Percorrer por autor "Antonini, Angelo"
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- Does the 5–2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5–2-1-positive patients in 7 countriesPublication . Malaty, Irene A.; Martinez-Martin, Pablo; Chaudhuri, K. Ray; Odin, Per; Skorvanek, Matej; Jimenez-Shahed, Joohi; Soileau, Michael J.; Lindvall, Susanna; Domingos, Josefa; Jones, Sarah; Alobaidi, Ali; Jalundhwala, Yash J.; Kandukuri, Prasanna L.; Onuk, Koray; Bergmann, Lars; Femia, Samira; Lee, Michelle Y.; Wright, Jack; Antonini, AngeloBackground: The burden of Parkinson’s disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson’s disease (APD) and suboptimal medication control. The 5–2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5–2-1 screening criteria. Methods: Data were drawn from the Adelphi Parkinson’s Disease Specific Program (DSP™), a multi-country point-in-time survey (2017–2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5–2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) “off” symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5–2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. Results: From the analytic sample (n = 4714), 33% of patients met the 5–2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5–2-1 positive. Concordance between clinician judgment and 5–2-1 screening criteria was > 75%. 5–2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5–2-1-negative group, 5–2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5–2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5–2-1-positive patients also had significantly lower quality of life and worse caregiver burden. Conclusions: 5–2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5–2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.
- Dysphagia predicts poor outcome in late-stage Parkinson's diseasePublication . Fabbri, Margherita; Coelho, Miguel; Abreu, Daisy; Guedes, Leonor Correia; Rosa, Mario M.; Godinho, Catarina; Cardoso, Rita; Guimarães, Isabel; Antonini, Angelo; Zibetti, Maurizio; Lopiano, Leonardo; Ferreira, Joaquim J."BACKGROUND: Few data exist on the rate of clinical progression for Parkinson's disease (PD) patients who have entered a late stage of the disease. OBJECTIVE: Study the clinical progression of a late-stage PD (LSPD) population over one year follow-up. METHODS: 50 LSPD patients (Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 in MED ON) underwent an extensive clinical assessment at baseline and after one year and an acute levodopa test at baseline. RESULTS: Mean age of LSPD patients (female 46%) was 77.5 ± 5.9 years and mean disease duration was 15.5 ± 6.5 years. At baseline, 76% had levodopa-induced motor complications (MC), usually non-troublesome, 68% were demented, 54% had psychosis and 68% depression. Caregiver distress was high. l-dopa responsiveness was mild (18% ± 12 of improvement on MDS-UPDRS-III). After one-year, 20% of the patients were dead, institutionalized or HY 5. MDS-UPDRS-motor mean score worsened 7.2 ± 10.3 points although there was heterogeneity between patients, and there was a global worsening of non-motor symptoms, mostly in cognition/mood, urinary and gastrointestinal domains. Nevertheless, MC improved despite similar levodopa equivalent dose. Functional independence and quality of life worsened. Dysphagia severity at baseline predicted a poor outcome (death, institutionalization or HY 5) (Hazard ratio 2.3, 95% CI 1.12-4.4; p = 0.01), whereas magnitude of l-dopa response of LSPD patients did not. CONCLUSIONS: LSPD patients still present a significant, although heterogeneous, motor and non-motor progression over 1 year. Dysphagia severity predicts the occurrence of additional disease severity milestones and its management must be prioritized."
- Dysphagia predicts poor outcome in late-stage Parkinson's diseasePublication . Fabbri, Margherita; Coelho, Miguel; Abreu, Daisy; Guedes, Leonor Correia; Rosa, Mario M; Godinho, Catarina; Cardoso, Rita; Guimarães, Isabel; Antonini, Angelo; Zibetti, Maurizio; Lopiano, Leonardo; Ferreira, Joaquim J
- Psychometric properties of clinical indicators for identification and management of advanced Parkinson’s disease : real-world evidence from G7 countriesPublication . Antonini, Angelo; Pahwa, Rajesh; Odin, Per; Henriksen, Tove; Soileau, Michael J.; Rodriguez-Cruz, Ramon; Isaacson, Stuart H.; Merola, Aristide; Lindvall, Susanna; Domingos, Josefa; Alobaidi, Ali; Jalundhwala, Yash J.; Kandukuri, Prasanna L.; Parra, Juan Carlos; Kukreja, Pavnit K.; Onuk, Koray; Bergmann, Lars; Pike, James; Chaudhuri, K. RayIntroduction: 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.
- Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: results of a levodopa challenge testPublication . Fabbri, Margherita; Coelho, Miguel; Guedes, Leonor Correia; Chendo, Inês; Sousa, Catarina; Rosa, Mario M.; Abreu, Daisy; Costa, Nilza; Godinho, Catarina; Antonini, Angelo; Ferreira, Joaquim J."BACKGROUND: Non-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated. OBJECTIVE: To assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients. METHODS: 20 LSPD patients, defined as Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge. RESULTS: Systolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients. CONCLUSIONS: This exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients."
