The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson's disease in a dynamic environment.

BACKGROUND: An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants. OBJECTIVE: To describe which methodological adjustments were made to the study protocol because of these developments. METHODS: We compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan. DISCUSSION: This manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment.

Specialized Allied Health Care for Parkinson's Disease: State of the Art and Future Directions.

People with Parkinson's disease (PD) experience a range of progressive motor and non-motor symptoms, that negatively affect their daily functioning, social participation and quality of life. Allied health therapies have emerged as an effective treatment approach-complementary to pharmacological and neurosurgical treatments-which reduces the impact of PD in daily life. In this article, we propose criteria for what constitutes specialized allied health care for PD, and we review allied health research in PD in terms of meeting these criteria and its outcomes for monodisciplinary approaches as well as multi- or interdisciplinary allied health interventions. We focus on the three most studied allied health disciplines in PD: physical therapy, occupational therapy and speech-language therapy. Overall, the available evidence underscores the importance and potential benefits of specialized allied health care for people with PD. Our proposed criteria and recommendations for future research might help in further delineating specialized allied health care.

Patient Experience and Feasibility of a Remote Monitoring System in Parkinson's Disease.

BACKGROUND: Remote monitoring systems have the potential to measure symptoms and treatment effects in people with Parkinson's disease (PwP) in the home environment. However, information about user experience and long-term compliance of such systems in a large group of PwP with relatively severe PD symptoms is lacking. OBJECTIVE: The aim was to gain insight into user experience and long-term compliance of a smartwatch (to be worn 24/7) and an online dashboard to report falls and receive feedback of data. METHODS: We analyzed the data of the "Bringing Parkinson Care Back Home" study, a 1-year observational cohort study in 200 PwP with a fall history. User experience, compliance, and reasons for noncompliance were described. Multiple Cox regression models were used to identify determinants of 1-year compliance. RESULTS: We included 200 PwP (mean age: 69 years, 37% women), of whom 116 (58%) completed the 1-year study. The main reasons for dropping out of the study were technical problems (61 of 118 reasons). Median wear time of the smartwatch was 17.5 h/day. The online dashboard was used by 77% of participants to report falls. Smartphone possession, shorter disease duration, more severe motor symptoms, and less-severe freezing and balance problems, but not age and gender, were associated with a higher likelihood of 1-year compliance. CONCLUSIONS: The 1-year compliance with this specific smartwatch was moderate, and the user experience was generally good, except battery life and data transfer. Future studies can build on these findings by incorporating a smartwatch that is less prone to technical issues.

Natural Health Products for Symptomatic Relief of Parkinson's Disease: Prevalence, Interest, and Awareness.

Background: Natural health products have emerged as a potential symptomatic therapeutic approach for people with Parkinson's disease (PD). Objective: To determine the prevalence of natural health product use, interest in natural health products, awareness of potential herb-drug interactions, and consultation of healthcare professionals regarding natural health products use among people with PD. Methods: Cross-sectional 4-item survey embedded in the PRIME-NL study, which is a population-based cohort of PD. Results: Of 367 people with PD, 36% reported having used natural health products to alleviate PD-related symptoms, with coffee, cannabis and turmeric being the most popular. Furthermore, 71% of people with PD were interested in learning more about natural health products. 39% of natural health products users were aware that these products could interact with PD medication and 39% had discussed their use with their healthcare professional. Conclusions: Natural health products are commonly used to alleviate symptoms by people with PD, but most users are unaware that these products can interact with PD medication and do not discuss their consumption with their healthcare professional.

