Integrating Optimization and Sampling for Robot Motion Planning with Applications in Healthcare

Robots deployed in human-centric environments, such as a person's home in a home-assistance setting or inside a person's body in a surgical setting, have the potential to have a large, positive impact on human quality of life. However, for robots to operate in such environments they must be able to move efficiently while avoiding colliding with obstacles such as objects in the person's home or sensitive anatomical structures in the person's body. Robot motion planning aims to compute safe and efficient motions for robots that avoid obstacles, but home assistance and surgical robots come with unique challenges that can make this difficult. For instance, many state of the art surgical robots have computationally expensive kinematic models, i.e., it can be computationally expensive to predict their shape as they move. Some of these robots have hybrid dynamics, i.e., they consist of multiple stages that behave differently. Additionally, it can be difficult to plan motions for robots while leveraging real-world sensor data, such as point clouds. In this dissertation, we demonstrate and empirically evaluate methods for overcoming these challenges to compute high-quality and safe motions for robots in home-assistance and surgical settings. First, we present a motion planning method for a continuum, parallel surgical manipulator that accounts for its computationally expensive kinematics. We then leverage this motion planner to optimize its kinematic design chosen prior to a surgical procedure. Next, we present a motion planning method for a 3-stage lung tumor biopsy robot that accounts for its hybrid dynamics and evaluate the robot and planner in simulation and in inflated porcine lung tissue. Next, we present a motion planning method for a home-assistance robot that leverages real-world, point-cloud obstacle representations. We then expand this method to work with a type of continuum surgical manipulator, a concentric tube robot, with point-cloud anatomical representations. Finally, we present a data-driven machine learning method for more accurately estimating the shape of concentric tube robots. By effectively addressing challenges associated with home assistance and surgical robots operating in human-centric environments, we take steps toward enabling robots to have a positive impact on human quality of life.Doctor of Philosoph

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

International audienceBACKGROUND Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2: 1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (>= 3 points), an outcome that indicates improvement in at least two motor skills. RESULTS In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P< 0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P< 0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.