Current status and evolving role of abuse-deterrent opioids in managing patients with chronic pain.

Opioids are widely used for the treatment of patients with chronic pain; yet, the increase in their abuse, misuse, and diversion is an ongoing focus of regulatory, governmental, and legal scrutiny. As a consequence, clinicians are faced with numerous challenges in an effort to use opioids in appropriate patients with pain while minimizing the potential for opioid abuse, misuse, and diversion. Policies and programs such as state prescription monitoring programs, which have been in existence for decades, are but one attempt to address some of the issues regarding the prescribing of opioids. Another is a risk evaluation and mitigation strategy for opioids under consideration by the US Food and Drug Administration. At the clinical level, a universal precautions and risk management package that includes risk assessment and patient monitoring is a recommended approach. This approach can also include the use of abuse-deterrent and abuse-resistant formulations designed to reduce the nonmedical use of opioids. Several of these opioid formulations have been approved or should soon be on the market for use in the United States; however, their role and other questions regarding their use remain unanswered. The authors offer their clinical perspective on several of these key questions.

Validation of computed tomography image integration into the EnSite NavX mapping system to perform catheter ablation of atrial fibrillation.

INTRODUCTION: The complex anatomy of the left atrium (LA) makes location of ablation catheters difficult using fluoroscopy alone, and therefore 3D mapping systems are now routinely used. We describe the integration of a CT image into the EnSite NavX System with Fusion and its validation in patients undergoing atrial fibrillation (AF) or left atrial tachycardia (AT) catheter ablation. METHODS AND RESULTS: Twenty-three patients (61 +/- 9.2 years, 16 male) with paroxysmal (14) and persistent (8) AF and persistent (1) AT underwent ablation using CT image integration into the EnSite NavX mapping system with the EnSite Fusion Dynamic Registration software module. In all cases, segmentation of the CT data was accomplished using the EnSite Verismo segmentation tool, although repeat segmentation attempts were required in seven cases. The CT was registered with the NavX-created geometry using an average of 24 user-defined fiducial pairs (range 9 to 48). The average distance from NavX-measured lesion positions to the CT surface was 3.2 +/- 0.9 mm (median 2.4 mm). A large, automated, retrospective test using registrations with random subsets of each patient's fiducial pairs showed this average distance decreasing as the number of fiducial pairs increased, although the improvement ceased to be significant beyond 15 pairs. In confirmation, those studies which had used 16 or more pairs had a smaller average lesion-to-surface distance (2.9 +/- 0.7 mm) than those using 15 or fewer (4.3 +/- 0.8 mm, P < 0.02). Finally, for the 13 patients who underwent left atrial circumferential ablation (LACA), there was no significant difference between the circumference computed using NavX-measured positions and CT surface positions for either the left pulmonary veins (178 +/- 64 vs. 177 +/- 60 mm; P = 0.81) or the right pulmonary veins (218 +/- 86 vs. 207 +/- 81 mm; P = 0.08). CONCLUSION: CT image integration into the EnSite NavX Fusion system was successful in all patients undergoing catheter ablation. A learning curve exists for the Verismo segmentation tool; but once the 3D model was created, the registration process was easily accomplished, with a registration error that is comparable with registration errors using other mapping systems with CT image integration. All patients went on to have subsequent successful ablation procedures. Where LACA was performed (13 patients), only four patients required segmental ostial lesions to achieve electrical isolation.

Special treatments for valve/hole regions in endocardial potential estimates from non-contact intracavitary probes.

The EnSite intracavitary probe system developed by Endocardial Solutions, Inc (St. Jude Medical, St. Paul, MN) was used to simultaneously record geometric information, probe potentials, and endocardial potentials within the right atria for four patients. First-order Tikhonov regularization was then used to estimate endocardial potentials from the probe potentials for each patient at each endocardial site, and relative errors and correlation coefficients between the estimates and measured data were computed. Next, three treatments for valve/hole regions of the heart were examined to determine whether they were able to improve the endocardial potential estimates outside the valve/hole regions: thetaphi/theta(n) = 0, c thetaphi/theta(n) = phi, and infinite elements. The correlation coefficients and relative errors for the estimates with the special treatments were extremely close to (and sometimes slightly worse than) the estimates without any special treatments, for all four patients.

Estimates of endocardial potentials from non-contact intracavitary probes.

The EnSitetrade intracavitary probe system developed by Endocardial Solutions, Inc (St. Jude Medical, St. Paul, MN) was used to simultaneously record geometric information, probe potentials, and selected endocardial potentials within the right atria for four patients. Tikhonov regularization was then used to estimate endocardial potentials from probe measurements for each patient at each endocardial site. The correlation coefficients and relative errors between the estimated potentials and the measured endocardial potentials were then calculated. This inverse problem was quite ill-conditioned, and first-order Tikhonov regularization performed better than zero-order or second-order Tikhonov regularization in producing stable and accurate results. In choosing the regularization parameter micro, a constant value of micro=0.3 performed as well as CRESO and maximum curvature, which pick a different micro for each time instant.

Assessing autonomic function by analysis of heart rate recovery from exercise in healthy subjects.

Although delayed recovery of heart rate (HR) after exercise indicates poor prognosis, the relative role of parasympathetic reactivation versus sympathetic withdrawal in controlling exercise HR recovery remains controversial. Quantifying HR recovery is difficult because the rate of recovery varies with exercise level. This study develops a model of HR recovery applicable to multiple exercise levels simultaneously. Using the Levenberg-Marquardt method for nonlinear models, HR curves for 11 healthy volunteers recovering from 4 different levels of exercise were fit to equations incorporating 1 first-order time constant for parasympathetic reactivation and 1 for sympathetic withdrawal. Results provided time constants for parasympathetic reactivation of 44 +/- 37 seconds and for sympathetic withdrawal of 65 +/- 56 seconds. The model fit the HR recovery curves very closely, explaining 99.7 +/- 0.1% of the variance in the data. In conclusion, this study presents a unique method for quantitatively testing theories on the relative roles of sympathetic withdrawal and parasympathetic reactivation during recovery from exercise. It provides indexes of dynamic sympathetic and parasympathetic functions, with the parasympathetic system having a faster response time. It supports theories of coordinated interaction of parasympathetic reactivation and sympathetic withdrawal during exercise recovery and does not support using simple measures of exercise HR recovery as indexes of vagal function alone.

A peek into Pandora's box: the medical excuse marijuana controversy.

The smoking of marijuana for medicinal applications is a volatile and difficult issue for the medical and regulatory communities which has reached the forefront of discussions of public policy. Any consideration of this issue must take into account the substantial toxicity, impurity, and morbidity associated with marijuana use. Several states have passed ballot initiatives or legislation that allow a medical excuse for possession of marijuana. These initiatives bypass the Food and Drug Administration process of proving safety and efficacy, and they have created serious regulatory dilemmas for state regulatory boards. Several examinations of the issue have consistently drawn question to the validity of smoking an impure substance while voicing concern for the well being of patients in need. The historical, social, medical, and legal issues are examined.