In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia^®350 (S350) and pH sensitive material Eudragit^® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl^®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS.     

Trends in advanced imaging and hospitalization for emergency department syncope care before and after ACEP clinical policy

ObjectivesTo describe recent trends in advanced imaging and hospitalization of emergency department (ED) syncope patients, both considered “low-value”, and examine trend changes before and after the publication of American College Emergency Physician (ACEP) syncope guidelines in 2007, compared to conditions that had no changes in guideline recommendations.MethodsWe analyzed 2002–2015 National Hospital Ambulatory Medical Care Survey data using an interrupted-time series with comparison series design. The primary outcomes were advanced imaging among ED visits with principal diagnosis of syncope and headache and hospitalization for ED visits with principal diagnosis of syncope, chest pain, dysrhythmia, and pneumonia. We adjusted annual imaging and hospitalization rates using survey-weighted multivariable logistic regression, controlling for demographic and visit characteristics. Using adjusted outcomes as datapoints, we compared linear trends and trend changes of annual imaging and hospitalization rates before and after 2007 with aggregate-level multivariable linear regression.ResultsFrom 2002 to 2007, advanced imaging rates for syncope increased from 27.2% to 42.1% but had no significant trend after 2007 (trend change: ?3.1%; 95%CI ?4.7, ?1.6). Hospitalization rates remained at approximately 37% from 2002 to 2007 but declined to 25.7% by 2015 (trend change: ?2.2%; 95%CI ?3.0, ?1.4). Similar trend changes occurred among control conditions versus syncope, including advanced imaging for headache (difference in trend change: ?0.6%; 95%CI ?2.8, 1.6) and hospitalizations for chest pain, dysrhythmia, and pneumonia (differences in trend changes: 0.1% [95%CI ?1.9, 2.0]; ?0.9% [95%CI ?3.1, 1.3]; and ?1.2% [95%CI ?5.3, 2.9], respectively).ConclusionsBefore and after the release of 2007 ACEP syncope guidelines, trends in advanced imaging and hospitalization for ED syncope visits had similar changes compared to control conditions. Changes in syncope care may, therefore, reflect broader practice shifts rather than a direct association with the 2007 ACEP guideline. Moreover, utilization of advanced imaging remains prevalent. To reduce low-value care, policymakers should augment society guidelines with additional policy changes such as reportable quality measures.     

Management of massive gastrointestinal haemorrhage

Acute gastrointestinal bleeding is a common medical emergency, accounting for approximately 85,000 admissions in the United Kingdom per annum. It is associated with significant morbidity and mortality. GI haemorrhage is commonly categorized according to source of blood loss; either upper GI (above the ligament of Treitz) or lower GI (below the ligament of Treitz). Rapid assessment, resuscitation and correction of coagulopathy should be undertaken to stabilize the haemodynamically compromised patient and definitive intervention should not be delayed. Clinicians may use of a range of treatment modalities, including endoscopic and interventional radiological techniques in order to get control of haemorrhage, which should be tailored to the site of bleeding and pathology. Where control is not achieved the clinician should consider either repeat intervention, use of alternative haemostatic techniques or different modalities to achieve haemostasis. Rarely is surgery the chosen treatment modality and surgical intervention should only be undertaken where all other measures to control haemorrhage have failed.     

Numerical Investigation of Analytical Models of Drug Flux Through Microporated Skin

In this study, drug flux through microporated skin was modeled using detailed numerical solution of the diffusion equation. The results of the modeling were compared to previously published simplified and easy to use analytical equations. Limitations and accuracy of these equations were investigated. Appropriate modifications of the equations were identified to expand them to wider practical applications when pore shape is not circular. Numerical simulations have shown a good accuracy of the new simple equations when these are used within their limits of application.     

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial

Study objective

We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients.