Feasibility of home initiation of subcutaneous apomorphine infusion for patients with Parkinson’s Disease

doi:10.21203/rs.3.rs-1968020/v1

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Feasibility of home initiation of subcutaneous apomorphine infusion for patients with Parkinson’s Disease

https://doi.org/10.21203/rs.3.rs-1968020/v1

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Background: Continuous subcutaneous apomorphine infusion (CSAI) is increasingly being used to treat patients with Parkinson’s disease who are experiencing motor fluctuations. However, the need to initiate this treatment during a hospital stay, more often than not in a specialist center, may restrict patients’ access to it.

Objective: To assess the feasibility and benefits of initiating CSAI in the patient’s own home.

Method: A prospective multicenter longitudinal observational study (APOKADO Study) among patients with Parkinson’s disease who required subcutaneous apomorphine, comparing in-hospital versus home initiation. We assessed patients’ quality of life with the 8-item Parkinson’s Disease Questionnaire, rated the improvement in their clinical status on the 7-point Clinical Global Impression – Improvement scale, recorded adverse events, and ran a cost benefit analysis.

Results: Participants were145 patients with motor fluctuations (mean age: 70 years; mean disease duration: 11.1 years). Of these, 106 (74%) were initiated onto CSAI at home, and 38 (26%) in hospital. At inclusion, the two groups were comparable on all demographic and clinical characteristics. Quality of life improved more quickly in the home group than in the hospital one, and the percentages of patients whose clinical status was much or very much improved were also higher. Adverse events and early dropout rates were similar and similarly rare across the two groups. Patients in the home group became more autonomous in managing the device than those in the hospital group, and their care cost less.

Conclusion: This study shows that home (versus in-hospital) initiation of CSAI is feasible, improves patients’ quality of life more and more quickly, with a greater clinical benefit and exactly the same level of tolerance. It is also less expensive. This finding should make it easier for patients to access this treatment in the future.

Apomorphine has been used as a treatment in Parkinson’s disease (PD) since the 1980s, as it acts on both D1 and D2 receptors, as well as on the nigrostriatal pathway, making it more similar to levodopa in terms of action and tolerance than most other dopamine agonists. It is quick acting, but has to be given as a subcutaneous injection. For the past 20 years, it has been possible to administer it either continuously, using an infusion pump, or intermittently, using an injector pen.¹ Extensive research in this area has yielded a fairly accurate picture of the indications and benefits of apomorphine, in terms of motor function and quality of life.^2,3

Up to now, initiation of continuous subcutaneous apomorphine infusion (CSAI) has required a hospital stay, generally in a PD specialist center or a hospital department with experience of the disease. Patients stay in hospital for between 5 and 10 days,^3–6 in order to enable clinicians to adjust the flow rate on a daily basis, modify patients’ oral medication, and look out for potential adverse effects. The stay also gives patients and their caregivers an opportunity to familiarize themselves with the treatment. Once they have returned home, patients receive care from a team of local district nurses⁴ trained by the medical device supplier, who is responsible for the technical follow-up. They are monitored either by the neurologist who initiated the CSAI, or by their treating neurologist.

Over time, a number of medical, social and geographical drawbacks have become apparent.⁷ Some patients who could benefit from CSAI are put off by the wait for an appointment and the length of the subsequent hospital stay, as well as the physical distance from the nearest specialist center. Neurologists may be reluctant to prescribe a treatment if they cannot initiate themselves and to become involved in the follow-up. Lastly, the cost of the hospital stay comes on top of the cost of initiation and follow-up.^8,9

Home initiation would overcome these drawbacks and allow more patients to access CSAI. So far, most studies have focused on in-hospital initiation, but a recent Expert Consensus Group report indicated that it should be possible to initiate patients onto therapy at home, providing the team has the necessary experience.⁵ We nevertheless need to confirm that home initiation is equivalent to in-hospital initiation in terms of efficacy, tolerance, and quality of life.

The aim of the present study was therefore to demonstrate the feasibility of home initiation, and to compare the two modalities on clinical efficacy, tolerance, improvement in quality of life, and cost.

APOKADO was a prospective multicenter longitudinal observational nonrandomized study approved by the CCP Ile de France V institutional review board (18.07.16.4828 CAT3, 3 August 2016). It included patients who had been diagnosed with PD at least 5 years earlier and who had an indication for apomorphine according to their neurologist. We excluded patients with an atypical Parkinsonian syndrome, as well as those exhibiting cognitive decline or severe psychotic disorders, or who were unable to complete the self-report questionnaires and did not have a caregiver to assist them. All the patients included in the study took part on a voluntary basis and signed an informed consent form.