- Speech and voice response to a Levodopa challenge in late-stage Parkinson’s DiseasePublication . Fabbri, Margherita; Guimarães, Isabel; Cardoso, Rita; Coelho, Miguel; Guedes, Leonor Correia; Rosa, Maria M.; Godinho, Catarina; Abreu, Daisy; Gonçalves, Nilza; Antonini, Angelo; Ferreira, Joaquim J."Background: Parkinson’s disease (PD) patients are affected by hypokinetic dysarthria, characterized by hypophonia and dysprosody, which worsens with disease progression. Levodopa’s (l-dopa) effect on quality of speech is inconclusive; no data are currently available for late-stage PD (LSPD). Objective: To assess the modifications of speech and voice in LSPD following an acute l-dopa challenge. Method: LSPD patients [Schwab and England score <50/Hoehn and Yahr stage >3 (MED ON)] performed several vocal tasks before and after an acute l-dopa challenge. The following was assessed: respiratory support for speech, voice quality, stability and variability, speech rate, and motor performance (MDS-UPDRS-III). All voice samples were recorded and analyzed by a speech and language therapist blinded to patients’ therapeutic condition using Praat 5.1 software. Results: 24/27 (14 men) LSPD patients succeeded in performing voice tasks. Median age and disease duration of patients were 79 [IQR: 71.5–81.7] and 14.5 [IQR: 11–15.7] years, respectively. In MED OFF, respiratory breath support and pitch break time of LSPD patients were worse than the normative values of non-parkinsonian. A correlation was found between disease duration and voice quality (R = 0.51; p = 0.013) and speech rate (R = −0.55; p = 0.008). l-Dopa significantly improved MDS-UPDRS-III score (20%), with no effect on speech as assessed by clinical rating scales and automated analysis. Conclusion: Speech is severely affected in LSPD. Although l-dopa had some effect on motor performance, including axial signs, speech and voice did not improve. The applicability and efficacy of non-pharmacological treatment for speech impairment should be considered for speech disorder management in PD."
- Speech and voice response to a Levodopa challenge in late-stage Parkinson’s diseasePublication . Fabbri, Margherita; Guimarães, Isabel; Cardoso, Rita; Coelho, Miguel; Guedes, Leonor Correia; Rosa, Mário M; Godinho, Catarina; Abreu, Daisy; Gonçalves, Nilza; Antonini, Angelo; Ferreira, JoaquimBackground: Parkinson’s disease (PD) patients are affected by hypokinetic dysarthria, characterized by hypophonia and dysprosody, which worsens with disease progression. Levodopa’s (l-dopa) effect on quality of speech is inconclusive; no data are currently available for late-stage PD (LSPD). Objective: To assess the modifications of speech and voice in LSPD following an acute l-dopa challenge. Method: LSPD patients [Schwab and England score <50/Hoehn and Yahr stage >3 (MED ON)] performed several vocal tasks before and after an acute l-dopa challenge. The following was assessed: respiratory support for speech, voice quality, stability and variability, speech rate, and motor performance (MDS-UPDRS-III). All voice samples were recorded and analyzed by a speech and language therapist blinded to patients’ therapeutic condition using Praat 5.1 software. results: 24/27 (14 men) LSPD patients succeeded in performing voice tasks. Median age and disease duration of patients were 79 [IQR: 71.5–81.7] and 14.5 [IQR: 11–15.7] years, respectively. In MED OFF, respiratory breath support and pitch break time of LSPD patients were worse than the normative values of non-parkinsonian. A correlation was found between disease duration and voice quality (R = 0.51; p = 0.013) and speech rate (R = −0.55; p = 0.008). l-Dopa significantly improved MDS-UPDRS-III score (20%), with no effect on speech as assessed by clinical rating scales and automated analysis. conclusion: Speech is severely affected in LSPD. Although l-dopa had some effect on motor performance, including axial signs, speech and voice did not improve. The applicability and efficacy of non-pharmacological treatment for speech impairment should be considered for speech disorder management in PD.
- Speech and voice response to levodopa in late-stage Parkinson’s Disease patients : report from an acute levodopa challengePublication . Fabbri, Margherita; Guimarães, Isabel; Coelho, Miguel; Cardoso, R.; Guedes, Leonor Correia; Rosa, Mario M.; Godinho, Catarina; Antonini, Angelo; Ferreira, Joaquim J.
- Substantia nigra area evaluated by neuromelanin-sensitive MRI as an imaging biomarker of disease progression in Parkinson's diseasePublication . Fabbri, Margherita; Reimão, Sofia; Carvalho, Miguel; Nunes, Rita G.; Abreu, Daisy; Guedes, Leonor Correia; Bouça, Raquel; Lobo, Patricia P.; Godinho, Catarina; Coelho, Miguel; Gonçalves, Nilza C.; Rosa, Mario Miguel; Antonini, Angelo; Ferreira, Joaquim J.
- Substantia nigra neuromelanin as an imaging biomarker of disease progression in Parkinson’s DiseasePublication . Fabbri, Margherita; Reimão, Sofia; Carvalho, Miguel; Nunes, Rita G.; Abreu, Daisy; Guedes, Leonor Correia; Bouça, Raquel; Lobo, Patrícia P.; Godinho, Catarina; Coelho, Miguel; Gonçalves, Nilza C.; Rosa, Mario Miguel; Antonini, Angelo; Ferreira, Joaquim J."BACKGROUND: A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE: to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages. METHODS: A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods. RESULTS: 13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinson's Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1). CONCLUSION: SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients."
