Patients accept therapy using embryonic stem cells for Parkinson’s disease:a discrete choice experiment

Background: New disease-modifying ways to treat Parkinson’s disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future. Methods: Patients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents’ preferences. Results: A substantial difference in respondents’ preferences was observed in three latent preference patterns (classes). “Effect on symptoms” was the most important attribute in class 1, closely followed by “type of treatment,” with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on “type of treatment” in the decision-making. Respondents’ class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs. Conclusions: Most of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells.</p

Разработка и оптимизация дистанционного режима управления станцией механической очистки СУ-МОК4310V

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.FLOAT - Flexibel levodopa-optimerings och individanpassningstekni

Back to Analogue: Self-Reporting for Parkinson’s Disease.

We report the process used to create artefacts for self-reporting Parkinson's Disease symptoms. Our premise was that a technology-based approach would provide participants with an effective, flexible, and resilient technique. After testing four prototypes using Bluetooth, NFC, and a microcontroller we accomplished almost full compliance and high acceptance using a paper diary to track day-to-day fluctuations over 49 days. This diary is tailored to each patient's condition, does not require any handwriting, allows for implicit reminders, provides recording flexibility, and its answers can be encoded automatically. We share five design implications for future Parkinson's self-reporting artefacts: reduce participant completion demand, design to offset the effect of tremor on input, enable implicit reminders, design for positive and negative consequences of increased awareness of symptoms, and consider the effects of handwritten notes in compliance, encoding burden, and data quality

Pharmacotherapy for Parkinson's Disease - Observations and Innovations

Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies. To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary. To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies

A survey of lifestyle factors in dystonia.

BACKGROUND: Knowledge about what causes dystonia is highly incomplete, especially about the impact of nongenetic factors. AIMS OF THE STUDY: This cross-sectional survey-based explorative study examined different nongenetic factors in patients with dystonia. METHODS: Information from both medical records and a questionnaire was collected. In total, 220 patients with dystonia were identified, of which 51 participated in the survey. RESULTS: Women had a higher prevalence for cervical dystonia than men. Smoking was approximately twice as common in our studied population compared to the general Swedish population. Significantly more men than women met the criteria for low level of physical activity, yet the proportion of missing data was high in this category. CONCLUSIONS: Conclusions on causality cannot be drawn in this preliminary study, further research is encouraged regarding the link between smoking and dystonia

Optimizing Treatment of Parkinson's Disease

The holy grail of therapy in Parkinson’s disease (PD) is treatment that would halt the disease process or restore the degenerated neuronal circuits [...

Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

The duration of action of oral levodopa becomes shorter as Parkinson’s disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa–carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in ‘off’ time and ‘on’ time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment

Short-Term Cost and Health Consequences of Duodenal Levodopa Infusion in Advanced Parkinson's Disease in Sweden: An Exploratory Study

Background: Levodopa is the cornerstone treatment for Parkinson's disease, but the short half-life of levodopa limits its usefulness in late stages of the disease. Duodenal levodopa infusion (DLI) allows more stable plasma levels and better motor symptom control. Objective: To explore the costs and health benefits of replacing conventional oral polypharmacy with DLI in patients with advanced Parkinson's disease, from a Swedish healthcare payer perspective. Methods: Based on a clinical, randomized, crossover study with 24 patients (DIREQT), a decision analytic model predicted 2-year drug costs and QALYs for conventional oral therapy and for DLI. Health-related quality of life (HR-QOL) was recorded using a 15-dimensional (15D) utility instrument at baseline and during the two 3-week trial periods, and then at eight follow-up visits during the subsequent 6 months. Use of medication was based on data from DIREQT and previous studies. Unit costs were based on market prices (drugs) and customary charges in Sweden. All costs were expressed in Swedish kronor (SEK), year 2004 values (&U20AC;1.00 &ap; SEK9.17, &dollar;US1.00 - SEK7.47). Future costs and outcomes were discounted at 3%. One-way and probabilistic sensitivity analyses were conducted. Results: The mean utility scores were 0.77 for DLI and 0.72 for conventional therapy (p - 0.02). A considerable variation in the scores was observed during the study. The expected per-patient 2-year cost of DLI was SEK562 000 while it was SEK172 000 for conventional therapy. The mean number of QALYs was 1.48 and 1.42, respectively, representing an incremental cost of SEK6.1 million per QALY for DLI (all values discounted at 3%). Using other assumptions in sensitivity analyses, the cost per QALY could be as low as SEK456 000. Conclusion: This analysis can be considered exploratory only; it is based on very limited data. Nevertheless, our findings suggest that DLI results in a significant improvement in HR-QOL. However, the cost per QALY is likely to be higher than customary cost-effectiveness thresholds. Whether these benefits justify the additional costs depends on how the health benefits are measured and how these benefits are valued by society.

