MaDoPO: Magnetic Detection of Positions and Orientations of Segmented Deep Brain Stimulation Electrodes: A Radiation-Free Method Based on Magnetoencephalography

Background: Current approaches to detect the positions and orientations of directional deep brain stimulation (DBS) electrodes rely on radiative imaging data. In this study, we aim to present an improved version of a radiation-free method for magnetic detection of the position and the orientation (MaDoPO) of directional electrodes based on a series of magnetoencephalography (MEG) measurements and a possible future solution for optimized results using emerging on-scalp MEG systems. Methods: A directional DBS system was positioned into a realistic head–torso phantom and placed in the MEG scanner. A total of 24 measurements of 180 s each were performed with different predefined electrode configurations. Finite element modeling and model fitting were used to determine the position and orientation of the electrode in the phantom. Related measurements were fitted simultaneously, constraining solutions to the a priori known geometry of the electrode. Results were compared with the results of the high-quality CT imaging of the phantom. Results: The accuracy in electrode localization and orientation detection depended on the number of combined measurements. The localization error was minimized to 2.02 mm by considering six measurements with different non-directional bipolar electrode configurations. Another six measurements with directional bipolar stimulations minimized the orientation error to 4°. These values are mainly limited due to the spatial resolution of the MEG. Moreover, accuracies were investigated as a function of measurement time, number of sensors, and measurement direction of the sensors in order to define an optimized MEG device for this application. Conclusion: Although MEG introduces inaccuracies in the detection of the position and orientation of the electrode, these can be accepted when evaluating the benefits of a radiation-free method. Inaccuracies can be further reduced by the use of on-scalp MEG sensor arrays, which may find their way into clinics in the foreseeable future

CLOVER-DBS: Algorithm-Guided Deep Brain Stimulation-Programming Based on External Sensor Feedback Evaluated in a Prospective, Randomized, Crossover, Double-Blind, Two-Center Study

BACKGROUND Recent technological advances in deep brain stimulation (DBS) (e.g., directional leads, multiple independent current sources) lead to increasing DBS-optimization burden. Techniques to streamline and facilitate programming could leverage these innovations. OBJECTIVE We evaluated clinical effectiveness of algorithm-guided DBS-programming based on wearable-sensor-feedback compared to standard-of-care DBS-settings in a prospective, randomized, crossover, double-blind study in two German DBS centers. METHODS For 23 Parkinson's disease patients with clinically effective DBS, new algorithm-guided DBS-settings were determined and compared to previously established standard-of-care DBS-settings using UPDRS-III and motion-sensor-assessment. Clinical and imaging data with lead-localizations were analyzed to evaluate characteristics of algorithm-derived programming compared to standard-of-care. Six different versions of the algorithm were evaluated during the study and 10 subjects programmed with uniform algorithm-version were analyzed as a subgroup. RESULTS Algorithm-guided and standard-of-care DBS-settings effectively reduced motor symptoms compared to off-stimulation-state. UPDRS-III scores were reduced significantly more with standard-of-care settings as compared to algorithm-guided programming with heterogenous algorithm versions in the entire cohort. A subgroup with the latest algorithm version showed no significant differences in UPDRS-III achieved by the two programming-methods. Comparing active contacts in standard-of-care and algorithm-guided DBS-settings, contacts in the latter had larger location variability and were farther away from a literature-based optimal stimulation target. CONCLUSION Algorithm-guided programming may be a reasonable approach to replace monopolar review, enable less trained health-professionals to achieve satisfactory DBS-programming results, or potentially reduce time needed for programming. Larger studies and further improvements of algorithm-guided programming are needed to confirm these results

HIV-1 drug resistance before initiation or re-initiation of first-line ART in eight regions of Mexico: a sub-nationally representative survey.

BackgroundHIV pretreatment drug resistance (PDR) to NNRTIs in persons initiating ART is increasing in Mexico.ObjectivesTo compare HIV PDR in eight sub-regions of Mexico.Patients and methodsA large PDR survey was implemented in Mexico (September 2017-March 2018) across eight sub-regions. All larger clinics (which provide ART to 90% of all initiators) were included, allocating sample size using the probability-proportional-to-size method. Both antiretroviral-naive and prior antiretroviral-exposed persons were included. HIV PDR levels were estimated from pol Sanger sequences obtained at a WHO-designated laboratory.ResultsA total of 2006 participants were enrolled from 74 clinics. PDR to NNRTIs was higher than to other drug classes (P < 0.0001), crossing the 10% threshold in the North-East, East, South-West and South-East. NNRTI PDR was higher in the South-West (P = 0.02), coinciding with the highest proportion of restarters in this sub-region (14%). We observed higher PDR prevalence to any drug in women compared with men (16.5% versus 12.2%, P = 0.04). After multivariable adjustment, higher NNRTI PDR remained significantly associated with previous antiretroviral exposure in the Centre-North, North-West, South-West and South-East [adjusted OR (aOR): 21, 5, 8 and 25, respectively; P < 0.05]. Genetic network analyses showed high assortativity by sub-region (P < 0.0001), with evidence of drug resistance mutation transmission within local clusters.ConclusionsDiversification of the public health response to HIV drug resistance based on sub-regional characteristics could be considered in Mexico. Higher NNRTI PDR levels were associated with poorer regions, suggesting opportunities to strengthen local HIV programmes. Price and licensing negotiations of drug regimens containing integrase inhibitors are warranted