Clinical Parkinsonism Related Disorders最新文献

Introduction

Parkinson’s disease (PD) affects multiple facets of patients’ lives, many of which may not be recognized or addressed by their healthcare team. A growing body of evidence has shown that palliative care improves patients’ quality of life with PD; however, little is currently known about how patients with PD perceive palliative care.

Methods

An 8-question multiple choice survey was created and given to patients with established care for PD at a movement disorders clinic in a quaternary care center. Patients with less than two years of follow-up or that had atypical features of PD were excluded from the survey.

Results

There were 106 respondents to the survey. A third of patients reported having never heard of palliative care and an additional 25% had heard of it but did not know what it was. Eighty-eight percent reported being familiar with or very knowledgeable about hospice, though 50% of respondents did not know the difference between hospice and palliative care. 93% had never been offered either service. 37.7% thought their neurologist should discuss advance care planning early in the course of their disease.

Conclusion

Even among established patients with Parkinson’s disease in a quaternary center, over half were not familiar with palliative care, and the majority had never been offered palliative or hospice services despite growing evidence that it could improve their quality of life. Additionally, patients would like to be introduced to advanced care planning early in the course of their disease.

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.

After Alzheimer’s disease, Frontotemporal dementia (FTD) is the most common cause of early-onset dementia. Several genetic mutations have been identified in familial FTD, with mutations in progranulin (GRN) accounting for approximately 20–25% of familial FTD cases and about 10% of total FTD cases. We report the case of a familial FTD patient with atypical parkinsonism who was found to have GRN frontotemporal dementia (GRN-FTD) with a pathogenic splice site mutation (c.709-2A > G) and notable phenotypic heterogeneity among family members.

Introduction

The 12-item Vietnamese smell identification test (VSIT) has been developed to evaluate the olfactory function of the Vietnamese population. This study aimed to investigate the normative value of the VSIT in different age groups and sexes.

Methods

This cross-sectional study was conducted at Ho Chi Minh University Medical Center, Vietnam. All participants were evaluated for odor identification ability using the VSIT. We included healthy participants aged 18 years or older with no history of olfactory disturbances.

Results

A total of 391 healthy volunteers were recruited with a mean age of 45.80 years (SD: 17.62; range: 18–86; female: 63.4 %). The tenth percentile of scores on the 0–12 VSIT scale was 8.3 in participants aged 18–29 years, 9.0 in 30–39 years, 8.0 in 40–49 years, 7.8 in 50–59 years, 7.9 in 60–69 years and 6.0 in over 70 years. Young adults (18–39 years old) had better olfactory identification ability than older adults (over 50 years), p < 0.001. There was a significant main effect of sex on VSIT score (p = 0.02), suggesting that females outperformed males. Sensitivity to 8 odors were negatively correlated with age: lemon, garlic, banana, coffee, mango, guava, apple and watermelon (p < 0.05 in all cases) whereas four odors were age-independent including orange, fish sauce, soy sauce, and fish.

Conclusion

Normative data provide guidance for assessing individual olfactory function. However, there were significant sex and age effects on olfactory identification scores on the VSIT. Therefore, future studies should be conducted to better adjust for those confounders mentioned above.

Background and objectives

Patients with cervical dystonia (CD) demonstrate significant non-motor symptoms including sensory, psychiatric and cognitive features. It has been shown that the non-motor symptoms have a major influence on quality of life. Social cognition, particularly deficits in Theory of Mind (ToM), can affect the development of interpersonal relationships, understanding of social situations and can affect patient outcomes.

We used the “Faux Pas” measure of social cognition to assess ToM in patients with CD and compared this with quality of life, disease severity and psychiatric symptoms.

Methods

Patients with adult-onset idiopathic isolated cervical dystonia were assessed using the “Faux Pas” questionnaire. Validated questionnaires were used to assess mood symptoms (BAI/BDI and HADS) and quality of life (CDIP-58). Disease-specific disability, motor severity and psychosocial symptoms were measured using TWSTRS2. Faux pas results were compared with published healthy control values.

Results

32 participants (19 female) were included with a mean age of 57.7 years. 20 participants met criteria for excess mood symptoms (anxiety and/or depression). Mean CDIP-58 was 31.9. There was no relationship between faux pas outcomes and motor severity. However, correlation analyses showed that participants who performed worse on the faux pas questionnaire had lower quality of life.

Conclusion

The non-motor symptoms, including social cognition, are often neglected. We have demonstrated that low quality of life in CD is associated with to abnormal social cognition. Clinicians should be mindful of these symptoms, particularly in patients reporting low treatment satisfaction.

Introduction

Data on Huntington’s disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce.

