Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community

OBJECTIVE: To evaluate the dose-related benefit of angiotensin-converting enzyme (ACE) inhibitor therapy among older adults with heart failure and to evaluate whether low-dose ACE inhibitor therapy is better than none. DESIGN: Observational cohort study. SETTING: Community-dwelling older adults in Ontario, Canada. PATIENTS/PARTICIPANTS: We identified 16539 adults 66 years or older who survived 45 days following their first heart failure hospitalization discharge. MEASUREMENT AND MAIN RESULTS: Multivariate techniques including propensity scores were used to study the association between the dose of ACE inhibitor therapy dispensed and 3 outcomes: survival, survival or heart failure rehospitalization, and survival or all-cause hospitalization at 1 year of follow-up. Logistic regression models explored the association between initial dose dispensed and subsequent dose reduction or drug cessation. Overall, 10793 (65.3%) of patients were dispensed ACE inhibitor therapy, with more than a third (3935; 36.5%) initiated on low-dose therapy. Relative to dispensing of low-dose ACE inhibitor therapy, nonuse was associated with increased mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02 to 1.22). Dispensing medium-dose therapy provided a benefit similar to low-dose (HR, 0.94; CI, 0.86 to 1.03) and dispensing of high-dose therapy was associated with improved survival benefit (HR, 0.76; CI, 0.68 to 0.85). Relative to dispensing of low-dose ACE inhibitor therapy, dispensing high-dose conferred a benefit (HR, 0.87; CI, 0.80 to 0.95) on the composite outcome of 1-year mortality or heart failure hospitalization and the composite outcome of 1-year mortality or all-cause hospitalization (HR, 0.87; CI, 0.81 to 0.93). Relative to those dispensed low-dose ACE inhibitor therapy, those initially dispensed high-dose therapy were twice as likely to have their subsequent dose reduced or the therapy discontinued (odds ratio, 2.36; CI, 2.07 to 2.69). CONCLUSION: Our findings suggest that when possible, older adults should be titrated to the higher doses of ACE inhibitor therapy evaluated in clinical trials. If older adults cannot tolerate higher doses, then low-dose ACE inhibitor therapy is superior to none. High-dose ACE inhibitor therapy is not as well tolerated as lower doses.     

Shaving effects on percutaneous penetration: clinical implications

Context: Human/animal shaving biology.

Objective: To assess the effect of shaving on percutaneous penetration and skin function.

Methods: We screened 500+publications in Pub Med, Scopus, Cochrane Library and pertinent journals out of which only 17 were deemed relevant. Terms for searches included shaving and skin, percutaneous penetration and shaving, skin absorption and shaving, absorption of dyes and shaving, skin penetration, effects of shaving and absorption, shave and dyes, axillary shaving and stratum corneum, shaving and breast cancer, shaving and infections, etc.

Result: Shaving appears to have an exaggerated effect on percutaneous absorption; however, some studies do not support this evidence.

Conclusion: Shaving enhances percutaneous penetration of some chemicals; however this effect is species and chemical specific. Further investigations of chemicals of varying physio-chemical properties are mandated before a generalized theory can be promulgated.     

Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH–sensitive acrylic acid–polyvinyl alcohol hydrogel

Background

The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid–polyvinyl alcohol hydrogel.

Methods

In the present work, pH sensitive acrylic acid–polyvinyl alcohol hydrogels have been prepared by free radical polymerization technique in the presence of benzoyl peroxide as an initiator. Different crosslinker contents were used to observe its effect on swelling and on drug release. Dynamic and equilibrium swelling studies of prepared hydrogels were investigated in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strengths. Hydrogels were evaluated for polymer volume fraction, solvent interaction parameter, molecular weight between crosslinks, number of links per polymer chain, diffusion coefficient, sol–gel fraction and porosity. To demonstrate the release pattern of the drug, zero-order, first-order, higuchi and korsmeyer-peppas models were applied. Quality and consistency of hydrogels was examined by FTIR and surface morphology of hydrogels was examined by SEM.

Results

Decrease in swelling and in drug release was seen by increasing content of ethylene glycol dimethacrylate. A remarkable high swelling was observed at high pH indicating the potential of this hydrogel for delivery of drugs to intestine. By increasing the concentration of ethylene glycol dimethacrylate, porosity decreased. Order of release was observed first order in all cases and the mechanism was non–fickian diffusion. FTIR confirmed the formation of network. SEM results showed the incorporation of drug.

Conclusion

The prepared hydrogels can be suitably used for targeted drug delivery to the intestine.