The Multi-gene claudin (CLDN) family of tight junction proteins have isoform-specific roles in blood-tissue barrier regulation. Although CLDN17, a putative anion pore-forming CLDN, is assumed to regulate anion balance across the blood-tissue barriers, our knowledge about CLDN17 is limited. The current study investigated how Cldn17 deficiency in mice affects blood-tissue barrier integrity and vascular permeability. Cldn17−/− mice revealed no breeding abnormalities, but the newborn pups exhibited delayed growth until they turned 8-weeks. Adult Cldn17−/− mice displayed electrolyte imbalance, oxidative stress, increased vascular leakage, increased bone density, and organ injury. In addition, these mice demonstrated increased leukocytosis. A xenograft model to study pathological neovascularization showed higher vascular density in tumors developed in Cldn17−/− mice compared to wild-type controls. RNA-sequencing revealed hyperactivation of signaling pathways associated with inflammation and reactive oxygen species generation, demonstrating the importance of Cldn17 in blood-tissue barrier maintenance.

Background: Patients with Chronic Kidney Disease are at increased risk for potentially harmful prescribing. The selection of appropriate dosing for patients with Chronic Kidney Disease is important to avoid unwanted drug effects, maximize therapeutic efficacy and ensure optimal patient outcomes. Aim: To study the impact of renal dosing guidelines on prescribing pattern in patients with CKD. Methods: This was a prospective, interventional study conducted at a tertiary care centre. In the pre-interventional phase, the case sheets of all the in-patients with CKD with creatinine clearance of <50mL/min were collected and reviewed for the demographics, lab parameters and medications prescribed. The pre-intervention phase served as the control.As a part of intervention, pocket guides were prepared listing out the drug dosing in renal impairment and were distributed to all clinicians and the patient care areas. In the post-interventional phase, the drug charts were reviewed to observe any improvement in the dosing pattern of renally eliminated drugs. Results: In the pre-intervention study, drug dosing adjustment was needed in 246 drugs where 59 drugs (23%) were inappropriately dosed. In the post-intervention study, this number was significantly lowered to 23 (8%) drugs out of 284 drugs (p=0.0001) which needed renal dosing. Statistically significant improvements were seen with prescribing of antibiotics (p=0.0017), hypolipidemics (p=0.0449) and antiarrhythmic agents (p=0.0034). Conclusion: The dosing of majority of the renally eliminated drugs followed the recommendations of the package inserts. With the increasing awareness created by the pocket guides, there was a significant improvement in renal dosing. There is a need in health care settings to monitor the use of renally eliminated medications to reduce the adverse effects. The clinical pharmacists in collaboration with clinicians play a significant role in optimizing patient outcomes.

s235 management with continued utilization of either drug. Sensitivity analysis was conducted using one-way probabilistic analyses with 10% variation in all probabilities and costs. Results: Total pharmaceutical costs accrued after 3 years among patients treated with tobramycin was estimated at $114,400 compared to azithromycin at $62,400. Life expectancy was 0.29 years lower among patients taking tobramycin. Azithromycin was the dominant strategy compared to tobramycin in the base case. Sensitivity analyses indicated pharmaceutical costs for azithromycin were most influential on the ICER. ConClusions: Tobramycin was not cost-effective due to higher cost and reduced capacity to prolong life years without discontinuation of medication in the management of severe exacerbations, compared to azithromycin. This study does not preclude clinical intervention via implementation of both medications in treatment pathways. Further research is needed to determine health economics and outcomes among patients treated with azithromycin and tobramycin as adjunct therapy in management of severe exacerbations. PRS32 CoSt-MiniMization analySiS of adding a new Single inhaleR tRiPle theRaPy (Sitt) foR the tReatMent of PatientS with ChRoniC obStRuCtive PulMonaRy diSeaSe (CoPd) in the uK