Parkinson's disease is a complex neurodegenerative disorder for which current treatments are limited to symptomatic relief, and prescribed medication often causes side effects. In this context, there is an increasing interest in non-pharmacological interventions, and people living with Parkinson's disease may want to explore natural health products to alleviate disease-associated symptoms. Examples of these products include cannabis, coffee, or velvet bean (as a natural source of Levodopa). However, it remains unclear how many people with Parkinson's disease have ever used, or wish to use, natural health products to relieve disease-related symptoms. In addition, limited information is available to evaluate whether they are aware of possible interactions between these products and prescribed medication. Therefore, the aim of this study was to investigate these questions in a large representative group of people with Parkinson's disease. A total of 367 people responded to the survey, and 36% reported that they had used natural health products to relieve Parkinson's disease-related symptoms. Among the supplements listed in our survey, coffee (16%), cannabis (13%) and turmeric (10%) were the most popular. Additionally, 71% of participants were interested in learning more about natural health products, and we found that 39% of natural health product users were aware of possible interactions with prescribed Parkinson's disease medication. However, it appeared that only 39% of users had discussed these supplements with their healthcare provider. These observations are important because a concern regarding the integration of natural health products into clinical practice is their potential interactions with prescribed medication. Therefore, these findings support the need for additional research efforts into the health benefits and safety of these products. We conclude that natural health products are used by people with Parkinson's disease to provide symptomatic relief, and open discussions with their healthcare providers are encouraged to ensure efficacy and safety.

Assessing the validity of a Parkinson's care evaluation: the PRIME-NL study.

INTRODUCTION: The PRIME-NL study prospectively evaluates a new integrated and personalized care model for people with parkinsonism, including Parkinson's disease, in a selected region (PRIME) in the Netherlands. We address the generalizability and sources of selection and confounding bias of the PRIME-NL study by examining baseline and 1-year compliance data. METHODS: First, we assessed regional baseline differences between the PRIME and the usual care (UC) region using healthcare claims data of almost all people with Parkinson's disease in the Netherlands (the source population). Second, we compared our questionnaire sample to the source population to determine generalizability. Third, we investigated sources of bias by comparing the PRIME and UC questionnaire sample on baseline characteristics and 1-year compliance. RESULTS: Baseline characteristics were similar in the PRIME (n = 1430) and UC (n = 26,250) source populations. The combined questionnaire sample (n = 920) was somewhat younger and had a slightly longer disease duration than the combined source population. Compared to the questionnaire sample in the PRIME region, the UC questionnaire sample was slightly younger, had better cognition, had a longer disease duration, had a higher educational attainment and consumed more alcohol. 1-year compliance of the questionnaire sample was higher in the UC region (96%) than in the PRIME region (92%). CONCLUSION: The generalizability of the PRIME-NL study seems to be good, yet we found evidence of some selection bias. This selection bias necessitates the use of advanced statistical methods for the final evaluation of PRIME-NL, such as inverse probability weighting or propensity score matching. The PRIME-NL study provides a unique window into the validity of a large-scale care evaluation for people with a chronic disease, in this case parkinsonism.

Age and gender differences in non-motor symptoms in people with Parkinson's disease.

Background: Non-motor symptoms of Parkinson's disease (PD) are highly prevalent and heterogenic. Previous studies aimed to gain more insight on this heterogeneity by investigating age and gender differences in non-motor symptom severity, but findings were inconsistent. Furthermore, besides examining the single effects of age and gender, the interaction between them in relation to non-motor functioning has -as far as we know- not been investigated before. Objectives: To investigate the association of age and gender identity -as well as the interaction between age and gender identity- with non-motor symptoms and their impact on quality of life. Methods: We combined three large and independent studies. This approach resulted in a total number of unique participants of 1,509. We used linear regression models to assess the association of age and gender identity, and their interaction, with non-motor symptoms and their impact on quality of life. Results: Older people with PD generally had worse cognitive functioning, worse autonomic functioning and worse quality of life. Women with PD generally experienced more anxiety, worse autonomic functioning and worse quality of life compared to men with PD, whereas men with PD generally had worse cognitive functioning. In interaction analyses by age and gender identity, depressive symptoms and anxiety were disproportionally worse with increasing age in women compared to men. Conclusion: Our findings indicate that both age and gender -as well as their interaction- are differentially associated with non-motor symptoms of PD. Both research and clinical practice should pay more attention to demographic subgroups differences and possible different treatment approaches with respect to age and gender. We showed how combining datasets is of added value in this kind of analyses and encourage others to use similar approaches.

