Clinical classification systems and long-term outcome in mid- and late-stage Parkinson's disease.
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ABSTRACT:
SUBMITTER: Ygland Rodstrom E
PROVIDER: S-EPMC8329298 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Safinamide is a novel ?-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline.This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients.Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test.For the overall treated population (with or without baseline dyskinesia), safinamide 100?mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p?=?0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p?=?0.0153) in patients with or without changes in levodopa dose, and nearly significant (p?=?0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions.While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation.
| S-EPMC4923744 | biostudies-literature
Project description:Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can predict future long-term reading gains in dyslexia. No behavioral measure, including widely used and standardized reading and language tests, reliably predicted future reading gains in dyslexia. Greater right prefrontal activation during a reading task that demanded phonological awareness and right superior longitudinal fasciculus (including arcuate fasciculus) white-matter organization significantly predicted future reading gains in dyslexia. Multivariate pattern analysis (MVPA) of these two brain measures, using linear support vector machine (SVM) and cross-validation, predicted significantly above chance (72% accuracy) which particular child would or would not improve reading skills (behavioral measures were at chance). MVPA of whole-brain activation pattern during phonological processing predicted which children with dyslexia would improve reading skills 2.5 y later with >90% accuracy. These findings identify right prefrontal brain mechanisms that may be critical for reading improvement in dyslexia and that may differ from typical reading development. Brain measures that predict future behavioral outcomes (neuroprognosis) may be more accurate, in some cases, than available behavioral measures.
| S-EPMC3017159 | biostudies-literature
Project description:PurposeTo report mid- to long-term clinical and radiological outcomes after microfracturing for symptomatic chondral defects of the glenohumeral joint.MethodsAll patients who underwent glenohumeral arthroscopic microfracturing between 2002 and 2012 at a single center were considered for inclusion in this retrospective study. Clinical outcome was evaluated using the Constant Score, Oxford Shoulder Score, and Subjective Shoulder Value. Progression of joint space narrowing, sclerosis, marginal osteophytes, and presence of cysts over time were assessed using 4 different radiological grading systems.ResultsA total of 16 patients (n = 9 female, n = 7 male) with a mean age of 51.8 ± 12.6 years at the time of surgery and a mean follow-up of 122 ± 51.2 months (range, 61-204 months) were included in this retrospective study. Nine patients (56.3%) showed an isolated chondral defect, while 7 patients (43.8%) had concomitant pathologies. Constant Score (60.3 ± 12.7 vs. 85.9 ± 9.3; P < .001), Oxford Shoulder Score (29.0 ± 5.8 vs. 42.4 ± 4.5; P < .001), and Subjective Shoulder Value (23.9 ± 7.4 vs. 84.3 ± 10.9; P < .001) changed significantly from pre- to postoperative. The majority of patients (88%) were able to return to their preoperative level of activity. Three patients (19.8%) developed radiological signs of progressive glenohumeral degeneration during the study period. However, only 1 patient (6.25%) showed a progression of arthritic changes of more than 1 grade according to radiographic classifications. Two patients (12.5%) underwent revision surgery to a hemi shoulder arthroplasty during the study period at 12 and 36 months after the initial procedure.ConclusionsGlenohumeral microfracturing is commonly performed together with other procedures, but seems to be a feasible treatment option for contained cartilage lesions in active patients reproducibly yielding good mid- to long-term outcome.Level of evidenceLevel IV, therapeutic case series.
| S-EPMC7451850 | biostudies-literature
Project description:The form of hereditary childhood blindness Leber congenital amaurosis (LCA) caused by biallelic RPE65 mutations is considered treatable with a gene therapy product approved in the US and Europe. The resulting vision improvement is well accepted, but long-term outcomes on the natural history of retinal degeneration are controversial. We treated four RPE65-mutant dogs in mid-life (age = 5-6 years) and followed them long-term (4-5 years). At the time of the intervention at mid-life, there were intra-ocular and inter-animal differences in local photoreceptor layer health ranging from near normal to complete degeneration. Treated locations having more than 63% of normal photoreceptors showed robust treatment-related retention of photoreceptors in the long term. Treated regions with less retained photoreceptors at the time of the intervention showed progressive degeneration similar to untreated regions with matched initial stage of disease. Unexpectedly, both treated and untreated regions in study eyes tended to show less degeneration compared to matched locations in untreated control eyes. These results support the hypothesis that successful long-term arrest of progression with RPE65 gene therapy may only occur in retinal regions with relatively retained photoreceptors at the time of the intervention, and there may be heretofore unknown mechanisms causing long-distance partial treatment effects beyond the region of subretinal injection.
