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BackgroundPain is a troublesome non-motor symptom of Parkinson’s disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance.MethodsPD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting ‘any’ pain (pain score ≥1) at baseline, and subgroups reporting ‘mild’ (score 1–3), and ‘moderate-to-severe’ pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory.ResultsOf 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported ‘any’ pain; of these 87 (33%) reported ‘mild’, and 100 (37%) ‘moderate-to-severe’ pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with ‘any’ pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with ‘moderate-to-severe’ pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders.ConclusionsThe results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings.

Background: Inhaled formulations using extrafine particles of long-acting β₂-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. Objectives: This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Methods: Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster®; Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). Results: After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Conclusions: Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment.

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Background: RECOVER (NCT00474058), a double-blind, placebo-controlled trial in patients with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control, demonstrated significant improvements with rotigotine in early-morning motor function (Unified Parkinson's Disease Rating Scale [UPDRS] III), and nocturnal sleep disturbances (modified Parkinson's Disease Sleep Scale [PDSS-2]), and improvements in nonmotor symptoms (NMS; Non-Motor Symptom Scale [NMSS]). Methods: Post hoc analyses investigated the correlation between motor symptom and NMS severity in PD by evaluating associations between UPDRS III and both NMSS and PDSS-2 scores. Categories were defined for UPDRS III, NMSS, and PDSS-2 total scores; analyses were conducted for the full analysis set (n = 267). Results: There was a trend toward increasing PDSS-2 and NMSS total and domain scores with increasing UPDRS III category at baseline and end of maintenance (EoM). Pearson correlation coefficients between UPDRS III and both NMSS and PDSS-2 total and domain scores were r = 0.12-0.44 (r² = 0.01-0.19) at baseline, r = 0.05-0.38 (r² = 0.00-0.14) at EoM, and r = -0.02-0.36 (r² = 0.00-0.13) for change from baseline to EoM. Conclusion: There was only a small correlation between severity of early-morning motor symptoms and overall burden of NMS and nocturnal sleep disturbances in RECOVER, suggesting that motor symptoms and NMS originate, at least partly, from distinct pathophysiological pathways.