Abstract
Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the major advances in the clinical management of Parkinson’s disease (PD). Although DAT are being increasingly offered earlier in the disease course, their classical indication remains advanced PD. Theoretically, every patient should be offered transition to DAT when faced with refractory motor and nonmotor fluctuations and functional decline. Worldwide clinical reality is far from these ideal, and, therefore, question the “real-world” equal opportunity of access to DAT for PD patients with advanced PD—even within a single health care system. Differences in access to care, referral pattern (timing and frequency), as well as physician biases (unconscious/implicit or conscious/explicit bias), and patients’ preferences or health-seeking behaviour are to be considered. Compared to DBS, little information is available concerning infusion therapies, as well as neurologists’ and patients’ attitudes towards them. This viewpoint aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm their own biases, patient perspective, ethical concerns as well as the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.
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Introduction
“The existing guidance tends to imply that right answers exist rather than recognising the complex trade-offs that have to be made between conflicting aims.”
Barber BMJ. 1995 Apr 8; 310(6984): 923–925.
Device-aided therapies (DAT), which include brain surgery and pump-based continuous dopaminergic stimulation (with either levodopa or apomorphine), are among the major advances in the clinical management of Parkinson’s disease (PD) (Krüger et al. 2016; Obeso et al. 2022). Stemming from brilliant empirical clinical experiments led in the 1970s and having entered clinical practice in the late 1990s–early 2000s (Table 1), they have revolutionised treatment options and patients’ quality of life. Their development is intertwined with the understanding of PD pathophysiology and, more broadly, of ever-growing technological advances (neurosurgery, pump technology). Four DAT are currently available in many parts of the world: (1) deep brain stimulation (DBS) of different targets (subthalamic nucleus—STN and globus pallidus internus—Gpi to treat dopaminergic fluctuations, and ventral intermediate nucleus of the thalamus—VIM for parkinsonian and non-parkinsonian tremor), (2) continuous subcutaneous apomorphine infusion (CSAI), (3) levodopa–carbidopa intestinal gel (LCIG), also designated in the United States of America (USA) as carbidopa–levodopa enteral suspension (CLES) (Burack et al. 2018), and (4) levodopa–entacapone–carbidopa intestinal gel (LECIG).
New formulations and devices, allowing the continuous subcutaneous infusion of levodopa, are getting close to entering the therapeutic armamentarium of PD specialists: ND0612 (Ramot et al. 2017; Olanow et al. 2021; Giladi et al. 2021; Poewe et al. 2021; LeWitt et al. 2022) and ABBV-951, a 24-h/day continuous subcutaneous infusion of a soluble levodopa/carbidopa phosphate prodrug combination (Rosebraugh et al. 2021a, b, 2022a, b; Soileau et al. 2022).
When faced with so many options, how to make a choice for a given patient? In other terms, and as worded by Nick Barber: “what constitutes good prescribing?” (Barber 1995). Patients may be suitable for a single DAT only (due to contraindication) but, most of the time, they face two or more choices (Volkmann et al. 2013). The Barber’s model encompasses four critical aims of drug prescribing: maximising effectiveness, minimising risks, respecting patient’s choice, and minimising costs (the latter being from both the healthcare system and patient’s perspective). The same considerations apply to medical devices, hence to DAT in PD. This viewpoint, therefore, aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm topics with which they are not necessarily familiar: their own biases, patient perspective, ethical concerns, and the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.
When to start thinking about DAT in advanced PD? On what grounds?
Although DAT are increasingly being offered earlier in the disease course in many expert centres (Schuepbach et al. 2013; Fernández-Pajarín et al. 2022), their classical indication remains advanced PD. Despite its wide use, the term “advanced PD” is still controversial, ambiguous, and rather subjective (Antonini et al. 2018; Fasano et al. 2019). It is largely defined by the emergence of dopaminergic motor and nonmotor complications leading to functional decline (worsening of quality of life, reduced independence in daily life activities), and by a reduction of response to conventional optimised oral therapy (Titova et al. 2017; Sesar et al. 2021). For non-PD specialists, identifying patients progressing to this stage, and, therefore, suitable for DAT, can be quite challenging (Luquin et al. 2017; Williams et al. 2017; Antonini et al. 2018; Fasano et al. 2019). Several attempts have, therefore, been made to reach consensus on the key factors for diagnosing advanced PD. In 2015, the NAVIGATE-PD program offered a collective physician perspective on DAT initiation (Odin et al. 2015). It was followed by the Spanish CEPA-study and the validation of a neurologist-based questionnaire, aiming at quickly identifying patients with advanced PD in the clinical setting (Luquin et al. 2017; Martinez-Martin et al. 2018). The international dissemination of this screening tool does not appear to be successful so far, probably because clinical key indicators of a transition to advanced PD were subsequently defined by a multi-country Delphi-panel involving PD specialists from 10 European countries (Antonini et al. 2018). The abbreviated version, known as the “5–2–1 criteria” (≥ five-times daily oral levodopa, ≥ two daily hours with ‘Off’ symptoms or ≥ one daily hour with troublesome dyskinesia) was launched in 2018 (Antonini et al. 2018), and has since been recognised as an objective, relevant and reliable tool, suitable for clinical practice (Santos-Garcia et al. 2020; Aldred et al. 2020; Malaty et al. 2022; Stefani et al. 2022; Antonini et al. 2022a). Nevertheless, the OBSERVE-PD study showed that this tool is not yet fully integrated into standard practice in many countries, as more than half of the patients identified by physicians as “non-advanced PD” actually met the 5–2–1 criteria (Fasano et al. 2022). Another screening tool, known as the MANAGE-PD tool (Making Informed Decisions to Aid Timely Management of Parkinson’s Disease) was recently designed by an international panel of PD experts (Antonini et al. 2021). Sound methodological questions regarding its development were, however, raised (Moes et al. 2022), and its relevance and accuracy still need to be assessed in the “real world” clinical practice. To date, identification of advanced PD patients, therefore, remains a challenge in many clinical settings.
Identifying patients with advanced PD is a critical but insufficient step. As highlighted by the OBSERVE-PD study (Fasano et al. 2019, 2022), apart from a few exceptions (Takáts et al. 2020; Evans et al. 2021; Möller et al. 2021), only a fraction of the patients deemed eligible for a DAT were initiated (Table 2).
Most advanced PD patients are, therefore, chronically treated in a suboptimal way, because (1) they were either never referred to a PD specialist, (2) they were wrongly labelled as “non-advanced PD”, or (3) they were eligible but delaying or on a waiting list for DAT initiation (Fasano et al. 2019; Szasz et al. 2021; Stefani et al. 2022; Pedrosa et al. 2022). In 2017, one study estimated that only 10–15% of patients eligible for DBS were referred to specialised centres (Lange et al. 2017).
Theoretically, when faced with refractory motor and nonmotor fluctuations relevant to quality of life and activities of daily living, patients with advanced PD should be offered counselling for DAT to evaluate the risk–benefit ratio of an individual patient to undergo DAT. The real-world practice is far from these ideal. Factors accounting for these discrepancies need to be acknowledged and studied, whether they are linked to clinicians, patients and/or health systems.
Looking at worldwide prescription patterns of DAT: does every patient with advanced PD has the same treatment opportunities?
Despite general guidelines issued by expert consensus or scientific international societies—including for DAT prescribing in PD (Hilker et al. 2011; Trenkwalder et al. 2015; Fabbri et al. 2018; Dijk et al. 2020), therapeutic approaches and prescription patterns differ internationally, but also nationally (Kalilani et al. 2019; Bruno et al. 2022).
Worldwide use and repartition of DAT
Not all DAT are approved nor realistically available worldwide, due to financial limitations (including DAT costs and reimbursement issues), resource capacity and local expertise (Volkmann et al. 2013; Szaz et al. 2019; Henriksen et al. 2020; Bhidayasiri et al. 2020; Cramer et al. 2022). Apart from the OBSERVE-PD cohort (Fasano et al. 2019), data regarding national use and repartition of DAT are scarce (Ezat et al. 2017; Richter et al. 2019; Henriksen et al. 2020; Nordin et al. 2021; Thaler et al. 2022), particularly outside of Europe (Tables 2 and 3).
DBS appears to be the oldest DAT available in many countries (~ 30 years) and the most prescribed (except in Denmark) with more than 150,000 implants worldwide (Henriksen 2020; Montemayor et al. 2022). Infusion therapies are less commonly used: within the OBSERVE-PD cohort, 39% of patients used LCIG, and only 8% were receiving CSAI (Fasano et al. 2019). The same ranking, with CSAI as the least used DAT, is found in most countries (Ezat et al. 2017; Richter et al. 2019; Henriksen et al. 2020; Nordin et al. 2021; Thaler et al. 2022). Of note, CSAI remains unavailable in many countries, including the United States of AmericaFootnote 1 and Japan (Auffret et al. 2018; Fasano et al. 2022; Fujioka et al. 2023). Although specialised clinical settings (including access to neurosurgery/gastroenterologist) are needed for DBS and LCIG/LECIG implementation (Richter et al. 2019; Henriksen et al. 2020), it is not the case for CSAI, which is considered as the easiest DAT to implement (Fasano et al. 2020). This striking lack of access to CSAI is, therefore, concerning, given its ease of initiation (minimally invasive, completely reversible, and no need of any kind of surgery), its strongly established efficacy on PD motor and nonmotor symptoms, and its good safety profile (Auffret et al. 2018; Katzenschlager et al. 2018, 2021; De Cock et al. 2022). LECIG has still limited data regarding its rate of implementation and repartition at the time of our writing, being a very recent addition to DAT therapies (Nyholm and Jost 2022).
Globally, there has been an increase in the use of DAT over the past decades (Richter et al. 2019; Henriksen et al. 2020; Norlin et al. 2021; Cramer et al. 2022), consistent with the overall increase in PD cases (Richter et al. 2019; Ou et al. 2021). However, the acute and long-term effects of the Covid-19 pandemic on this trend need to be determined. On one hand, the crisis created opportunities in the remote management of PD patients (Abate et al. 2020; Fasano et al. 2020; Roszmann et al. 2022) and even bolstered outpatient initiation of CSAI in France (Zagnoli et al. 2023). On the other hand, it led to acute, severe, and lasting disruptions and/or delays in DAT initiation requiring scheduled hospitalisations and/or surgeries (Fasano et al. 2020; Richter et al. 2021; Roszmann et al. 2022), as well as patient education (Roszmann et al. 2022). In addition, patients already receiving a DAT were also differently impacted by the pandemic, as demonstrated by an Italian study (Montanaro et al. 2022). PD patients treated with either DBS or LCIG during the lockdown experienced psychological distress, related to the fear of device dysfunction (and subsequent difficulties of obtaining adequate and rapid healthcare assistance), or the risk of a caregiver Covid-19 infection (Montanaro et al. 2022).
Documented disparities in accessing DAT
Addressing global disparities in PD has been recently defined as a World Health Organization priority (Schiess et al. 2022). Unfortunately, there are known racial, gender and socioeconomic disparities in the general care of PD patients, even within a single healthcare system (Dahodwala et al. 2009; Willis et al. 2011; Henriksen et al., 2020; Nwabuobi et al. 2021; Subramanian et al. 2022). Yet, disparities in accessing DAT have been seldomly studied, apart from DBS (Crispo et al. 2020; Jost et al. 2022), for which most of the studies were led in the USA (Willis et al. 2014; Chan et al. 2014; Shpiner et al. 2019; Shirane et al. 2020; Watanabe et al. 2022). For DBS, concerning disparities regarding race (Willis et al. 2014; Chan et al. 2014; Shirane et al. 2020; Watanabe et al., 2022; Cramer et al. 2022), gender (Willis et al. 2014; Hariz et al. 2011; Shpiner et al. 2019; Shirane et al. 2020; Henriksen et al., 2020; Cramer et al. 2022; Watanabe et al. 2022; Jost et al. 2022), socioeconomic status (Willis et al. 2014), as well as insurance availability and type (Chan et al. 2014; Shpiner et al. 2019; Cramer et al. 2022) are consistently reported. White men are more likely to be referred and undergo DBS compared to women or their non–Caucasian counterparts (Willis et al. 2014; Chan et al. 2014; Shirane et al. 2020; Watanabe et al. 2022; Cramer et al. 2022; Deshpande et al. 2022; Jost et al. 2022). Moreover, greater disease severity and disability at the time of DBS referral is more common for women and non-Caucasian patients (Hariz et al. 2003; Shirane et al. 2020; Cramer et al. 2022; Jost et al. 2022), which can significantly reduce the window of opportunity to initiate surgery. Despite similar indications for all DAT, patients who are initiated on infusion therapies are older than those undergoing DBS, and more likely female (Richter et al. 2019).
