritaprevir, 64 (22.46%); ritonavir, 54 (18.95%); atazanavir, 52 (18.25%); lopinavir/ritonavir, 48 (16.84%); and darunavir, 26 (9.12%). Twelve out of the 15 studied PIs, including lopinavir/ritonavir, darunavir and nelfinavir, which are potential therapeutics for COVID-19, were associated with AP. Of all the reported adverse events involving AP related to PIs, 64.56% occurred in men, which was a much higher proportion than what was observed in women (28.42%). The median time to onset of AP was 103 (IQR: 26-408) days after the initiation of PI treatment. Patients treated with ritonavir/dasabuvir/ombitasvir/paritaprevir appeared to have an earlier onset of AP than those receiving atazanavir (31 [IQR: 17–68.25] days vs 187.5 [IQR: 80.5–556.5] days, p=0.0379) or ritonavir (31 [IQR: 17–68.25] days vs 177 [IQR: 56–539] days, p=0.0371). Compared with AP cases induced by all studied PIs, which had a fatality rate of 14.02%, AP cases associated with ritonavir (18.87%) and lopinavir/ritonavir (22.73%) appeared to be associated with a higher risk of death. Conclusions: Analysis of the FAERS data provides a more precise understanding of the occurrence and characteristics of AP after different PI regimens. Signals for AP associated with various PI regimens have been detected. The findings support continued surveillance, risk factor identification, and comparative studies.

Introduction Intrathecal therapy (ITT) via an implanted system was demonstrated for the treatment of refractory cancer pain for decades. Recently, the dissemination of ITT is enhanced in an external system way in Asia for a lower implantation cost. This study compares the efficacy, safety, and cost of the two ITT systems in refractory cancer pain patients in China. Methods One hundred and thirty‐nine cancer pain patients who underwent implantation of the ITT system were included. One hundred and three patients received ITT via the external system (external group), while 36 patients received ITT via the implanted system (implanted group). A 1:2 propensity score matching procedure was used to yield a total of 89 patients for the final analysis. Medical records of included patients were retrospectively reviewed and pain scores, incidences of complications, and costs were compared. Results ITT via the external system provided pain relief as potent as ITT via the implanted system but was less time‐consuming in the implantation phase (13 vs. 19 days, p < .01). Nausea/vomiting and urinary retention were the most frequent adverse events in both external and implanted groups (32.14%, 16.07% vs. 36.36%, 21.21%). No significant difference was found in the incidences of all kinds of complications. Compared to the implanted group, the external group cost less for the initial implantation (7268 vs. 26,275 US dollar [USD], p < .001) but had a significant higher maintenance cost (606.62 vs. 20.23 USD calculated monthly, p < .001). Conclusions ITT via the external system is as effective and safe as that via the implanted system and has the advantage of being cheap in the upfront implantation but costs more during the maintenance process in China.

Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome’s role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.