Performance of a clinical decision support system and of clinical pharmacists in preventing drug–drug interactions on a geriatric ward

Background Drug–drug interactions (DDIs) can lead to adverse drug events and compromise patient safety. Two common approaches to reduce these interactions in hospital practice are the use of clinical decision support systems and interventions by clinical pharmacists. Objective To compare the performance of both approaches with the main objective of learning from one approach to improve the other. Setting Acute geriatric ward in a university hospital. Methods Prospective single-centre, cohort study of patients admitted to the geriatric ward. An independent pharmacist compared the clinical decision support alerts with the DDIs identified by clinical pharmacists and evaluated their interventions. Contextual factors used by the clinical pharmacists for evaluation of the clinical relevance were analysed. Adverse drug events related to DDIs were investigated and the causality was evaluated by a clinical pharmacologist based on validated criteria. Main outcome measure Number of alerts, interventions and the acceptance rates. Results Fifty patients followed by the clinical pharmacists, were included. The clinical pharmacists identified 240 DDIs (median of 3.5 per patient) and advised a therapy change for 16 of which 13 (81.2 %) were accepted and three (18.8 %) were not. The decision support system generated only six alerts of which none were accepted by the physicians. Thirty-seven adverse drug events were identified for 29 patients that could be related to 55 DDIs. For two interactions the causality was evaluated as certain, for 31 as likely, for ten as possible and for 12 as unlikely. Mainly intermediate level interactions were related to adverse drug events. Contextual factors taken into account by the clinical pharmacists for evaluation of the interactions were blood pressure, international normalised ratio, heart rate, potassium level and glycemia. Additionally, the clinical pharmacists looked at individual administration intervals and drug sequence to determine the clinical relevance of the interactions. Conclusion Clinical pharmacists performed better than the decision support system mainly because the system screened only for high level DDIs and because of the low specificity of the alerts. This specificity can be increased by including contextual factors into the logic and by defining appropriate screening intervals that take into account the sequence in which the drugs are given.     

New insights into the mechanisms of the vasorelaxant effects of apocynin in rat thoracic aorta

Apocynin is a naturally occurring acetophenone widely used as an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Recent data suggested that apocynin might exert NADPH oxidase‐independent pharmacological properties. Among them, vasorelaxant properties have been described, but the mechanisms still give rise to debates. The present study investigated the mechanisms involved in the vasorelaxant effect of apocynin on the in vitro model of rat isolated thoracic aortic rings. Apocynin (30 μm to 10 mm ) induced a dose‐dependent relaxation in both endothelium‐intact and endothelium‐denuded aortic rings with respective EC₅₀ values of 0.78 ± 0.08 and 1.91 ± 0.21 mm . Endothelium removal or inhibition of nitric oxide (NO) synthase with N^ω‐nitro‐l ‐arginine‐methyl ester (l ‐NAME) significantly decreased but did not abolish the effect of apocynin. By contrast, apocynin‐induced relaxation was unchanged after incubation with indomethacin or charybdotoxin plus apamin. In endothelium‐denuded aortas, the vasorelaxant effect of apocynin was significantly reduced by glibenclamide but not by 4‐aminopyridine nor by iberiotoxin. Apocynin significantly decreased Ca²⁺‐induced contraction and inhibited intracellular Ca²⁺mobilization after contraction with phenylephrine. Finally, the acute intravenous injection of apocynin led to an immediate and transient hypotensive effect in spontaneously hypertensive rats (SHR). In conclusion, our data demonstrated that apocynin induces both endothelium‐independent relaxant effects involving inhibition of Ca²⁺mobilization and activation of K_ATP channels in vascular smooth muscle cells and endothelium‐dependent effects mediated by NO. These results should provide a basis for caution when interpreting results on the vascular effects of apocynin.     

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.