Patients were assigned to one of two groups (home or hospital), depending on whether their neurologist worked at a hospital or in a private practice, and taking account of their wishes.

Patients’ clinical status when they joined the study (Day 0, D0) was assessed by the investigating neurologist according to the Hoehn and Yahr score, the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III), and the Montreal Cognitive Assessment (MoCA). A quality of life scale (8-item Parkinson's Disease Questionnaire, PDQ-8) and a scale measuring the ability to perform everyday activities (Instrumental Activities of Daily Living, IADL) were completed by the patient and/or informal caregiver.

Progressive apomorphine dose titration was performed according to a pre-established protocol that was the same for both groups (see Supplementary Material). Oral medication was adjusted by the investigating neurologist according to the patient’s clinical status.

Patients were seen by the investigating neurologist at 1 month (M1), 3 months (M3), and 6 months (M6) post-initiation. On each occasion, the investigator assessed their clinical status and recorded any adverse events. Patients completed the PDQ-8 and a self-report questionnaire created especially for this study to assess their autonomy in managing their treatment. The Clinical Global Impression – Improvement scale (CGI-I) assessing patients’ clinical improvement on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse) was completed by both the patient and the investigating neurologist at M1, M3 and M6. Lastly, we calculated the number of days spent in hospital, and the numbers of patient transport journeys, medical consultations, and visits by district nurses and the medical device supplier.

The criteria for the analysis were changes in patients’ perceived quality of life and their clinical status, assessed by both patient and investigator, as well as the occurrence of adverse effects, patients’ autonomy in managing their treatment, and the estimated cost of the treatment over the 6-month follow-up period. For quality of life, we analyzed the PDQ-8 scores at each timepoint (continuous variable), as well as the percentages of patients with a better, poorer or stable quality of life (categorical variable). More specifically, we deemed quality of life to have improved if the PDQ-8 score fell by at least 5.94 points, compared with baseline (D0), and to have worsened if this score rose by at least 4.91 points. Between the two, we considered quality of life to be stable.¹⁰ To calculate the cost of CSAI initiation, we obtained the prices of the different healthcare services and procedures from the National Health Insurance Fund.

First, for each continuous variable, we computed the mean value and standard deviation (SD), the minimum and maximum values, the median, and the interquartile range (Q1Q3). For each categorical variable, we calculated the number of patients and the percentage (%). Next, for the continuous variables, after we had checked the normality of the distribution (ShapiroWilk test), we ran group comparisons using either the Student t test (normal distribution) or the nonparametric KruskalWallis test (non-normal distribution). For the categorical variables, we performed comparisons with the chi-square or Fisher test when the numbers and percentages were sufficiently high. For quality of life (PDQ-8 score; continuous variable), we ran an analysis of variance (ANOVA) to assess the effects of time and initiation modality (home vs. in-hospital), and the possible interactions between the two. To compare any improvements in quality of life (PDQ-8 score; categorical variable) and clinical status (CGI-I) over the 6-month follow-up, we ran a chi² test to assess the effect of modality, and Cochran’s Q test to assess the effect of time. The significance threshold was set at 0.05 for all these tests.

According to the study protocol, we needed 64 patients in each group (i.e., total of 128 patients) in order to detect a meaningful difference between the two groups (≥ 0.5 x SD), corresponding to a medium effect size, with an alpha risk of 5% and power of 80%.

Data Availability statement

A minimal data set is provided in supplementary information files (see Supplementary Material 2) and complete data are available on demand from the corresponding author.

A total of 145 patients (84 men and 61 women), with a mean age of 70.1 years (range: 37‑92) were included between 17 September 2018 and 30 December 2020. Mean disease duration was 11.1 years (range: 2‑30). The mean Hoehn and Yahr score was 2.2 (range: 0‑5) on medication, and 2.8 (1‑5) off medication. The mean UPDRS-III score off medication was 35.1 (8‑68). The mean MoCA score was 25/30 (range: 6‑30). The mean IADL score was 1.35 (0‑4), and the mean baseline PDQ-8 score was 39.6 (0‑69). A total of 80% of patients had an informal caregiver, 8.6% were in employment, and 17.1% were registered as having a disability because of their disease. A total of 40% had at least a high-school diploma. CSAI was indicated for motor fluctuations (91% of patients), gait problems (29%), difficulty swallowing (4.8%), or as a stop-gap whilst awaiting deep-brain stimulation (2.1%). Patients could have more than one indication.

