Diagnostic accuracy of ultrasonography in acute lateral ankle ligament injury: A systematic review and meta-analysis.

BACKGROUND: The gold standard diagnostic method for acute lateral ankle ligament sprain is magnetic resonance imaging (MRI). However, it is hardly accessible and is time-consuming. Therefore, additional diagnostic methods are warranted. Point-of-care ultrasound, on the other hand, is inexpensive, widely available, time-efficient testing method. PURPOSE: Therefore, the aim of this meta-analysis is to determine the diagnostic accuracy of ultrasound for acute ankle ligament injuries compared to MRI. METHODS: In our systematic review and meta-analysis, we followed the recommendations of the Cochrane Handbook. We searched the following databases from inception to March 31, 2022: Medline (PubMed), EMBASE, and Cochrane Library. Eligible studies investigated the diagnostic accuracy of US compared to MRI for diagnosing acute lateral ankle ligament injuries. Finally, we calculated pooled sensitivity and specificity with a 95 % confidence interval (CI). RESULTS: Eight studies met our eligibility criteria, involving 434 patients. For anterior tibiofibular ligament (ATFL) injury, the summary sensitivity and specificity were Se = 0.97 (CI: 0.89-0.99) and Sp = 0.93 (CI: 0.84-0.97). For calcaneofibular ligament (CFL) injury, the summary sensitivity and specificity were Se.: Se = 0.81 (CI: 0.58-0.93) and Sp = 0.92 [0,81;0,97]. In addition, subgroup analysis based on US performed by different types of investigators was comparable between each other (radiologist group Se = 0.98, CI: 0.24-1, and Sp = 0.91, CI: 0.74-0.97, and the orthopedic/ emergency department group Se = 0.96, CI: 0-1, and Sp = 0.97, CI: 0-1). CONCLUSION: Ultrasound showed high diagnostic accuracy for acute lateral ankle ligament injury, irrespective of the investigator. Therefore, based on the current available data, it could be used in primary diagnostics of acute lateral ankle ligament injury.

A quick balance assessment tool for all clinical settings: validity and reliability of the Hungarian version of the activities-specific balance confidence scale.

BACKGROUND: The Activities-specific Balance Confidence Scale was developed for testing the balance confidence of elderly individuals, and it has been used extensively for evaluating various patients. No such scale has been adapted for the Hungarian population. OBJECTIVE: To translate and culturally adapt the Activities-specific Balance Confidence Scale and test the reliability and validity of the Hungarian version. METHODS: The study included 167 independently mobile subjects, of whom 39 filled in the questionnaire twice, 1 week apart. Beaton's six-step principle was applied for cross-cultural adaptation. Reliability was assessed by internal consistency measured by Cronbach's alpha and through test-retest analysis. Types of validity evaluated were concurrent validity using the Berg Balance Scale and cross-cultural validity. RESULTS: Excellent internal consistency was shown by Cronbach's alpha = 0.977. Test-retest analysis resulted in an Intra-Class Correlation Coefficient of 0.962 (0.865-0.961, 95% CI, p < .001) for the whole test; no floor or ceiling effects were found. The convergent validity of the scale was tested by Spearman's rank correlation analysis using the Berg Balance scale for external validation and showed a strong positive correlation (Rho = 0.755, p < .001). Receiver Operating Characteristic curve analysis showed an Area Under the Curve of 0.821 (CI 95% 0.75, 0.892). Mean detectable change based on the 95% confidence interval was 10.49% on the scale ranging from 0 to 100%. CONCLUSIONS: The Hungarian version of the Activities-Specific Balance Confidence Scale provides a valid and reliable picture of the patients' self-assessed balance. It is recommended both for clinicians and for clinical studies.

A Strep-Tag Imprinted Polymer Platform for Heterogenous Bio(electro)catalysis.

Molecularly imprinted polymers (MIPs) are artificial receptors equipped with selective recognition sites for target molecules. One of the most promising strategies for protein MIPs relies on the exploitation of short surface-exposed protein fragments, termed epitopes, as templates to imprint binding sites in a polymer scaffold for a desired protein. However, the lack of high-resolution structural data of flexible surface-exposed regions challenges the selection of suitable epitopes. Here, we addressed this drawback by developing a polyscopoletin-based MIP that recognizes recombinant proteins via imprinting of the widely used Strep-tag II affinity peptide (Strep-MIP). Electrochemistry, surface-sensitive IR spectroscopy, and molecular dynamics simulations were employed to ensure an utmost control of the Strep-MIP electrosynthesis. The functionality of this novel platform was verified with two Strep-tagged enzymes: an O2-tolerant [NiFe]-hydrogenase, and an alkaline phosphatase. The enzymes preserved their biocatalytic activities after multiple utilization confirming the efficiency of Strep-MIP as a general biocompatible platform to confine recombinant proteins for exploitation in biotechnology.

p.L1795F LRRK2 variant is a common cause of Parkinson's disease in Central Europe.

Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson's disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research.

No Evidence for the Superiority of 3-T Magnetic Resonance Imaging Over 1.5-T Magnetic Resonance Imaging for Diagnosing Wrist Ligamentous Lesions: A Systematic Review and Meta-analysis.

PURPOSE: To determine the diagnostic accuracy of native magnetic resonance imaging (MRI) regarding different ligamentous lesions of the wrist and to analyze the influence of technical characteristics, such as field strength, application of fat saturation, 3-dimensional sequences, and wrist coils. METHODS: A systematic search was performed using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Studies that were published before February 12, 2024, were included. All studies comparing the diagnostic accuracy of native wrist MRI with that of wrist arthroscopy for suspected ligamentous lesions were included. Results were analyzed by anatomic localization and technical aspects of the MRI. To assess the quality of included studies, we used the revised Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: The systematic search revealed 5,181 articles. Thirty-seven studies, reporting 3,893 ligamentous lesions, were eligible for inclusion. The studies displayed heterogeneity in terms of technical conditions, such as field strength, the use of wrist coils, the application of 3-dimensional sequences, and fat saturation. Research methods also varied. Overall sensitivity and specificity were 0.78 (0.66-0.86) and 0.81 (0.70-0.89) for 1.5-T MRI, whereas sensitivity was 0.73 (0.68-0.78) and specificity was 0.90 (0.59-0.98) for 3-T MRI. There was no significant difference between the 2 subgroups (P = .3807 and P = .4248). Sensitivity was 0.82 (0.75-0.87) for triangular fibrocartilage complex lesions, 0.63 (0.50-0.74) for scapholunate ligament tears, and 0.41 (0.25-0.60) for lunotriquetral ligament lesions. Specificity for triangular fibrocartilage complex lesions was 0.82 (0.73-0.89), for scapholunate ligament tears was 0.86 (0.73-0.93), and for lunotriquetral ligament lesions was 0.93 (0.81-0.98). CONCLUSIONS: The sensitivity and specificity of MRI are influenced by the anatomic location of the lesion and technical conditions. In terms of diagnostic accuracy, no significant difference was found between 1.5-T and 3-T MRI. LEVEL OF EVIDENCE: Level III, systematic review of Level II-III studies.

Specific features of epitope-MIPs and whole-protein MIPs as illustrated for AFP and RBD of SARS-CoV-2.

Molecularly imprinted polymer (MIP) nanofilms for alpha-fetoprotein (AFP) and the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 using either a peptide (epitope-MIP) or the whole protein (protein-MIP) as the template were prepared by electropolymerization of scopoletin. Conducting atomic force microscopy revealed after template removal and electrochemical deposition of gold a larger surface density of imprinted cavities for the epitope-imprinted polymers than when using the whole protein as template. However, comparable affinities towards the respective target protein (AFP and RBD) were obtained for both types of MIPs as expressed by the KD values in the lower nanomolar range. On the other hand, while the cross reactivity of both protein-MIPs towards human serum albumin (HSA) amounts to around 50% in the saturation region, the nonspecific binding to the respective epitope-MIPs is as low as that for the non-imprinted polymer (NIP). This effect might be caused by the different sizes of the imprinted cavities. Thus, in addition to the lower costs the reduced nonspecific binding is an advantage of epitope-imprinted polymers for the recognition of proteins.

Hyaluronate Acid Plus Platelet-Rich Plasma Is Superior to Steroids for Pain Relief Less Than 6 Months Using Injection Therapy of Partial Rotator Cuff Tears: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of steroid injections to other injectable therapies in partial-thickness rotator cuff (RC) tears. METHODS: A systematic literature search was performed until October 25, 2021, in 3 databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE). Eligible studies compared the efficacy of steroid, hyaluronic acid (HA), platelet-rich plasma (PRP), the combination of HA and PRP (HA + PRP), and adipose-derived regenerative cells in RC tears. The primary outcomes were the visual analog scale (VAS), Constant-Murley Shoulder Outcome Score (CMS) and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form. Using paired and network meta-analysis, we calculated pooled mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: We included a total of 7 articles in the quantitative synthesis. In shorter periods, the HA + PRP combination was superior to the other substances we investigated (HA + PRP: VAS [0-4 weeks]: MD: -0.99 [95% CI, -1.62 to -0.36]; CMS [0-3 months]: 20.56 [95% CI, 16.18 to 24.94]. This combination was followed by the use of HA or PRP alone, depending on the duration of follow-up and the outcome being studied. In our study, short-term results suggest that saline is superior to steroids for partial tears, but this trend is reversed at 6-month follow-up. CONCLUSIONS: The HA and PRP combination is currently the most effective in partial RC tear treatment in the short term. After 6 months, there is no meaningful difference, so the benefits of the combination are short term. LEVEL OF EVIDENCE: Level II, including Level I to II studies.

Nonoperative Treatment as an Option for Isolated Anterior Cruciate Ligament Injury: A Systematic Review and Meta-analysis.

Background: An anterior cruciate ligament (ACL) tear is a risk factor for early osteoarthritis (OA) onset. Generally, ACL reconstruction (ACLR) is associated with better outcomes. However, there is a lack of evidence regarding the effect of operative versus nonoperative treatment for preventing premature knee OA in isolated ACL tears while achieving good functional outcomes. Purpose/Hypothesis: The purpose of the study was to compare the outcomes of ACLR to primarily nonoperative management of isolated ACL tears. It was hypothesized that the outcomes between treatment types would be similar. Study Design: Systematic review; Level of evidence, 3. Methods: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registration No. CRD42021285901) and was conducted according to the Cochrane Handbook guidelines. We systematically searched for randomized and nonrandomized studies that compared ACLR with nonoperative treatments in isolated ACL tears in 3 databases until October 25, 2021. The risk of bias and quality of evidence of the included studies was assessed in accordance with the Cochrane guidelines. The primary outcome was radiologic signs of OA, and the secondary outcomes were functional parameters. Using the common effects model, we calculated pooled mean differences (MDs) and odds ratios (ORs) with 95% CIs. Results: Five studies-2 randomized controlled trials (RCTs) and 3 retrospective non-RCTs-were included. There was a moderate risk of bias in 2 studies and a serious risk of bias in 1 study. The quality of evidence was rated low because of the higher risk of bias and inconsistency. Nonoperatively treated knees showed a trend toward lower odds of developing radiological signs of OA (OR, 1.84 [95% CI, 0.90 to 3.75]); however, surgically reconstructed knees had significantly better stability (MD, -2.44 [95% CI, -3.21 to -1.66 ]) and a trend toward better but clinically not meaningful Lysholm scores (MD, 2.88 [95% CI, -1.09 to 6.85]). The qualitative synthesis showed that surgical reconstruction was protective against subsequent injuries but not superior when returning to previous activity levels or various functional tests. Conclusion: Findings indicated that there is no certain evidence that ACLR for an isolated ACL tear is superior to nonoperative treatment. Clinicians should consider nonoperative treatments with a well-designed rehabilitative program as a primary option. However, these findings must be interpreted with caution because of low study quality and high risk of bias.

Dyskinesia and Pain in Advanced Parkinson's Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study.

INTRODUCTION: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD. METHODS: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60). RESULTS: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001). CONCLUSIONS: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02799381.

A generic approach based on long-lifetime fluorophores for the assessment of protein binding to polymer nanoparticles by fluorescence anisotropy.

Quantitation of protein-nanoparticle interactions is essential for the investigation of the protein corona around NPs in vivo and when using synthetic polymer nanoparticles as affinity reagents for selective protein recognition in vitro. Here, a method based on steady-state fluorescence anisotropy measurement is presented as a novel, separation-free tool for the assessment of protein-nanoparticle interactions. For this purpose, a long-lifetime luminescent Ru-complex is used for protein labelling, which exhibits low anisotropy when conjugated to the protein but displays high anisotropy when the proteins are bound to the much larger polymer nanoparticles. As a proof of concept, the interaction of lysozyme with poly(N-isopropylacrylamide-co-N-tert-butylacrylamide-co-acrylic acid) nanoparticles is studied, and fluorescence anisotropy measurements are used to establish the binding kinetics, binding isotherm and a competitive binding assay.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes.

Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

Gray Matter Changes Following Mild COVID-19: An MR Morphometric Study in Healthy Young People.

BACKGROUND: Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings. PURPOSE: To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination. STUDY TYPE: Prospective. POPULATION: Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23). FIELD STRENGTH/SEQUENCE: Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo. ASSESSMENT: MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance. RESULTS: In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3 , η2 p = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3 , η2 p = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2 = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2 = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p = 0.112). DATA CONCLUSION: Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Are Parkinson's disease patients referred too late for device-aided therapies and how can better informed and earlier referrals be encouraged?

In the advanced Parkinson's disease, motor and non-motor symptoms become more severe and more difficult to treat. Oral therapy may become insufficient in controlling a patient´s motor complications, which results in a substantial deterioration of the patient's quality of life, ability to work and self-reliance. This is when device-aided treatments should be considered and offered, if suitable for a given patient. They include subcutaneous and intestinal infusion therapies, deep brain stimulation and, more recently, MRI-guided focussed ultrasound. Device-aided treatments should be offered in accordance with guidelines and treatment standardization. Also there is a need to ensure availability of treatment and education of patients and physicians.

SARS-CoV-2 virus-like-particles via liposomal reconstitution of spike glycoproteins.

The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using its spike glycoprotein through an angiotensin converting enzyme 2 (ACE-2) receptor-mediated pathway. Recent research suggests that spatial distributions of the spike protein may influence viral interactions with target cells and immune systems. The goal of this study has been to develop a liposome-based virus-like particle (VLP) by reconstituting the SARS-CoV-2 spike glycoprotein within a synthetic nanoparticle membrane, aiming to eventually establish tunability in spike protein presentation on the nanoparticle surface. Here we report on first steps to this goal, wherein liposomal SARS-CoV-2 VLPs were successfully produced via detergent mediated spike protein reconstitution. The resultant VLPs are shown to successfully co-localize in vitro with the ACE-2 receptor on lung epithelial cell surfaces, followed by internalization into these cells. These VLPs are the first step toward the overall goal of this research which is to form an understanding of the relationship between spike protein surface density and cell-level immune response, eventually toward creating better vaccines and anti-viral therapeutics.

White matter hyperintensities associated with impulse control disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are increasingly recognized as clinically significant non-motor features that potentially impair the quality of life. White matter hyperintensities (WMHs), detected by magnetic resonance imaging, are frequently observed in PD and can be associated with both motor- and certain non-motor symptoms. Given the limited number of non-motor features studied in this context, our aim was to reveal the potential association between the severity of WMHs and ICDs in PD. Fluid-attenuated inversion recovery magnetic resonance images were retrospectively evaluated in 70 patients with PD (48 males; 59.3 ± 10.1 years). The severity of WMHs was assessed by Fazekas scores and by the volume and number of supratentorial WMHs. ICDs were evaluated using the modified Minnesota Impulsive Disorders Interview. Significant interaction between age and the severity of WMHs was present for ICDs. In our younger patients (< 60.5 years), severity of WMHs was positively associated with ICDs (p = 0.004, p = 0.021, p < 0.001 and p < 0.001, respectively for periventricular white matter and total Fazekas scores and the volume and number of WMHs). Our study supports the hypothesis that WMHs of presumed vascular origin may contribute to ICDs in PD. Future prospective studies are needed to assess the prognostic relevance of this finding.

Levodopa Carbidopa Intestinal Gel in Advanced Parkinson's Disease: DUOGLOBE Final 3-Year Results.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD). OBJECTIVE: To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713). METHODS: DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported "Off" time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs). RESULTS: Significant improvements in "Off" time were maintained over 3 years (mean [SD]: -3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (-5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (-14.3 [40.5]; p = 0.002), Parkinson's Disease Sleep Scale-2 (-5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (-1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson's Disease Questionnaire Summary Index, -6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, -2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study. CONCLUSION: DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG.

Validation of the Rainbow Model of Integrated Care Measurement Tool in Parkinson's Disease.

BACKGROUND: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. OBJECTIVE: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC-MT, provider version) for healthcare professionals involved in PD care. METHODS: A cross-sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC-MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. RESULTS: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community-centeredness, person-centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness-of-fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. CONCLUSIONS: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC-MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Systematic Review and Consensus by the Ataxia Global Initiative Working Group on Digital-motor Biomarkers.

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias.