Criteria for identification of advanced Parkinson's disease: the results of the Italian subgroup of OBSERVE-PD observational study.

BACKGROUND: Frequency of Advanced Parkinson's Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria. METHODS: This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician's judgment and Delphi criteria were also assessed. RESULTS: According to physician's judgment, 60 out of 140 patients (43%) had APD. The correlation between physician's judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633-0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3-5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide. CONCLUSION: APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.

Long-term effectiveness of levodopa-carbidopa intestinal gel on motor and non-motor symptoms in advanced Parkinson's disease: results of the Italian GLORIA patient population.

INTRODUCTION: The GLORIA registry included 375 advanced Parkinson's disease (PD) patients and evaluated the efficacy and safety of a 24-month levodopa-carbidopa intestinal gel (LCIG) treatment in routine medical care. This analysis focuses on the Italian population, 60 patients treated with LCIG in 7 specialised PD care centres. METHODS: Hours of "Off" and "On" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV items 39 and 32. Motor fluctuations, dyskinesia, non-motor symptoms, quality of life and safety were evaluated. RESULTS: Overall, 42 (70%) out of 60 patients completed the registry. LCIG treatment reduced "Off" time (- 3.3 ± 2.7 h at month 24 (M24), P < 0.0001), increased "On" time with dyskinesia (- 2.6 ± 5.2 h at M12, P = 0.0160), and improved UPDRS II and UPDRS III total scores at M24 (- 4.5 ± 10.6, P = 0.0333 and - 4.9 ± 11.7, P = 0.0229, respectively), Non-Motor Symptom Scale (NMSS) total score (- 21.8 ± 28.5, P < 0.0001) and Parkinson's Disease Questionnaire-8 item (PDQ-8) total score (- 12.5 ± 23.9, P = 0.0173) versus previous oral therapy. Adverse drug reactions (ADR) possibly or probably related to treatment were reported in 16 (28.6%) patients. Decreased weight (7.1%), polyneuropathy (7.1%) and abdominal pain (5.4%) were the most frequent ADRs while device malfunction (5.4%) and medical device change (5.4%) were the most reported device complaints. CONCLUSIONS: LCIG improved motor fluctuations, non-motor symptoms and quality of life over 24 months while tolerability was consistent with the established safety profile.

Motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study.

Several levodopa/carbidopa intestinal gel (LCIG) studies showed a significant reduction of OFF time and a significant increase of ON time, as well as a reduction of dyskinesia, and improvement of non-motor symptoms and quality of life. However, few studies have been conducted in a large population for more than 3 years. Interim outcomes from GREENFIELD observational study on a large Italian cohort of advanced PD patients who started LCIG in routine care between 2007 and 2014, still on treatment at the enrollment, are presented. Comparison between baseline (before LCIG start) and visit 1 (at enrollment) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS) IV Item 39; secondary endpoints were UPDRS I and II, as outcome of quality of life. Overall, 145 of 148 enrolled patients from 14 Movement Disorder Centers in Italy were evaluable with a mean LCIG treatment period of 1.38 ± 1.66 years at enrollment. Compared with baseline, the mean score regarding daily time spent in OFF (UPDRS IV Item 39) at visit 1 significantly decreased from 2.1 ± 0.8 to 0.9 ± 0.7 (57 % reduction vs baseline, P < 0.0001); UPDRS IV improved by 39 % (P < 0.0001); scores for dyskinesia duration and disability were reduced by 28 % (1.8 ± 1.0-1.3 ± 0.9; P < 0.0001) and 33 % (1.5 ± 1.1 to 1.0 ± 1.0; P < 0.0001), respectively; and the scores for painful dyskinesia and early morning dystonia were reduced by 56 % (0.9 ± 1.0-0.4 ± 0.7; P < 0.0001) and 25 % (0.4 ± 0.5-0.3 ± 0.5; P < 0.001), respectively. The preliminary results of this interim analysis support the efficacy of LCIG on motor complications and activities of daily living.

Impact of Supporting People with Advanced Parkinson's Disease on Carer's Quality of Life and Burden.

