Intercountry comparisons of advanced Parkinson's disease symptoms and management: Analysis from the OBSERVE-PD observational study.

OBJECTIVES: In the absence of widely accepted criteria, determining when a patient with Parkinson's disease (PD) may benefit from more advanced treatments such as device-aided therapy (DAT) so far remains a matter of physician judgment. This analysis investigates how classification of PD varies across countries relative to measures of disease severity. MATERIALS AND METHODS: The OBSERVational, cross-sEctional PD (OBSERVE-PD) study included consecutive patients with PD at centers that offer DATs in 18 countries. In this subgroup analysis, we explore intercountry differences in identification of advanced versus non-advanced PD based on physician's clinical judgment, symptoms assessed using Delphi consensus criteria, use of DAT, motor and non-motor symptoms, and caregiver support. Demographic and clinical characteristics were obtained through review of medical records. RESULTS: Overall, 1342 of 2615 patients (51.3%) were assessed by physicians as having advanced PD. The proportion of patients in different countries identified as having advanced PD (24.4-82.2%) varied. In 15 of 18 countries, a greater proportion of patients with advanced PD, according to select Delphi criteria, were identified by physicians as having advanced PD than with non-advanced PD. There was a wide variability across countries in the proportion of patients with no dyskinesia, disabling dyskinesia, dyskinesia pain, and non-motor symptoms who were identified by physicians as having advanced versus non-advanced PD. CONCLUSIONS: The proportion of patients identified with advanced PD symptoms varies widely across countries, despite differences on the patients' profiles, indicating a need for objective diagnostic criteria to help identify patients who may benefit from DAT.

Concomitant Medication Usage with Levodopa-Carbidopa Intestinal Gel: Results from the COSMOS Study.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is administered directly to the small intestine of patients with advanced Parkinson's disease (APD) to help maintain stable plasma levodopa levels. OBJECTIVE: The objective of this study was to investigate the effect of LCIG in reducing polypharmacy for the treatment of APD. METHODS: The COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) is a large, real-world, multinational observational study investigating comedication use with LCIG. All enrolled patients had used LCIG for ≥12 months and data were collected cross-sectionally (study visit) and retrospectively. The primary endpoint was the percentage of patients using LCIG as monotherapy (without add-on PD medications) at initiation and at 3, 6, 9, and 12 months thereafter. RESULTS: Overall, 409 patients were enrolled from 14 countries and were treated with LCIG for a mean of 35.8 ± 23.2 months. A total of 15.2% of patients initiated LCIG as monotherapy and 31.7% were receiving monotherapy at 12 months after initiation. The mean duration of LCIG monotherapy was 39.3 ± 25.6 months. Use of add-on medications decreased over time with all LCIG regimens. From LCIG initiation to the patient visit, mean off time decreased by 3.8, 4.6, and 3.9 hours/day for LCIG monotherapy, LCIG daytime monotherapy, and LCIG polytherapy groups, respectively, while duration of dyskinesia decreased by 1.7, 2.0, and 1.9 hours/day, respectively. Adverse events likely related to study treatment occurred in 112 patients (27.4%) during LCIG treatment. CONCLUSIONS: LCIG is an effective long-term monotherapy option with a positive risk-benefit profile and contributes to reduced polypharmacy for patients with APD. © 2021 The AbbVie Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Characterizing advanced Parkinson's disease: OBSERVE-PD observational study results of 2615 patients.