Methods

Annual prevalence and incidence of HD (ICD-9-CM 333.4) were assessed in the Israel-based Maccabi Healthcare Services (MHS) database 2016–2018. Adherence (medication possession rate [MPR], proportion of disease covered) were assessed for adult people with HD (PwHD) 2013–2018. Healthcare resources utilization (HCRU) and costs related to inpatient and outpatient visits and all medications in 2018 were assessed for PwHD, who were randomly matched to MHS members without HD (1:3) by birth-year and sex.

Results

Overall, 164 patients had at least one HD diagnosis. Annual prevalence and incidence were 4.45 and 0.24/100,000, respectively. A total of 67.0% of adult patients (n = 106) were taking tetrabenazine (median MPR and proportion of disease covered, 74.3% and 30.2%, respectively), 65.1% benzodiazepines (75.8% and 32.3%), and 11.3% amantadine (79.2% and 6.0%). Over a 1-year follow-up, PwHD (n = 81) had significantly more neurologist, psychiatrist, physiotherapist, and speech therapist visits (P < 0.05 for each) and more hospitalization days (P < 0.0001) compared with matched controls (n = 243). Total healthcare and medication costs per patient (US dollars) were significantly higher for PwHD than controls ($7,343 vs. $3,625; P < 0.001).

Discussion/Conclusion

PwHD have greater annual HCRU and medical costs than MHS members without HD in Israel. Among those who have taken medications, adherence was lower than 80% (both MPR and proportion of disease covered), which may translate into suboptimal symptom relief and quality of life.

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as providing relevant information on antiemetic prophylaxis with initiation of injectable apomorphine. The first study demonstrated that nausea was significantly more common in patients who received 3-days of trimethobenzamide pretreatment compared with those who did not, while the primary endpoint of second study found no significant effect on the binary incidence of nausea and/or vomiting on Day 1 of apomorphine treatment. In the third study, which used a slow titration scheme for apomorphine, transient nausea was reported in just 23.1% of the antiemetic nonusers.

Conclusions

Based on the reviewed trials and our clinical experience, we suggest that subcutaneous apomorphine therapy can be initiated using a slow titration scheme without antiemetic pretreatment.

Introduction

Parkinson’s disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures.

Methods

Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT).

Results

Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs.

Conclusions

Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.

Introduction

IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson’s disease (PD) patients.

Methods

IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations. The PK and pharmacodynamics of IPX203 were compared with IR CD-LD in a Phase 2, open-label, rater-blinded, multicenter, crossover study in patients with advanced PD.

Results

Pharmacokinetic data showed that on Day 15, LD concentrations were sustained above 50% of peak for 6.2 h with IPX203 vs. 3.9 h with IR CD-LD (P = 0.0002). Pharmacodynamic analysis demonstrated that mean MDS-UPDRS Part III scores prior to administration of the first daily dose were significantly lower among patients receiving IPX203 than IR CD-LD (LS mean difference –8.1 [25.0], P = 0.0255). In a study conducted in healthy volunteers, a high-fat, high-calorie meal delayed plasma LD T_max by 2 h, and increased C_max and AUC_tau by approximately 20% compared with a fasted state. Sprinkling capsule contents on applesauce did not affect PK parameters.

Conclusion

These data confirm that the unique design of IPX203 addresses some of the limitations of oral LD delivery.

Objectives

To characterize patients with Parkinson’s disease (PD) who initiated dopamine agonist (DA) monotherapy, describe medication utilization and provider types, and estimate medication adherence and discontinuation rates.

Methods

Retrospective study identified patients with PD in the Optum Research Database and included those with ≥1 claim for DA or levodopa between 09/01/2012 and 12/31/2018, ≥2 PD diagnoses, commercial or Medicare Advantage Part D (MAPD) insurance, ≥40 years old, and continuous medical and pharmacy coverage ≥12 months before and after index date. A subset of patients receiving DA monotherapy was selected for this analysis. Variables were analyzed descriptively. Adherence was measured with medication possession ratio (MPR) and proportion of days covered (PDC); defined as ≥0.80.

Results

Patients (N = 642) had mean (SD) age of 70.2 (9.9) years, 70.6 % had MAPD coverage, and 61.7 % were male. Neurologists prescribed 64.6 % of DA monotherapy, and 56.9 % of patients had ≥2 PD diagnoses before or on the index date. Index therapy was discontinued by 44.1 % of patients, and 55.9 % persisted for 12 months without change. Mean (SD) time to discontinuation was 102 (79) days. Mean (SD) MPR for patients (n = 562) with ≥2 fills was 0.84 (0.2); 70.3 % were MPR adherent. Mean (SD) PDC for all 642 patients was 0.66 (0.3); 50.5 % were PDC adherent.

Conclusion

Adherence and continuation of therapy were suboptimal, which could translate into poor patient outcomes. Future studies could provide insights on the impact of low adherence and persistence with DA monotherapy.