A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels

BACKGROUND:Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists.OBJECTIVES:To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab.METHODS:Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab.RESULTS:One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; P<0.001).CONCLUSION:One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events.     

Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model – a functional multineuron calcium imaging study

Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure‐like events (SLEs) at single‐cell resolution. Using functional multineuron Ca²⁺ imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg²⁺‐free conditions. Bicuculline induced recurrent synchronous Ca²⁺ influx, and the events were correlated with SLEs. Other proconvulsants, such as 4‐aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca²⁺ influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline‐induced synchronous Ca²⁺ influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca²⁺ influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca²⁺ influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca²⁺ influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs.     

Randomized Comparison of FFR-Guided and Angiography-Guided Provisional Stenting of True Coronary Bifurcation Lesions: The DKCRUSH-VI Trial (Double Kissing Crush Versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions VI)

ObjectivesThis study sought to compare the outcomes of fractional flow reserve (FFR)–guided and angiography (Angio)–guided provisional side-branch (SB) stenting for true coronary bifurcation lesions.BackgroundAngio-guided provisional SB stenting after stenting of the main vessel provides favorable outcomes for the majority of coronary bifurcation lesions. Whether an FFR-guided provisional stenting approach is superior has not been studied.MethodsA total of 320 patients with single Medina 1,1,1 and 0,1,1 coronary bifurcation lesions undergoing stenting with a provisional SB approach were randomly assigned 1:1 to Angio-guided and FFR-guided groups. SB stenting was performed for Thrombolysis In Myocardial Infarction flow grade <3, ostial SB stenosis >70%, or greater than type A dissection after main vessel stenting in the Angio-guided group and for SB-FFR <0.80 in the FFR-guided group. The primary endpoint was the 1-year composite rate of major adverse cardiac events (cardiac death, myocardial infarction, and clinically driven target vessel revascularization).ResultsComparing the Angio-guided and FFR-guided groups, treatment of the SB (balloon or stenting) was performed in 63.1% and 56.3% of lesions respectively (p = 0.07); stenting of the SB was attempted in 38.1% and 25.9%, respectively (p = 0.01); and, when attempted, stenting was successful in 83.6% and 73.3% of SBs, respectively (p = 0.01). The 1-year composite major adverse cardiac event rate was 18.1% in both groups (hazard ratio: 0.91, 95% confidence interval: 0.48 to 1.88; p = 1.00). The 1-year target vessel revascularization and stent thrombosis rates were 6.9% and 5.6% (p = 0.82) and 1.3% and 0.6% (p = 0.56) in the Angio-guided and FFR-guided groups, respectively.ConclusionsIn this multicenter, randomized trial, angiographic and FFR guidance of provisional SB stenting of true coronary bifurcation lesions provided similar 1-year clinical outcomes. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChiCTR-TRC-07000015)     

Incidence,Causes, and Predictors of Early (≤30 Days) and Late Unplanned Hospital Readmissions After Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to determine the incidence, causes, and predictors of unplanned hospital readmissions after transcatheter aortic valve replacement (TAVR).BackgroundData regarding unplanned hospital readmissions after TAVR in a real-world all-comers population are scarce.MethodsA total of 720 consecutive patients undergoing TAVR at 2 centers who survived the procedure, were included. Median follow-up was 23 months (interquartile range [IQR]: 12 to 39 months), available in 99.9% of the initial population. The occurrence, timing, and causes of hospital readmission within the first year post-TAVR were obtained in all cases. Early and late readmissions were defined as those occurring ≤30 days and >30 days to 1 year post-TAVR, respectively.ResultsThere were 506 unplanned readmissions in 316 patients (43.9%) within the first year post-TAVR (median time: 63 days; IQR: 19 to 158 days post-discharge). Of these, early readmission occurred in 105 patients (14.6%), and 118 patients (16.4%) had multiple (≥2) readmissions. Readmissions were due to noncardiac and cardiac causes in 59% and 41% of cases, respectively. Noncardiac readmissions included, in order of decreasing frequency, respiratory, infection, and bleeding events as the main causes, whereas heart failure and arrhythmias accounted for most cardiac readmissions. The predictors of early readmission were periprocedural major bleeding complications (p = 0.001), anemia (p = 0.019), lower left ventricular ejection fraction (p = 0.042), and the combined presence of antiplatelet and anticoagulation therapy at hospital discharge (p = 0.014). The predictors of late readmission were chronic obstructive pulmonary disease (p = 0.001), peripheral vascular disease (p = 0.023), chronic renal failure (p = 0.013), and atrial fibrillation (p = 0.012). Early readmission was an independent predictor of mortality during the follow-up period (hazard ratio: 1.56, 95% confidence interval: 1.02 to 2.39, p = 0.043).ConclusionsThe readmission burden after TAVR in an all-comers population was high. Nearly one-fifth of the patients were readmitted early after hospital discharge, increasing the risk of mortality at follow-up. Reasons for readmission were split between noncardiac and cardiac causes, with respiratory causes and heart failure as the main diagnoses in each group, respectively. Whereas early readmissions were mainly related to periprocedural bleeding events, most late readmissions were secondary to baseline patient comorbidities. These results underscore the importance of and provide the basis for implementing specific preventive measures to reduce readmission rates after TAVR.     