BACKGROUND: There are currently no standard diagnostic criteria for characterizing advanced Parkinson's disease (APD) in clinical practice, a critical component in determining ongoing clinical care and therapeutic strategies, including transitioning to device-aided treatment. The goal of this analysis was to determine the proportion of APD vs. non-advanced PD (non-APD) patients attending specialist PD clinics and to demonstrate the clinical burden of APD. METHODS: OBSERVE-PD, a cross-sectional, international, observational study, was conducted with 2615 PD patients at 128 movement disorder centers in 18 countries. Motor and non-motor symptoms, activities of daily living, and quality-of-life end points were assessed. The correlation between physician's global assessment of advanced PD and the advanced PD criteria from a consensus of an international group of experts (Delphi criteria for APD) were evaluated. RESULTS: According to physician's judgment, 51% of patients were considered to have APD. There was a moderate correlation between physician's judgment and Delphi criteria for APD (K = 0.430; 95% CI 0.406-0.473). Activities of daily living, motor symptom severity, dyskinesia duration/disability, "Off" time duration, non-motor symptoms, and quality-of-life scores were worse among APD vs. non-APD patients (p < 0.0001 for all). APD patients (assessed by physicians) had higher disease burden by motor and non-motor symptoms compared with non-APD patients and a negative impact on activities of daily living and quality of life. CONCLUSIONS: These findings aid in identifying standard APD classification parameters for use in practicing physicians. Improvements in identification of APD patients may be particularly relevant for optimizing treatment strategies including transitioning to device-aided treatment.

Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: long-term results from COSMOS.

BACKGROUND: While immediate benefits of levodopa-carbidopa intestinal gel (LCIG) are evident in patients with Parkinson's disease (PD), long-term LCIG effects require further study. OBJECTIVES: We explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD). METHODS: Data were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1-2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety. RESULTS: Out of 387 patients, the number of patients per LCIG group was: > 1- ≤ 2 years LCIG (n = 156); > 2- ≤ 3 years LCIG (n = 80); > 3- ≤ 4 years LCIG (n = 61); > 4- ≤ 5 years LCIG (n = 30); > 5 years LCIG (n = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in "off" time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG. CONCLUSIONS: LCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.

Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum: Revelations from the MANAGE-PD validation cohort.

INTRODUCTION: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories. METHODS: Device-aided therapy-naïve patients receiving oral treatments were identified from the Adelphi Parkinson's Disease Programme. Patients were categorized (category 1 to 3) using MANAGE-PD. PD-specific QoL (PDQ-39), care partner burden (ZBI), satisfaction with current treatment, healthcare resource utilization, associated healthcare costs, and future treatment discussion with providers were measured. Categories were compared using ANOVA, t-test, chi square and adjusted regression analyses. RESULTS: Of the analytical sample (n = 2709), 18.9% were inadequately controlled on current therapy and potentially eligible for device-aided therapies (category 3). As expected, they had worse patient/caregiver reported outcomes versus patients in categories 1 or 2. However, the degree of difference in healthcare resource utilization, including: greater number of hospitalizations, emergency room (ER) visits and consultations, higher likelihood of being recipients of respite care, and greater PD treatment burden, was unexpected. Importantly, of patients in category 3 and their care partners, >40% did not report discussions with providers about device-aided therapies. CONCLUSION: MANAGE-PD category 3 patients had significantly higher burden on healthcare resources versus patients well-controlled with oral treatment or requiring only oral medication adjustments; yet almost half had no discussion on device-aided therapies with providers. Device-aided therapies may be considered in these patients.

Impact of advanced Parkinson's disease on caregivers: an international real-world study.

BACKGROUND: Caring for a partner or family member with Parkinson's disease (PD) negatively affects the caregiver's own physical and emotional well-being, especially those caring for people with advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status. METHODS: Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson's Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers). RESULTS: Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day). CONCLUSIONS: This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD. TRIAL REGISTRATION: N/A.

Motor and nonmotor symptoms in patients treated with 24-hour daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS).

INTRODUCTION: Patients with advanced Parkinson's disease (APD) commonly experience motor and nonmotor symptoms (NMS) associated with functional limitations and decreased quality of life. We compared motor and nonmotor outcomes in patients with APD receiving 24- versus 16-h levodopa-carbidopa intestinal gel (LCIG). METHODS: Data from COSMOS, a large, real-world, retrospective and cross-sectional, observational study on LCIG and comedication in APD were obtained from medical records and a single patient visit for patients receiving 24- and 16-h LCIG infusion. Changes from baseline were evaluated for motor symptoms, NMS, and clinical characteristics. Safety was also assessed. RESULTS: Data for 401 patients were included in this subanalysis. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. "Off" time and dyskinesia (duration and severity) were reduced in both groups. In both LCIG treatment groups, prevalence of most symptoms was reduced. There were significant differences in the change from baseline in severity and frequency of freezing of gait with 24-h LCIG versus 16-h LCIG (p = 0.011 and p = 0.038), severity of urinary symptoms (p = 0.006), and frequency of cognitive impairment (p = 0.014) with 24-h LCIG versus 16-h LCIG. Adverse events were similar for both treatment groups and considered tolerable. CONCLUSIONS: LCIG 24-h infusion may be a useful treatment option, when clinically justified, for select patients with APD. CLINICAL TRIAL NUMBER: NCT03362879.

