Introduction
Patients and methods
Study design
Patient selection
Assessments
Parkinson’s disease features
Measures on caregiver and economic resources
Measures of quality of life and treatment satisfaction
Statistical analysis
Determination of sample size
Results
Demographics and clinical characteristics
LCIG (n = 53) | CSAI (n = 19) | SOC (n = 54) | |
---|---|---|---|
Patients | |||
Demographics | |||
Age (years); mean ± SD (range) | 70.26 ± 7.1 (53–84) | 66.0 ± 6.6 (54–77) | 69.57 ± 9.1 (42–88) |
Female; n (%) | 28 (53%) | 9 (47%) | 25 (46%) |
Male; n (%) | 25 (47%) | 10 (53%) | 29 (54%) |
Employment status; N (%) | |||
Worker | 0 | 3 (16%) | 5 (9%) |
Retired | 45 (85%) | 16 (84%) | 48 (89%) |
House keeper | 7 (13%) | 0 | 1 (2%) |
Unemployed | 1 (2%) | 0 | 0 |
Caregivers | |||
Demographics | |||
Age (years); mean ± SD (range) | 59.19 ± 13.2 (36–84) | 60.26 ± 12.9 (29–78) | 55.89 ± 12.6 (29–85) |
Female; n (%) | 30 (56%) | 15 (79%) | 43 (80%) |
Male; n (%) | 23 (43%) | 4 (21%) | 11 (20%) |
Patient relationship; N (%) | |||
Spouse | 33 (62%) | 13 (68%) | 30 (56%) |
Son/daughter | 16 (30%) | 4 (21%) | 20 (37%) |
Brother/sister | 1 (2%) | 0 | 3 (5%) |
Other relative | 3 (6%) | 2 (11%) | 1 (2%) |
Educational level; N (%) | |||
Elementary/middle school | 29 (55%) | 9 (48%) | 17 (31%) |
High school | 20 (38%) | 5 (26%) | 28 (52%) |
Academic degree | 4 (7%) | 5 (26%) | 9 (17%) |
Employment status; N (%) | N = 51 | N = 19 | N = 54 |
Worker | 14 (27%) | 5 (26%) | 20 (37%) |
Retired | 22 (43%) | 7 (37%) | 12 (22%) |
Student | 0 | 1 (5%) | 1 (2%) |
House keeper | 13 (26%) | 6 (32%) | 16 (30%) |
Unemployed | 2 (4%) | 0 | 5 (9%) |
Caregiver assistance duration | N = 52 | N = 18 | N = 53 |
Since 6–12 months | 7 (14%) | 0 | 3 (6%) |
≥ 12 months | 45 (86%) | 18 (100%) | 50 (94%) |
Time spent during the day for the assistance | N = 53 | N = 19 | N = 52 |
Day and night (24 h) | 26 (49%) | 12 (63%) | 29 (56%) |
During daytime | 8 (15%) | 4 (21%) | 9 (17%) |
From 3 to 6 h per day | 19 (36%) | 3 (16%) | 14 (27%) |
LCIG (n = 53) | CSAI (n = 19) | SOC (n = 54) | p value*,** | |
---|---|---|---|---|
Age at PD diagnosis (years), mean ± SD, (range) | 53.89 ± 9.1 (32–72) | 52.42 ± 6.9 (40–62) | 56.74 ± 9.4 (33–76) | 0.524* 0.113** |
PD duration (years), mean ± SD, (range) | 16.38 ± 5.8 (7–33) | 13.58 ± 4.1 (8–21) | 12.83 ± 5.1 (4–35) | 0.085* 0.0003** |
Age at onset of motor fluctuations (years), mean ± SD, (range) | 61.91 ± 8.8 (37–78) | 60.53 ± 5.9 (52–72) | 64.35 ± 9.4 (40–86) | 0.529* 0.168** |
Duration of motor fluctuations (years), mean ± SD, (range) | 8.36 ± 4.8 (1–26) | 5.47 ± 3.5 (2–14) | 5.22 ± 4.1 (1–25) | 0.0099* < 0.000**1 |
Duration of motor fluctuations (h/day), mean ± SD, (range) | 2.69 ± 2.5 (0–11) | 2.79 ± 1.5 (0–5) | 5.42 ± 2.6 (1–14) | 0.362* < 0.0001** |
