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BACKGROUND: Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. METHODS: This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. RESULTS: In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change -7.0 [p = 0.012], -2.4 [p = 0.007] and - 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. CONCLUSION: Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. STUDY REGISTRATION: University Hospital Medical Information Network in Japan; study ID: UMIN000044341.
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Alanina , Antiparkinsonianos , Benzilaminas , Levodopa , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Masculino , Benzilaminas/uso terapêutico , Benzilaminas/efeitos adversos , Feminino , Idoso , Levodopa/uso terapêutico , Levodopa/efeitos adversos , Alanina/análogos & derivados , Alanina/uso terapêutico , Japão , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento , Quimioterapia Combinada , Idoso de 80 Anos ou mais , Índice de Gravidade de Doença , População do Leste AsiáticoRESUMO
Purpose: To report a case of cyclic esotropia successfully treated with prismatic correction. Observations: A 9-year-old girl presented with intermittent esotropia and diplopia occurring over the previous 4 months. The patient had 30 prism diopters (PD) of esotropia at both distance and near. Ocular motility testing, other ophthalmic examinations, and brain magnetic resonance imaging revealed no abnormalities. At the third visit, the patient had 6 PD of intermittent esotropia without diplopia, and the eye position diary demonstrated esotropia every other day, which led to a diagnosis of cyclic esotropia with a 48-h cycle. The cyclic pattern persisted for 9 months following the initial visit. However, during a subsequent regular visit, the patient reported a newfound ability to self-adjust from "esotropic" days to "straight" days by tightly closing the eyes immediately after waking up in the morning, particularly when wishing to avoid strabismus. To address the condition, we affixed a Fresnel membrane prism on the glasses to compensate for the latent deviation on a "straight" day. During the subsequent 18 months, the esotropia completely resolved, and the patient was followed up with gradual decreases in prism power. Conclusions and Importance: Correcting latent deviation using a prism lens is a simple approach without potential side effects. The present findings suggest that this approach is a viable treatment option for cyclic esotropia during its early and periodic stages.
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INTRODUCTION: A higher levodopa dose is a risk factor for motor complications in Parkinson's disease (PD). Istradefylline (IST) is used as adjunctive treatment to levodopa in PD patients with off episodes, but its impact on levodopa dose titration remains unclear. The objective of this study was to investigate the effect of IST on levodopa dose escalation in PD patients with wearing-off. METHODS: This was a multicenter, open-label, randomized, parallel-group controlled study (ISTRA ADJUST PD) in which PD patients experiencing wearing-off (n = 114) who were receiving levodopa 300-400 mg/day were randomized to receive IST or no IST (control). Levodopa dose was escalated according to clinical severity. The primary endpoint was cumulative additional levodopa dose, and secondary endpoints were changes in symptom rating scales, motor activity determined by a wearable device, and safety outcomes. RESULTS: The cumulative additional levodopa dose throughout 37 weeks and dose increase over 36 weeks were significantly lower in the IST group than in the control group (both p < 0.0001). The Movement Disorder Society Unified Parkinson's Disease Rating Scale Part I and device-evaluated motor activities improved significantly from baseline to 36 weeks in the IST group only (all p < 0.05). Other secondary endpoints were comparable between the groups. Adverse drug reactions (ADRs) occurred in 28.8% and 13.2% of patients in the IST and control groups, respectively, with no serious ADRs in either group. CONCLUSION: IST treatment reduced levodopa dose escalation in PD patients, resulting in less cumulative levodopa use. Adjunctive IST may improve motor function more objectively than increased levodopa dose in patients with PD. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180248.
