Electrochemical Detection of Oxycodone and Its Main Metabolites with Nafion-Coated Single-Walled Carbon Nanotube Electrodes.

Oxycodone is a strong opioid frequently used as an analgesic. Although proven efficacious in the management of moderate to severe acute pain and cancer pain, use of oxycodone imposes a risk of adverse effects such as addiction, overdose, and death. Fast and accurate determination of oxycodone blood concentration would enable personalized dosing and monitoring of the analgesic as well as quick diagnostics of possible overdose in emergency care. However, in addition to the parent drug, several metabolites are always present in the blood after a dose of oxycodone, and to date, there is no electrochemical data available on any of these metabolites. In this paper, a single-walled carbon nanotube (SWCNT) electrode and a Nafion-coated SWCNT electrode were used, for the first time, to study the electrochemical behavior of oxycodone and its two main metabolites, noroxycodone and oxymorphone. Both electrode types could selectively detect oxycodone in the presence of noroxycodone and oxymorphone. However, we have previously shown that addition of a Nafion coating on top of the SWCNT electrode is essential for direct measurements in complex biological matrices. Thus, the Nafion/SWCNT electrode was further characterized and used for measuring clinically relevant concentrations of oxycodone in buffer solution. The limit of detection for oxycodone with the Nafion/SWCNT sensor was 85 nM, and the linear range was 0.5-10 µM in buffer solution. This study shows that the fabricated Nafion/SWCNT sensor has potential to be applied in clinical concentration measurements.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Occlusal treatments in temporomandibular disorders: a qualitative systematic review of randomized controlled trials.

Occlusal treatments (occlusal splints and occlusal adjustment) are controversial but widely used treatment methods for temporomandibular disorders (TMD). To investigate whether studies are in agreement with current clinical practices, a systematic review of randomized controlled trials (RCTs) of occlusal treatment studies from the period 1966 to March 1999 was undertaken. Eighteen studies met the inclusion criteria, 14 on splint therapy, and 4 on occlusal adjustment. The trials were scored using the quality scale presented by Antczak et al., 1986a (A.A. Antczak, J. Tang, T.C. Chalmers, Quality assessment of randomized control trials in dental research. I. Methods, J. Periodontal Res. 1986a;21:305-314). The overall quality of the trials was fairly low, the mean quality score was 0.43/1.00 (range 0.12-0.78). The most obvious methodological shortcomings were inadequate blinding, small sample sizes, short follow-up times, great diversity of outcome measures and numerous control treatments, some of unknown effectiveness. Splint therapy was found superior to 3, and comparable to 12 control treatments, and superior or comparable to 4 passive controls, respectively. Occlusal adjustment was found comparable to 2 and inferior to one control treatment and comparable to passive control in one study. Because of the methodological problems, only suggestive conclusions can be drawn. The use of occlusal splints may be of some benefit in the treatment of TMD. Evidence for the use of occlusal adjustment is lacking. There is an obvious need for well designed controlled studies to analyse the current clinical practices.

Application of principles of evidence-based medicine to occlusal treatment for temporomandibular disorders: are there lessons to be learned?

Critical evaluation of treatment methods has become an important part of health care and will certainly have a major influence on decisions about acceptable treatment methods in the future. Evidence-based medicine (EBM) means the systematic, explicit, and judicious implementation of the best evidence in patient care. The most reliable sources of evidence are high-quality systematic reviews and randomized controlled trials (RCTs). A systematic EBM approach could be particularly useful in the treatment of temporomandibular disorders (TMD), where controversial and conflicting ideas about management are common. In this field, concerns about the lack of evidence are often expressed. This article aims to elucidate and discuss the application of EBM to the treatment of TMD, using the most controversial treatments (i.e., occlusal treatments) as an example. By applying the principles of EBM to TMD treatments, we wish to highlight some of the important issues that form the basis for high-quality care in this field. A systematic review of occlusal treatments (occlusal splints and occlusal adjustment) updated to January 2003 revealed 16 RCTs of occlusal splints and 4 of occlusal adjustment. The overall quality of the trials was fairly low. Recently, however, some high-quality RCTs of occlusal splints have been published. The most obvious methodologic shortcomings in published trials included problems in defining the patient population, inadequacies in performing randomization and blinding, problems in defining the therapies or appropriate control treatments, short follow-ups, and problems in monitoring patient compliance. Occlusal splint studies yielded equivocal results. Even in the most studied area, stabilization splints for myofascial face pain, the results do not justify definite conclusions about the efficacy of splint therapy. Their clinical effectiveness to relieve pain also seems modest when compared with pain treatment methods in general. None of the occlusal adjustment studies provided evidence supporting the use of this treatment method. The clinical implications of the findings and future perspectives are discussed.