| S-EPMC6951840 | biostudies-literature
Project description:Improved knowledge of long-term social and environmental trends and their drivers in coupled human and natural systems is needed to guide nature and society along a more sustainable trajectory. Here we combine common property theory and experimental impact evaluation methods to develop an approach for analyzing long-term outcome trajectories in social-ecological systems (SESs). We constructed robust counterfactual scenarios for observed vegetation outcome trajectories in the Indian Himalaya using synthetic control matching. This approach enabled us to quantify the contribution of a set of biophysical and socioeconomic factors in shaping observed outcomes. Results show the relative importance of baseline vegetation condition, governance, and demographic change in predicting long-term ecological outcomes. More generally, the findings suggest the broad potential utility of our approach to analyze long-term outcome trajectories, target new policy interventions, and assess the impacts of policies on sustainability goals in SESs across the globe.
| S-EPMC6464167 | biostudies-literature
Project description:The management of patients with subaxial cervical injuries lacks consensus, particularly in regard to the decision which surgical approach or combination of approaches to use and which approach yields the best clinical outcome in the distinct injury. The trauma literature is replete with reports of surgical techniques, complications and gross outcome assessment in heterogeneous samples. However, data on functional and clinical outcome using validated outcome measures are scanty. Therefore, the authors performed a study on plated anterior cervical decompression and fusion for unstable subaxial injuries with focus on clinical outcome. For the purpose of a strongly homogenous subgroup of patients with subaxial injuries without spinal cord injuries, robust criteria were applied that were fulfilled by 28 patients out of an original series of 131 subaxial injuries. Twenty-six patients subjected to 1- and 2-level fusions without having spinal cord injury could be surveyed after a mean of 5.5 years (range 16-128 months). The cervical spine injury severity score averaged 9.6. Cross-sectional outcome assessment included validated outcome measures (Neck pain disability index, Cervical Spine Outcome Questionnaire, SF-36), the investigation of construct failure and successful surgical outcome were defined by strict criteria, the reconstruction and maintenance of local and total cervical lordosis, adjacent-segment degeneration and intervertebral motion, and the fusion-rate using an interobserver assessment. Self-rated clinical outcome was excellent or good in 81% of patients and moderate or poor in 19% that corresponded to the results of the validated outcome measures. Results of the NPDI averaged 12.4 +/- 12.7% (0-40). With the SF-36 mean physical and mental component summary scores were 47.0 +/- 9.8 (18.2-59.3) and 52.2 +/- 12.4 (14.6-75.3), respectively. Using merely non-constrained plates, construct failure was observed in 31% of cases and loss of local lordosis, expressed as a mean injury angle of 14 degrees, postoperative angle of -5.5 degrees and follow-up angle of -1 degree, was significant. However, total cervical lordosis was within the limits of normalcy (-24.3 degrees +/- 13.3) and fusion-rate was 88.5%. The progression of adjacent-level degeneration was shown to be significantly influenced by a decreased plate-to-disc-distance. Adjacent-level intervertebral motion was not altered due to the adjacent fusion, but reduced in the presence of advanced adjacent-level degeneration. Patients were more likely to maintain a high satisfaction level if they succeeded to maintain segmental lordosis (<0 degree), had a solid fusion, an increased plate-to-disc distance, and if they were judged to have a successful surgical outcome that included the absence of construct failure and reconstruction of lordosis within +/-1 SD of normalcy. Using validated outcome vehicles the interdependencies between radiographical, functional and clinical outcome parameters could be substantiated with statistically significant correlations. The use of validated outcome vehicles in a subgroup of patients with plated anterior cervical fusions for subaxial injuries is recommended. With future studies, it enables objective comparison of surgical techniques and related radiographical, functional and clinical outcome.