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BACKGROUND: Chronic constipation is a common digestive complication of Parkinson's disease (PD). OBJECTIVES: To verify the usefulness of elobixibat, an ileal bile acid transporter inhibitor, for chronic constipation in PD. METHODS: This double-blind, placebo-controlled study consisted of a 2-week observation/washout period and a 4-week treatment period. All patients received a Bowel Movement Diary at Week -2 and were allocated to elobixibat (10 mg) or placebo at Week 0. Patients visited at Weeks 2 and 4 to report daily spontaneous bowel movements (SBM), stool form, drug use, quality of life (QOL), and safety. Changes in these parameters were assessed. RESULTS: The study included 38 patients in the elobixibat group and 39 in the placebo group, and 37 each completed the study. SBM frequency/week (mean ± standard deviation) increased significantly from 4.2 ± 2.6 at baseline to 5.9 ± 3.2 at Week 4 in the elobixibat group (P = 0.0079), but not in the placebo group (4.5 ± 2.7 to 5.3 ± 3.5; P = 0.0889). On analysis of covariance, the between-group difference in frequency changes at Week 4 (primary endpoint) was not significant after adjustment by baseline and sex (point estimate = 0.8; 95% confidence interval = -0.57 to 2.09, P = 0.2601), although a significant difference (P = 0.0011) was evidenced at Week 1 by a similar analysis. Stool form and scores of satisfaction and stigma were improved by elobixibat. Adverse events were as previously reported. CONCLUSIONS: Elobixibat improved the SBM frequency, though the defined primary endpoint was not evidenced. QOL parameters (stool consistency and treatment satisfaction) were also improved. Elobixibat may have therapeutic benefits in PD patients suffering from chronic constipation. TRIAL REGISTRATION INFORMATION: Trial Registration Number: JPRN-jRCTs031200172 (submitted: October 26, 2020; first patient enrolment: December 23, 2020; https://jrct.niph.go.jp/en-latest-detail/jRCTs031200172).
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Dipeptídeos , Gastroenteropatias , Doença de Parkinson , Tiazepinas , Humanos , Doença Crônica , Constipação Intestinal/tratamento farmacológico , Doença de Parkinson/complicações , Qualidade de Vida , Método Duplo-CegoRESUMO
OBJECTIVE: Midbrain atrophy is considered specific to progressive supranuclear palsy (PSP) compared with Parkinson's disease (PD). We aimed to determine how often midbrain atrophy is observed in pathologically diagnosed Lewy body disease (LBD) and clinically diagnosed PD and the robustness of midbrain atrophy assessed by the One-Line Method previously developed for the diagnosis of PSP. METHODS: We studied two separate cohorts with MRI: the first pathologically diagnosed cohort consisted of patients with LBD (n = 13), PSP (n = 6), multiple system atrophy (MSA, n = 7), and corticobasal degeneration (CBD, n = 2); the second cohort consisted of patients with PD (n = 122). Midbrain length was measured using the One-Line Method and FreeSurfer estimated volumes of the subcortical nuclei. RESULTS: The area under the curve of midbrain length differentiating PSP from LBD, MSA, and CBD in a pathologically diagnosed cohort was 0.91. Midbrain length with cut-off values of 10.5 mm and 9.5 mm had a sensitivity of 100% and 67% and a specificity of 68% and 96%, respectively. In the first cohort, 7.7% and 23.0% of patients with LBD showed midbrain lengths <9.5 mm and 10.5 mm, respectively, and in the second cohort, 4.9% and 19.7% showed midbrain lengths <9.5 mm and 10.5 mm, respectively. INTERPRETATION: Midbrain length measured using the One-Line Method is helpful in the diagnosis of PSP. Some cases of pathologically diagnosed LBD and clinically diagnosed PD present with midbrain atrophy.
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Doença por Corpos de Lewy , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Paralisia Supranuclear Progressiva , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/patologia , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/patologia , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Atrofia/patologiaRESUMO
PURPOSE: To describe clinical presentations of acquired comitant esotropia and digital device use in children, adolescents, and young adults without neurological problems. STUDY DESIGN: Multicenter prospective observational study. METHODS: Patients with acquired comitant esotropia, without intracranial diseases aged 5-35 years at the time of visit, who were seen at pre-registered facilities within 1 year of onset were enrolled. The duration from the onset of symptoms and the time of digital device usage approximately 1 month before onset and their lifestyles were surveyed. Visual acuity, cycloplegic refraction, and strabismus angles were measured. Data were analyzed in three age groups (Child: 5-12 years, Adolescent: 13-18 years, and Young adult: 19-35 years). RESULTS: Between November 2019 and December 2021, 218 patients were enrolled from 55 facilities, and 194 patients (including 62 children, 69 adolescents, and 63 young adults) were analyzed. The child group spent the least amount of time using digital devices (children: 159; adolescents: 210; young adults: 267 min/work day, p < 0.05; (mean time in the same order below) 229, 338, 314 min/holiday, p < 0.05) and had the largest strabismus angle (mean strabismus angle at near: 30, 22, 18 PD, p < 0.01; at far: 28, 26, 21 PD, p<0.05). CONCLUSION: The clinical features of acquired comitant esotropia and hand-held digital device usage differed between children aged ≤ 12 years and older patients. This report gives the current clinical characteristics of young patients with acquired esotropia and digital device usage.
