Evaluation of in vitro penetration of fluticasone propionate from MP-AzeFlu and fluticasone propionate nasal spray through EpiAirway (TM) 606 tissues using vertical diffusion cells

Purpose: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model. Materials and Methods: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway (TM) 606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 mu L of MP-AzeFlu (3.65 mu g; n = 8) and 10 mu L of FP nasal spray (5.00 mu g; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry. Results: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells. Conclusion: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief

Platinum Priority -Voiding Dysfunction Solifenacin Plus Tamsulosin Combination Treatment in Men With Lower Urinary Tract Symptoms and Bladder Outlet Obstruction: A Randomized Controlled Trial

Abstract Background: Alpha blockers are prescribed to manage lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Antimuscarinics are prescribed to treat overactive bladder (OAB). Objective: To investigate the safety of a combination of solifenacin (SOLI) and tamsulosin oral controlled absorption system (TOCAS) in men with LUTS and bladder outlet obstruction (BOO). Design, setting, and participants: Randomized, double-blind, parallel-group, placebocontrolled study in men aged >45 yr with LUTS and BOO for !3 mo, total International Prostate Symptom Score (IPSS) !8, BOO index !20, maximum urinary flow rate (Q max ) 12 ml/s, and voided volume !120 ml. Interventions: Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg, TOCAS 0.4 mg plus SOLI 9 mg, or placebo for 12 wk. Outcome measurements and statistical analysis: Primary (safety) measurements: Q max and detrusor pressure at Q max (P det Q max ). Other safety assessments included postvoid residual (PVR) volume. Secondary end points included bladder contractile index (BCI) score and percent bladder voiding efficiency (BVE). An analysis of covariance model compared each TOCAS plus SOLI combination with placebo. Results and limitations: Both active treatment groups were noninferior to placebo at end of treatment (EOT) for P det Q max and Q max . Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg, and at weeks 2, 12, and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo. Both treatment groups were similar to placebo for BCI and BVE. Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg. Limitations of the study were that prostate size and prostate-specific antigen level were not measured. Conclusions: TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P det Q max and Q max in men with LUTS and BOO, and there was no clinical or statistical evidence of increased risk of urinary retention

Hernia incidence following single-site vs standard laparoscopic colorectal surgery.

AIM: Compared with standard laparoscopic (SDL) approaches, less is known about the incidence of hernias after single-site laparoscopic (SSL) colorectal surgery. This study hypothesized that SSL colorectal surgery was associated with an increased risk of hernia development. METHOD: Institutional retrospective chart review (September 2008-June 2013) identified 276 evaluable patients who underwent laparoscopic colorectal procedures. The following data were collected: demographic data, risk factors for the development of a hernia, operative details and postoperative course including the development of a hernia. Patients were stratified by laparoscopic technique to compare the characteristics of those undergoing SDL and SSL. Patients were subsequently stratified by the presence or absence of a hernia to identify associated factors. RESULTS: One hundred and nineteen patients (43.1%) underwent SDL and 157 patients (56.9%) underwent SSL surgery. The development of an incisional hernia was observed in 7.6% (9/119) of SDL patients compared with 17.0% (18/106) of SSL patients (P = 0.03) over a median 18-month follow-up. Similar proportions of patients developed parastomal hernias in both groups [SDL 16.7% (10/60) vs SSL 15.9% (13/80)]. Hernias were diagnosed at a median of 8.1 (SDL) and 6.5 (SSL) months following the index operation and were less likely to be incarcerated in the SSL group [SDL 38.9% (7/18) vs SSL 6.5% (2/31), P = 0.01]. CONCLUSION: SSL colorectal surgery is associated with an increase in the incidence of incisional hernias but not parastomal hernias. Site of specimen extraction in SSL may contribute to the development of an incisional hernia

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength