Cost-Effectiveness and Cost-Utility of Early Levodopa in Parkinson's Disease

Background: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start).Objective: This paper reports the results of the economic evaluation performed alongside the LEAP-study.Methods: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up.Results: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of D 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated.Conclusion: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa.Neurological Motor Disorder

Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease

BACKGROUND Levodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in the course of the disease the treatment with this drug should be initiated. METHODS In a multicenter, double-blind, placebo-controlled, delayed-start trial, we randomly assigned patients with early Parkinson's disease to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group). The primary outcome was the between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS; scores range from 0 to 176, with higher scores signifying more severe disease). Secondary analyses included the progression of symptoms, as measured by the UPDRS score, between weeks 4 and 40 and the noninferiority of early initiation of treatment to delayed initiation between weeks 44 and 80, with a noninferiority margin of 0.055 points per week. RESULTS A total of 445 patients were randomly assigned: 222 to the early-start group and 223 to the delayed-start group. The mean (+/- SD) UPDRS score at baseline was 28.1 +/- 11.4 points in the early-start group and 29.3 +/- 12.1 points in the delayed-start group. The change in UPDRS score from baseline to week 80 was -1.0 +/- 13.1 points and -2.0 +/- 13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], -1.5 to 3.5; P = 0.44); this finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect. Between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04 +/- 0.23 in the early-start group and 0.06 +/- 0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10 +/- 0.25 and 0.03 +/- 0.28 (difference, 0.07; two-sided 90% CI, 0.03 to 0.10); the difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt. The rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups. CONCLUSIONS Among patients with early Parkinson's disease who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect

Analysis of reflex modulation with a biologically realistic neural network

In this study, a neuromusculoskeletal model was built to give insight into the mechanisms behind the modulation of reflexive feedback strength as experimentally identified in the human shoulder joint. The model is an integration of a biologically realistic neural network consisting of motoneurons and interneurons, modeling 12 populations of spinal neurons, and a one degree-of-freedom musculoskeletal model, including proprioceptors. The model could mimic the findings of human postural experiments, using presynaptic inhibition of the Ia afferents to modulate the feedback gains. In a pathological case, disabling one specific neural connection between the inhibitory interneurons and the motoneurons could mimic the experimental findings in complex regional pain syndrome patients. It is concluded that the model is a valuable tool to gain insight into the spinal contributions to human motor control. Applications lay in the fields of human motor control and neurological disorders, where hypotheses on motor dysfunction can be tested, like spasticity, clonus, and tremor

A Survey of Crowdsourcing in Medical Image Analysis

Rapid advances in image processing capabilities have been seen across many domains, fostered by the application of machine learning algorithms to "big-data". However, within the realm of medical image analysis, advances have been curtailed, in part, due to the limited availability of large-scale, well-annotated datasets. One of the main reasons for this is the high cost often associated with producing large amounts of high-quality meta-data. Recently, there has been growing interest in the application of crowdsourcing for this purpose; a technique that a technique that is well established in a number of disciplines, including astronomy, ecology and meteorology for creating large-scale datasets across a range of disciplines, from computer vision to astrophysics. Despite the growing popularity of this approach, there has not yet been a comprehensive literature review to provide guidance to researchers considering using crowdsourcing methodologies in their own medical imaging analysis. In this survey, we review studies applying crowdsourcing to the analysis of medical images, published prior to July 2018. We identify common approaches and challenges and provide recommendations to researchers implementing crowdsourcing for medical imaging tasks. Finally, we discuss future opportunities for development within this emerging domain

Spreading of complex regional pain syndrome: not a random process

Complex regional pain syndrome (CRPS) generally remains restricted to one limb but occasionally may spread to other limbs. Knowledge of the spreading pattern of CRPS may lead to hypotheses about underlying mechanisms but to date little is known about this process. The objective is to study patterns of spread of CRPS from a first to a second limb and the factors associated with this process. One hundred and eighty-five CRPS patients were retrospectively evaluated. Cox’s proportional hazards model was used to evaluate factors that influenced spread of CRPS symptoms. Eighty-nine patients exhibited CRPS in multiple limbs. In 72 patients spread from a first to a second limb occurred showing a contralateral pattern in 49%, ipsilateral pattern in 30% and diagonal pattern in 14%. A trauma preceded the onset in the second limb in 37, 44 and 91%, respectively. The hazard of spread of CRPS increased with the number of limbs affected. Compared to patients with CRPS in one limb, patients with CRPS in multiple limbs were on average 7 years younger and more often had movement disorders. In patients with CRPS in multiple limbs, spontaneous spread of symptoms generally follows a contralateral or ipsilateral pattern whereas diagonal spread is rare and generally preceded by a new trauma. Spread is associated with a younger age at onset and a more severely affected phenotype. We argue that processes in the spinal cord as well as supraspinal changes are responsible for spontaneous spread in CRPS

Safe Design Suggestions for Vegetated Roofs

Rooftop vegetation is becoming increasingly popular because of its environmental benefits and its ability to earn green-building certification credits. With the exception of one international guideline, there is little mention of worker safety and health in vegetated-roof codes and literature. Observations and field investigations of 19 vegetated roofs in the United States revealed unsafe access for workers and equipment, a lack of fall-protection measures, and other site-specific hazards. Design for safety strategies and the integration of life-cycle safety thinking with green-building credits systems are the preferred methods to reduce risk to workers on vegetated roofs. Design suggestions have been developed to add to the body of knowledge. The findings complement several National Institute for Occupational Safety and Health (NIOSH) construction and prevention through design (PtD) goals and are congruent with NIOSH’s Safe Green Jobs initiative. Organizations that install and maintain vegetated roofs can utilize the findings to understand hazards, take precautions, and incorporate safety into their bids The published version of this article is available here: 10.1061/(ASCE)CO.1943-7862.0000500Support from the the Virginia Tech Occupational Safety and Health Research Center through the Kevin P. Granata Pilot Program funded by the Institute for Critical Technology and Applied Sciences

Preoperative electroencephalography‐based machine learning predicts cognitive deterioration after subthalamic deepbrain stimulation

Algorithms and the Foundations of Software technolog

Predicting motor outcome and quality of life after subthalamic deep brain stimulation for Parkinson's disease: the role of standard screening measures and wearable data

Background:Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim.Objective:To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery.Methods:Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function.Results:Eighty-three patients were included (median (interquartile range) age 63 (56–68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models.Conclusion:Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.

OBJECTIVE: We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates. METHODS: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. RESULTS: Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did not reach significance. INTERPRETATION: Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685