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Esotropia , Estrabismo , Criança , Adolescente , Adulto Jovem , Humanos , Pré-Escolar , Adulto , Esotropia/diagnóstico , População do Leste Asiático , Estrabismo/diagnóstico , Acuidade Visual , Análise de Dados , Estudos Retrospectivos , Músculos Oculomotores , Doença AgudaRESUMO
BACKGROUND: It is known that the pharmacokinetics (PK) of levodopa (LD) varies considerably. Difference in PK shapes is expected to affect drug efficacy and development of dyskinesia. In this study, the authors aimed to explore correlations between PK series data of LD and clinical characteristics and dyskinesia in patients with Parkinson's disease (PD). METHODS: We studied 270 PD patients who underwent PK assessment after administration of LD/carbidopa (100/10 mg) in non-compartmental analysis. The patients were grouped according to similarities in time series data of blood LD concentration. Each group was analyzed with respect to clinical characteristics and PK parameters. We created a model to predict PK patterns based on these findings. RESULTS: PD patients were divided into three groups by clustering analysis: blood LD concentration of the patients in Groups 1 (n = 129), 3 (n = 44) and 2 (n = 97) rose rapidly, relatively slowly and at an intermediate rate, respectively. There were no statistically significant differences in patient characteristics except age among the three groups (one-way ANOVA). Multivariate analysis showed that frequency of dyskinesias in Group 1 was significantly higher than that in Group 2. We successfully created a PK pattern prediction model based on body weight and blood LD concentration at 15 and 30 min after administration. CONCLUSIONS: The PK series data of LD was classified into three patterns. The rapid absorption was associated with dyskinesias. Patients' PK patterns were successfully predicted based on their body weight and two-point LD concentration.
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Discinesias , Doença de Parkinson , Humanos , Levodopa , Antiparkinsonianos , Carbidopa , Doença de Parkinson/tratamento farmacológico , Combinação de MedicamentosRESUMO
PURPOSE: Although breast compression has been an efficient practice to reduce the breast dose in mammography, there may be some differences between analog and digital systems. The purpose of this study was to evaluate the dose-reduction efficiency by breast compression in digital mammography under its own criterion that signal difference-to-noise ratio (SDNR) be kept at a certain value. METHOD: By adopting SDNR as an image quality indicator and average glandular dose (AGD) as a dose indicator, we measured SDNR versus AGD relationship for each breast depth. Then by utilizing figure of merit (FOM), we calculated the breast depth that we had to reduce for halving the breast dose while keeping the SDNR. RESULT: To halve the dose, 1.49 cm compression was necessary for 0% breast density, 1.25 cm for 50%, and 1.06 cm for 100%. CONCLUSION: Through FOM analysis, we quantitatively revealed the dose-reduction efficiency by breast compression in digital mammography.
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Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson's disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor-derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51-1.44 for clinical assessments and 0.56-1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62-0.80 for scores derived from weekly averages and 0.24-0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings.Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.
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Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Reprodutibilidade dos Testes , Japão , TecnologiaRESUMO
The proper use of anthracycline-containing regimens in combination with anti-HER2-targeted therapy in a neoadjuvant setting for patients with HER2-positive breast cancer has not been resolved. Regimens preceded by anthracyclines have become the standard of care, and although the order has no significant impact on HER2-negative breast cancer, it is inconclusive as to whether a taxane-first sequence would have a similar effect on HER2-positive breast cancer. The present study aimed to investigate the benefit of a taxane-first sequence and of adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab and docetaxel (PTD). The present single-center prospective observational study was performed to investigate PTD followed by AC, and aimed to clarify the cCR rate after PTD alone and the pathological clinical response (pCR) rate after subsequent AC in patients without cCR after PTD alone. A total 24 patients were analyzed; of these, 14 achieved pCR (pCR rate, 58.3%). While four of 14 patients (28.6%) in the intention-to-treat population achieved pCR, nine of 14 patients (64.3%) achieved pCR with AC but not cCR after PTD. The median tumor reduction rate after four cycles of PTD was 58.9% (range, 20.8-100%) in all 24 patients, whereas the reduction rate after PTD-AC was 76.9% (range, 31.1-100%). Cardiac serious adverse events occurred in three patients (12.5%). In conclusion, a high pCR rate was observed for the taxane-first sequence. Patients were highly responsive to PTD, but some cases achieved additional antitumor effects after AC, which resulted in pCR without cCR after PTD alone. Since cardiotoxicity remains a significant problem, a higher risk-benefit treatment strategy is required to aim for AC omission. Trial registration number: UMIN000046338, name of registry: UMIN-CTR, date of registration: December 10, 2021.
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PURPOSE: To investigate the clinical factors influencing the prism adaptation response of acquired non-accommodative comitant esotropia (ANAET) and evaluate the surgical outcomes. STUDY DESIGN: Retrospective observational study. METHODS: This study assessed patients with ANAET who underwent strabismus surgery based on the results of a short prism adaptation test (PAT). Patients wore Fresnel trial prisms based on alternate prism cover tests in outpatient clinics. The cover test was then performed after 15-20 minutes; if the deviation increased, the power of the prism was increased to neutralize the angle. The test was repeated until the angle was stable. Patients were classified as either prism builders (angle increased by ≥ 10 prism diopters [PD] compared with the entry angle) or prism non-builders (angle increased by < 10 PD). The following clinical characteristics were noted: age at onset, age at surgery, duration of esotropia, refractive error, angle of deviation, presence or absence of intermittent esotropia at near, and pre- and postoperative sensory status. RESULTS: A total of 41 patients (median age, 15.4 years) were evaluated. The mean (standard deviation) spherical equivalent refractions were -3.03 (3.33) diopters (D) and -3.05 (3.23) D in the right and left eyes, respectively. Twenty-seven (66%) patients were prism builders. The prism builders had greater myopia (builders vs. non- builders, right eye: -3.97 [2.97] vs. -1.22 [3.33] D, P = .01; left eye: -4.08 [2.78] vs. -1.07 [3.20] D; P = .003), lower angle of deviation at near (median [interquartile range] 30.0 [20.0, 35.0] vs. 42.5 [35.0, 49.4] PD; P = .009), much more preoperative intermittent esotropia or esophoria at near (44% vs. 7%, P = .03) and diplopia (96% vs. 64%, P = .01), and better postoperative stereoacuity (50 [40, 110] vs. 100 [60, 400] arcsec, P = .02) than the prism non-builders. The overall success rate was 83%, without a significant difference between the two groups (builders vs. non-builders, 89% vs. 71%, P = .21). CONCLUSION: In cases of myopic refractive error, a small entry angle with intermittency at near, and good binocularity, it is recommended that surgery is performed based on prism-adapted angle to prevent under-correction.
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Esotropia , Miopia , Erros de Refração , Humanos , Adolescente , Esotropia/cirurgia , Músculos Oculomotores/cirurgia , Diplopia/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Oftalmológicos/métodosRESUMO
The effective focal spot size of x-ray tubes is one of the major factors that substantially affect the resultant x-ray images, and it is known to be dependent on the x-ray exposure setting used. This study aims to evaluate the relationship between the effective focal spot size and the tube current and voltage and assess its reproducibility among several x-ray tubes. The evaluation was performed using edge response analysis, in which a 1-mm thick tungsten edge was projected onto a flat panel detector with a magnification factor of 2. The edge image was then differentiated to obtain the line spread function, followed by a detector blur-removing process through Fourier analysis to obtain the true focus profile. The resultant focal spot size increased as the tube current increased, whereas it decreased as the tube voltage increased, as expected. The rate of change was similar along the width and the length directions, while the small focus changed more significantly than the large focus. The reproducibility among four x-ray tubes of the same model was excellent as the maximum variation < 20%. In conclusion, the edge response method can provide useful information on the x-ray focal spot relationship with the x-ray exposure settings used, as well as its reproducibility among several x-ray tubes.
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Intensificação de Imagem Radiográfica , Tomografia Computadorizada por Raios X , Raios X , Reprodutibilidade dos Testes , Radiografia , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS: This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS: Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION: Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.
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Doença de Parkinson , Transtorno do Comportamento do Sono REM , Sinucleinopatias , Humanos , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/complicações , Proteínas da Membrana Plasmática de Transporte de Dopamina , 3-Iodobenzilguanidina , Japão , alfa-Sinucleína , Estudos Transversais , Estudos Prospectivos , Doença de Parkinson/complicações , BiomarcadoresRESUMO
Wolfram syndrome (WS) is a monogenic diabetes caused by variants of the WFS1 gene. It is characterized by diabetes mellitus (DM) and optic atrophy (OA). Individuals with WS initially present with autoantibody-negative type 1 DM (T1BDM). The diagnosis is often delayed or misdiagnosed even after visual impairment becomes apparent. We report a case of WS diagnosed by ophthalmologic screening before the appearance of visual impairment. A 7-year-old male patient developed T1BDM at the age of 3 years. At 6 years of age, his endogenous insulin secretion decreased but was not completely depleted, and glycemic control was good with insulin treatment. Fundus examination at that time revealed optic nerve head pallor, and WFS1 gene analysis confirmed a compound heterozygous variant (c.2483delinsGGA/c.1247T>A). Ophthalmologic screening can help in early diagnosis of WS in T1BDM especially when if endogenous insulin secretion is preserved, which would facilitate effective treatment.