A total of 44 neurologists took part in the present study: 19 were working at a hospital, and 25 in private practice. They were free to choose the initiation modality (home vs. in-hospital), which they did so mainly according to their place of practice, as well as their patients’ wishes. As a result, 106 patients were initiated on CSAI at home, and 38 in hospital (data were missing for one patient, who was excluded from group analyses). The home and hospital groups were similar on age, sex ratio, disease duration, motor symptoms (UPDRS-III, Hoehn and Yahr), cognitive status (MoCA), ability to perform everyday activities (IADL), quality of life (PDQ-8), CSAI indication, presence of an informal caregiver, and socioeconomic status (Table 1). They were also similar on education level and medical history (data not shown).

Quality of Life

PDQ-8 scores fell over time (Fig. 1), reflecting an improvement in patients’ quality of life. These scores fell significantly between CSAI initiation (baseline) and the final assessment at M6 (ANOVA, p < 0.001), with reductions of 4.9 points at M1, 6.4 points at M3, and 9.2 points at M6 representing improvements of 11%, 15%, and 21%. There was a significant improvement as early as the first month of treatment (p = 0.007). Furthermore, quality of life at M1 was significantly better (ANOVA, p = 0.004) in the home group than in the hospital group, with a difference of 4.5 points (10%) in the PDQ-8 score between the two.

The percentage of patients whose quality of life improved after CSAI initiation (reduction in PDQ-8 score of more than 5.94 points) was significantly higher in the home group than in the hospital group (p = 0.048). This percentage varied over time: between 43% and 50% for the home group, and between 34% and 42% for the hospital group (Fig. 2). The percentage of patients whose quality of life remained stable (4.91 ≥ PDQ-8 score ≤ -5.94) was higher in the home group (43‑50%) than in the hospital group (32‑42%) (Fig. 2), and there were fewer patients with a reduced quality of life (increase in PDQ-8 score of more than 4.91 points) in the home group (13‑18%) than in the hospital group (18‑29%) (Fig. 2).

Clinical Improvement

As early as the first month, many patients experienced an improvement in their clinical status, from both their own point of view and that of the investigator, particularly in the home group. The percentages of patients whose clinical status was much improved or very much improved remained stable and even increased over time (Figs. 3 & 4).

The distribution of patients across the seven CGI-I categories (patient ratings) differed significantly between groups (p = 0.023). At every timepoint, the percentages of patients who reported that their status was much improved or very much improved were significantly higher in the home group than in the hospital group (Fig. 3). The results were the same for the investigator ratings (p = 0.010) (Fig. 4).

The distribution of patients across the CGI-I categories according to the investigator ratings varied over time (p < 0.001). The number of patients whose clinical status was perceived by the investigator to have only minimally improved was higher at M1 than at M3 and M6, whereas the number of patients whose clinical status was perceived to be much improved or very much improved was higher at M6 than at M1 and M3 (Fig. 4). Although the distribution of patients across the CGI-I categories according to the patient ratings did not differ significantly, the p value (0.067) was close to the significance threshold (0.05), and the percentages of patients who reported that their status was much improved or very much improved tended to increase after M1 in both groups (Fig. 3).

Autonomy

At M1, M3, and M6, at least as many patients in the home group as in the hospital group, if not more, stated that they were in control of their treatment and autonomous in its management, but there were generally no significant differences between the two groups (Fig. 5).

Side Effects and Dropouts

Bruising or itching at the injection site was reported by around 25% of patients, and small nodules by 33% of them, regardless of initiation modality. There was a single reported case of skin necrosis in each group.

Nausea was reported by at least 20% of patients at M1 and 10% at M6, but this did not affect the prescribing of apomorphine. Episodes of mental confusion were reported in around 10% of patients across follow-up, and light to moderate hallucinations in 20% of patients at M1 and 26.4% at M6. Only three patients, all in the home group, exhibited severe forms of hallucinations, and these regressed once their treatment had been adjusted. Behavioral disorders were reported in 5.3% cases at M1. These were light to moderate, and did not worsen over time. Orthostatic hypotension was found in 16.7% of patients. This only warranted corrective treatment in five cases (four in the home group, and one in the hospital group). Dyskinesias were noted in approximately 25% of cases, two of which (both in the home group) were described as severe.

