Long-Term Care Resident Awareness and Interest in Spasticity Treatments.

Spasticity is common in long-term care settings (affecting up to one in three residents), yet it remains under-treated despite safe and effective, Food and Drug Administration (FDA)-approved therapies. One barrier to treatment may be lack of awareness of available therapies for long-term care residents living with spasticity. A standardized spasticity treatment awareness and interest interview was conducted with 18 nursing home residents and 11 veterans' home residents in this cross-sectional study. Veterans' home residents were also asked about potential barriers to receiving spasticity treatment. Many residents across both long-term care facilities were unaware of most of the treatment options for spasticity. Participants were most aware of physical/occupational therapy (83%, 95% CI: 65-93%) and least aware of intrathecal baclofen (21%, 95% CI: 9-39%). After learning about treatments, only 7% of participants (95% CI: 0-23%) were not interested in receiving any form of spasticity treatment. Among residents previously unaware of spasticity treatments, at least one quarter became interested in receiving treatment and at least one-fifth indicated possibly being interested in the treatment after learning about it. Potential barriers to receiving treatment included traveling to see a doctor and limited knowledge of insurance coverage of spasticity treatments. These results suggest that patient-centered approaches, including education and discerning patient preferences, may improve spasticity treatment in long-term care settings.

Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes.

OBJECTIVE: To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial. METHODS: The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models. RESULTS: Early STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, ß = -240 mg, 95% confidence interval [CI] -471 to -8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups. CONCLUSIONS: These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

Recruitment and Retention in Clinical Trials of Deep Brain Stimulation in Early-Stage Parkinson's Disease: Past Experiences and Future Considerations.

BACKGROUND: Clinical trials are often hindered by inadequate patient recruitment. Overly optimistic investigator predictions of participation can lead to unmet recruitment goals and costly trial extensions. A patient-focused approach estimating recruitment in clinical trials may provide higher accuracy. OBJECTIVE: To assess the feasibility of recruitment in a future deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) multicenter trial by understanding motivations and concerns to participation of past and potential future DBS in early-stage PD clinical trial subjects. METHODS: To identify motivating factors and barriers influencing trial participation, an end-of-trial survey was administered to subjects enrolled in a DBS in early-stage PD pilot trial with subjects randomized to receive DBS plus optimal drug therapy (DBS+ODT) or ODT alone (NCT#00282152, IDE#G050016). Pilot trial survey results were analyzed in conjunction with results of a previously-reported survey querying PD patients about potential participation in a trial for DBS in early-stage PD with similar inclusion/exclusion criteria. RESULTS: Pilot trial subjects reported high levels of satisfaction with their participation in the study. Similar motivations and barriers to participation were expressed in comparable proportions by subjects who successfully completed the pilot trial and patients with early-stage PD considering enrollment in a comparable DBS study. CONCLUSIONS: The FDA has approved a prospective, randomized, double-blind, phase III, multicenter, pivotal clinical trial evaluating DBS in early-stage PD (IDE#G050016). These results suggest that the successful recruitment and retention of early-stage PD subjects, as observed in the pilot trial, is attainable in a future pivotal trial.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

OBJECTIVE: To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. METHODS: The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. RESULTS: UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001). CONCLUSIONS: These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT (n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p > 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson's disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). OBJECTIVE: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. METHODS: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. RESULTS: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04-0.97). CONCLUSIONS: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD.