Is Duhuo Jisheng Tang containing Xixin safe? A four-week safety study

<p>Abstract</p> <p>Background</p> <p>Though the nephrotoxicity and carcinogenicity of aristolochic acid (AA) are known, its safety in clinical usage is not clear. This study aims to evaluate the safety of <it>Duhuo Jisheng Tang </it>(DJT) in a four-week study to treat osteoarthritis (OA) of the knee.</p> <p>Methods</p> <p>A qualitative and quantitative investigations on DJT were conducted. A list of adverse events (AEs), complete blood counts, and liver and kidney function tests were measured for participants with knee OA at their scheduled hospital visits. Each detected AEs was independently assessed for severity and causality by site investigators (Chinese medical doctors) and study nurses.</p> <p>Results</p> <p>A total of 71 eligible subjects were included in the clinical study where 287 AEs were reported. DJT did not contain detectable aristolochic acid (AA) under thin-layer chromatography (TLC) analysis and gas chromatography coupled with mass spectrometry (GC-MS). There were no significant changes in liver or kidney functions.</p> <p>Conclusion</p> <p>In four-week use of DJT, no renal tubular damage, no severe incidences of AEs and adverse drug reactions (ADRs) were observed. The present study obtained safety data from active surveillance of DJT.</p

Clinical outcomes in low risk coronary artery disease patients treated with different limus-based drug-eluting stents--a nationwide retrospective cohort study using insurance claims database.

The clinical outcomes of different limus-based drug-eluting stents (DES) in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES), Endeavor zotarolimus-eluting stent (E-ZES) and everolimus-eluting stent (EES), using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES). After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group). Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan

Table_1_Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study.DOCX

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04–4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98–5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13–10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.</p

Relative risk of individual clinical end-point in two composite end-points among E-ZES and EES groups.

<p>The SES group was used as the reference. Abbreviations: CABG: coronary artery bypass grafting; CI: confidence interval; EES: everolimus-eluting stent; E-ZES: Endeavor zotarolimus-eluting stent; HR: hazard ratio; PCI: percutaneous coronary intervention; SES: sirolimus-eluting stent.</p

Flow chart of the study.

<p>Abbreviations: CABG: coronary artery bypass grafting; DES: drug-eluting stent; EES: everolimus-eluting stent; EPC: endogenous progenitor cell; E-ZES: Endeavor zotarolimus-eluting stent; NHI: National Health Insurance; PCI: percutaneous coronary intervention; PES: paclitaxel-eluting stent; SES: sirolimus-eluting stent; ZES: zotarolimus-eluting stent.</p

Baseline characteristics of patients who received SES, E-ZES and EES.

<p>Abbreviations: ACEi: angotensin-converting-enzyme inhibitor; ACS: acute coronary syndrome, ARB: angiotensin receptor blocker; EES: everolimus-eluting stent; E-ZES: Endeavor zotarolimus-eluting stent; H₂-blocker: histamine-2 receptor blocker; MI: myocardial infarction; PPI: proton pump inhibitor; SES: sirolimus-eluting stent; SD: standard deviation.</p><p>^aIn accordance with privacy regulations in Taiwan, the exact number of patients is not specified if it is less than 2.</p><p>Baseline characteristics of patients who received SES, E-ZES and EES.</p

Clinical end-points of patients receiving SES, E-ZES and EES.

<p>Abbreviations: CI: confidence interval; EES: everolimus-eluting stent; E-ZES: Endeavor zotarolimus-eluting stent; HF: heart failure; HR: hazard ratio; PY: person-year; SES: sirolimus-eluting stent.</p><p>Clinical end-points of patients receiving SES, E-ZES and EES.</p

Kaplan-Meier cumulative incidences of different clinical end-points in three stent groups.

<p>All-cause mortality (Panel A), acute coronary events (Panel B), heart failure needing hospitalization (Panel C), cerebrovascular disease (Panel D), and repeated coronary revascularization (Panel E). Abbreviations: EES: everolimus-eluting stent; E-ZES: Endeavor zotarolimus-eluting stent; SES: sirolimus-eluting stent.</p