Clinical assessment of a new wearable tool for continuous and objective recording of motor fluctuations and ON/OFF states in patients with Parkinson's disease.

Clinical rating scales typically includes subjective evaluations, and their time-limited duration may fail to capture daily fluctuations in motor symptoms resulting from Parkinson's disease (PD). Recently, a new tool (i.e. the PD-Watch) has been proposed for the objective and continuous assessment of PD motor manifestations based on evaluating frequency data from a wrist-worn tri-axial accelerometer and identifying specific movement patterns typically associated with disorders. This reduces the probability of confusing physiological or pathological movements occurring at the same frequency. In this work, we present a new method for assessing motor fluctuations through a wrist-worn accelerometer. We also explore the agreement between the continuous data generated by the proposed method and data reported in the patient diaries. In this study, twelve PD patients were recruited with an overall recording duration of 528 hours. Results of this preliminary study show that the proposed tool has suitable and adequate performances for analysing the motor signs of PD patients, and the estimated sensitivity, specificity, and accuracy of the tool are 85%, 94%, and 91%, respectively.

Effectiveness of an herbaceous derivatives, PHGG, plus sodium hyaluronate in the treatment of chronic constipation in patients with Parkinson's disease: a pilot study.

Chronic constipation is a highly prevalent and often under-appreciated gastrointestinal disorder in PD associated with significant impairment in quality of life. In this study, we investigated the efficacy and safety of PHGG plus hyaluronate (PHGG+) in patients suffering from PD and constipation. Thirty-four PD patients have been recruited in an open-label pilot study and measured symptoms and quality of life instruments related to constipation. PHGG+ showed to have a minimal still significant effect in improving constipation as measured by PAC Symp and CGI-S. PHGG+ is safe and well tolerated. Data suggests that PHGG+ may be considered efficacious in alleviating symptoms of constipation in PD patients. Trial registration number: NCT04569656/24 Sept. 2020.

Effect of family history, occupation and diet on the risk of Parkinson disease: A case-control study.

BACKGROUND: The aetiology of Parkinson's disease (PD) is still very controversial, with a peculiar lack of established risk factors or protective behavior. METHODS: We carried out a case-control study of 634 idiopathic PD patients admitted from 2011 to 2015 to two hospitals located in central Italy and 532 controls matched by hospital, gender and age (± 5 years). The study questionnaire included questions on host factors, family history, residence, occupation and lifestyle. Odds ratios (ORs) for PD and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for actual and potential confounders. RESULTS: A lower OR was observed in females (0.74; 95%CI:0.58-0.96), while older age classes showed a constantly increased risk for PD (p<0.005) starting from the class 65-69 years. Subjects who reported a first degree relative affected by PD showed a borderline increase which was more evident in those enrolled in the urban center of Rome (OR = 1.65; 95%CI: 1.09-2.50). Significant reduction of the risk was associated to current smoking (OR = 0.48; 95%CI: 0.24-0.54), and to vegetables consumption (p<0.03), while borderline increases were associated to meat and cold cut consumption. Occupational activities classified according to ISCO-08 categories did not show increased risk, while higher ORs' were found for pilots and physicians. CONCLUSIONS: The results from this study confirmed the higher risk of PD in males and in elderly, and the inverse association with smoking habit. The possible etiological role of familial clustering, dietary habit, and some job tasks is suggested.

Applications of the European Parkinson's Disease Association sponsored Parkinson's Disease Composite Scale (PDCS).

This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson's Disease Association sponsored Parkinson's Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35-0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists.

Clinical and pharmacokinetics equivalence of multiple doses of levodopa benserazide generic formulation vs the originator (Madopar).

AIMS: While several generic preparations of levodopa/carbidopa and levodopa/benserazide (LBD) are currently available, pharmacokinetic (PK) equivalence and therapeutic equivalence studies with levodopa generics are not available in Italy. Lack of data on generic formulations is a critical factor for their limited use in this country and often lead patients to refuse the generic version of the branded drug. METHODS: An experimental, 2-centre, randomized, double-blind, 2-sequence, noninferiority cross-over study was designed to evaluate both the PK equivalence and clinical equivalence of multiple doses of the generic preparation of LDB, Teva Italia, compared to the originator (Madopar). Forty-three out-patients with a diagnosis of idiopathic Parkinson's disease on LDB, were recruited and randomly assigned to 1 of 2 study sequences: generic-originator or originator-generic. Clinical evaluations were performed at the end of each study period. A PK study with an LDB fixed dose (100 + 25 mg) was performed in a subpopulation of 14 subjects. RESULTS: Clinical data showed a reduction of 0.49 and 1.54 in the mean UPDRS III scores for the LDB and the originator, respectively. The 95% CIs [-2.21: 0.11] of the mean difference original vs LDB are smaller than the clinically significant difference of 3 UPDRS III points, supporting the conclusion that the treatment with LDB is not inferior to the originator. No statistically significant differences were found with respect to area under the curve to last dose, half-life, maximum concentration, time to maximum concentration and last observed concentration. CONCLUSION: These findings prove the therapeutic clinical equivalence as well the PK equivalence of the generic LDB and the originator (Madopar).

Non motor symptoms in progressive supranuclear palsy: prevalence and severity.

NMSs have been extensively studied in PD patients but not in other forms of parkinsonism such as Progressive Supranuclear Palsy (PSP). The primary objective of this study was to analyze the frequency, severity and the type of non-motor symptoms (NMS) in PSP patients using the non-motor symptoms scale (NMSS). The secondary objective was to differentiate NMS between PSP and Parkinson's disease (PD). We enrolled in this cross-sectional study 50 consecutive PSP and 100 matched Parkinson's disease (PD) patients, in the proportion PSP/PD = 1/2, matched in age, sex, and disease duration. Motor and Non Motor symptoms (different scales for each disease) were evaluated at baseline using PSP scale, SCOPA Motor, Montreal Cognitive Assessment (MOCA), HADS, Hamilton, and Non Motor Symptom scale (NMSS). Comparative analysis was done using chi-squared test, Mann-Whitney test and Fisher's exact test. Fifty PSP (56% female) and 100 PD (59% female) patients completed the study protocol and were included for statistical analysis. The NMSS total domains score in the PSP group was 77.58 ± 42.95 (range 14-163) with NMS burden grade: 4, very severe, and the in the PD group was 41.97 ± 35.45 (range: 0-215) with NMS burden grade: 3, severe. The comparative analysis showed that NMS total score (p < 0.0001), Sleep/Fatigue (p = 0.0007), Mood/Apathy (p = 0.0001), Gastrointestinal (p < 0.0001), and Urinary dysfunction (p = 0.0001) domains were significantly more severe in PSP patients than in PD. This observational study reports that NMSs are very frequent in PSP patients hence the higher burden of NMS in PSP specifically related to mood/apathy, attention/memory, gastrointestinal, urinary disturbances compared to PD.