ObjectiveTo quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population.DesignRetrospective cohort study.SettingSurgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016.Participants1 015 116 opioid naive patients undergoing surgery.Main outcome measuresUse of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose.Results568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively.ConclusionsEach refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact.

Objective Motor Neural Interface Systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results Eighty-four percent of the recorded units showed a statistically significant change in apparent firing rate (3.8±8.71Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and seventy-four percent of the units showed a significant change in spike amplitude (3.7±6.5μV or 5.5% of mean spike amplitude). Forty percent of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional “bias” in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in fifty-six percent of all performance assessments in participant cursor control (n=2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. Significance We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs.

Objective Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs along with action potentials a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach We conducted intracortical multielectrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200–400Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70–400Hz), and increasing disparity with lower frequency bands (0–7, 10–40 and 50–65Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p=0.27[0.03]). Significance Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041)

Intracortical brain computer interfaces (iBCIs) are being developed to enable a person to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software which decodes the user’s intended movement from those signals. Here, we focus on recent advances in these two areas, with special attention being placed on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology’s capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications.

e p urpose of this paper is to propose a solution methodology for a missile defense problem involving the sequential allocation of defensive r esources over a series of engagements. The problem is cast as a dynamic programming/Markovian decision problem, which is computationally intractable by exact methods because of its large number o f s tates and its complex modeling issues. We h a ve employed a Neuro-Dynamic Programming (NDP) framework, whereby t he cost-to-go function is approximated using neural network architectures that are trained on simulated data. We report on the performance obtained using several different t raining methods, and we compare this performance with the optimal. Keywords| T h e ater Missile Defense, Dynamic Programming, Neuro-Dynamic Programming, Reinforcement L e a rning.

BACKGROUND Accidental falls among people aged 65 years and older caused approximately 2,700,000 injuries, 27,000 deaths, and cost more than 34 billion dollars in the United States annually in recent years. Here, we derive and validate a predictive model for falls based on a retrospective cohort of those 65 years and older. METHODS Insurance claims from a one year observational period were used to predict a fall-related claim in the following two years. The predictive model takes into account a person’s age, sex, prescriptions, and diagnoses. Through random assignment, half of the people had their claims used to derive the model, while the remaining people had their claims used to validate the model. RESULTS Out of 120,881 individuals, with Aetna health insurance coverage, 12,431 (10.3%) members fell. During validation, people were risk stratified across 20 levels, where those in the highest risk stratum had 10.5 times the risk as those in the lowest stratum (33.1% vs. 3.1%). CONCLUSIONS Using only insurance claims, individuals in this large cohort at high risk of falls could be readily identified up to two years in advance. Although external validation is needed, the findings support the use of the model to better target interventions.

Intracortical brain computer interfaces (iBCIs) decode intended movement from neural activity for the control of external devices such as a robotic arm. Standard approaches include a calibration phase to estimate decoding parameters. During iBCI operation, the statistical properties of the neural activity can depart from those observed during calibration, sometimes hindering a user’s ability to control the iBCI. To address this problem, we adaptively correct the offset terms within a Kalman filter decoder via penalized maximum likelihood estimation. The approach can handle rapid shifts in neural signal behavior (on the order of seconds) and requires no knowledge of the intended movement. The algorithm, called MOCA, was tested using simulated neural activity and evaluated retrospectively using data collected from two people with tetraplegia operating an iBCI. In 19 clinical research test cases, where a nonadaptive Kalman filter yielded relatively high decoding errors, MOCA significantly reduced these errors (10.6 ±10.1%; p<0.05, pairwise t-test). MOCA did not significantly change the error in the remaining 23 cases where a nonadaptive Kalman filter already performed well. These results suggest that MOCA provides more robust decoding than the standard Kalman filter for iBCIs.

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