PURPOSE: The aim of this study was to assess the burden and the quality of life (QoL) perceived by caregivers assisting advanced Parkinson's disease (PD) patients. PATIENTS AND METHODS: Consecutive advanced PD patients treated with levodopa/carbidopa intestinal gel (LCIG) or continuous subcutaneous apomorphine infusion (CSAI) or care as usual (CU) and their care partners were recruited during routine visits according to a cross-sectional design. Caregiver's distress was assessed by Zarit Burden Interview (ZBI) and a QoL survey to evaluate and understand the burden experienced by care partners during family and working activities. RESULTS: A total of 126 patients (53 LCIG, 19 CSAI and 54 CU) and their care partners were enrolled. The ZBI score boxplot showed that LCIG and CU populations have a similar distribution (ZBI inter-quartile range [IQR] values respectively 18-42 for LCIG and 19-43 for CU group), while the CSAI group has a wider score range (IQR 16-52). Caregivers assisting patients in treatment with LCIG have more time to perform family or household duties (p=0.0022), or to engage in leisure activities (p=0.0073) compared to CU, while no difference was found when compared to CSAI group. Approximately 50% of the care partners showed mood changes in the last 6 months and LCIG and CSAI had less impact on caregiver's mood compared to CU. Patients treated with LCIG were more independent in taking a bath or shower without assistance and were more able to move and walk without assistance. CONCLUSION: Care partners of advanced PD patients treated with device-aided therapies have more time for their own life and a better perception of their QoL with a tendency to an improvement of mood compared with those of patients treated with CU.

Correction to: Caregiver burden and its related factors in advanced Parkinson's disease: data from the PREDICT study.

The original version of this article unfortunately contained a mistake. In the Figure.

Motor and non-motor outcomes in patients with advanced Parkinson's disease treated with levodopa/carbidopa intestinal gel: final results of the GREENFIELD observational study.

INTRODUCTION: The GREENFIELD observational study assessed the effect of levodopa/carbidopa intestinal gel (LCIG) on motor and non-motor symptoms, and the related impact on patient quality of life and caregiver burden up to 8 years. METHODS: Final results of a large Italian cohort of patients who started LCIG in routine care between 2007 and 2014 are presented. Comparison between baseline (before LCIG) and follow-up visits on yearly basis (visit 2/3) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS-IV) Item 39; secondary endpoints were UPDRS I and II, dyskinesia items, PD Quality of Life Questionnaire-39, Parkinson's Disease Sleep Scale-2, Gait and Falls Questionnaire, Questionnaire on Impulsive Disorders, and Relative Stress Scale. RESULTS: Overall, 145 patients from 14 centers were assessed with a mean time since LCIG start of 2.8 ± 1.7 years at visit 2. The mean UPDRS-IV item 39 score showed significant reductions compared to baseline (mean score 2.0 ± 0.81) at visit 2 (mean score 0.9 ± 0.69; - 55%; p < 0.001) and at visit 3 (mean score 1.0 ± 0.75; - 50%; p < 0.001). At visit 3, significant reductions were observed for dyskinesia duration score (- 28%; p < 0.001), dyskinesia disability (- 40%; p < 0.001), and painful dyskinesia (- 50%; p < 0.001). Overall, 40 (27.6%) patients experienced 49 serious adverse events which were considered related to PEG/J procedure or to device in 16.3% of the cases. CONCLUSIONS: The results of this study support the long-term efficacy of LCIG on PD symptoms as well as on activities of daily living. The adverse events were consistent with the established LCIG safety profile.

Caregiver burden and its related factors in advanced Parkinson's disease: data from the PREDICT study.

INTRODUCTION: Caring for a person with Parkinson's disease (PD) is associated with an increased risk of psychiatric morbidity and persistent distress. The objective of this study was to describe the burden and the related factors of caregivers of advanced PD (APD) patients either treated with continuous dopaminergic delivery systems or standard therapy. METHODS: This cross-sectional, epidemiologic study conducted in 13 Italian sites enrolled PD patients treated with continuous dopaminergic delivering systems [either levodopa/carbidopa intestinal gel (LCIG) infusion or continuous subcutaneous apomorphine infusion (CSAI)] or continuation of standard of care (SOC) with a caregiver. Patient quality of life (QoL) and caregiver burden were assessed using the Parkinson's Disease Questionnaire (PDQ-8) and Zarit Burden Inventory (ZBI), respectively. RESULTS: 126 patients (mean age 69.3 ± 8 years) and their caregivers (mean age 57.9 ± 12.9) were enrolled. Most caregivers were spouses. Fifty-three patients were treated with LCIG, 19 with CSAI, and 54 with SOC. Mean ZBI scores were 29.6 ± 14.4 for LCIG, 35.8 ± 20.2 for CSAI, and 31.4 ± 16.0 for SOC. Caregivers of LCIG, CSAI, and SOC patients showed no burden or mild/moderate burden in 74, 53, and 63% of the cases, respectively. Mean PDQ-8 scores were 11.25 ± 5.67, 11.26 ± 5.55, and 14.22 ± 6.51 in LCIG, CSAI, and SOC patients. Neurologists considered patients "very much or much improved" in 89, 58, and 13% of the LCIG, CSAI, and SOC groups using the Clinical Global Impression-Global Improvement Scale. Predictors significantly associated with caregiver burden were patients and caregivers' judgment of QoL and caregivers' need to change work. CONCLUSIONS: Caregiver burden showed a tendency to be lower when patients are treated with LCIG than with CSAI or SOC.