All the above, therefore, question the “real-world” equal opportunity for PD patients, even within a single health system, and hint at differences in access to care, referral pattern biases (timing and frequency), physician biases (unconscious/implicit or conscious/explicit bias), patients’ preferences and health-seeking behaviour (Shirane et al. 2020; Crsipo et al. 2020; Cramer et al. 2022).
Referral and access to PD specialists
Worldwide, physicians have been largely dichotomised into generalists and specialists (Swarztrauber and Vickrey 2004). Perceived as difficult by both medical students and physicians (Flanagan et al. 2007; Zinchuk et al. 2010), neurology has the same dichotomy, adding another layer of complexity (general neurologists and movement disorders specialists). Studies have shown differences in primary care physicians’ and neurologists’ preferences for involving a specialist in the care of patients with neurological conditions (Swarztrauber et al. 2002), as well as disagreement for the extent of specialty involvement in patients’ evaluation and management (Swarztrauber and Vickrey 2004). To be considered eligible for any DAT, patients must be referred to a neurologist, and preferably to a movement disorders specialist, who will assess whether they are suffering from advanced PD. The lack of referral has been consistently reported as a major impediment, notably for DBS, in North America, Asia and Europe (Henriksen et al. 2020; Zhang et al. 2020). Notably, women and minorities obtain neurologist care less often than white men (Willis et al. 2011), whereas early referral to a movement disorder specialist is important to maintain satisfactory levels of quality of life and ensure access to DAT (Williams et al. 2017).
Lack of awareness or knowledge on PD, and misjudgement of the need for referral among primary care physicians (or even general neurologists) are, therefore, a potentially insurmountable obstacle at the very first level of the care pathway (Swarztrauber et al. 2002; Swarztrauber and Vickrey 2004; Li et al. 2014; Ahlskog et al. 2020; Zhang et al. 2020).
Do clinician biases exist when selecting DAT in advanced PD?
Available DAT are all indicated for advanced PD and show efficacy in treating both motor and nonmotor symptoms (Timpka et al. 2017; Dafsari et al. 2019; Deuschl et al. 2022). However, as previously highlighted, there are significant disparities in their repartition and prescription patterns, suggesting local habits and/or individual preferences (Carron et al. 2011; Richter et al. 2019). No established standard referral criteria, including timing or cut-off of improvement from medical management before proceeding with DAT, are used across providers (Cabrera et al. , 2019, 2021a; Marsili et al. 2021), paving the way to physician biases-related disparities (Hariz et al. 2003; Willis et al. 2014; Chan et al. 2014; Cabrera et al. 2019; Shirane et al. 2020; Watanabe et al. 2022; Cramer et al. 2022; Deshpande et al. 2022; Jost et al. 2022).
In the era of evidence-based medicine, clinical decision making involves the use of evidence, and encompasses both clinical expertise and the needs and wishes of individual patients (Bate et al. 2012). However, like the general population, health care providers (including neurologists and nurses) are faced with cognitive and affective, implicit and explicit biases, including racial and gender biases (Ryn et al. 2011; Lilienfeld and Lynn 2014; Marcum et al. 2017; Featherston et al. 2020; Tolsa et al. 2022; Thirsk et al. 2022). Numerous cognitive biases exist in clinical practice, particularly when using cognitive short-cutting (Croskerry 2002; Dobler et al. 2019). They need to be acknowledged as they influence clinicians’ behaviour and can seriously impact the quality, consistency and accuracy of clinical decision making, hence care delivery and patient’s outcome (Croskerry 2002; Bate et al. 2012; Klocko 2016; Featherston et al. 2020; Thirsk et al. 2022). They include anchoring bias (“undue emphasis given to an early salient feature during a consultation”), ascertainment bias (thinking influenced and shaped by prior expectations, like gender bias and stereotyping), availability bias (“recent experience dominates evidence”), Bandwagon effect (“We do it this way here”), confirmation bias (looking for supporting evidence rather than seeking information ruling it out), omission bias (tendency towards inaction, reluctance to treat) or playing the odds (opposite of the “rule out the worst case” scenario), framing bias (reaction to a choice varies depending on its presentation, for instance, as a loss or as a gain), Sutton’s slip (going for the obvious), Gambler’s fallacy (law of averages, sequence effect: “tendency to think that a run of diagnoses means the sequence cannot continue, rather than taking each case on its merits”), search satisficing (premature closure, or to stop investigating after having found one diagnosis, hence other co-existing conditions are not detected), vertical line failure (thinking in silos, or inside the box), triage cueing (“to create bias at the initiation of triage that then influences the ultimate choice of patient management”), blind spot bias (“Other people are susceptible to these biases but I am not”), visceral bias (emotional involvement), and illusory correlation/superstition (seeing a causal relationship between conditions, events or actions when there is none) (Croskerry 2002; Bate et al. 2012; Klocko 2016; Dobler et al. 2019). Emotional biases encompass personal values (anticipation of patient’s behaviour based on own values), negative experience (recollection of negative events) and cultural bias (judging exclusively from own cultural reference system) (Tolsa et al. 2022). Several clinicians related factors are, therefore, to be considered, encompassing the entire care pathway, from patient identification and referral to DAT selection, initiation, and follow-ups.
Unfamiliarity or lack of personal experience
Not all neurologists have had personal experience with the implementation, management, and follow-up of the four existing DAT (Lange et al. 2017; Burack et al. 2018; Henriksen et al. 2020), even though a recent survey in Japan suggested that experience with DATs did not influence the directions of neurologist’s preferences (Fujioka et al. 2023).
Some consider themselves incompetent to determine whether a PD patient would be eligible for any DAT (Moes et al. 2022), notably due to limited knowledge about selection criteria (Lange et al. 2017). Knowledge about new indications or shift in DAT timing can also be limited (Cabrera et al. , 2019, 2021a), and uptake on new treatment guidelines has been shown to be slow, one explanation being the lack of neurologists with sufficient DAT experience (Norlin et al. 2021) or, more broadly, attachment to clinical experience, the latter possibly being related to the Bandwagon effect (Bate et al. 2012; Klocko 2016; Tolsa et al. 2022).
Neurologists’ preferences and attitudes
Neurologists’ preferences for DAT in advanced PD have only been recently surveyed in Japan, (Fujioka et al. 2023). Based on hypothetical decision-making, treatment without the need for surgery (under development continuous subcutaneous infusion of levodopa–carbidopa) was strongly preferred, regardless of its need for frequent management, over DAT requiring surgery, namely LCIG and DBS (Fujioka et al. 2023). The findings of this study are thought-provoking, though they may not transfer to other countries, given that CSAI and LECIG are currently unavailable in Japan.
Contrary to infusion therapies, neurologists’ knowledge and attitude towards DBS and its timing has been investigated (Shih and Tarsy 2011, 2019, 2021a; Li et al. 2014; Cabrera et al. ). Significant differences between movement disorders specialists and non-specialists regarding medication and use of DBS in advanced PD are found (Shih and Tarsy 2011). Knowledge about DBS for movement disorders has been investigated in young neurologists from Egypt, as well as general neurologists from China, and deemed limited in both cases (Li et al. 2014; El-Jaafary et al. 2021).
More studies are needed to better understand neurologists’ preferences worldwide and how they transfer to clinical practice.
Pitfalls of clinical trials
Clinical trials are an essential part of today’s evidence-based medicine. However, patients with advanced PD encountered in real-world practice often differ from those participating in clinical trials (Volkmann et al. 2013; Burack et al. 2018). This can lead to inadequate translation of study results into clinical practice (i.e. dose adjustment, severity of motor and nonmotor symptoms, side effects, degrees of improvement). In the BALANCE study, clinical practice regarding LCIG has been found to differ from the available evidence on best use, with delaying treatment initiation to elderly and more advanced patients, which led to higher rates of treatment-emergent adverse effects and inferior quality of life outcomes (Weiss et al. 2022).
Similarly, until the publication of the TOLEDO study, the only available data regarding CSAI were coming from observational or retrospective cohorts (Katzenschlager et al. 2018, 2021). As a result, these data coming from “real-word settings” were often criticised and/or disregarded in the scientific and medical literature, despite their relevance in clinical practice (Antonini et al. 2022b). On the contrary, STN-DBS has been extensively studied (Deuschl et al. 2022), and the abundance of scientific and medical literature may play in favour of its use.
Medical myths and misconceptions
Over the years, various myths and misconceptions about neurology (neurophobia), PD and its treatment (i.e. levodopa phobia) have spread and flourished in the medical community, including among neurologists (Espay and Lang 2017; Ahlskog et al. 2020). These misconceptions also extend to DAT (Table 4). For instance, the need to (self-)inject has long been associated to a general perception of a “needle phobia”, with patients consequently being unwilling to use CSAI, but physicians may overestimate its extent among PD patients actually experiencing fluctuations (Imamovic et al. 2021).
Social media are increasingly used by health care professionals and students for various reasons, including education or teaching purposes (Ventola 2014; Al Busaidi and Alamri 2020; Lynn 2022). Lack of content quality and reliability, as well as direct or indirect marketing exposures (sponsored content) on different platforms are matters of concerns in this regard (Ventola 2014; Gardner et al. 2019). Overly optimistic portrayals of DBS on social media have indeed been reported, particularly in YouTube videos (Gardner et al. 2019). These considerations may extend to other DATs, although this has not been studied yet.
Patient preference, biases, and perspective: when and how do they come into play?
Patient-related demographics (age, race, sex), socioeconomic factors (educational background, insurance availability), personal experience (DAT exposure, including through social media and online communities), as well as educational influence of and trust in the therapy-applying clinician have all been shown to influence DAT access (referral), preference (surgery or infusion therapies), or acceptance (Smailhodzic et al. 2016; Kim et al. 2017; Shpiner et al. 2019; Richter et al. 2019; Montanaro et al. 2019; Cabrera et al. 2021a, b; Henriksen et al. 2020; Al Busaidi and Alamri 2020; Tripathi et al. 2020; Das et al. 2021; Braczynski et al. 2021).
Transitioning from oral drug administration to DAT is considered as an important step for patients (Fasano et al. 2022). Hence, fear of invasive treatments labelled as “advanced” therapies, excessive anxiety, lack of motivation, “need to have more time to decide”, fear of lifestyle limitations and personalised social stigma are common patients-related reasons for non-initiation (Volkmann et al. 2013; Burack et al. 2018; Stefani et al. 2022; Pedrosa et al. 2022). They may be underpinned by knowledge gaps and/or misconceptions (Table 4) about PD and therapeutic options (Lökk et al. 2011; Jitkritsadakul et al. 2017; Salinas et al. 2020). Cognitive biases (attentional, interpretation, and recall) are also prevalent in chronic illness and may influence patients’ motivation and decision making, hence health management (Savioni and Triberti 2020). Of note, PD patients have been shown to exhibit an attributional bias (cognitive bias, mistakenly attributing a situation to one cause) compared to controls, particularly when treated with DBS (Decombe et al. 2022).
PD patients exhibit different preference patterns when weighting treatment benefits and harms, focussing either on optimising the process of care, or controlling motor symptoms (Weernink et al. 2013). In addition, preferences for participation in decision making (how patients want to be involved in their own care) are known to vary in PD patients, depending on decision type, context, and relational factors (Zizzo et al. 2017). Broadly speaking, PD patients can (1) prefer to make the final decision, (2) opt for a shared choice (largely preferred in most cases), or (3) prefer to delegate final decisions to the physician (Zizzo et al. 2017). In all cases, however, they want to be informed of treatment options and involved in the deliberation (Zizzo et al. 2017). Careful assessment of individuals’ preferences on an ongoing basis and appropriate clinical guidance and education are, therefore, needed.
Patient preferences for DAT in advanced PD
Patient preference is a significant part of the decision-making process (Carron et al. 2011; Volkmann et al. 2013; Richter et al. 2019). It is also critical for treatment adherence, as DAT initiation and management requires patient’s full cooperation (Carron et al. 2011; Volkmann et al. 2013; Richter et al. 2019). Patient preferences for DAT in advanced PD have received some attention in the recent years (Marshall et al. 2017; Aydemir et al. 2022), particularly for DBS (Shpiner et al. 2019; Das et al. 2021; Jost et al. 2022; Vinke et al. 2022; Alfonso et al. 2022; Montemayor et al. 2022), including preferences for its earlier use (Cabrera et al. 2020, b; Sperens et al. 2017; Alfonso et al. 2022; Montemayor et al. 2022).