Duration of OFF periods (h/day), mean ± SD, (range) | 1.38 ± 1.5 (0–6) | 2.32 ± 1.7 (0–8) | 5.47 ± 2.2 (3–12) | 0.009* < 0.0001** |
Duration of dyskinesia (h/day), mean ± SD, (range) | 2.92 ± 3 (0–12) | 2.79 ± 2 (0–8) | 2.85 ± 3 (0–12) | 0.5424* 0.7358** |
UPDRS-IV Item 39, N (%) | ||||
Not present | 6 (11%) | 1 (5%) | 0 | 0.037* < 0.001** |
1–25% | 37 (70%) | 8 (42%) | 9 (17%) | |
26–50% | 9 (17%) | 8 (42%) | 36 (67%) | |
51–75% | 1 (2%) | 2 (11%) | 8 (15%) | |
76–100% | 0 | 0 | 1 (2%) | |
Hoehn & Yahr in OFF, N (%) | 0.121* 0.039** | |||
1 | 1 (2%) | 0 | 0 | |
1.5 | 2 (4%) | 0 | 1 (2%) | |
2 | 5 (9%) | 2 (11%) | 0 | |
2.5 | 17 (32%) | 13 (68%) | 10 (19%) | |
3 | 21 (40%) | 3 (16%) | 35 (65%) | |
4 | 7 (13%) | 1 (5%) | 8 (15%) | |
PD-associated symptoms N (%) | 98% | 100% | 100% | 0.547* 0.311** |
Falls | 28 (54%) | 11 (58%) | 31 (57%) | 0.704* 0.364** |
Confusion | 18 (35%) | 9 (47%) | 17 (31%) | 0.300* 0.784** |
Forgetfulness | 17 (33%) | 7 (37%) | 18 (33%) | 0.705* 0.890** |
Bladder control problems | 26 (50%) | 10 (53%) | 27 (50%) | 0.789* 0.922** |
Increased sweating | 26 (50%) | 12 (63%) | 22 (41%) | 0.291* 0.397** |
Sexual disturbances | 10 (19%) | 10 (53%) | 20 (37%) | 0.005* 0.036** |
Apathy | 14 (27%) | 9 (47%) | 16 (30%) | 0.093* 0.711** |
Having felt sad or in a depressed mood for longer than 2 weeks | 13 (25%) | 5 (26%) | 14 (26%) | 0.877* 0.868** |
Hallucinations | 10 (19%) | 2 (11%) | 11 (20%) | 0.403* 0.845** |
Anxiety | 22 (42%) | 12 (63%) | 32 (59%) | 0.105* 0.066** |
Cognitive function decline | 19 (37%) | 4 (21%) | 16 (30%) | 0.235* 0.493** |
Sleep disturbances | 29 (56%) | 11 (58%) | 35 (65%) | 0.811* 0.287** |
Impulse control disorders | 4 (8%) | 4 (21%) | 8 (15%) | 0.108* 0.234** |
Fatigue | 31 (60%) | 15 (79%) | 34 (63%) | 0.111* 0.636** |
Caregiver burden and associated factors
ZBI total score and | p value |
---|---|
Spearman correlation | |
Patient’s age (years) | 0.906 |
Caregiver’s age (years) | 0.935 |
PD duration (years) | 0.811 |
Duration of motor fluctuations (years) | 0.729 |
Duration of motor fluctuations (h/day) | 0.736 |
Duration of dyskinesias (h/day) | 0.470 |
Duration of OFF periods (h/day) | 0.372 |
CGI-I score | 0.303 |
PDQ-8 score | 0.002 |
ANOVA models (univariate) | |
Patient’s gender | 0.380 |
Caregiver’s gender | 0.093 |
Presence of PD-associated symptoms | 0.924 |
Caregiver’s duration of assistance | 0.347 |
Caregiver’s change in work | 0.001 |
Caregiver’s change in capability to perform family duties/leisure activities | < 0.001 |
Need of professional assistance | 0.019 |
Hoehn & Yahr stage | 0.848 |
Caregiver’s time spent for assistance | 0.168 |
UPDRS-IV item 39 | 0.474 |
Patient’s judgment on quality of life | 0.010 |