The frequency of side effects was similar regardless of initiation modality (Fig 6). Most of these side effects were light to moderate, while out of the 34 severe side effects we recorded, 23 were reported in the home group, and 11 in the hospital group. In most cases, they took the form of sleepiness (seven cases in the home group, and six in the hospital one). There were four cases of hypotension and three of nausea in the home group.

Altogether, there were 22 dropouts (i.e., 15.3% of patients): 17 (16%) in the home group, and five (13%) in the hospital one. Eight occurred within the first month of treatment. Ten (7%), including seven (6.6%) in the home group and three (7.8%) in the hospital group, were due to a loss of motivation when confronted with the challenges of using the device. Three were due to difficulty controlling impulses, and three to the onset of mental confusion. All of these occurred within the first few weeks of treatment. A single patient had to stop the treatment owing to severe orthstatic hypotension.

Lastly, there were four deaths, three following lung infections that occurred shortly after CSAI initiation in patients who had started the treatment because of severe difficulty swallowing.

Cost Analysis

On average, the financial cost per person for the first month following home initiation comprised 1.6 neurology consultations, 7.4 visits by the medical device supplier, and 42 visits by a district nurse. During this same month, patients in the hospital group spent an average of 7.3 days in hospital. On average, there were 5.1 visits by the device supplier, and 30 by the district nurse. Beyond M1, on average, there were slightly more medical consultations and slightly fewer visits by district nurses for the home group than for the hospital one, as well as fewer days in hospital.

Across the 6-month follow-up, patients in the home (versus hospital) group required more medical consultations (3.4 vs. 1.5) and visits by district nurses (114 vs. 75), but virtually the same number of patient transport journeys (2.2 vs. 2.5), and they crucially avoided 10 hospital inpatient days (0.9 vs. 10.9). As the medical device supplier charged a monthly fee based on the number of days, this fee was lower for the hospital group than for the home one at M1, but the same across the two groups in all subsequent months. The mean difference in cost between the two modalities was therefore estimated at €11 387 per patient (Table 2).

Our sample was slightly older (M_age = 70 years) than those in most other studies,^10–13 but similar in terms of disease duration,^13–15 clinical status (as assessed with Hoehn & Yahr and UPDRSIII),^10,13,14 and quality of life (as assessed with the PDQ-8^10,16 or PDQ-39^14,18) to those in other studies assessing the efficacy of CSAI. For 91% of participants in our study, the motivation for initiating this therapy was the presence of motor fluctuations, as was the case in most studies.^6,13,18 Moreover, as elsewhere, 80% of our patients had an informal caregiver.^3,14 Given that our two groups (i.e., home and hospital) did not differ on any of the above characteristics, we were able to run intergroup comparisons.

Although several studies did not objectively measure the improvement in quality of life, using either the PDQ-8¹⁵ or PDQ-39¹⁸, many others did do so, reporting mean improvements of between 11% and 42%,^{2,10,13,14,16,19} particularly during the first 612 months of CSAI.²⁰ In our study, quality of life as measured with the PDQ-8 had improved by an average of 9.2 points (i.e., 21%) after 6 months of treatment across the whole sample, and by 13.7 points (= 9.2 + 4.5) points (i.e., 32%) for patients in the home group. Moreover, this improvement generally happened sooner in the home group than in the hospital group, with 43.4% of patients reporting an improved quality of life (reduction of 5.94 points or more in the PDQ-8 score)¹⁰ as early as M1, compared with 34.2% in the hospital group. It should be noted that the mean improvement at M1 was 9.4 points for the home group versus 4.7 points for the hospital group.

Some studies^11,15 that also administered the CGI-I found that more than 70% of patients improved after commencing CSAI. However, when we looked solely at patients whose clinical status had either much or very much improved, this proportion was a more modest 30% after 3 months of treatment,⁶ rising to between 45% and 66% after 6 months.^1,18 These figures are similar to those we found for our participants, and reflect the gradual nature of the clinical improvement and the value of maintaining the treatment for several months at least, to properly gauge its usefulness.

We observed a significant difference according to the modality of initiation: half the patients in the home group stated that their clinical status had much or very much improved after the first month of treatment, compared with just a third in the hospital group.