Assessing the effectiveness of serious game training designed to assist in upper limb prothesis rehabilitation.

Introduction: Controlling a myoelectric upper limb prosthesis is difficult, therefore training is required. Since training with serious games showed promising results, the current paper focuses on game design and its effectivity for transfer between in-game skill to actual prosthesis use for proportional control of hand opening and control of switching between grips. We also examined training duration and individual differences. Method: Thirty-six participants were randomly assigned to one of three groups: a task-specific serious game training group, a non-task-specific serious game training group and a control group. Each group performed a pre-test, mid-test and a post-test with five training sessions between each test moment. Test sessions assessed proportional control using the Cylinder test, a test designed to measure scaling of hand aperture during grabbing actions, and the combined use of proportional and switch control using the Clothespin Relocation Test, part of the Southampton Hand Assessment Procedure and Tray Test. Switch control was assessed during training by measuring amplitude difference and phasing of co-contraction triggers. Results: Differences between groups over test sessions were observed for proportional control tasks, however there was lack of structure in these findings. Maximum aperture changed with test moment and some participants adjusted maximum aperture for smaller objects. For proportional and switch control tasks no differences between groups were observed. The effect of test moment suggests a testing effect. For learning switch control, an overall improvement across groups was found in phasing of the co-contraction peaks. Importantly, individual differences were found in all analyses. Conclusion: As improvements over test sessions were found, but no relevant differences between groups were revealed, we conclude that transfer effects from game training to actual prosthesis use did not take place. Task specificity nor training duration had effects on outcomes. Our results imply testing effects instead of transfer effects, in which individual differences played a significant role. How transfer from serious game training in upper limb prosthesis use can be enhanced, needs further attention.

Successful implementation of technology in the management of Parkinson's disease: Barriers and facilitators.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with a fast increasing prevalence. Several pharmacological and non-pharmacological interventions are available to alleviate symptoms. Technology can be used to improve the efficiency, accessibility and feasibility of these treatments. Although many technologies are available, only few are actually implemented in daily clinical practice. Aim: Here, we study the barriers and facilitators, as experienced by patients, caregivers and/or healthcare providers, to successful implement technology for PD management. Methods: We performed a systematic literature search in the PubMed and Embase databases until June 2022. Two independent raters screened the titles, abstracts and full texts on: 1) people with PD; 2) using technology for disease management; 3) qualitative research methods providing patients', caregivers and/or healthcare providers' perspective, and; 4) full text available in English or Dutch. Case studies, reviews and conference abstracts were excluded. Results: We found 5420 unique articles of which 34 were included in this study. Five categories were made: cueing (n = 3), exergaming (n = 3), remote monitoring using wearable sensors (n = 10), telerehabilitation (n = 8) and remote consultation (n = 10). The main barriers reported across categories were unfamiliarity with technology, high costs, technical issues and (motor) symptoms hampering the use of some technologies. Facilitators included good usability, experiencing beneficial effects and feeling safe whilst using the technology. Conclusion: Although only few articles presented a qualitative evaluation of technologies, we found some important barriers and facilitators that may help to bridge the gap between the fast developing technological world and actual implementation in day-to-day living with PD.

Time trends in demographic characteristics of participants and outcome measures in Parkinson's disease research: A 19-year single-center experience.