Caregiver’s occupational status | 0.577 |
No. of outpatient visits in the last 6 months due to PD | 0.203 |
No. of accesses to emergency departments in the last 6 months due to PD | 0.757 |
No. of hospitalizations in the last 6 months due to PD | 0.415 |
Caregiver’s judgment on quality of life | < 0.001 |
Multiple regression linear analysis (model on ranks) | Estimate | p value | 95% CI | |
---|---|---|---|---|
Lower limit | Upper limit | |||
Intercept | 34.97 | 0.175 | − 15.84 | 85.79 |
Caregiver’s change in work | ||||
Change vs no change | 23.57 | 0.001 | 10.38 | 36.76 |
Caregiver’s change in capability to perform family duties and leisure activities | ||||
Change vs no change | 9.21 | 0.072 | − 0.83 | 19.25 |
Need of professional assistance | ||||
Need vs no need | 7.24 | 0.278 | − 5.92 | 20.40 |
Patient’s judgment on quality of life | ||||
Poor vs very poor | 41.20 | 0.113 | − 9.94 | 92.34 |
Good vs very poor | 31.23 | 0.234 | − 20.49 | 82.94 |
Very good vs very poor | 21.88 | 0.416 | − 31.28 | 75.04 |
Caregiver’s judgment on quality of life | ||||
Poor vs very poor | − 3.48 | 0.737 | − 24.04 | 17.08 |
Good vs very poor | 0.003 | − 53.28 | ||
Very good vs very poor | 0.005 | − 59.01 |
Patients’ treatment
Parameter | LCIG (N = 53) | CSAI (N = 19) |
---|---|---|
Duration of infusion (h/day); mean ± SD (range) | 14.1 ± 2.1 (11.0–24.0) | Not applicable |
Levodopa equivalent daily dose (LEDD) (mg); mean ± SD (range) | 1112.6 ± 473.4 (532–2960) | 1665.3 ± 1309.0 (180–5600) |
Duration of treatment (months); mean ± SD (range) | 17.8 ± 9.1 (5.98–41.89) | 24.7 ± 9.9 (5.65–40.15) |
Patients using concomitant anti-parkinson medications during the day; N (%) | 14 (26.4%) | 13 (68.4%) |
Number of anti-parkinson drug units/day; mean ± SD (range) | 1.4 ± 0.7 (1–3) | 6.7 ± 4.4 (1–19) |
Parameter | N (%) | No. of tablets/day (mean ± SD) (range) | LEDD (mg) (mean ± SD) (range) |
---|---|---|---|
Standard treatments before LCIG (N = 50) | |||
Oral levodopa | 50 (94%) | 6.0 ± 1.4 (2–9) | 972.5 ± 417.9 (250–2350) |
Dopamine agonists | 33 (62%) | 1.5 ± 0.7 (1–3) | 274.6 ± 123.9 (100–560) |
COMT inhibitors | 23 (43%) | 4.3 ± 1.9 (1–10) | 322.6 ± 230.8 (100–1200) |
MAO inhibitors | 17 (32%) | 1.1 ± 0.2 (1–2) | 100.0 ± 0.0 (100–100) |
Othersa | 12 (23%) | 2.6 ± 2.4 (1–10) | 204.3 ± 108.3 (100–360) |
Standard treatments before CSAI (N = 19) | |||
Oral levodopa | 19 (100%) | 6.3 ± 1.8 (4–10) | 1185 ± 686.3 (500–2500) |
Dopamine agonists | 12 (63%) | 2.4 ± 2 (2–8) | 437.2 ± 596.5 (105–2000) |
COMT inhibitors | 13 (68%) | 4.4 ± 1.8 (2–8) | 442.7 ± 403.1 (75–1400) |
MAO inhibitors | 3 (16%) | 1 ± 0 (1–1) | 100 ± 0 (100–100) |
Amantadine | 1 (5%) | 2 | 200 (200–200) |
Standard treatments in SOC-continuing patients (N = 54) | |||