Despite the high prevalence of DBS among DAT in real-world clinical practice, as previously highlighted, several studies show that patients generally view it as a secondary treatment option to medication (Marshall et al. 2017; Sperens et al. 2017; Cabrera et al. 2021b; Aydemir et al. 2022; Montemayor et al. 2022). In a web-based survey of American patients with advanced PD (N = 401), the idea of treatment delivery via an infusion pump (LCIG) was preferred over DBS (Marshall et al. 2017). In a Turkish survey, PD patients (N = 58) were more likely to decline STN-DBS and LCIG due to surgical concerns, while CSAI was declined due to the need of repeated injections (Aydemir et al. 2022). Disease severity and age also played a role in patient preference, with STN-DBS being preferred by younger, less severe patients, and CSAI by older patients with a longer disease duration (Aydemir et al. 2022). In this Turkish survey, LCIG was the least preferred treatment (Aydemir et al. 2022).
Again, contrary to infusion therapies, patients’ preference and attitude have been largely studied for DBS (Hamberg and Hariz 2014; Sperens et al. 2017; LaHue et al. 2017; Shpiner et al. 2019; Furlanetti et al. 2020; Cabrera et al. 2020, 2021b; Hauber et al. 2021; Montemayor et al. 2022; Vinke et al. 2022; Jost et al. 2022; Alfonso et al. 2022; Cramer et al. 2022). Three different approaches to DBS were identified among PD patients: “taking own initiative”, “agreeing when offered”, and “hesitating and waiting” (Hamberg and Hariz, 2014). When offered, female patients are more likely to decide against undergoing DBS, possibly due to “greater fear of surgery” (Jost et al. 2022) and/or “strong fear of complications” (Hamberg and Hariz 2014; Shpiner et al. 2019). However, women are more likely to undergo DBS when offered to be operated asleep (Vinke et al. 2022). These findings suggest that gender-related factors may be playing a role in the gender disparity in DBS (Shpiner et al. 2019), but whether this is due to a distinct PD profile (higher level of anxiety in women, Cerri et al. 2019) or implicit/explicit biases remains to be determined. Factors contributing to preference between asleep or awake surgery may include concerns or fear of being awake during neurosurgery, claustrophobia, anxiety, pain or discomfort during the procedure (stereotactic frame placement, surgery), comorbid pain conditions, severe off-medication symptoms, but also feeling self-conscious or being curious (LaHue et al. 2017). DBS perception and timing, assessed in a US cohort of patients with PD but without DBS (N = 285), showed differences in concerns regarding DBS safety, efficacy, and favourability comparing to medical management (Alfonso et al. 2022). Exposure to the reality of DBS, through PD organisation or associations, may also have a “deglamourizing” effect on patients, particularly regarding side effects, and influence their preference (Sperens et al. 2017). Patients’ attitudes on the early use of DBS appear to be mixed (Sperens et al. 2017; Cabrera et al. 2020; Montemayor et al. 2022), including in those who already benefited from DBS, and who would not necessarily have endorsed its implementation earlier in their own PD course (Cabrera et al. 2020). Patients’ tolerance for risk (worsening depression or anxiety, brain bleed or death) and willingness to wait for potential benefits of new devices also vary, and are related to patients age, ambulation, and prior neurostimulation experience (Hauber et al. 2021). Patients may also express preferences regarding DBS systems, notably on the battery life duration, rechargeability, and size (Furlanetti et al. 2020; Lee et al. 2022). When choosing between fixed-life or rechargeable battery, the size of the battery seems to be an important factor in long-term satisfaction, while being quite overlooked preoperatively (Furlanetti et al. 2020). Finally, patient preference for innovative technologies may differ between ethnic groups (Cramer et al. 2022).
Unfamiliarity—lack of information
Lack of information and misconceptions are prevalent among PD patients (Li et al. 2014), as highlighted by the recent KnowPD study (Salinas et al. 2020). Moreover, only a small proportion of patients are informed about DAT options, particularly earlier in the course of the disease (Lökk et al. 2011).
To meet their information needs, patients frequently turn to online communities and social media (Chu and Jang 2022). For instance, questions regarding DBS, other patients’ experiences or choices relating to treatment, decision making on treatment options, and health coverage were frequently found in free-posting messages of a large online community of South Korean patients and family members (Chu and Jang 2022). Social media platforms are a readily accessible and ever-growing source of health-related information and medical education for patients and caregivers, despite contents of unverified origin (medical, health-related commercial entities, individual users?) and of extremely variable scientific quality, reliability, and accuracy (Smailhodzic et al. 2016; Kim et al. 2017; Al Busaidi and Alamri 2020; Tripathi et al. 2020; Braczynski et al. 2021). The consequences of social media use on patients have been carefully studied, and encompass improved self-management and control, enhanced psychological well-being, enhanced or diminished subjective well-being, addiction to social media, loss of privacy, and being targeted for promotion (Smailhodzic et al. 2016). The latter is of great concern, particularly as corporate interests are sometimes hidden behind seemingly genuine patients’ testimony YouTube videos (Gardner et al. 2019). A significant amount of DBS-related YouTube videos indeed offers over-optimistic portrayals, with dramatic “before and after” or “on/off” effects, without equally highlighting risks, thus contributing to the misleading myth of a “technological fix” and raising public expectations (Gilbert and Ovadia 2011; Gardner et al. 2019). Social media use also affects the relationship between patients and healthcare practitioners (Smailhodzic et al. 2016).
The influence of PD on medical decision and treatment choice
The question of decision-making abilities (including decisional capacity, medical information processing, capacity to consent, and ability to understand informed consent) of (1) patients with advanced PD and potential cognitive impairment or fluctuations, impairment and/or adverse cognitive effects related to their PD treatment (impulsive cognitive disorders, apathy), and (2) younger-onset PD patients assessed for early-DBS eligibility (but more prone to risk-taking behaviour and impulse control disorders) is currently far from being sufficiently investigated (Dymek et al. 2001; Cranston 2001; Griffith et al. 2005; Martin et al. 2008; Eygelshoven et al. 2017; Sokol et al. 2019; Koerts et al. 2020; Alfonso et al. 2022).
In a Dutch study, no impairment in medical decision making was found in non-demented PD patients compared to healthy controls (Eygelshoven et al. 2017). However, the sample consisted of fairly young patients (mean age 60.9 years old), with rather early disease stages (mean Hoehn and Yahr stage 2, mean disease duration 5 years and mean Levodopa Equivalent Daily Dose 565 mg). Cognitive complaints in non-demented PD patients were found to impact their capacity to understand, appreciate and reason, and, therefore, to make a valid decision (Abu Snineh et al. 2017). While patients still express a choice, it does not necessarily mean that they fully understand the information presented to them and evaluate their congruence with their values and goals of care (Abu Snineh et al. 2017). Cognitive fluctuations are also a reality in PD (Trachsel et al. 2015). Finally, executive dysfunction may impair PD patient’s abilities to weigh different factors and to anticipate personal consequences of treatment decisions (Griffith et al. 2005). Impairment in decisional capacity increases as PD progresses (Griffith et al. 2005; Martin et al. 2008; Eygelshoven et al. 2017; Abu Snineh et al. 2017). Timing of patient’s information about DAT is, therefore, critical, and whether the patient’s cognitive capacity is already reduced needs to be carefully assessed before moving forward with DAT choice and initiation (Hug et al. 2021).
Embracing prognostic uncertainty and unforeseeable outcomes: long-term safety and individual trajectories
The four ethical principles of healthcare encompass autonomy, justice, beneficence and non-maleficence, the latter referring to avoiding or preventing harm (Koerts et al. 2020). PD subtypes (Katz et al. 2015; Xu et al. 2018; Campbell et al. 2020), genetic background (Chan 2022), and unpredictable long-term side effects of DAT are elements which at present remain in the realm of uncertainty as to the patient’s individual response. Currently, there is limited knowledge on patient progression and DAT long-term outcomes. DAT are not risk-free and may pose ethical challenges (Hug et al. 2021).
Notably, DBS and its earlier use (i.e. briefly after the onset of the first dopaminergic response fluctuations) raise multiple questions regarding safety, as atypical parkinsonism can mimic early PD, dopaminergic treatment may influence risk-taking behaviour (impacting risk preference and/or assessment), unanticipated changes in personality, self, and relationships behaviour may emerge, and the risk of a floor effect or iatrogenic harms in the long run cannot be excluded (Schüpbach et al. 2006; Schuepbach et al. 2013; Cyron 2016; Kim and Jeon 2019; Thomson et al. 2020; Gilbert and Lancelot 2021). DBS may also be considered as an exclusion criterion in current and future clinical trials looking at disease-modifying treatment. It is the case for the AMBITIOUS study, a multicentre, randomised, double-blind, placebo-controlled clinical trial investigating whether the prolonged administration of ambroxol can change glucocerebrosidase (GBA) enzyme activity and alpha-synuclein levels in PD patients with GBA mutations.Footnote 2 This aspect must be disclosed to patients, particularly when considering early-DBS.
Infusion therapies are not without adverse effects either. LCIG treatment requires long-term tube placement, necessitating a careful monitoring of the PEG-J tube, but also periodic tube replacement, exposing the patient to both material and procedural risks (Epstein et al. 2016; Yamashita et al. 2021).Without good skin management, CSAI-related cutaneous side effects jeopardise the long-term retention of this therapy and patients’ comfort and are one of the main reasons for its discontinuation (Olivola et al. 2019; Henriksen and Staines 2021).
Increasing evidence point out to a direct influence of PD subtypes on therapeutic response to DBS, and even mortality rate (Katz et al. 2015; Xu et al. 2018; Campbell et al. 2020). Similar studies have yet to be undertaken for infusion therapies.
There is very preliminary insight, on whether genetic background would affect DBS long-term outcome (Chan 2022). Most studies suffer from essential limited sample sizes needed for clinico-genetic association studies, and based on very small cohorts, LRRK2 and PRKN mutations carriers were more likely to enjoy good surgical outcomes. There is uncertainty on GBA carriers that may show more severe nonmotor and cognitive disease progression—one study reported that STN-DBS might deteriorate cognitive performance over what might be expected from disease progression (Chan 2022). However, all these rather hypothesis generating than confirmatory studies need independent confirmation including larger cohorts.
“Only one answer” or “Choose all that apply”: is there really only one option that is better than all others for a given patient?
Advanced PD patients are often eligible for two or more DAT (Volkmann et al. 2013). Beyond the contraindications of each of the currently available DAT, one can question the mutually exclusive and competing approach often found in the literature (Carron et al. 2011). Is one DAT truly better than the others, and is that choice irrevocable? From our perspective, it is quite the opposite: the diversity of options allows a fine adjustment to each patient’s needs, considering disease course, burden, iatrogenic risk, and goals of care. It is, therefore, time to advocate for a dynamic approach, involving DAT switch and/or combination, as part of a continuum in the management of a chronic multisystem disorder (Table 5).
Switching between device-aided therapies: a sequential approach
Switches between DAT are frequent in clinical practice (Georgiev et al. 2022). Currently, all DAT are considered reversible (Volkmann et al. 2013). This, however, needs to be tempered for DBS, as undesirable non-stimulation-dependent effects may occur and deserve to be further investigated (Pugh 2019; Hug et al. 2021). White matter lesions, induced by brain surgery and electrode(s) trajectory (notably intersecting with caudate nuclei), may have deleterious effects on patient’s cognitive status (Witt et al. 2013; Blume et al. 2017). Nonetheless, if one DAT becomes unsuitable, patients have the option of trying another (Volkmann et al. 2013).
Most notably, PD patients on the waiting list for DBS frequently benefit from infusion therapies before surgery. Being minimally invasive, CSAI appears to be the DAT of choice in this case (Alegret et al. 2004; Fernández-Pajarín et al. 2021; Henriksen and Staines 2021; Georgiev et al. 2022) but LCIG can also be used (Georgiev et al. 2022). The infusion therapy is usually stopped after DBS initiation.
Confronted with the limitations of one approach, either because of adverse effects, DAT-related complications or symptoms resurgence (i.e. sleepiness with CSAI, infections with DBS, digestive complications with LCIG), patients can be switched from one DAT to another: CSAI to DBS (Varma et al. 2003; Kimber et al. 2017; Sesar et al. 2017; Olivola et al. 2019; Georgiev et al. 2022), CSAI to LCIG (Kimber et al. 2017; Georgiev et al. 2022), LCIG to DBS (van Poppelen et al. 2021) or DBS to infusion therapies (Sesar et al. 2019).
Improvements in the drug/device combination may also lead to a change, as recently evidenced by the addition of entacapone to the levodopa/carbidopa intestinal gel, and the subsequent switch from LCIG to LECIG (Senek et al. 2017; Öthman et al. 2021; Jost et al. 2023).
Within the next few years, switches to continuous subcutaneous levodopa infusion are expected.