The PDQ-8 and CGI-I therefore highlighted improvements in most patients, comparable to those reported in the literature, but these improvements took place sooner among patients in the home group. Although the impact of using nurse specialists is still difficult to demonstrate²², this swifter and stronger improvement in our study probably reflects the importance of personalized care delivered to patients in their own home by the medical device supplier and team of district nurses. Regular visits by a single specialist supplier who is prepared to spend time with the patient and caregiver ensure continuity of care in the initial phase and install a climate of confidence that reinforces treatment adherence. Daily visits from district nurses, often already known to the patients, are another reassuring factorand a source of patient and caregiver satisfaction.^23–25 We can therefore conclude that this personalized approach has a genuine impact on patients’ assessment of the care they receive and on the degree of improvement in their clinical status and quality of life. This underlines the fact that the success of a given treatment depends not only on the choice of medication, but also on the extent to which the patient (and caregiver, where relevant) understands the disease and is able to manage the device,²⁶ and the latter is enhanced when assistance is given in the patient’s own home.^24,27

For some patients, being able to insert the needle and set up the device themselves may be an additional convenience (fewer home visits from healthcare professionals, easier to travel and go on holiday) but autonomy is not an end in itself, and frailer patients may find daily visits by a district nurse reassuring. In our study, patients had generally acquired a degree of autonomy by the end of the first month of treatment, particularly when it came to changing the syringe and inserting the needle.

Similar proportions of mild to moderate side effects were found in each group. Problematic subcutaneous nodules were reported by more than a third of patients in our study, which is equivalent to the proportions reported in other recent studies (44%),^6,15 and lower than those reported in earlier ones,^28,29 probably reflecting an improvement in treating this particular side effect in recent years.

Troublesome though moderate sleepiness was found in 3.4% of our patients, which is a similar result to those of other studies.^10,16,29,30 The same was true for episodes of mental confusion (9%), visual hallucinations (20.3%), and behavioral problems (5.3%).^29,31,32

Dyskinesias persisted in around 25% of patients, but only 3.3% found them problematic, which is comparable to other studies.³³ Their continuing presence did not have a negative impact on either their quality of life or their impression of improvement.

The two groups did not differ on dropout frequency which, at 15% of patients, was lower than that reported in the literature after 6 months of treatment (approx. 30%^12,13,15). As for the reasons given for dropping out, lack of efficacy and loss of motivation accounted for 45% of dropouts among our patients, while side effects, mainly neuropsychiatric, accounted for 30%, which is comparable to the data in the literature.^{11–13, 34}

A total of four (2.5%) deaths were observed: one in the hospital group, and three in the home group (p = 0.8). These occurred within the first few weeks of treatment for two of the patients, and during the fourth and fifth months for the two others. Three were among the seven patients who had severe difficulty swallowing. The cause of death was aspiration pneumonia for two of these patients, and choking for the third one. The frequency of occurrence was comparable to the rates reported in the literature: 2.5% at 6 months¹³ and 7.3% at 12 months.¹²

The different medical devices used to treat patients with PD (neurostimulator, duodopa pump, and apomorphine pump) are all relatively expensive,^8,9 so it is important to try and reduce their cost without impacting quality of life. Although we found that home initiation required more visits by district nurses during the first month, patients became autonomous more quickly, meaning that the final number of visits was the same across the two groups. Moreover, although home initiation required two additional neurology consultations, this has to be set against a 7-day hospital stay. It is also worth pointing out that although home initiation required more visits by the device supplier (2.5 on average), this did not modify the cost, as the supplier charged a set fee. Home initiation requires greater commitment and more human resources from the supplier, but the latter is recompensed in the medium and long term by greater patient satisfaction and longer use of the pump. Home initiation where the patient is supported by the device’s supplier and by a team of district nurses, supervised by the neurologist, brings about a swifter improvement in the patient’s clinical status and quality of life and incurs a lower cost, as far fewer days are spent in hospital.

The main limitation of this prospective study was the absence of randomization. The decision to embark on this treatment was made by the neurologist, but the patient and patient’s caregiver also had their say. Although patients were evenly distributed across the two groups at the beginning of the recruitment period, the success of the method, together with the difficulty of accessing routine or planned hospital care after the COVID-19 pandemic struck in March 2020, led some neurologists working in hospitals to favor home initiation. This further emphasizes its usefulness, not least in terms of planning and delivering patient care. It should be noted that the imbalance that emerged between the two groups did not hinder our group comparisons.