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BACKGROUND: Levodopa remains the most effective symptomatic treatment for Parkinson's disease (PD) more than 50 years after its clinical introduction. However, the onset of motor complications can limit pharmacological intervention with levodopa, which can be a challenge when treating PD patients. Clinical data suggest using the lowest possible levodopa dose to balance the risk/benefit. Istradefylline, an adenosine A2A receptor antagonist indicated as an adjunctive treatment to levodopa-containing preparations in PD patients experiencing wearing off, is currently available in Japan and the US. Preclinical and preliminary clinical data suggested that adjunctive istradefylline may provide sustained antiparkinsonian benefits without a levodopa dose increase; however, available data on the impact of istradefylline on levodopa dose titration are limited. The ISTRA ADJUST PD study will evaluate the effect of adjunctive istradefylline on levodopa dosage titration in PD patients. METHODS: This 37-week, multicenter, randomized, open-label, parallel-group controlled study in PD patients aged 30-84 years who are experiencing the wearing-off phenomenon despite receiving levodopa-containing medications ≥ 3 times daily (daily dose 300-400 mg) began in February 2019 and will continue until February 2022. Enrollment is planned to attain 100 evaluable patients for the efficacy analyses. Patients will receive adjunctive istradefylline (20 mg/day, increasing to 40 mg/day) or the control in a 1:1 ratio, stratified by age, levodopa equivalent dose, and presence/absence of dyskinesia. During the study, the levodopa dose will be increased according to symptom severity. The primary study endpoint is the comparison of the cumulative additional dose of levodopa-containing medications during the treatment period between the adjunctive istradefylline and control groups. Secondary endpoints include changes in efficacy rating scales and safety outcomes. DISCUSSION: This study aims to clarify whether adjunctive istradefylline can reduce the cumulative additional dose of levodopa-containing medications in PD patients experiencing the wearing-off phenomenon, and lower the risk of levodopa-associated complications. It is anticipated that data from ISTRA ADJUST PD will help inform future clinical decision-making for patients with PD in the real-world setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031180248 ; registered 12 March 2019.
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Levodopa , Doença de Parkinson , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Humanos , Levodopa/efeitos adversos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Doença de Parkinson/tratamento farmacológico , Purinas/farmacologia , Purinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
To investigate the prevalence and genotype-phenotype correlations of parkin RBR E3 ubiquitin protein ligase (PRKN) variants in Parkinson's disease (PD), we first included 2,527 patients with PD. Through the defined selection, we enrolled 2,322 patients, including 1,204 with familial and 1,118 with sporadic PD. We identified 242 patients harboring PRKN variants, which were thought to be susceptibility factors, comprising 137 patients with familial and 105 with sporadic PD; among the 26 identified variants, 13 were novel. We divided our cohort into 2 groups: heterozygote (hereafter called one-allele) and homozygote or compound heterozygote (hereafter called two-allele). The patients with two-allele were significantly younger at onset than those with one-allele. Six families harbored the complex forms of one- and two-allele in different individuals of the same family. The presence of two-allele reflected more frequent normal values of [123I] metaiodobenzylguanidine myocardial scintigraphy. The log-rank test revealed an exacerbation associated with two-allele over 15 years of the disease course. The patients with PRKN variants showed specific symptoms dependent on the number of mutated alleles.
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Doença de Parkinson , Idade de Início , Estudos de Associação Genética , Heterozigoto , Humanos , Doença de Parkinson/epidemiologia , Ubiquitina-Proteína Ligases/genéticaRESUMO
INTRODUCTION: Chronic constipation worsens the quality of life (QOL) of patients with Parkinson's disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation. METHODS AND ANALYSIS: The study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week -2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients' motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals. TRIAL REGISTRATION NUMBER: JPRN-jRCTs031200172; Pre-results.