| S-EPMC3233996 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-31 | GSE126025 | GEO
Project description:ObjectiveTo assess clinical outcomes in patients that underwent open single-stage complex abdominal wall reconstruction (CAWR) with biosynthetic mesh.MethodsRetrospective observational study of two prospectively registered series of consecutive patients undergoing CAWR with either long-term degradable (LTD) Phasix™ or mid-term degradable (MTD) BIO-A® biosynthetic mesh in a single institution between June 2016 and December 2019.ResultsFrom 169 patients with CAWR, 70 consecutive patients were identified who underwent CAWR with either LTD or MTD biosynthetic mesh. More than 85% of patients had an incisional hernia that could be classified as moderately complex to major complex due to a previous wound infection (67%), one or more complicating comorbidities (87.1%), one or more complicating hernia characteristics (75.7%) or contaminated or dirty defects (37.1%). Concomitant component separation was performed in 43 of 70 patients (61.4%). Overall surgical site infection (SSI) rate in these CAWR patients was 45.7%. Seventeen of 70 patients (24.3%) had computed tomography (CT) - and culture-confirmed SSI in direct contact of mesh, suspicious of mesh infection. Mesh removal for persistent local infection occurred in 10% (7 of 70) after a median of 229 days since surgery. Salvage rate of mesh after direct contact with infection was 58.8%. All removed meshes were in the LTD group. Seven patients (10%) had a recurrence; four patients in the LTD group (10%) had a recurrence at a median follow-up of 35 months and three patients in the MTD group (10%) at a median follow-up of 11 months. Three of the seven recurrences occurred in patients with SSI in persistent and direct contact with mesh.ConclusionsComorbid patients undergoing open complex abdominal wall reconstruction are at high risk of postoperative wound complications regardless of which type of biosynthetic mesh is used. When in persistent and direct contact with infection, long-term biodegradable biosynthetic meshes may need to be removed, whereas mid-term biodegradable biosynthetic meshes can be salvaged.
| S-EPMC8182350 | biostudies-literature
Project description:ObjectivesTo describe and compare the medium to long-term effectiveness of hydrodilatation and post-hydrodilatation physiotherapy in patients with primary and secondary glenohumeral joint contracture associated with rotator cuff pathology.MethodsPatients with primary and secondary glenohumeral contractures associated with rotator cuff pathology were recruited into a 2-year study. They all underwent hydrodilatation, followed by a structured physiotherapy programme. Patients were assessed at baseline, 3 days, 1 week, 3 months, 1 year and 2 years after hydrodilatation with primary outcome measures (Shoulder Pain and Disability Index, Shoulder Disability Index and percentage rating of "normal" function; SD%) and secondary outcome measures (range of shoulder abduction, external rotation and hand behind back). Comparisons in recovery were made between the primary and secondary glenohumeral contracture groups at all timeframes and for all outcome measures.ResultsA total of 53 patients (23 with primary and 30 with secondary glenohumeral contractures) were recruited into the study. At the 2-year follow-up, 12 patients dropped out from the study. At baseline, the two contracture groups were similar with respect to their demographic and physical characteristics. The two groups of patients recovered in a similar fashion over the 2-year follow-up period. A significant improvement was observed in all outcomes measures over this period (p<0.01), so that both function and range of movement increased. The rate of improvement was dependent on the outcome measure that was used.ConclusionsHydrodilatation and physiotherapy increase shoulder motion in individuals with primary and secondary glenohumeral joint contracture associated with rotator cuff pathology. This benefit continues to improve or is maintained in the long term, up to 2 years after hydrodilatation.
| S-EPMC2465214 | biostudies-literature
Project description:BackgroundLevodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD).ObjectiveTo identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients.MethodsPD patients were assessed for clinical and therapeutic variables, before LCIG treatment (T0) and at last outpatient visit (T1). Sub-groups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment.ResultsWe included 53 PD patients. After a mean of 51.7 ± 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at T1 (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at T1 (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at T1 (sum of the items 32 and 33: P = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration.ConclusionDyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients.
| S-EPMC7604637 | biostudies-literature