Combining device-aided therapies: a dual perspective
Combining DAT are not uncommon in clinical practice (Sesar et al. 2017, 2019; Fasano et al. 2019; Boura et al. 2021; Thaler et al. 2022; Georgiev et al. 2022). If studies rigorously (as defined by evidence-based medicine) assessing the efficacy of a dual therapy are currently lacking, retrospective cohorts and case series from different countries point out to improvements in fluctuations and quality of life in patients treated with a combination of surgery and infusion therapy (Sesar et al. 2017, 2019; Boura et al. 2021; Georgiev et al. 2022).
The increasing prevalence of DBS patients, and particularly of patients operated early in the disease course (Schuepbach et al. 2013), raises the probability of the need for combined therapies, as DBS does not prevent nor modify disease progression. In patients who previously benefited from DBS, but whose symptoms are inadequately controlled (persistent or reemergent fluctuations) or in case of DBS failure, CSAI (Sesar et al. 2017, 2019; Georgiev et al. 2022) or LCIG (Buhmann et al. 2017; El Kouzi et al. 2018; van Poppelen et al. 2021; Georgiev et al. 2022; Isaacson et al. 2022; Abu Al-Melh et al. 2023) can be initiated concomitantly, with an additional and complementary beneficial effect, even in advanced PD.
Similarly, but more rarely, adding DBS to LCIG treatment allows an improvement in motor fluctuations, but also a reduction in levodopa dose, of clear interest when patients suffer from dopaminergic side effects (Buhmann et al. 2017; Boura et al. 2021; van Poppelen et al. 2021).
Again, we may expect to see in the future combinations of DBS and continuous subcutaneous levodopa infusion.
How can we ensure the most appropriate and personalised treatment for patients with advanced PD? A summary and looking at future perspectives
As movement disorder specialists expect to see a rise in the number of PD patients needing DAT in the future (Marsili et al. 2021), persistent disparities need to be addressed (Cramer et al. 2022; Subramanian et al. 2022). Moving through the process of DAT selection can be complex (Fig. 1).
Although guidelines and recommendations have been regularly published and updated (see Fig. 2 for a pragmatic approach relevant to clinical practice, based on Putzke et al. 2003; Rouaud et al. 2010; Hilker et al. 2011; Fereshtehnejad et al. 2015; Trenkwalder et al. 2015; Bonenfant et al. 2017; Katzenschlager et al. 2018; Dafsari et al. 2019; Fabbri et al. 2018; Dijk et al. 2020), their pertinence regarding a specific patient’s situation can be questioned. Several challenges must be overcome, both in clinical practice and research, to improve patients’ identification (referral), eligibility (DAT approval and availability), DAT selection, initiation, and follow-up (cost, available resources).
Reducing disparities in health care (notably racial, gender and socioeconomic disparities) requires changing physician behaviour on a local and institutional level (Cramer et al. 2022): this can be achieved with medical training, and educational, real-time workplace strategies (Dobler et al. 2019; Cramer et al. 2022). Lengthy waiting times or financial restrictions must be fought at local, regional, national, and international level: it is now necessary for patient associations, medical teams, device companies and governments to work together and ensure that all PD patients have equitable access to DAT. Home initiation, titration and follow-up, with the help of telemedicine, can be resource-efficient, well-accepted and satisfactory for both patients and the clinical team (Willows et al. 2017; Zagnoli et al. 2023): these approaches need to be developed to ensure DAT access, particularly in areas where access to specialists can be challenging. Devices’ approval and availability should be a top priority in the list of actions to end global disparities in PD.
Research is needed to better understand what factors shape clinicians’ willingness to (not) refer PD patients for DAT information and assessment earlier in the disease course (Cabrera et al. , 2019, 2021a). Notably, studies exploring referral patterns among general practitioners and neurologists are needed to reach better informed and earlier referrals (Evans et al. 2021; Jost et al. 2022). Indeed, advance planning perspective must be given priority, owing to PD-related impairments in decisional capacity (Griffith et al. 2005; Hug et al. 2021). Early and multiple discussions are critical to identify patients ‘values and priorities, address knowledge gaps, build familiarity (and overcome potential negative prejudices) with available DAT options (Burack et al. 2018; Hug et al. 2021; Möller et al. 2021; Alfonso et al. 2022). Though time consuming, increased education regarding the risks and benefits of DAT, as well as community outreach, will allow patients and caregivers to make an informed decision as to the most appropriate therapy to their individual needs, and to move forward with implementation at the appropriate timing (Volkmann et al. 2013; Burack et al. 2018; Shpiner et al. 2019; Alfonso et al. 2022). Patient education should also involve critical assessment of healthcare-related YouTube videos (Tripathi et al. 2020). Recent efforts towards identifying PD patient-centred regulatory endpoints for medical devices have been undertaken with the FDA (Benz et al. 2021). Along with improving shared-decision processes, these initiatives should be pursued to ensure a patient-centred standard of care.
In addition, recent progresses have been made in identifying different PD sub-phenotypes through the analysis of brain connectivity (Yassine et al. 2022, 2023). In the near future, this innovative profiling may play a pivotal in the patients’ selection process, as a potential biomarker for individual trajectories.
Compared to DBS (Shih and Tarsy 2011; Lange et al. 2017), little information is available concerning the use of infusion therapies, as well as neurologist and patients attitudes towards them. Studies focussing on both physician and patient’s attitude, knowledge, and perspective towards LCIG, LECIG and CSAI are, therefore, urgently needed.
Conclusion
The landscape is rapidly evolving in the therapeutic armamentarium of advanced PD, with the approval of LECIG, hopes for CSAI approval in the USA, and the forthcoming arrival of continuous subcutaneous levodopa infusion in clinical settings. Although clinical practices are heterogeneous and treatment individualisation mandatory, advance planning, ongoing education, and a multidisciplinary approach are advisable in all cases (Burack et al. 2018). New methods of initiation and titration (particularly at home) are likely to change the preferences of both patients and clinicians, and to improve accessibility (Zagnoli et al., 2023). Studies focussing on infusion therapies are urgently needed, as little information is available concerning neurologists’ and patients’ attitudes towards them, compared to DBS.
Data availability
Not applicable.
Notes
Supernus provides regulatory update on SPN-830. News release. Supernus Pharmaceuticals, Inc. October 10, 2022. Accessed February 21st, 2023. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830.
References
Abate F, Erro R, Barone P, Picillo M (2020) Managing device-aided treatments in Parkinson’s disease in times of COVID-19. Movement Disord Clin Pract 7(6):737–738. https://doi.org/10.1002/mdc3.12985
Abu Al-Melh M, Farghal M, Abdelall N (2022) Levodopa-carbidopa intestinal gel (LCIG) as an add-on therapy to deep brain stimulation (DBS) for managing progressive symptoms of advanced idiopathic Parkinson’s disease during the COVID-19 pandemic: case report [abstract]. Mov Disord 37 (suppl 1). https://www.mdsabstracts.org/abstract/levodopa-carbidopa-intestinal-gel-lcig-as-an-add-on-therapy-to-deep-brain-stimulation-dbs-for-managing-progressive-symptoms-of-advanced-idiopathic-parkinsons-disease-during-the-covid-19-p/. Accessed Feb 21, 2023
Abu Snineh M, Camicioli R, Miyasaki JM (2017) Decisional capacity for advanced care directives in Parkinson’s disease with cognitive concerns. Parkinsonism Relat Disord 39:77–79. https://doi.org/10.1016/j.parkreldis.2017.03.006
Ahlskog JE (2020) Common Myths and Misconceptions That Sidetrack Parkinson Disease Treatment, to the Detriment of Patients. Mayo Clin Proc 95(10):2225–2234. https://doi.org/10.1016/j.mayocp.2020.02.006
Al-Busaidi IS, Alamri Y (2020) Chper 8—Parkinson’s disease and social media. In: Martin CR, Preedy VR (eds) Diagnosis and Management in Parkinson’s Disease. Academic Press, pp 125–138. https://doi.org/10.1016/B978-0-12-815946-0.00008-9
Aldred J, Anca-Herschkovitsch M, Antonini A et al. (2020) Application of the “5-2-1” screening criteria in advanced Parkinson’s disease: interim analysis of DUOGLOBE. Neurodegener Dis Manag 10(5):309–323. https://doi.org/10.2217/nmt-2020-0021
Alegret M, Valldeoriola F, Martí M et al. (2004) Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson’s disease. Mov Disord 19(12):1463–1469. https://doi.org/10.1002/mds.20237
Alfonso D, Cabrera LY, Sidiropoulos C, Wang F, Sarva H (2022) How Parkinson’s patients in the USA perceive deep brain stimulation in the 21st century: results of a nationwide survey. J Clin Neurosci 95:20–26. https://doi.org/10.1016/j.jocn.2021.11.017
Antonini A, Stoessl AJ, Kleinman LS et al. (2018) Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease: a multi-country Delphi-panel approach. Curr Med Res Opin 34(12):2063–2073. https://doi.org/10.1080/03007995.2018.1502165
Antonini A, Odin P, Schmidt P et al. (2021) Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson’s disease patients inadequately controlled on oral medications. Parkinsonism Relat Disord 92:59–66. https://doi.org/10.1016/j.parkreldis.2021.10.009
Antonini A, Pahwa R, Odin P et al. (2022a) Psychometric properties of clinical indicators for identification and management of advanced Parkinson’s disease: real-world evidence from G7 countries. Neurol Ther 11(1):303–318. https://doi.org/10.1007/s40120-021-00313-9
Antonini A, Pahwa R, Odin P et al. (2022b) Comparative effectiveness of device-aided therapies on quality of life and off-time in advanced Parkinson’s disease: a systematic review and Bayesian network meta-analysis. CNS Drugs 36(12):1269–1283. https://doi.org/10.1007/s40263-022-00963-9
Auffret M, Drapier S, Vérin M (2018) Pharmacological insights into the use of apomorphine in Parkinson’s disease: clinical relevance. Clin Drug Investig 38(4):287–312. https://doi.org/10.1007/s40261-018-0619-3
Aydemir ST, Kumcu MK, Ulukan Ç, Bakirarar B, Akbostancı MC (2022) Patient preference of device-based treatment of Parkinson’s disease. Int J Neurosci 132(9):925–929. https://doi.org/10.1080/00207454.2020.1853723
Barber N (1995) What constitutes good prescribing? BMJ 310(6984):923–925. https://doi.org/10.1136/bmj.310.6984.923
Bate L, Hutchinson A, Underhill J, Maskrey N (2012) How clinical decisions are made. Br J Clin Pharmacol 74(4):614–620. https://doi.org/10.1111/j.1365-2125.2012.04366.x
Bechtereva NP, Bondartchuk AN, Smirnov VM, Meliutcheva LA, Shandurina AN (1975) Method of electrostimulation of the deep brain structures in treatment of some chronic diseases. SFN 37(1–3):136–140. https://doi.org/10.1159/000102727
Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Nneurophysiol. https://doi.org/10.1159/000100803
Benabid AL, Pollak P, Hoffmann D et al. (1991) Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. The Lancet 337(8738):403–406. https://doi.org/10.1016/0140-6736(91)91175-T
Benz HL, Caldwell B, Ruiz JP et al. (2021) Patient-centered identification of meaningful regulatory endpoints for medical devices to treat Parkinson’s disease. MDM Policy Pract 6(1):23814683211021380. https://doi.org/10.1177/23814683211021380
