Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Is There Material Loss at the Conical Junctions of Modular Components for Total Knee Arthroplasty?

BackgroundClinical concern exists regarding fretting corrosion and material loss from taper junctions in orthopedic devices, with previous research focusing on the modular components from total hip arthroplasty. Comparatively little has been published regarding the fretting corrosion and material loss in modular knee devices. The purpose of this study is to evaluate fretting corrosion damage and quantify material loss for conical total knee arthroplasty taper interfaces.MethodsStem tapers of 166 retrieved modular knee devices were evaluated for fretting corrosion using a semiquantitative scoring method. High precision profilometry was then used to determine volumetric material loss and maximum wear depth for a subset of 37 components (implanted for 0.25-18.76 years). Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to characterize the observed damage.ResultsMild to severe fretting corrosion was observed on the majority of tapers, with 23% receiving a maximum visually determined damage score of 4. The median rate of volumetric material loss was 0.11 mm³/y (range 0.00-0.76) for femoral components (both cone and bore taper surfaces combined) and 0.01 mm³ (range 0.00-8.10) for tibial components. Greater rates of material loss were associated with mixed metal pairings. There was a strong correlation between visual fretting corrosion score and calculated material loss (ρ = 0.68, P < .001). Scanning electron microscopy revealed varying degrees of scratching, wear, fretting corrosion, and instances of cracking with morphology not consistent with fretting corrosion, wear, or fatigue.ConclusionAlthough visual evidence of fretting corrosion damage was prevalent and correlated with taper material loss, the measured volumetric material loss was low compared with prior reports from total hip arthroplasty.     

“Unselling” Drugs: The Marketing of Prevention

By borrowing from the field of social marketing, the examination and execution of drug prevention strategies should be more rigorous and disciplined by the year 2000. This article briefly describes marketing strategies and techniques which can assist in the maximization of drug prevention communications and programs.     

Market模式在手术室高值耗材管理中的应用

目的探讨新形势下手术室高值耗材的科学管理方法。方法将2012年1-5月使用的高值耗材10 200件作为对照组,2012年6-10月使用的高值耗材12 324件作为观察组,对照组使用传统管理,观察组实施Market模式管理。结果观察组每日清点费时数、耗材漏帐次数和提供耗材时间均低于对照组,手术医生满意度优于对照组,差异均有统计学意义(P0.05或P0.01)。结论 Market模式的应用可有效提高手术室高值耗材的管理水平,值得在临床推广应用。     

Confirmatory versus explorative endpoint analysis: Decision-making on the basis of evidence available from market authorization and early benefit assessment for oncology drugs

The early benefit assessment of pharmaceuticals in Germany and their preceding market authorization pursue different objectives. This is reflected by the inclusion of varying confirmatory endpoints within the evaluation of oncology drugs in early benefit assessment versus market authorization, with both relying on the same evidence. Data from assessments up to July 2015 are used to estimate the impact of explorative in comparison to confirmatory endpoints on market authorization and early benefit assessment by contrasting the benefit-risk ratio of EMA and the benefit-harm balance of the HTA jurisdiction. Agreement between market authorization and early benefit assessment is examined by Cohen’s kappa (k). 21 of 41 assessments were considered in the analysis. Market authorization is more confirmatory than early benefit assessment because it includes a higher proportion of primary endpoints. The latter implies a primary endpoint to be relevant for the benefit-harm balance in only 67% of cases (0.078). Explorative mortality endpoints reached the highest agreement regarding the mutual consideration for the risk-benefit ratio and the benefit-harm balance (0.000). For explorative morbidity endpoints (−0.600), quality of life (−0.600) and side effects (−0.949) no agreement is ascertainable. To warrant a broader confirmatory basis for decisions supported by HTA, closer inter-institutional cooperation of approval authorities and HTA jurisdictions by means of reliable joint advice for manufacturers regarding endpoint definition would be favorable.