Double-blind, randomized, multicenter study comparing the effect of betahistine and flunarizine on the dizziness handicap in patients with recurrent vestibular vertigo.

OBJECTIVE: The aim of this double-blind, randomized, multicenter study was to compare the efficacy of betahistine dihydrochloride (BH) and flunarizine (FL) using the Dizziness Handicap Inventory (DHI), a validated self-assessment questionnaire that has not previously been used in a clinical trial to evaluate antivertigo drugs. MATERIAL AND METHODS: Patients with recurrent vertigo of peripheral vestibular origin and who were severely handicapped by vertigo were randomized to an 8-week course of treatment with oral BH 48 mg daily or oral FL 10 mg daily. The efficacy endpoints were the total DHI score and the physical, functional and emotional subscores. RESULTS: Fifty-two patients completed the study. After 8 weeks of treatment the mean total DHI score and the physical subscore were significantly lower in the BH group compared to the FL group (7.5 and 3.6 points, respectively). The mean total DHI score as well as the three subscores decreased significantly after 4 and 8 weeks in both treatment groups. CONCLUSION: This study showed that at 8 weeks BH is significantly more effective than FL in terms of improving the total DHI score and the physical subscore. It was also established that the DHI is a useful and reliable method for evaluating the efficacy of antivertigo drugs.

Hypertension and migraine comorbidity: prevalence and risk of cerebrovascular events: evidence from a large, multicenter, cross-sectional survey in Italy (MIRACLES study).

OBJECTIVES: To estimate the prevalence of hypertension-migraine comorbidity; to determine their demographic and clinical characteristics versus patients with hypertension or migraine alone; and to see whether a history of cerebrovascular events was more common in the comorbidity group. METHODS: The MIRACLES, multicenter, cross-sectional, survey included 2973 patients with a known diagnosis of hypertension or migraine in a general practitioner setting in Italy. RESULTS: Five hundred and seventeen patients (17%) suffered from hypertension-migraine comorbidity, whereas 1271 (43%) suffered from hypertension only, and 1185 (40%) from migraine only. In the comorbidity group, the onset of comorbidity occurred at about 45 years of age, with migraine starting significantly later than in the migraine-only group, and hypertension significantly before than in the hypertension-only group; a familial history of both hypertension and migraine had a significantly higher frequency as compared with the hypertension and migraine group. Compared to hypertension (3.1%) and migraine (0.7%), the comorbidity group had a higher prevalence (4.4%) of history of cerebrovascular events, with an odds ratio of a predicted history of stroke/transient ischemic attack (TIA) of 1.76 [95% confidence interval (CI) 1.01-3.07] compared to the hypertension group. In patients without other recognized risk factors for stroke, stroke/TIA occurred more frequently in the comorbidity group, compared to the hypertension group. In the age range 40-49 years, prevalence of history of stroke/TIA was five-fold greater (4.8% in comorbidity vs. 0.9% in hypertension group). CONCLUSION: This cross-sectional study indicates that the prevalence of comorbidity hypertension-migraine is substantial and that patients with comorbidity have a higher probability of history of cerebrovascular events, compared to hypertensive patients.

Ambulatory monitoring of systolic hypertension in the elderly: Eprosartan/hydrochlorothiazide compared with losartan/hydrochlorothiazide (INSIST trial).

INTRODUCTION: Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy. METHODS: After a 3-week placebo wash-out, 155 patients with an Office trough sitting systolic blood pressure (Office sitSBP) >or=160 mmHg and <180 mmHg were randomized to eprosartan 600 mg (n=78) or losartan 50 mg (n=77) once daily for 6 weeks. In patients not optimally responding to monotherapy (Office sitSBP>or=130 mmHg) 12.5 mg HCTZ was added as fixed combination once daily for 6 weeks. A 24-hour ambulatory blood pressure monitoring (ABPM) was performed at the end of wash-out and at the end of the fixed-combination period. RESULTS: No statistically significant difference was found between eprosartan/HCTZ and losartan/HCTZ on the primary endpoint (24-hour ABPM SBP) with an adjusted mean difference between treatments of 3.1 mmHg (95% CI: -0.32-6.59). However, the mean 24-hour ABPM SBP significantly decreased by 16.7 mmHg with eprosartan/HCTZ and 20.3 mmHg with losartan/HCTZ (P<0.001 vs. baseline). The mean Office sitSBP significantly decreased by 28.7 mmHg and 29.6 mmHg respectively, with eprosartan/HCTZ and losartan/HCTZ (P<0.001 vs.baseline and vs. monotherapy). CONCLUSION: In this study, eprosartan/HCTZ did not demonstrate to be superior to losartan/HCTZ in reducing ABPM systolic hypertension in the elderly.