Factors Predictive of Treatment-Emergent Adverse Events of Prucalopride: An Integrated Analysis of Four Randomized,Double-Blind,Placebo-Controlled Trials

Background/AimsThis integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks.MethodsPooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies ({"type":"clinical-trial","attrs":{"text":"NCT00488137","term_id":"NCT00488137"}}NCT00488137, {"type":"clinical-trial","attrs":{"text":"NCT00483886","term_id":"NCT00483886"}}NCT00483886, {"type":"clinical-trial","attrs":{"text":"NCT00485940","term_id":"NCT00485940"}}NCT00485940, and {"type":"clinical-trial","attrs":{"text":"NCT01116206","term_id":"NCT01116206"}}NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model.ResultsOverall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs.ConclusionsPrucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.     

Introducing seasonal influenza vaccine in low‐income countries: an adverse events following immunization survey in the Lao People's Democratic Republic

Objective

In 2012, Lao PDR introduced seasonal influenza vaccine in pregnant women, persons aged ≥50 years, persons with chronic diseases, and healthcare personnel. We assessed adverse events following immunization (AEFI).

Methods

We used a multistage randomized cluster sample design to interview vaccine recipients.

Findings

Between April and May 2012, 355 902 were vaccinated. Of 2089 persons interviewed, 261 (12·5%) reported one or more AEFI. The most commonly reported AEFIs were local reactions. No hospitalizations or deaths were reported; 16% sought medical care. Acceptance and awareness of vaccination were high.

Conclusions

Following the introduction of seasonal influenza vaccine in Lao PDR, self-reported adverse events were mild.     

Changing Pattern of Sputum Cell Counts During Successive Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease exacerbations are associated with worsening of airway inflammation, the nature of which may be neutrophilic, eosinophilic, or both.

Objective: The primary objective was to examine the cellular nature of airway inflammation in successive COPD exacerbations in order to ascertain if they changed in individual patients. The secondary objective was to estimate the relative risk indicating the extent to which a particular type of exacerbation changed as a function of the most recent exacerbation. Design: This was a retrospective survey performed on a computerised sputum cell count database of a referral respiratory service in Hamilton, Canada. Recurrent event analyses were used to model the incidence of exacerbations and subtypes of exacerbations. Results: 359 patients and 148 patients had sputum examined during stable condition and during exacerbations, respectively. It was found 65 patients had sputum examined during both situations. The exacerbations were eosinophilic in 15.9%, neutrophilic in 18%, combined in 2.6%, of unknown clinical significance in 19.6% and normal in 19.6%. There were missing counts for 24.3% samples. In 85.2% of patients, a different subtype of bronchitis was noted in successive exacerbations. The relative risk of a subsequent neutrophilic or eosinophilic exacerbation was 6.24 (p = 0.02) and 2.8 (p = 0.24) when the previous exacerbation was neutrophilic or eosinophilic respectively. Conclusions: This non-intervention study suggests that the cellular nature of bronchitis is largely unpredictable and needs to be examined at each COPD exacerbation This has important implications in choosing the appropriate therapy. Future intervention studies would provide further evidence.     

改进护理方式对冠心病PCI术后患者近期不良心脏事件的影响

目的：探讨改进护理方式对冠心病行冠状动脉介入治疗(PCI)患者心理应激反应及近期不良心脏事件的影响。方法：选取2012年6月至2014年6月在本院接受PCI治疗的128例冠心病患者为研究对象,根据患者入院时间将其分为对照组(2012年6月-2013年5月)62例以及观察组(2013年6月至2014年6月)66例,对照组实施常规性护理,观察组在对照组基础上改进护理方案,对比分析改进护理方式对冠心病PCI患者置入支架时心理应激反应、不良情绪及近期不良心脏事件的影响。结果：观察组干预后收缩压、舒张压、心率水平显著低于对照组(P<0.05)。观察组家属干预后汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评分显著低于对照组(P<0.05)。观察组住院期间心绞痛、心肌梗死、心律失常、心脏性猝死等不良心脏事件发生率低于对照组(P<0.05)。结论：改进行冠心病PCI患者临床护理方式,能有效减轻患者支架植入时心理应激反应及负性情绪,降低患者住院期间不良心脏事件发生率,有利于患者预后。