Bhidayasiri R, Phokaewvarangkul O, Sakdisornchai K et al. (2020) Establishing apomorphine treatment in Thailand: understanding the challenges and opportunities of Parkinson’s disease management in developing countries. Expert Rev Neurother 20(6):523–537. https://doi.org/10.1080/14737175.2020.1770598
Blond S, Siegfried J (1991) Thalamic stimulation for the treatment of tremor and other movement disorders. In: Hitchcock ER, Broggi G, Burzaco J, Martin-Rodriguez J, Meyerson BA, Tóth S (eds) Advances in Stereotactic and Functional Neurosurgery 9. Acta Neurochirurgica Supplementum. Springer, pp 109–111. https://doi.org/10.1007/978-3-7091-9160-6_30
Blume J, Lange M, Rothenfusser E et al. (2017) The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson’s disease. Clin Neurol Neurosurg 159:87–92. https://doi.org/10.1016/j.clineuro.2017.05.023
Bonenfant J, Drapier S, Houvenaghel JF et al. (2017) Pallidal stimulation in Parkinson’s patients with contraindications to subthalamic target: a 3 years follow-up. Parkinsonism Relat Disord 34:20–25. https://doi.org/10.1016/j.parkreldis.2016.10.007
Borgemeester RWK, van Laar T (2017) Continuous subcutaneous apomorphine infusion in Parkinson’s disease patients with cognitive dysfunction: a retrospective long-term follow-up study. Parkinsonism Relat Disord 45:33–38. https://doi.org/10.1016/j.parkreldis.2017.09.025
Boura I, Haliasos N, Giannopoulou ΙA, Karabetsos D, Spanaki C (2021) Combining device-aided therapies in Parkinson’s disease: a case series and a literature review. Movement Disord Clin Pract 8(5):750–757. https://doi.org/10.1002/mdc3.13228
Braczynski AK, Ganse B, Ridwan S, Schlenstedt C, Schulz JB, Hoog AC (2021) YouTube videos on Parkinson’s disease are a relevant source of patient information. J Parkinsons Dis 11(2):833–842. https://doi.org/10.3233/JPD-202513
Bredberg E, Nilsson D, Johansson K et al. (1993) Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson’s disease. Eur J Clin Pharmacol 45(2):117–122. https://doi.org/10.1007/BF00315491
Bruno MK, Watanabe G, Ishikawa K et al. (2022) Geographic variation in prescription patterns of Parkinson’s disease medications. Mov Disord 37(3):646–648. https://doi.org/10.1002/mds.28880
Buhmann C, Hilker R, Lingor P et al. (2017) Levodopa/carbidopa intestinal gel (LCIG) infusion as mono- or combination therapy. J Neural Transm 124(8):1005–1013. https://doi.org/10.1007/s00702-017-1698-7
Burack M, Aldred J, Zadikoff C et al. (2018) Implementing levodopa-carbidopa intestinal gel for Parkinson disease: insights from US practitioners. Mov Disord Clin Pract 5(4):383–393. https://doi.org/10.1002/mdc3.12630
Cabrera LY, Sarva H, Sidiropoulos C (2019) Perspectives on the earlier use of deep brain stimulation for Parkinson disease from a qualitative study of U.S. clinicians. World Neurosurg 128:e16–e20. https://doi.org/10.1016/j.wneu.2019.03.051
Cabrera LY, Kelly-Blake K, Sidiropoulos C (2020) Perspectives on deep brain stimulation and its earlier use for Parkinson’s Disease: a qualitative study of US patients. Brain Sci 10(1):34. https://doi.org/10.3390/brainsci10010034
Cabrera LY, Young Han C, Ostendorf T, Jimenez-Shahed J, Sarva H (2021a) Neurologists’ attitudes toward use and timing of deep brain stimulation. Neurol Clin Pract 11(6):506–516. https://doi.org/10.1212/CPJ.0000000000001098(Cabreraetal,2021a)
Cabrera LY, Mitchell SD, Bender A, Tvedten E, Sidiropoulos C, Sarva H (2021b) Attitudes toward use and timing of deep brain stimulation: a patient’s with DBS perspective. Clin Neurol Neurosurg 203:106553. https://doi.org/10.1016/j.clineuro.2021.106553
Campbell MC, Myers PS, Weigand AJ et al. (2020) Parkinson disease clinical subtypes: key features and clinical milestones. Ann Clin Transl Neurol 7(8):1272–1283. https://doi.org/10.1002/acn3.51102
Carron R, Fraix V, Maineri C et al. (2011) High frequency deep brain stimulation of the subthalamic nucleus versus continuous subcutaneous apomorphine infusion therapy: a review. J Neural Transm (vienna) 118(6):915–924. https://doi.org/10.1007/s00702-010-0556-7
Castaño B, Mateo D, Giménez-Roldán S (2007) Shifting to subcutaneous infusion of apomorphine in advanced Parkinson’s disease patients on an out-patient basis: experience and recommendations. Neurologia 22(3):133–137
Castro-Caldas A, Costa C, Sampaio C, Chin D (1986) Lisuride infusion pump for Parkinson’s disease. The Lancet 327(8490):1150–1151. https://doi.org/10.1016/S0140-6736(86)91861-1
Cerri S, Mus L, Blandini F (2019) Parkinson’s disease in women and men: What’s the difference? J Parkinsons Dis 9(3):501–515. https://doi.org/10.3233/JPD-191683
Chan GHF (2022) The role of genetic data in selecting device-aided therapies in patients with advanced Parkinson’s disease: a mini-review. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2022.895430
Chan AK, McGovern RA, Brown LT et al. (2014) Disparities in access to deep brain stimulation surgery for Parkinson disease: interaction between African American race and Medicaid use. JAMA Neurol 71(3):291–299. https://doi.org/10.1001/jamaneurol.2013.5798
Chu HS, Jang HY (2022) Exploring unmet information needs of people with Parkinson’s disease and their families: focusing on information sharing in an online patient community. Int J Environ Res Public Health 19(5):2521. https://doi.org/10.3390/ijerph19052521
Cramer SW, Do TH, Palzer EF et al. (2022) Persistent racial disparities in deep brain stimulation for Parkinson’s disease. Ann Neurol 92(2):246–254. https://doi.org/10.1002/ana.26378
Cranston RE (2001) Competency to consent to medical treatment in cognitively impaired patients with Parkinson’s disease. Neurology 56(12):1782–1783. https://doi.org/10.1212/WNL.56.12.1782-a
Crispo JAG, Lam M, Le B et al. (2020) Disparities in deep brain stimulation use for Parkinson’s disease in Ontario, Canada. Can J Neurol Sci 47(5):642–655. https://doi.org/10.1017/cjn.2020.79
Croskerry P (2002) Achieving quality in clinical decision making: cognitive strategies and detection of bias. Acad Emerg Med 9(11):1184–1204. https://doi.org/10.1197/aemj.9.11.1184
Cyron D (2016) Mental side effects of deep brain stimulation (DBS) for movement disorders: the futility of denial. Front Integrat Neurosci. https://doi.org/10.3389/fnint.2016.00017. (Accessed Feb 16, 2023)
Dafsari HS, Martinez-Martin P, Rizos A et al. (2019) EuroInf 2: subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Mov Disord 34(3):353–365. https://doi.org/10.1002/mds.27626
Dahodwala N, Xie M, Noll E, Siderowf A, Mandell DS (2009) Treatment disparities in Parkinson’s disease. Ann Neurol 66(2):142. https://doi.org/10.1002/ana.21774
Das S, Matias CM, Ramesh S et al. (2021) Capturing initial understanding and impressions of surgical therapy for Parkinson’s disease. Front Neurol 12:605959. https://doi.org/10.3389/fneur.2021.605959
De Cock VC, Dodet P, Leu-Semenescu S et al. (2022) Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson’s disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study. Lancet Neurol 21(5):428–437. https://doi.org/10.1016/S1474-4422(22)00085-0
Deshpande N, Gibbs R, Ali R (2022) Evaluation of DBS timeline in movement disorders: a comparison between genders. World Neurosurg 164:e256–e262. https://doi.org/10.1016/j.wneu.2022.04.092
Deuschl G, Antonini A, Costa J et al. (2022) European Academy of Neurology/Movement Disorder Society—European Section guideline on the treatment of Parkinson’s disease: I. Invasive Therapies. Eur J Neurol 29(9):2580–2595. https://doi.org/10.1111/ene.15386
Dijk JM, Espay AJ, Katzenschlager R, de Bie RMA (2020) The choice between advanced therapies for Parkinson’s disease patients: Why, What, and When? J Parkinsons Dis 10(s1):S65–S73. https://doi.org/10.3233/JPD-202104
Dobler CC, Morrow AS, Kamath CC (2019) Clinicians’ cognitive biases: a potential barrier to implementation of evidence-based clinical practice. BMJ Evidence-Based Med 24(4):137–140. https://doi.org/10.1136/bmjebm-2018-111074
Dymek MP, Atchison P, Harrell L, Marson DC (2001) Competency to consent to medical treatment in cognitively impaired patients with Parkinson’s disease. Neurology 56(1):17–24. https://doi.org/10.1212/WNL.56.1.17
El-Jaafary S, Salem M, Sabbah A, Nasreldein A, Amer H (2021) Knowledge and Attitudes among young Neurologists towards Surgery in Movement Disorders [abstract]. Mov Disord 36 (suppl 1). https://www.mdsabstracts.org/abstract/knowledge-and-attitudes-among-young-neurologists-towards-surgery-in-movement-disorders/. (Accessed Feb 27, 2023)
Epstein M, Johnson DA, Hawes R et al. (2016) Long-term PEG-J tube safety in patients with advanced Parkinson’s disease. Clin Transl Gastroenterol 7(3):e159. https://doi.org/10.1038/ctg.2016.19
Espay AJ, Lang AE (2017) Common myths in the use of levodopa in Parkinson disease: when clinical trials misinform clinical practice. JAMA Neurol 74(6):633–634. https://doi.org/10.1001/jamaneurol.2017.0348
Evans A, Fung VSC, O’Sullivan JD et al. (2021) Characteristics of advanced Parkinson’s disease patients seen in movement disorder clinics—Australian results from the cross-sectional OBSERVE study. Clin Parkinsonism Relat Disord 4:100075. https://doi.org/10.1016/j.prdoa.2020.100075
Eygelshoven S, van den Hout A, Tucha L et al. (2017) Are non-demented patients with Parkinson’s disease able to decide about their own treatment? Parkinsonism Relat Disord 38:48–53. https://doi.org/10.1016/j.parkreldis.2017.02.021
Ezat B, Pihlstrøm L, Aasly J, Tysnes OB, Egge A, Dietrichs E (2017) Use of advanced therapies for Parkinson’s disease in Norway. Tidsskrift for Den Norske Legeforening. https://doi.org/10.4045/tidsskr.16.0711. (Published online May 2, 2017)
Fabbri M, Rosa MM, Ferreira JJ (2018) Adjunctive therapies in Parkinson’s disease: how to choose the best treatment strategy approach. Drugs Aging 35(12):1041–1054. https://doi.org/10.1007/s40266-018-0599-2
Fasano A, Fung VSC, Lopiano L et al. (2019) Characterizing advanced Parkinson’s disease: OBSERVE-PD observational study results of 2615 patients. BMC Neurol 19(1):50. https://doi.org/10.1186/s12883-019-1276-8
Fasano A, Antonini A, Katzenschlager R et al. (2020) Management of advanced therapies in Parkinson’s disease patients in times of humanitarian crisis: the COVID-19 experience. Mov Disord Clin Pract 7(4):361–372. https://doi.org/10.1002/mdc3.12965
Fasano A, Fung VSC, Seppi K et al. (2022) Intercountry comparisons of advanced Parkinson’s disease symptoms and management: analysis from the OBSERVE-PD observational study. Acta Neurol Scand 146(2):167–176. https://doi.org/10.1111/ane.13648
Featherston R, Downie LE, Vogel AP, Galvin KL (2020) Decision making biases in the allied health professions: a systematic scoping review. PLoS ONE 15(10):e0240716. https://doi.org/10.1371/journal.pone.0240716
Fereshtehnejad SM, Romenets SR, Anang JBM, Latreille V, Gagnon JF, Postuma RB (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 72(8):863–873. https://doi.org/10.1001/jamaneurol.2015.0703
Fernández-Pajarín G, Sesar Á, Ares B et al. (2021) Continuous subcutaneous apomorphine infusion before subthalamic deep brain stimulation: a prospective, comparative study in 20 patients. Mov Disord Clin Pract 8(8):1216–1224. https://doi.org/10.1002/mdc3.13338
Fernández-Pajarín G, Sesar Á, Jiménez Martín I, Ares B, Castro A (2022) Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson’s disease: a prospective study of 22 patients. Clin Park Relat Disord 6:100129. https://doi.org/10.1016/j.prdoa.2021.100129
Flanagan E, Walsh C, Tubridy N (2007) ‘Neurophobia’– attitudes of medical students and doctors in Ireland to neurological teaching. Eur J Neurol 14(10):1109–1112. https://doi.org/10.1111/j.1468-1331.2007.01911.x
Fujioka S, Mishima T, Yamazaki T et al. (2023) Neurologists’ preferences for device-aided therapy for advanced Parkinson’s disease in Japan. Curr Med Res Opin 39(1):91–104. https://doi.org/10.1080/03007995.2022.2129800
Furlanetti L, Raslan A, Khaleeq T et al. (2020) Fixed-life or rechargeable battery for deep brain stimulation: a prospective long-term study of patient’s preferences. Stereotact Funct Neurosurg 98(1):43–47. https://doi.org/10.1159/000505700
Gardner J, Warren N, Addison C, Samuel G (2019) Persuasive bodies: testimonies of deep brain stimulation and Parkinson’s on YouTube. Soc Sci Med 222:44–51. https://doi.org/10.1016/j.socscimed.2018.12.036
Georgiev D, Delalić S, Zupančič Križnar N, Socher A, Gurevich T, Trošt M (2022) Switching and combining device-aided therapies in advanced Parkinson’s disease: a double centre retrospective study. Brain Sci 12(3):343. https://doi.org/10.3390/brainsci12030343
Giladi N, Gurevich T, Djaldetti R et al. (2021) ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson’s disease and motor response fluctuations: a randomized, placebo-controlled phase 2 study. Parkinsonism Relat Disord 91:139–145. https://doi.org/10.1016/j.parkreldis.2021.09.024
Gilbert F, Lancelot M (2021) Incoming ethical issues for deep brain stimulation: when long-term treatment leads to a “new form of the disease.” J Med Ethics 47(1):20–25. https://doi.org/10.1136/medethics-2019-106052
Gilbert F, Ovadia D (2011) Deep brain stimulation in the media: over-optimistic portrayals call for a new strategy involving journalists and scientists in ethical debates. Front Integr Neurosci 5:16. https://doi.org/10.3389/fnint.2011.00016
Griffith HR, Dymek MP, Atchison P, Harrell L, Marson DC (2005) Medical decision-making in neurodegenerative disease: Mild AD and PD with cognitive impairment. Neurology 65(3):483–485. https://doi.org/10.1212/01.wnl.0000171346.02965.80
Hariz GM, Lindberg M, Hariz MI, Bergenheim AT (2003) Gender differences in disability and health-related quality of life in patients with Parkinson’s disease treated with stereotactic surgery. Acta Neurol Scand 108(1):28–37. https://doi.org/10.1034/j.1600-0404.2003.00092.x
Hariz GM, Nakajima T, Limousin P et al. (2011) Gender distribution of patients with Parkinson’s disease treated with subthalamic deep brain stimulation; a review of the 2000–2009 literature. Parkinsonism Relat Disord 17(3):146–149. https://doi.org/10.1016/j.parkreldis.2010.12.002
Hauber B, Mange B, Zhou M et al. (2021) Parkinson’s patients’ tolerance for risk and willingness to wait for potential benefits of novel neurostimulation devices: a patient-centered threshold technique study. MDM Policy Pract 6(1):2381468320978407. https://doi.org/10.1177/2381468320978407
Henriksen T, Staines H (2021) Continuous subcutaneous apomorphine infusion in Parkinson’s disease: a single-center, long-term follow-up study of the causes for discontinuation. J Pers Med 11(6):525. https://doi.org/10.3390/jpm11060525
Hilker R, Antonini A, Odin P (2011) What is the best treatment for fluctuating Parkinson’s disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus? J Neural Transm (vienna) 118(6):907–914. https://doi.org/10.1007/s00702-010-0555-8
Hug K (2021) Bringing advanced therapies for Parkinson’s disease to the clinic: an analysis of ethical issues. J Parkinson’s Dis 11(s2):S147–S155. https://doi.org/10.3233/JPD-212639
Imamovic A, Melyan Z, Kasibhatla C, Kumar R (2021) “Needle Phobia” in Patients with Parkinson’s Disease (PD) Experiencing OFF Episodes is Uncommon (2356). Neurology. 96(15 Supplement). https://n.neurology.org/content/96/15_Supplement/2356. (Accessed Jan 5, 2023)
Isaacson SH, Dewey RB, Pahwa R, Kremens DE (2023) How to manage the initiation of apomorphine therapy without antiemetic pretreatment: a review of the literature. Clin Park Relat Disord 8:100174. https://doi.org/10.1016/j.prdoa.2022.100174
Isaacson S, Pahwa R, Thakkar S, Kandukuri P, Jalundhwala Y, Kukreja P, Bao Y, Gupta N, Pan I, Aldred J (2019) Efficacy of carbidopa/levodopa enteral suspension (CLES) in advanced Parkinson’s disease patients previously treated with deep brain stimulation (DBS)—a subgroup analysis from PROviDE study [abstract]. Mov Disord 34 (suppl 2). https://www.mdsabstracts.org/abstract/efficacy-of-carbidopa-levodopa-enteral-suspension-cles-in-advanced-parkinsons-disease-patients-previously-treated-with-deep-brain-stimulation-dbs-a-subgroup-analysis-from-provid/. (Accessed Feb 20, 2023)
Jitkritsadakul O, Boonrod N, Bhidayasiri R (2017) Knowledge, attitudes and perceptions of Parkinson’s disease: a cross-sectional survey of Asian patients. J Neurol Sci 374:69–74. https://doi.org/10.1016/j.jns.2016.12.063
Jost WH (2023) A novel treatment option for intrajejunal levodopa administration. Expert Rev Neurother 23(1):9–13. https://doi.org/10.1080/14737175.2023.2176222
Jost ST, Strobel L, Rizos A et al. (2022) Gender gap in deep brain stimulation for Parkinson’s disease. NPJ Parkinsons Dis 8(1):1–10. https://doi.org/10.1038/s41531-022-00305-y
Kalilani L, Friesen D, Boudiaf N, Asgharnejad M (2019) The characteristics and treatment patterns of patients with Parkinson’s disease in the United States and United Kingdom: a retrospective cohort study. Plos one 14(11):e0225723. https://doi.org/10.1371/journal.pone.0225723
Katz M, Luciano MS, Carlson K et al. (2015) Differential effects of deep brain stimulation target on motor subtypes in Parkinson’s disease. Ann Neurol 77(4):710–719. https://doi.org/10.1002/ana.24374
Katzenschlager R, Poewe W, Rascol O et al. (2018) Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 17(9):749–759. https://doi.org/10.1016/S1474-4422(18)30239-4
Katzenschlager R, Poewe W, Rascol O et al. (2021) Long-term safety and efficacy of apomorphine infusion in Parkinson’s disease patients with persistent motor fluctuations: results of the open-label phase of the TOLEDO study. Parkinsonism Relat Disord 83:79–85. https://doi.org/10.1016/j.parkreldis.2020.12.024
Kim HJ, Jeon B (2019) Decision under risk: argument against early deep brain stimulation in Parkinson’s disease. Parkinsonism Relat Disord 69:7–10. https://doi.org/10.1016/j.parkreldis.2019.10.008
Kim R, Park HY, Kim HJ, Kim A, Jang MH, Jeon B (2017) Dry facts are not always inviting: a content analysis of Korean videos regarding Parkinson’s disease on YouTube. J Clin Neurosci 46:167–170. https://doi.org/10.1016/j.jocn.2017.09.001
Kimber TE, Fang J, Huddy LJ, Thompson PD (2017) Long-term adherence to apomorphine infusion in patients with Parkinson disease: a 10-year observational study. Intern Med J 47(5):570–573. https://doi.org/10.1111/imj.13378
Klocko DJ (2016) Are cognitive biases influencing your clinical decisions? Clin Rev 26(3):32–39
Koerts J, Jansen J, Fuermaier ABM, Tucha L, Tucha O (2020) Chapter 11—Medical decision-making in patients with Parkinson’s disease. In: Martin CR, Preedy VR (eds) Diagnosis and management in Parkinson’s disease. Academic Press, pp 185–202. https://doi.org/10.1016/B978-0-12-815946-0.00011-9
El Kouzi A, Almeida L, Zamora AR et al. (2018) Levodopa-Carbidopa Intestinal Gel (LCIG) in Deep Brain Stimulation (DBS) Parkinson’s Patients. (P6.027). Neurology 90(15 Supplement). https://n.neurology.org/content/90/15_Supplement/P6.027. (Accessed Feb 21, 2023)
Krüger R, Hilker R, Winkler C et al. (2016) Advanced stages of PD: interventional therapies and related patient-centered care. J Neural Transm (vienna) 123(1):31–43. https://doi.org/10.1007/s00702-015-1418-0
LaHue SC, Ostrem JL, Galifianakis NB et al. (2017) Parkinson’s disease patient preference and experience with various methods of DBS lead placement. Parkinsonism Relat Disord 41:25–30. https://doi.org/10.1016/j.parkreldis.2017.04.010
Lange M, Mauerer J, Schlaier J et al. (2017) Underutilization of deep brain stimulation for Parkinson’s disease? A survey on possible clinical reasons. Acta Neurochir (wien) 159(5):771–778. https://doi.org/10.1007/s00701-017-3122-3
Lee T, Fullard M, Rogers T, Ojemann S, Kern D (2022) Patient Preferences for Deep Brain Stimulation Products in Parkinson’s Disease: What Really Matters to Them? (P5–11.001). Neurology. 98(18 Supplement). https://n.neurology.org/content/98/18_Supplement/133. (Accessed Jan 5, 2023)
LeWitt PA, Stocchi F, Arkadir D et al. (2022) The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program. Front Neurol 13:1036068. https://doi.org/10.3389/fneur.2022.1036068
Li J, Chen D, Song W et al. (2014) Survey on general knowledge on Parkinson’s disease in patients with Parkinson’s disease and current clinical practice for Parkinson’s disease among general neurologists from Southwest China. Clin Neurol Neurosurg 118:16–20. https://doi.org/10.1016/j.clineuro.2013.12.009
Lilienfeld SO, Lynn SJ (2014) Errors/Biases in Clinical Decision Making. In: The Encyclopedia of Clinical Psychology. John Wiley & Sons, Ltd, pp 1–9. https://doi.org/10.1002/9781118625392.wbecp567
Limousin P, Pollak P, Benazzouz A et al. (1995) Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345(8942):91–95. https://doi.org/10.1016/s0140-6736(95)90062-4
Luquin MR, Kulisevsky J, Martinez-Martin P, Mir P, Tolosa ES (2017) Consensus on the definition of advanced Parkinson’s disease: a neurologists-based Delphi study (CEPA study). Parkinsons Dis 2017:4047392. https://doi.org/10.1155/2017/4047392
Lynn PP (2022) The faces of Parkinson’s disease: helping students realize it is more than tremors. J Nurs Educ 61(4):221–221. https://doi.org/10.3928/01484834-20220209-08
Lökk J (2011) Lack of information and access to advanced treatment for Parkinson’s disease patients. J Multidiscip Healthc 4:433–439. https://doi.org/10.2147/JMDH.S27180
Malaty IA, Martinez-Martin P, Chaudhuri KR et al. (2022) 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 countries. BMC Neurol 22(1):35. https://doi.org/10.1186/s12883-022-02560-1
Marcum JA (2017) Clinical decision-making, gender bias, virtue epistemology, and quality healthcare. Topoi 36(3):501–508. https://doi.org/10.1007/s11245-015-9343-2
Marian LL (2021) Continuous and advanced treatment strategies in old and very old patients with Parkinson’s disease. Geriatr Psychol Neuropsychiatr Vieil. https://doi.org/10.1684/pnv.2020.0906. (Published online Mar 8, 2021)
Marshall T, Pugh A, Fairchild A, Hass S (2017) Patient preferences for device-aided treatments indicated for advanced Parkinson disease. Value Health 20(10):1383–1393. https://doi.org/10.1016/j.jval.2017.06.001
Marsili L, Bologna M, Miyasaki JM, Colosimo C (2021) Device-aided therapies for advanced Parkinson disease: insights from an international survey. Neurol Sci 42(7):2961–2964. https://doi.org/10.1007/s10072-021-05106-4
Martin RC, Okonkwo OC, Hill J et al. (2008) Medical decision-making capacity in cognitively impaired Parkinson’s disease patients without dementia. Mov Disord 23(13):1867–1874. https://doi.org/10.1002/mds.22170
Martínez-Castrillo JC, Martínez-Martín P, Burgos Á et al. (2021) Prevalence of advanced Parkinson’s disease in patients treated in the hospitals of the Spanish national healthcare system: the PARADISE study. Brain Sci 11(12):1557. https://doi.org/10.3390/brainsci11121557
Martinez-Martin P, Reddy P, Katzenschlager R et al. (2015) EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov Disord 30(4):510–516. https://doi.org/10.1002/mds.26067
Martinez-Martin P, Kulisevsky J, Mir P, Tolosa E, García-Delgado P, Luquin MR (2018) Validation of a simple screening tool for early diagnosis of advanced Parkinson’s disease in daily practice: the CDEPA questionnaire. NPJ Parkinsons Dis 4:20. https://doi.org/10.1038/s41531-018-0056-2
Menken M (2002) Demystifying neurology. BMJ 324(7352):1469–1470