The effect of scalable PDMS gas-entrapping microstructures on the dynamics of a single cavitation bubble.

The effect of gas-entrapping polydimethylsiloxane (PDMS) microstructures on the dynamics of cavitation bubbles laser-induced next to the PDMS surface is investigated and compared against the cavitation dynamics next to a flat smooth boundary. Local pressure gradients produced by a cavitation bubble cause the air pockets entrapped in the PDMS microstructures to expand and oscillate, leading to a repulsion of the cavitation bubble. The microstructures were fabricated as boxed crevices via a simple and scalable laser ablation technique on cast acrylic, allowing for testing of variable structure sizes and reusable molds. The bubble dynamics were observed using high speed photography and the surrounding flows were visualized and quantified using particle tracking velocimetry. Smaller entrapped air pockets showed an enhanced ability to withstand deactivation at three stand-off distances and over 50 subsequent cavitation events. This investigation provides insight into the potential to direct the collapse of a cavitation bubble away from a surface to mitigate erosion or to enhance microfluidic mixing in low Reynolds number flows.

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

INTRODUCTION: Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. RESULTS: A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. CONCLUSIONS: This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

Effects of Levodopa-Carbidopa Intestinal Gel on Dyskinesia and Non-Motor Symptoms Including Sleep: Results from a Meta-Analysis with 24-Month Follow-Up.

BACKGROUND: In advanced Parkinson's disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need. OBJECTIVE: To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. METHODS: A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model. RESULTS: Seventeen open-label studies evaluating 1243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (-1.10 [-1.69, -0.51] h/day) and 12 months (-1.35 [-2.07, -0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (-28.71 [-40.26, -17.15] points). Significant reduction of NMSS burden was maintained through 24 months (-17.61 [-21.52, -13.70] points). UPDRS I scores significantly improved at 3 months (-0.39 [-0.55, -0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies. CONCLUSION: Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.

Psychometric Properties of Clinical Indicators for Identification and Management of Advanced Parkinson's Disease: Real-World Evidence From G7 Countries.

INTRODUCTION: Standardized and validated criteria to define advanced Parkinson's disease (PD) or identify patient eligibility for device-aided therapy are needed. This study assessed the psychometric properties of clinical indicators of advanced PD and eligibility for device-aided therapy in a large population. METHODS: This retrospective analysis of the Adelphi Parkinson's Disease Specific Programme collected data from device-aided therapy-naïve people with PD in G7 countries. We assessed the presence of 15 clinical indicators of advancing PD and seven indicators of eligibility for device-aided therapy in patients classified with advanced PD or as eligible for device-aided therapy by the treating physician. Accuracy was assessed using area under the curve (AUC) and multivariable logistic regression models. Construct validity was examined via known-group comparisons of disease severity and burden among patients with and without each clinical indicator. RESULTS: Of 4714 PD patients, 14.9% were classified with advanced PD and 17.5% as eligible for device-aided therapy by physician judgment. The presence of each clinical indicator was 1.9- to 7.3-fold more likely in patients classified with advanced PD. Similarly, the presence of device-aided therapy eligibility indicators was 1.8- to 5.5-fold more likely in patients considered eligible for device-aided therapy. All indicators demonstrated high clinical screening accuracy for identifying advanced PD (AUC range 0.84-0.89) and patients eligible for device-aided therapy (AUC range 0.73-0.80). The Unified Parkinson's Disease Rating Scale (UPDRS) score, cognitive function, quality of life, and caregiver burden were significantly worse in indicator-positive patients. CONCLUSION: Specific clinical indicators of advanced PD and eligibility for device-aided therapy demonstrated excellent psychometric properties in a large sample, and thus may provide an objective and reliable approach for patient identification and treatment optimization.