Oral levodopa | 54 (100%) | 5.6 ± 1.8 (2–12) | 732.6 ± 230.1 (200–1200) |
Dopamine agonists | 36 (67%) | 1.4 ± 1.2 (1–8) | 211.6 ± 81.0 (100–360) |
COMT inhibitors | 20 (37%) | 4.5 ± 1.4 (2–7) | 548.7 ± 414.0 (132–1400) |
MAO inhibitors | 19 (35%) | 1.3 ± 1.2 (1–6) | 237.5 ± 388.9 (100–1200) |
Othersb | 15 (28%) | 2.3 ± 1.3 (1–5) | 293.2 ± 443.9 (100–1625) |
Attitude towards advanced therapies
LCIG (N = 53) | CSAI (N = 19) | SOC (N = 54) | |
---|---|---|---|
Information on MD centers | |||
General practitioner | 11 (21%) | 4 (21%) | 13 (24%) |
Community neurologist | 21 (40%) | 5 (26%) | 15 (28%) |
Media | 7 (13%) | 1 (5%) | 5 (9%) |
Patients’ association | 2 (4%) | 2 (11%) | 4 (7%) |
Others patients | 13 (25%) | 6 (32%) | 12 (22%) |
Other sources of information | 11 (21%) | 5 (26%) | 12 (22%) |
LCIG (N = 53) | CSAI (N = 19) | SOC (N = 51) | |
---|---|---|---|
Caregivers knowledge on advanced treatments | |||
Constantly informed | 38 (72%) | 17 (89%) | 18 (35%) |
Partially informed | 13 (26%) | 2 (11%) | 22 (43%) |
Not informed | 2 (4%) | 0 | 11 (22%) |
Source of first information received on advanced PD treatment options | ||
---|---|---|
Neurologist of the MD center | 41 (77%) | 16 (84%) |
Community neurologist | 7 (13%) | 0 |
Media | 1 (2%) | 0 |
Other patients | 2 (4%) | 3 (16%) |
General Practitioner | 1 (2%) | 0 |
Reasons for patients who decided to switch | LCIG (N = 53) | CSAI (N = 19) |
---|---|---|
N (%) | N (%) | |
Caregiver was willing and available to assist patient in managing the advanced PD treatment for a long period | 36 (68%) | 14 (74%) |
The patient could no longer tolerate poor quality of life | 42 (79%) | 16 (84%) |
The patient presented significant disabilities, with serious loss of autonomy | 45 (86%) | 13 (68%) |
The caregiver wished to reduce the stress he/she was undergoing | 8 (15%) | 3 (16%) |
The patient and/or caregiver showed interest in advanced treatment options | 23 (43%) | 9 (47%) |
Complexity of conventional treatments/scarce compliance | 10 (19%) | 3 (16%) |
Reasons for patients to remain in standard treatment | SOC (N = 54) |
---|---|
N (%) | |
The caregiver was not willing or available to assist patient in managing the advanced PD treatment for a long period | 8 (15%) |
The patient is afraid of advanced treatments | 30 (56%) |
The caregiver is worried for the patient | 14 (26%) |
The patient believes his or her conditions are not debilitating such as to require an advanced therapy | 21 (39%) |
The caregiver believes that advanced therapies have to be considered in the very late stage of disease | 17 (31%) |
The physician believes that the patient is unsuitable for an advanced therapy | 17 (31%) |
SOC patients who were proposed in the past an advanced therapy but they refused for any reason | 18 (33%) |