The present study demonstrated the efficacy and good tolerance of CSAI, regardless of initiation modality. Patients in the home group experienced a more rapid improvement in their quality of life and clinical status. Providing the treating neurologist has received the necessary training, and all the stakeholders (i.e., physician, patient, caregiver, nurse) are sufficiently motivated,^5,26 home initiation seems to bring satisfaction all round. Many patients could therefore benefit from it, if they have the relevant medical profile (motor fluctuations, few or no cognitive disorders)³⁵ and the right personal (motivation, understanding of the procedure and what it involves) and contextual (presence of a caregiver) characteristics. It is also important for neurologists to make themselves available during the initiation phase and to work closely with trusted suppliers, devoting the necessary time and energy to their patients’ care. The fact that home initiation is cheaper than in-hospital initiation means that CSAI should become more accessible to patients, with the treating neurologist playing a key role in patient follow-up. As neurologists working at a hospital or in private practice become more familiar with CSAI, they may start to prescribe it in more complex situations (difficulty swallowing, sleep problems, digestive surgery, palliative care),³⁶ to avoid sudden interruptions in treatment and the attendant complications, and improve patient comfort.

Author contributions

A.L, I.V.D, F.Z, R.B. designed and conceptualized the study.

F.Z., A.L., I.V.D., M.Z., M.V. contributed to the interpretation of data.

F.Z., A.L., M.Z., M.V. contributed to writing manuscript.

All authors contributed to data collection, to critical revision of the manuscript for intellectual content and final approval of the completed version.

Competing interests :

the Authors declare no Competing Financial Interests but the following Competing Non-Financial Interests. None of theses interests modify their analysis of the data.

F.Z. served on scientific advisory boards for Aguettant, Adsia and Elivie, received research support from Adelia and received travel grant from Aguettant;

A.L. served on scientific advisory boards for Adsia and Elivie, received research support from Adelia;

I.V.D. received travel grant from Adelia

J.P.D.M. received research support and received travel grant from Adelia;

A.P. received travel grant from Adelia

M.Z.

M.V. served on scientific advisory boards, received research support and received travel grant from Aguettant, Adelia, Elivie, LVL, Orkyn;

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Table 1 Baseline Characteristics of Patients in Each Group (N = 144)

	Home n = 106	Hospital n = 38	p value
Mean age in years (SD)	69.9 (9.3)	70.5(8.8)	0.74
Men: n (%)	64 (60.4)	20 (52.6)	0.52
Mean disease duration in years (SD)	11.1 (5.8)	11.3 (4.2)	0.26
Mean UPDRS-III OFF score (SD)	33.9 (18.0)	37.3 (17.1)	0.67
Mean Hoehn & Yahr ON score (SD)	2.2 (0,9)	2.3 (0,9)	0.63
Mean MoCA score (SD)	24.8 (4.1)	25.6 (2.9)	0.52
Mean IADL score (SD)	1.3 (1.4)	1.5 (1.5)	0.44
Mean PDQ-8 score (SD)	39 (14.7)	41 (15.1)	0.53
Informal caregiver: n (%)	89 (84.0)	27 (71.0)	0.14
Currently in employment: n (%)	10 (9.88)	2 (5.6)	0.73
Disabling motor fluctuations: n (%)	98 (92.5)	34 (89.5)	0.52

Note. Missing data were not replaced. Tests: Student t, chi², or Kruskal‑Wallis.

IADL: Instrumental Activities of Daily Living; MoCA: Montreal Cognitive Assessment; PDQ-8: 8-item Parkinson's Disease Questionnaire; SD: standard deviation; UPDRS-III: Unified Parkinson’s Disease Rating Scale Part III.

the Authors declare no Competing Financial Interests but the following Competing Non-Financial Interests F.Z. served on scientific advisory boards for Aguettant, Adsia and Elivie, received research support from Adelia and received travel grant from Aguettant; A.L. served on scientific advisory boards for Adsia and Elivie, received research support from Adelia; I.V.D. received travel grant from Adelia J.P.D.M. received research support and received travel grant from Adelia; A.P. received travel grant from Adelia M.Z.served on scientific advisory boards, and received travel grant from Aguettant, Adelia, Elivie, LVL, Orkyn; M.V. served on scientific advisory boards, received research support and received travel grant from Aguettant, Adelia, Elivie, LVL, Orkyn;

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Feasibility of home initiation of subcutaneous apomorphine infusion for patients with Parkinson’s Disease

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