Advanced Parkinson's disease (PD) refers to the stage of disease when motor complications are difficult to manage with standard therapy. Patients reaching this stage of the disease may benefit from a treatment change from pills to the so-called device-aided therapies. However, there is currently no unanimous definition of advanced PD, which makes it challenging to identify suitable candidates for device-aided therapies. There is urgent need to define specific features (or 'clinical indicators') to support healthcare professionals and patients in the identification of advanced PD as well as to define suitability for device-aided therapy. This study aimed to assess the accuracy of 15 clinical indicators and seven device-aided therapy eligibility criteria using information from a large database of 4714 patients in G7 countries. Physicians classified 14.9% of patients as having advanced PD and 17.5% were judged to be eligible for device-aided therapy. Each clinical indicator or device-aided therapy eligibility indicator was detected more frequently in patients classified as having advanced PD and in patients considered eligible for device-aided therapy, respectively. All indicators had high accuracy for identifying advanced PD and device-aided therapy-eligibility. These previously identified clinical indicators of advanced PD and device-aided therapy eligibility may provide an objective and reliable approach for patient screening and treatment optimization.

[Ophthalmic disease in diabetes mellitus: management from primary health care]. / Oftalmopatía en la diabetes mellitus: detección desde la Atención Primaria de salud.

OBJECTIVE: To study the feasibility of a basic ophthalmological examination for the eye disease in diabetic patients by Primary Health Care (PHC). PATIENTS AND METHODS: A multi-centre prospective study. A sample of 712 type 2 diabetics. INTERVENTIONS: Visual acuity examination, intraocular pressure measurement and the eye fundus photograph with a non-mydriatic camera taken by an optometrist. The interpretation and subsequent referral to an ophthalmology department by ophthalmologists and general practitioners (GP). RESULTS: Visual acuity deficiency: GP, 43.7%; ophthalmologist, 36.1%; concordance, 70%; glaucoma suspicion: GP, 8.8%; ophthalmologist, 7.6%; concordance, 94%; diabetic retinopathy: GP, 28.2%; ophthalmologist, 13.4%; concordance, 78%. Ophthalmology Department referral: GP, 56.8%; ophthalmologist, 41.3% (P=0.001). CONCLUSIONS: Agreement between GP and ophthalmologist leads to a reliable ophthalmological examination of the diabetic patient in PHC. Despite an over-diagnosis and 16% of non-justified referrals by the GP, Ophthalmology Department referral is avoided in almost half of the diabetic patients.

Advanced Parkinson's Disease Treatment Simplification and Long-Term Outcomes with Levodopa Carbidopa Intestinal Gel: COSMOS Romanian Subanalysis.

The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson's disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. "Off" time and "On" time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.

Patient and caregiver outcomes with levodopa-carbidopa intestinal gel in advanced Parkinson's disease.

Levodopa-carbidopa intestinal gel (LCIG) has shown to be efficacious in motor and non-motor symptoms (NMS). Nevertheless, studies with patient Quality of Life (QoL) as a primary endpoint are scarce. To assess the effect of LCIG on Advanced Parkinson's Disease (APD) patients QoL. Secondarily, the impact on motor symptoms and NMS, emotional well-being, treatment satisfaction, and caregiver QoL, stress, disease burden, anxiety, depression, and work impairment were also investigated. In this prospective, 6-month multicenter postmarketing observational study, LCIG was administered to 59 patients with APD. Endpoints were assessed using validated scales and questionnaires. LCIG significantly improved patient QoL (PDQ-39 mean change ± standard deviation from baseline, -12.8 ± 14.6; P < 0.0001), motor symptoms (UPDRS-III in "On," -6.5 ± 11.8; P = 0.0002), NMS (NMSS, -35.7 ± 31.1; P < 0.0001), mood (Norris/Bond-Lader VAS, -6.6 ± 21.1; P = 0.0297), fatigue (PFS-16, -0.6 ± 1.0; P = 0.0003), depression (BDI-II, -5.1 ± 9.4; P = 0.0002), anxiety (BAI, -6.2 ± 9.6; P < 0.0001), and patient treatment satisfaction (SATMED-Q, 16.1 ± 16.8; P < 0.0001). There were significant correlations between the change from baseline to 6 months between PDQ-39 and UPDRS-IV, NMSS, BAI, BDI-II, AS, and PFS-16 scores, and Norris/Bond-Lader alertness/sedation factor. Caregiver anxiety also improved (Goldberg anxiety scale, -1.1 ± 1.0; P = 0.0234), but the clinical relevance of this finding is questionable. The serious adverse events reported were similar to those previously described for LCIG. In patients with APD, LCIG improves QoL, motor symptoms and NMS, emotional well-being, and satisfaction with the treatment. Improvement in patient QoL is associated with improvements in motor complications, NMS, anxiety, depression, apathy and fatigue. Improvements in patients' QoL does not correspond with improvements in caregivers' QoL or burden.

Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications.

INTRODUCTION: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool. METHODS: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories. Validity and clinical value were elucidated using a two-pronged approach: (i) hypothetical patient vignettes (n = 10) developed based on the MANAGE-PD tool and rated by 17 PD specialists and 400 general neurologists (GN) and (ii) patients with PD (n = 2546) managed in real-world clinical settings. Vignette validity was based on concordance between PD experts' clinical judgement and MANAGE-PD vignette categorization. Patient-level data was used for known-group comparisons (validity) and discordant pair analysis (clinical value). RESULTS: The tool demonstrated strong validity and clinical value among PD specialists (intraclass coefficient [ICC] 0.843; Fleiss weighted kappa [ƙweighted] 0.79) and GN (ICC 0.690; ƙweighted 0.65) using patient vignettes. MANAGE-PD also demonstrated real-world validity and clinical value based on ability to identify patients with incrementally higher clinical, economic, and humanistic PD burden across categories of the tool (p < 0.01). CONCLUSIONS: MANAGE-PD demonstrated robust validity and clinical value in identifying patients with suboptimal PD symptom control. Clinical use of MANAGE-PD may complement treatment decision-making and facilitate timely and comprehensive management of patients with advancing PD.

Impact of Disease Duration in Effectiveness of Treatment with Levodopa-Carbidopa Intestinal Gel and Factors Leading to Discontinuation.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is effective in the treatment of advanced Parkinson's disease (PD). However, the patients' profile that might benefit from treatment with LCIG has not been characterized. OBJECTIVE: This retrospective study explored the influence of disease duration (DD) on the effectiveness of LCIG and identified factors associated with treatment discontinuation in a cohort of advanced PD patients. METHODS: Patients initiating LCIG therapy between Jan-2006 and Dec-2011 in 18 Spanish centers were included. Effectiveness in treating motor symptoms (MSs), non-motor symptoms (NMSs), and adverse events (AEs) occurrence was compared in DD≥10 or <10 years and LCIG continuation/discontinuation groups. Factors associated with LCIG discontinuation were evaluated using univariate and multivariate analyses. RESULTS: Overall, 177 PD patients were included (52.5% male; mean age 70.6±8.4 years; mean LCIG duration 35.6±18.6 months). Patients with DD≥10 years (n = 125) experienced less reduction in "off" time (-29%) than those with DD <10 years (-38%; n = 51; p = 0.021), and reported more severe AEs (32.8% vs. 17.6%; p = 0.043). DD did not significantly influence changes in NMSs or discontinuation rates. Fifty-four patients discontinued LCIG therapy, factors associated with discontinuation were higher percentages of waking day in the "off" state (OR, 1.028; 95% CI, 1.002-1.055; p = 0.0360) and in the "on" state with troublesome dyskinesia (OR, 1.032; 95% CI, 1.002-1.064; p = 0.0376) at baseline. CONCLUSIONS: Advanced PD patients with DD <10 years might benefit more from treatment with LCIG than patients with a longer DD. Although MSs severity at baseline was statistically associated with LCIG discontinuation, the probability was very low with little clinical significance.

Binocular vision alterations after refractive and cataract surgery: a review.