Moes HR, Buskens E, van Laar T (2022) Letter to the editor, “Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson’s disease patients inadequately controlled on oral medications.” Parkinsonism Relat Disord 97:99–100. https://doi.org/10.1016/j.parkreldis.2022.03.014
Möller JC, Baumann CR, Burkhard PR et al. (2021) Characterisation of advanced Parkinson’s disease: OBSERVE-PD observational study - results of the Swiss subgroup. Swiss Med Wkly 151:w20419. https://doi.org/10.4414/smw.2021.20419
Montanaro E, Artusi CA, Zibetti M, Lopiano L (2019) Complex therapies for advanced Parkinson’s disease: what is the role of doctor-patient communication? Neurol Sci 40(11):2357–2364. https://doi.org/10.1007/s10072-019-03982-5
Montanaro E, Artusi CA, Rosano C et al. (2022) Anxiety, depression, and worries in advanced Parkinson disease during COVID-19 pandemic. Neurol Sci 43(1):341–348. https://doi.org/10.1007/s10072-021-05286-z
Montemayor J, Sarva H, Kelly-Blake K, Cabrera LY (2022) Deep brain stimulation for Parkinson’s disease: why earlier use makes shared decision making important. Neuroethics 15(2):17. https://doi.org/10.1007/s12152-022-09496-w
Morgante L, Basile G, Epifanio A et al. (2004) Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson’s disease: a follow-up of two years. Arch Gerontol Geriatr Suppl 9:291–296. https://doi.org/10.1016/j.archger.2004.04.039
Nilsson D, Hansson LE, Johansson K, Nystrom C, Paalzow L, Aquilonius SM (1998) Long-term intraduodenal infusion of a water based levodopa-carbidopa dispersion in very advanced Parkinson’s disease. Acta Neurol Scand 97(3):175–183. https://doi.org/10.1111/j.1600-0404.1998.tb00633.x
Norlin JM, Willis M, Persson U, Andersson E, Pålhagen SE, Odin P (2021) Swedish guidelines for device-aided therapies in Parkinson’s disease —Economic evaluation and implementation. Acta Neurol Scand. https://doi.org/10.1111/ane.13434
Nwabuobi L, Agee J, Gilbert R (2021) Racial and social disparities in health and health care delivery among patients with Parkinson’s disease and related disorders in a multiracial clinical setting. J Cross Cult Gerontol 36(3):253–263. https://doi.org/10.1007/s10823-021-09436-w
Nyholm D, Jost WH (2022) Levodopa-entacapone-carbidopa intestinal gel infusion in advanced Parkinson’s disease: real-world experience and practical guidance. Ther Adv Neurol Disord 15:17562864221108018. https://doi.org/10.1177/17562864221108018
Obeso JA, Luquin MR, Martínez-Lage JM (1986) Lisuride infusion pump: a device for the treatment of motor fluctuations in Parkinson’s disease. Lancet 1(8479):467–470. https://doi.org/10.1016/s0140-6736(86)92929-6
Obeso JA, Grandas F, Vaamonde J, Rosario Luguin M, Martínez-Lage JM (1987) Apomorphine infusion for motor fluctuations in Parkinson’s disease. Lancet 1(8546):1376–1377. https://doi.org/10.1016/s0140-6736(87)90679-9
Obeso JA, Monje MHG, Matarazzo M (2022) Major advances in Parkinson’s disease over the past two decades and future research directions. Lancet Neurol 21(12):1076–1079. https://doi.org/10.1016/S1474-4422(22)00448-3
Odin P, Ray Chaudhuri K, Slevin JT et al. (2015) Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: consensus from an international survey and discussion program. Parkinsonism Relat Disord 21(10):1133–1144. https://doi.org/10.1016/j.parkreldis.2015.07.020
Olanow CW, Espay AJ, Stocchi F et al. (2021) Continuous subcutaneous levodopa delivery for Parkinson’s disease: a randomized study. J Parkinsons Dis 11(1):177–186. https://doi.org/10.3233/JPD-202285
Olivola E, Fasano A, Varanese S et al. (2019) Continuous subcutaneous apomorphine infusion in Parkinson’s disease: causes of discontinuation and subsequent treatment strategies. Neurol Sci 40(9):1917–1923. https://doi.org/10.1007/s10072-019-03920-5
Öthman M, Widman E, Nygren I, Nyholm D (2021) Initial experience of the levodopa-entacapone-carbidopa intestinal gel in clinical practice. J Pers Med 11(4):254. https://doi.org/10.3390/jpm11040254
Ou Z, Pan J, Tang S et al. (2021) Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Front Public Health 9:776847. https://doi.org/10.3389/fpubh.2021.776847
Paff M, Loh A, Sarica C, Lozano AM, Fasano A (2020) Update on current technologies for deep brain stimulation in Parkinson’s disease. J Mov Disord 13(3):185–198. https://doi.org/10.14802/jmd.20052
Pedrosa DJ, Gandor F, Jost WH, Arlt C, Onuk K, Timmermann L (2022) Characterization of advanced Parkinson’s disease in Germany: results of the non-interventional OBSERVE-PD study. Neurol Res Pract 4(1):9. https://doi.org/10.1186/s42466-022-00176-x
Poewe W, Stocchi F, Arkadir D et al. (2021) Subcutaneous levodopa infusion for Parkinson’s disease: 1-year data from the open-label BeyoND study. Mov Disord 36(11):2687–2692. https://doi.org/10.1002/mds.28758
Pugh J (2019) No going back? Reversibility and why it matters for deep brain stimulation. J Med Ethics 45(4):225–230. https://doi.org/10.1136/medethics-2018-105139
Putzke JD, Wharen RE, Wszolek ZK, Turk MF, Strongosky AJ, Uitti RJ (2003) Thalamic deep brain stimulation for tremor-predominant Parkinson’s disease. Parkinsonism Relat Disord 10(2):81–88. https://doi.org/10.1016/j.parkreldis.2003.09.002
Quinn N, Marsden CD, Parkes JD (1982) Complicated response fluctuations in Parkinson’s disease: response to intravenous infusion of levodopa. Lancet 2(8295):412–415. https://doi.org/10.1016/s0140-6736(82)90442-1
Ramot Y, Nyska A, Maronpot RR et al. (2017) Ninety-day local tolerability and toxicity study of ND0612, a novel formulation of levodopa/carbidopa, administered by subcutaneous continuous infusion in minipigs. Toxicol Pathol 45(6):764–773. https://doi.org/10.1177/0192623317729891
Richter D, Bartig D, Jost W et al. (2019) Dynamics of device-based treatments for Parkinson’s disease in Germany from 2010 to 2017: application of continuous subcutaneous apomorphine, levodopa-carbidopa intestinal gel, and deep brain stimulation. J Neural Transm (vienna) 126(7):879–888. https://doi.org/10.1007/s00702-019-02034-8
Richter D, Scherbaum R, Bartig D, Gold R, Krogias C, Tönges L (2021) Analysis of nationwide multimodal complex treatment and drug pump therapy in Parkinson’s disease in times of COVID-19 Pandemic in Germany. Parkinso Relat Disord. https://doi.org/10.1016/j.parkreldis.2021.03.006
Rosebraugh M, Liu W, Neenan M, Facheris MF (2021a) Foslevodopa/foscarbidopa is well tolerated and maintains stable levodopa and carbidopa exposure following subcutaneous infusion. J Parkinsons Dis 11(4):1695–1702. https://doi.org/10.3233/JPD-212813
Rosebraugh M, Voight EA, Moussa EM et al. (2021b) Foslevodopa/foscarbidopa: a new subcutaneous treatment for Parkinson’s disease. Ann Neurol 90(1):52–61. https://doi.org/10.1002/ana.26073
Rosebraugh M, Stodtmann S, Liu W, Facheris MF (2022a) Foslevodopa/foscarbidopa subcutaneous infusion maintains equivalent levodopa exposure to levodopa-carbidopa intestinal gel delivered to the jejunum. Parkinsonism Relat Disord 97:68–72. https://doi.org/10.1016/j.parkreldis.2022.03.012
Rosebraugh M, Neenan M, Facheris M (2022b) Comparability of foslevodopa/foscarbidopa pharmacokinetics in healthy asian and white participants. Clin Pharmacol Drug Dev. https://doi.org/10.1002/cpdd.1201. (Published online Nov 16, 2022)
Roszmann A, Podlewska AM, Lau YH, Boura I, Hand A (2022) Chapter Eight - Covid-19 and Parkinson’s disease: Nursing care, vaccination and impact on advanced therapies. In: Chaudhuri KR, Rodríguez-Violante M, Antonini A, Boura I (eds) International review of neurobiology. Vol 165. Covid-19 and Parkinsonism. Academic Press, pp 173–196. https://doi.org/10.1016/bs.irn.2022.04.005
Rota S, Boura I, Batzu L et al. (2020) “Dopamine agonist Phobia” in Parkinson’s disease: when does it matter? Implications for non-motor symptoms and personalized medicine. Expert Rev Neurother 20(9):953–965. https://doi.org/10.1080/14737175.2020.1806059
Rouaud T, Dondaine T, Drapier S et al. (2010) Pallidal stimulation in advanced Parkinson’s patients with contraindications for subthalamic stimulation. Mov Disord 25(12):1839–1846. https://doi.org/10.1002/mds.23171
Ruggieri S, Stocchi F, Agnoli A, Bittkau S, Przuntek H (1986) Lisuride infusion pump for Parkinson’s disease. The Lancet 328(8502):348–349. https://doi.org/10.1016/S0140-6736(86)90041-3
Ruggieri S, Stocchi F, Carta A, Catarci M, Agnoli A (1989) Jejunal delivery of levodopa methyl ester. The Lancet 334(8653):45–46. https://doi.org/10.1016/S0140-6736(89)90285-7
Sage JI, Trooskin S, Sonsalla PK, Heikkila RE (1989) Experience with continuous enteral levodopa infusions in the treatment of 9 patients with advanced Parkinson’s disease. Neurology 39(11 Suppl 2):60–63 (discussion 72-73)
Salinas MR, Chambers EJ, Ho T et al. (2020) Patient perceptions and knowledge of Parkinson’s disease and treatment (KnowPD). Clin Parkinson Relat Disord 3:100038. https://doi.org/10.1016/j.prdoa.2020.100038
Santos-García D, de Deus FT, Suárez Castro E, Aneiros Díaz A, McAfee D (2020) 5–2-1 Criteria: a simple screening tool for identifying advanced PD patients who need an optimization of Parkinson’s treatment. Parkinsons Dis 2020:7537924. https://doi.org/10.1155/2020/7537924
Savioni L, Triberti S (2020) Cognitive biases in chronic illness and their impact on patients’ commitment. Front Psychol 11:579455. https://doi.org/10.3389/fpsyg.2020.579455
Schiess N, Cataldi R, Okun MS et al. (2022) Six action steps to address global disparities in Parkinson disease: a World Health Organization priority. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2022.1783. (Published online July 11, 2022)
Schuepbach WMM, Rau J, Knudsen K et al. (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622. https://doi.org/10.1056/NEJMoa1205158
Schüpbach M, Gargiulo M, Welter ML et al. (2006) Neurosurgery in Parkinson disease: a distressed mind in a repaired body? Neurology 66(12):1811–1816. https://doi.org/10.1212/01.wnl.0000234880.51322.16
Senek M, Nielsen EI, Nyholm D (2017) Levodopa-entacapone-carbidopa intestinal gel in Parkinson’s disease: a randomized crossover study. Mov Disord 32(2):283–286. https://doi.org/10.1002/mds.26855
Sesar Á, Fernández-Pajarín G, Ares B, Rivas MT, Castro A (2017) Continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease: 10-year experience with 230 patients. J Neurol 264(5):946–954. https://doi.org/10.1007/s00415-017-8477-0
Sesar Á, Fernández-Pajarín G, Ares B et al. (2019) Continuous subcutaneous apomorphine in advanced Parkinson’s disease patients treated with deep brain stimulation. J Neurol. https://doi.org/10.1007/s00415-019-09184-5
Sesar Á, Fernández-Pajarín G, Ares B, Castro A (2021) Do we need to redefine the advanced stage in Parkinson’s disease? RMN 22(4):6167. https://doi.org/10.24875/RMN.20000119
Shih LC, Tarsy D (2011) Survey of US neurologists’ attitudes towards deep brain stimulation for Parkinson’s disease. Neuromodulation 14(3):208–213. https://doi.org/10.1111/j.1525-1403.2011.00350.x. (discussion 213)
Shirane R, Nisson M, Moran E, Shanker VL, Palmese CA (2020) Cultural Disparities in Deep Brain Stimulation (DBS) Decision Making in Patients with Parkinson Disease (PD) (1713). Neurology 94(15 Supplement). https://n.neurology.org/content/94/15_Supplement/1713. (Accessed Feb 11, 2021)
Shoulson I, Glaubiger GA, Chase TN (1975) On-off response: clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients. Neurology 25(12):1144–1144. https://doi.org/10.1212/WNL.25.12.1144
Shpiner DS, Di Luca DG, Cajigas I et al. (2019) Gender disparities in deep brain stimulation for Parkinson’s disease. Neuromodulation 22(4):484–488. https://doi.org/10.1111/ner.12973
Siegfried J, Lippitz B (1994) Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery 35(6):1126–1129. https://doi.org/10.1227/00006123-199412000-00016. (discussion 1129-1130)