Background: Females, people with young-onset PD and older individuals, and non-white populations are historically underrepresented in clinical Parkinson's disease (PD) research. Furthermore, research traditionally focused predominantly on motor symptoms of PD. Including a representative and diverse group of people with PD and also studying non-motor symptoms is warranted to better understand heterogeneity in PD and to generalize research findings. Objective: This project aimed to determine whether, within a consecutive series of PD studies performed within a single center in the Netherlands: (1) the proportion of included females, mean age and proportion of native Dutch people changed over time; and 2) reports of the ethnicity of participants and the proportion of studies with non-motor outcomes changed over time. Methods: Characteristics of participants and non-motor outcomes were analyzed using a unique dataset of summary statistics of studies with a large number of participants conducted at a single center during a 19-year period (2003-2021). Results: Results indicate no relationship between calendar time and proportion of females (mean 39 %), mean age (66 years), proportion of studies that reported ethnicity, and proportion of native Dutch people in studies (range 97-100 %). The proportion of participants in whom non-motor symptoms were assessed increased, but this difference was consistent with chance. Conclusion: Study participants in this center reflect the PD population in the Netherlands in terms of sex, but older individuals and non-native Dutch individuals are under-represented. We have still a lot to do in ensuring adequate representation and diversity in PD patients within our research.

User-relevant factors determining prosthesis choice in persons with major unilateral upper limb defects: A meta-synthesis of qualitative literature and focus group results.

OBJECTIVE: Considering the high rejection rates of upper limb prostheses, it is important to determine which prosthesis fits best the needs of each user. The introduction of the multi-grip prostheses hands (MHP), which have functional advantages but are also more expensive, has made prosthesis selection even harder. Therefore, we aimed to identify user opinions on factors determining prosthesis choice of persons with major unilateral upper limb defects in order to facilitate a more optimal fit between user and prosthesis. METHODS: A qualitative meta-synthesis using a 'best-fit framework' approach was performed by searching five databases (PROSPERO registration number: CRD42019126973). Studies were considered eligible if they contained qualitative content about adults with major unilateral upper limb defects experienced in using commercially available upper limb prostheses and focused on upper limb prosthesis users' opinions. Results of the meta-synthesis were validated with end-users (n = 11) in a focus group. RESULTS: Out of 6247 articles, 19 studies were included. An overview of six main themes ('physical', 'activities and participation', 'mental', 'social', 'rehabilitation, cost and prosthetist services' and 'prosthesis related factors') containing 86 subthemes that could affect prosthesis choice was created. Of these subthemes, 19 were added by the focus group. Important subthemes were 'work/school', 'functionality' and 'reactions from public'. Opinions of MHP-users were scarce. MHPs were experienced as more dexterous and life-like but also as less robust and difficult to control. CONCLUSION: The huge number of factors that could determine upper limb prosthesis choice explains that preferences vary greatly. The created overview can be of great value to identify preferences and facilitate user-involvement in the selection process. Ultimately, this may contribute to a more successful match between user and prosthesis, resulting in a decrease of abandonment and increase of cost-effectiveness.

Propionate oxidation by and methanol inhibition of anaerobic ammonium-oxidizing bacteria.

Anaerobic ammonium oxidation (anammox) is a recently discovered microbial pathway and a cost-effective way to remove ammonium from wastewater. Anammox bacteria have been described as obligate chemolithoautotrophs. However, many chemolithoautotrophs (i.e., nitrifiers) can use organic compounds as a supplementary carbon source. In this study, the effect of organic compounds on anammox bacteria was investigated. It was shown that alcohols inhibited anammox bacteria, while organic acids were converted by them. Methanol was the most potent inhibitor, leading to complete and irreversible loss of activity at concentrations as low as 0.5 mM. Of the organic acids acetate and propionate, propionate was consumed at a higher rate (0.8 nmol min(-1) mg of protein(-1)) by Percoll-purified anammox cells. Glucose, formate, and alanine had no effect on the anammox process. It was shown that propionate was oxidized mainly to CO(2), with nitrate and/or nitrite as the electron acceptor. The anammox bacteria carried out propionate oxidation simultaneously with anaerobic ammonium oxidation. In an anammox enrichment culture fed with propionate for 150 days, the relative amounts of anammox cells and denitrifiers did not change significantly over time, indicating that anammox bacteria could compete successfully with heterotrophic denitrifiers for propionate. In conclusion, this study shows that anammox bacteria have a more versatile metabolism than previously assumed.