To review binocular and accommodative disorders documented after corneal or intraocular refractive surgery, in normal healthy prepresbyopic patients. A bibliographic revision was performed; it included works published before 1st July 2017 where accommodation and/or binocularity was assessed following any type of refractive surgical procedure. The search in Pubmed yielded 1273 papers, 95 of which fulfilled the inclusion criteria. Few publications reporting binocular vision and/or accommodative changes after refractive surgery in normal subjects were found. The reduction in fusional vergence is the most frequently reported alteration. Anisometropia is an important risk factor for postoperative binocular vision-related complaints. Most diplopia-related visual complaints, irrespective of the surgical procedure, were in fact misdiagnosed preoperative disorders. The preoperative evaluation of patients seeking spectacle/contact lens independence should include a complete binocular and accommodation assessment where parameters such as the phoric posture, accommodative amplitude and facility, near point of convergence, fusional reserves and accommodative convergence/accommodation coefficient are measured. This would allow the identification of risk factors that could compromise the success of the refractive surgery and cause clinical symptoms.

Spherical subjective refraction with a novel 3D virtual reality based system.

PURPOSE: To conduct a clinical validation of a virtual reality-based experimental system that is able to assess the spherical subjective refraction simplifying the methodology of ocular refraction. METHODS: For the agreement assessment, spherical refraction measurements were obtained from 104 eyes of 52 subjects using three different methods: subjectively with the experimental prototype (Subj.E) and the classical subjective refraction (Subj.C); and objectively with the WAM-5500 autorefractor (WAM). To evaluate precision (intra- and inter-observer variability) of each refractive tool independently, 26 eyes were measured in four occasions. RESULTS: With regard to agreement, the mean difference (±SD) for the spherical equivalent (M) between the new experimental subjective method (Subj.E) and the classical subjective refraction (Subj.C) was -0.034D (±0.454D). The corresponding 95% Limits of Agreement (LoA) were (-0.856D, 0.924D). In relation to precision, intra-observer mean difference for the M component was 0.034±0.195D for the Subj.C, 0.015±0.177D for the WAM and 0.072±0.197D for the Subj.E. Inter-observer variability showed worse precision values, although still clinically valid (below 0.25D) in all instruments. CONCLUSIONS: The spherical equivalent obtained with the new experimental system was precise and in good agreement with the classical subjective routine. The algorithm implemented in this new system and its optical configuration has been shown to be a first valid step for spherical error correction in a semiautomated way.

An Observational Study of the Effect of Levodopa-Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson's Disease Patients.

INTRODUCTION: Continuous delivery of levodopa-carbidopa intestinal gel (LCIG) by percutaneous endoscopic gastrojejunostomy (PEG-J) in advanced Parkinson's disease (PD) patients reduces variability in plasma levels, providing better control of motor fluctuations ("on" and "off" states). The MONOTREAT study assessed the effect of LCIG on activities of daily living, motor and non-motor symptoms, and quality of life in advanced PD patients. METHODS: This prospective, observational study included patients with advanced, levodopa-responsive PD with either 2-4 h of "off" time or 2 h of dyskinesia daily. Patients received LCIG via PEG-J for 16 h continuously. Effectiveness was assessed using Unified PD Rating Scale parts II and III, the Non-Motor Symptom Scale, and the PD Questionnaire-8. RESULTS: The mean (SD) treatment duration was 275 (157) days. Patients experienced significant improvement from baseline in activities of daily living at final visit (p < 0.05) as well as at months 3 and 6 (p < 0.0001). Patients also experienced significant improvements from baseline in quality of life and non-motor symptoms at all time points (p < 0.001 for all). Specifically, patients manifested significant improvements in mean change from baseline at every study visit in five of nine non-motor symptom score domains: sleep/fatigue, mood/cognition, gastrointestinal tract, urinary, and miscellaneous. One-third of patients (32.8%) experienced an adverse event; 21.9% experienced a serious adverse event; 11.1% discontinued because of an adverse event. CONCLUSION: This study demonstrated significant and clinically relevant improvements in measures of activities of daily living, quality of life, and a specific subset of non-motor symptoms after treatment with LCIG. FUNDING: AbbVie Inc.