Smailhodzic E, Hooijsma W, Boonstra A, Langley DJ (2016) Social media use in healthcare: a systematic review of effects on patients and on their relationship with healthcare professionals. BMC Health Serv Res 16(1):442. https://doi.org/10.1186/s12913-016-1691-0
Soileau MJ, Aldred J, Budur K et al. (2022) Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson’s disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol 21(12):1099–1109. https://doi.org/10.1016/S1474-4422(22)00400-8
Sokol LL, Young MJ, Paparian J et al. (2019) Advance care planning in Parkinson’s disease: ethical challenges and future directions. NPJ Parkinsons Dis 5:24. https://doi.org/10.1038/s41531-019-0098-0
Sperens M, Hamberg K, Hariz GM (2017) Are patients ready for “EARLYSTIM”? Attitudes towards deep brain stimulation among female and male patients with moderately advanced Parkinson’s disease. Parkinsons Dis 2017:1939831. https://doi.org/10.1155/2017/1939831
Stefani A, Tessitore A, Tambasco N et al. (2022) Criteria for identification of advanced Parkinson’s disease: the results of the Italian subgroup of OBSERVE-PD observational study. BMC Neurol 22(1):41. https://doi.org/10.1186/s12883-022-02554-z
Subramanian I, Mathur S, Oosterbaan A, Flanagan R, Keener AM, Moro E (2022) Unmet needs of women living with Parkinson’s disease: gaps and controversies. Mov Disord 37(3):444–455. https://doi.org/10.1002/mds.28921
Swarztrauber K, Vickrey BG (2004) Do neurologists and primary care physicians agree on the extent of specialty involvement of patients referred to neurologists? J Gen Intern Med 19(6):654–661. https://doi.org/10.1111/j.1525-1497.2004.30535.x
Swarztrauber K, Vickrey BG, Mittman BS (2002) Physicians’ preferences for specialty involvement in the care of patients with neurological conditions. Med Care 40(12):1196–1209. https://doi.org/10.1097/00005650-200212000-00007
Szász JA, Constantin VA, Orbán-Kis K et al. (2019) Profile of patients with advanced Parkinson’s disease suitable for device-aided therapies: restrospective data of a large cohort of Romanian patients. NDT 15:3187–3195. https://doi.org/10.2147/NDT.S230052
Szasz JA, Jianu DC, Simu MA et al. (2021) Characterizing advanced Parkinson’s disease: romanian subanalysis from the OBSERVE-PD study. Parkinsons Dis 2021:6635618. https://doi.org/10.1155/2021/6635618
Takáts A, Aschermann Z, Vécsei L et al. (2020) Advanced Parkinson’s disease characteristics in clinical practice: results from the OBSERVE-PD study and sub-analysis of the Hungarian data. Ideggyogy Sz 73(7–08):261–268. https://doi.org/10.18071/isz.73.0261
Thaler A, Barer Y, Gross R et al. (2022) Long-term persistence and monotherapy with device-aided therapies: a retrospective analysis of an Israeli cohort of patients with advanced Parkinson’s disease. Adv Ther 39(5):2009–2024. https://doi.org/10.1007/s12325-022-02072-x
Thirsk LM, Panchuk JT, Stahlke S, Hagtvedt R (2022) Cognitive and implicit biases in nurses’ judgment and decision-making: a scoping review. Int J Nurs Stud 133:104284. https://doi.org/10.1016/j.ijnurstu.2022.104284
Thomson CJ, Segrave RA, Racine E, Warren N, Thyagarajan D, Carter A (2020) “He’s Back so I’m Not Alone”: the impact of deep brain stimulation on personality, self, and relationships in Parkinson’s disease. Qual Health Res 30(14):2217–2233. https://doi.org/10.1177/1049732320951144
Titova N, Martinez-Martin P, Katunina E, Chaudhuri KR (2017) Advanced Parkinson’s or “complex phase” Parkinson’s disease? Re-Evaluation is Needed J Neural Transm (vienna) 124(12):1529–1537. https://doi.org/10.1007/s00702-017-1799-3
Titova N, Levin O, Katunina E, Ray CK (2018) “Levodopa Phobia”: a review of a not uncommon and consequential phenomenon. NPJ Parkinsons Dis 4:31. https://doi.org/10.1038/s41531-018-0067-z
Tolsa L, Jones L, Michel P, Borasio GD, Jox RJ, Rutz VR (2022) “We Have Guidelines, but We Can Also Be Artists”: Neurologists discuss prognostic uncertainty, cognitive biases, and scoring tools. Brain Sci 12(11):1591. https://doi.org/10.3390/brainsci12111591
Trachsel M, Hermann H, Biller-Andorno N (2015) Cognitive fluctuations as a challenge for the assessment of decision-making capacity in patients with dementia. Am J Alzheimers Dis Other Demen 30(4):360–363. https://doi.org/10.1177/1533317514539377
Trenkwalder C, Chaudhuri KR, García Ruiz PJ et al. (2015) Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease—clinical practice recommendations. Parkinsonism Relat Disord 21(9):1023–1030. https://doi.org/10.1016/j.parkreldis.2015.06.012
Tripathi S, ReFaey K, Stein R et al. (2020) The reliability of deep brain stimulation YouTube videos. J Clin Neurosci 74:202–204. https://doi.org/10.1016/j.jocn.2020.02.015
van Poppelen D, Tromp ANM, de Bie RMA, Dijk JM (2021) Combined and sequential treatment with deep brain stimulation and continuous intrajejunal levodopa infusion for Parkinson’s disease. J Personaliz Med 11(6):547. https://doi.org/10.3390/jpm11060547
van Ryn M, Burgess DJ, Dovidio JF et al. (2011) The impact of racism on clinician cognition, behavior, and clinical decision making. Du Bois Rev 8(1):199–218. https://doi.org/10.1017/S1742058X11000191
Varma TRK, Fox SH, Eldridge PR et al. (2003) Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson’s disease patients previously reliant on apomorphine. J Neurol Neurosurg Psychiatry 74(2):170–174. https://doi.org/10.1136/jnnp.74.2.170
Ventola CL (2014) Social media and health care professionals: benefits, risks, and best practices. P T 39(7):491–520
Vinke RS, Georgiev D, Selvaraj AK et al. (2022) Gender distribution in deep brain stimulation for Parkinson’s disease: the effect of awake versus asleep surgery. J Parkinsons Dis 12(6):1965–1968. https://doi.org/10.3233/JPD-223315
Volkmann J, Albanese A, Antonini A et al. (2013) Selecting deep brain stimulation or infusion therapies in advanced Parkinson’s disease: an evidence-based review. J Neurol 260(11):2701–2714. https://doi.org/10.1007/s00415-012-6798-6
Watanabe G, Morden FTC, Gao F, Morita M, Bruno MK (2022) Utilization and gender disparities of Deep Brain Stimulation surgery amongst Asian Americans, Native Hawaiians, and Other Pacific Islanders with Parkinson’s disease in Hawai`i. Clin Neurol Neurosurg 222:107466. https://doi.org/10.1016/j.clineuro.2022.107466
Weernink MGM, van Til JA, van Vugt JPP, Movig KLL, Groothuis-Oudshoorn CGM, Ijzerman MJ (2016) Involving patients in weighting benefits and harms of treatment in Parkinson’s disease. PLoS ONE 11(8):e0160771. https://doi.org/10.1371/journal.pone.0160771
Weiss D, Ebersbach G, Möller JC et al. (2022) Do we start too late? Insights from the real-world non-interventional BALANCE study on the present use of levodopa/carbidopa intestinal gel in advanced Parkinson’s disease in Germany and Switzerland. Parkinsonism Relat Disord 103:85–91. https://doi.org/10.1016/j.parkreldis.2022.08.018
Williams DR, Evans AH, Fung VSC et al. (2017) Practical approaches to commencing device-assisted therapies for Parkinson disease in Australia. Intern Med J 47(10):1107–1113. https://doi.org/10.1111/imj.13398
Willis AW, Schootman M, Evanoff BA, Perlmutter JS, Racette BA (2011) Neurologist care in Parkinson disease: a utilization, outcomes, and survival study. Neurology 77(9):851–857. https://doi.org/10.1212/WNL.0b013e31822c9123
Willis AW, Schootman M, Kung N, Wang XY, Perlmutter JS, Racette BA (2014) Disparities in deep brain stimulation surgery among insured elders with Parkinson disease. Neurology 82(2):163–171. https://doi.org/10.1212/WNL.0000000000000017
Witt K, Granert O, Daniels C et al. (2013) Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson’s disease: results from a randomized trial. Brain 136(Pt 7):2109–2119. https://doi.org/10.1093/brain/awt151
Xu C, Zhuang P, Hallett M, Zhang Y, Li J, Li Y (2018) Parkinson’s disease motor subtypes show different responses to long-term subthalamic nucleus stimulation. Front Hum Neurosci. https://doi.org/10.3389/fnhum.2018.00365. (Accessed March 6, 2023)
Yamashita K, Yube Y, Yamazaki Y et al. (2021) The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study. BMC Neurol 21(1):242. https://doi.org/10.1186/s12883-021-02269-7
Yassine S, Gschwandtner U, Auffret M et al. (2022) Functional brain dysconnectivity in Parkinson’s disease: a 5-year longitudinal study. Mov Disord 37(7):1444–1453. https://doi.org/10.1002/mds.29026
Yassine S, Gschwandtner U, Auffret M et al. (2023) Identification of Parkinson’s disease subtypes from resting-state electroencephalography. Mov Disord. https://doi.org/10.1002/mds.29451. (Published online June 13, 2023)
Zagnoli F, Leblanc A, Viakhireva-Dovganyuk I et al. (2023) Feasibility and benefits of home initiation of subcutaneous apomorphine infusion for patients with Parkinson’s disease: the APOKADO study. J Neural Transm (vienna). https://doi.org/10.1007/s00702-023-02609-6. (Published online March 2, 2023)
Zhang C, Ramirez-Zamora A, Meng F et al. (2020) An international survey of deep brain stimulation utilization in Asia and Oceania: the DBS think tank east. Front Hum Neurosci 14:162. https://doi.org/10.3389/fnhum.2020.00162
Zinchuk AV, Flanagan EP, Tubridy NJ, Miller WA, McCullough LD (2010) Attitudes of US medical trainees towards neurology education: “Neurophobia”—a global issue. BMC Med Educ 10(1):49. https://doi.org/10.1186/1472-6920-10-49
Zizzo N, Bell E, Lafontaine AL, Racine E (2017) Examining chronic care patient preferences for involvement in health-care decision making: the case of Parkinson’s disease patients in a patient-centred clinic. Health Expect 20(4):655–664. https://doi.org/10.1111/hex.12497
Acknowledgements
The authors would like to thank Wolfgang H. Jost, Christian Riederer and Britannia Pharmaceuticals Limited for organising the December 2022 PD expert meeting in Frankfurt (Germany) that led to this paper, as well as Kallol Ray Chaudhuri for his input on the topic during the meeting.
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All the authors contributed to the study conception. Material preparation, data collection and analysis were performed by MA. The first draft of the manuscript was written by MA, and all the authors commented on the manuscript. All the authors read and approved the final manuscript.
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Manon Auffret reports travel grants, speakers and consultancy honoraria and/or research grants from France Parkinson, Plateforme Nationale pour la Recherche sur la Fin de Vie, Institut des Neurosciences Cliniques de Rennes, Aguettant, Britannia Pharmaceutical Ltd, Adelia Medical, Linde Homecare, Homeperf, Asdia, France Développement Electronique and Society for Dental Science. Dr. Auffret is employed by France Développement Electronique (FDE) and works as a hosted researcher at the Pontchaillou University Hospital and University of Rennes. Daniel Weiss: reports travel grants, speakers and consultancy honoraria and research grants from Abbvie, Abbott, Bial, Boston Scientific, Medtronic, Kyowa Kirin, Stadapharm. Fabrizio Stocchi: received compensation from Lundbeck, Biogen, Zambon, Bial, Britannia, Abbvie, Kiowa, Synegile, Sunovion, Neuroderm, Contera, Ever. Marc Vérin: served on scientific advisory boards, received research support and received travel grant from Aguettant, Britannia Pharmaceutical Ltd, Adelia Medical, Asdia Elivie, LVL, Orkyn. Wolfgang Jost is or was a consultant and/or speaker for the following companies: Abbvie, Bial, Brittania, Desitin, Stada, UCB, Zambon.
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Auffret, M., Weiss, D., Stocchi, F. et al. Access to device-aided therapies in advanced Parkinson’s disease: navigating clinician biases, patient preference, and prognostic uncertainty. J Neural Transm 130, 1411–1432 (2023). https://doi.org/10.1007/s00702-023-02668-9
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DOI: https://doi.org/10.1007/s00702-023-02668-9