Preparation and in vitro Evaluation of Ethylcellulose Coated Egg Albumin Microspheres of Diltiazem Hydrochloride

The aim of the present investigation was to develop sustained release ethylcellulose-coated egg albumin microspheres of diltiazem hydrochloride (DH) to improve patient compliance. The microspheres were prepared by the w/o emulsion thermal cross-linking method using different proportion of the polymer to drug ratio (1.0:1.0, 1.0:1.5 and 1.0:2.0). A 32 full factorial design was employed to optimize two independent variables, polymer to drug ratio (X1) and surfactant concentration (X2) on dependent variables, namely % drug loading, % drug release in 60 min (Y60) and the time required for 80 % drug release (t80) were selected as dependable variable. Optimized formulation was compared to its sustained release tablet available in market. The polymer to drug ratio was optimized to 1:1 at which a high drug entrapment efficiency 79.20% ± 0.7% and the geometric mean diameter 47.30 ± 1.5 mm were found. All batches showed a biphasic release pattern; initial burst release effect (55% DH in 1 h) and then were released completely within 6 h. In situ coating of optimized egg albumin DH microspheres using 7.5% ethylcellulose significantly reduced the burst effect and provided a slow release of DH for 8-10 h. Finally, it was concluded that ethylcellulose-coated egg albumin DH microspheres is suitable for oral SR devices in the treatment of angina pectoris, cardiac arrhythmias, and hypertension due to their size and release profile

Analysis of the ROADSTER pivotal and extended-access cohorts shows excellent 1-year durability of transcarotid stenting with dynamic flow reversal

Objective: We report the 1-year outcomes of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial. This trial introduced a novel transcarotid neuroprotection system (NPS), the ENROUTE transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif). Postoperative results demonstrated that the use of the ENROUTE transcarotid NPS is safe and effective. The aim of this study was to evaluate the safety of transcarotid artery revascularization (TCAR) and to present the 1-year outcomes. Methods: This study is a prospective, single-arm clinical trial. Current enrollment occurs in 14 centers. Primary end points were incidence rates of ipsilateral stroke at 1 year after TCAR. Occurrence of stroke was ascertained by an independent Clinical Events Committee. Patients with anatomic or medical high-risk factors for carotid endarterectomy (CEA) were eligible to be enrolled in the ROADSTER trial. Results: Overall, 165 patients were included in the long-term follow-up (112 of 141 patients from the pivotal phase and 53 of 78 patients from the extended access). Mean age was 73.9 years (range, 42.1-91.3 years). Patients aged 75 years and older were 43.3% of the cohort. The majority of patients were white (92.7%) and male (75.2%). Most patients were asymp- tomatic (79.9%). Anatomic risk factors were distributed as follows: contralateral carotid artery occlusion (11.0%), tandem stenosis of >70% (1.8%), high cervical carotid artery stenosis (25.0%), restenosis after CEA (25.6%), bilateral stenosis requiring treatment (4.3%), and hostile neck (14.6%). Medical high-risk criteria included two-vessel coronary artery disease (14.0%) and severe left ventricular dysfunction with ejection fraction <30% (1.8%). In general, 43.3% of patients had at least one anatomic high-risk factor, whereas 29.9% of patients had medical high-risk factors. Both subsets of factors were present simultaneously in 26.8% of the cohort. At 1-year follow-up, ipsilateral stroke incidence rate was 0.6%, and seven patients (4.2%) died. None of the deaths were neurologic in origin. Conclusions: TCAR with dynamic flow reversal had previously shown favorable 30-day perioperative outcomes. This excellent performance seems to extend to 1 year after TCAR as illustrated in this analysis. The promising results from the ROADSTER trial likely stem from the novel cerebral protection provided through the ENROUTE transcarotid NPS in comparison to distal embolic protection devices as well as the transcarotid approach’s circumventing diseased aortic arch manipulation and minimizing embolization. TCAR offers a safe and durable revascularization option for patients who are deemed to be at high risk for CEA. (J Vasc Surg 2019;69:1786-96.

Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

Background: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel’s effects on the gut resistome remain largely unknown. Methods: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers’ gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, blaCTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.</p