Effects of Helicobacter pylori on Levodopa Pharmacokinetics

Background: Infection with Helicobacter pylori seems overrepresented in Parkinson’s disease. Clinical observations suggest a suboptimal treatment effect of levodopa in Helicobacter positive patients. Objective: Describe and explain the connection between a Helicobacter pylori infection of the upper gut and changes in pharmacokinetics of oral levodopa treatment in Parkinson’s disease. Methods: PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: Bioavailability, drug metabolism, dyskinesia, Helicobacter, L-dopa, levodopa, motor control, pharmacodynamics, pharmacokinetics, prevalence, unified Parkinson’s disease rating scale. Results: The prevalence of Helicobacter pylori in Parkinson’s disease patients is reported to be about 1.6-fold higher than in a control population in some studies. Helicobacter has therefore been assumed to be linked to Parkinson’s disease, but the mechanism is unclear. As regards symptoms and treatment, patients with Parkinson’s disease on levodopa therapy and with Helicobacter pylori infection display worse motor control than those without Helicobacter infection. Eradication of the infection improves levodopa response in Parkinson’s disease, likely as a consequence of an increased oral pre-systemic bioavailability of levodopa, likely to be explained by reduced Helicobacter-dependent levodopa consumption in the stomach. In addition, small intestinal bacterial overgrowth may also have an impact on the therapeutic setting for levodopa treatment but is less well established. Conclusion: Eradication of Helicobacter pylori improves levodopa bioavailability resulting in improved motor control. Eradication of Helicobacter should be considered in patients with poor symptomatic control and considerable motor fluctuations

Levodopa-entacapone-carbidopa intestinal gel infusion in advanced Parkinson's disease : real-world experience and practical guidance

As Parkinson's disease (PD) progresses, treatment needs to be adapted to maintain symptom control. Once patients develop advanced PD, an optimised regimen of oral and transdermal medications may no longer provide adequate relief of OFF periods and motor complications can emerge. At this point, patients may wish to consider a device-aided therapy (DAT) that provides continuous dopaminergic stimulation to help overcome these issues. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed DAT option. The aim of this article is twofold: (1) to give an overview of the pharmacokinetics of LECIG infusion and clinical experience to date of its use in patients with advanced PD, including real-world data and patient-reported outcomes from a cohort of patients treated in Sweden, the first country where it was introduced, and (2) based on that information to provide practical guidance for healthcare teams starting patients on LECIG infusion, whether they are transitioning from oral medications or from other DATs, including recommendations for stepwise dosing calculation and titration. In terms of clinical efficacy, LECIG infusion has been shown to have a similar effect on motor function to standard levodopa-carbidopa intestinal gel (LCIG) infusion but, due to the presence of entacapone in LECIG, the bioavailability of levodopa is increased such that lower overall levodopa doses can be given to achieve therapeutically effective plasma concentrations. From a practical standpoint, LECIG infusion is delivered using a smaller cartridge and pump system than LCIG infusion. In addition, for patients previously treated with LCIG infusion who have an existing percutaneous endoscopic transgastric jejunostomy (PEG-J) system, this is compatible with the LECIG infusion system. As it is a relatively new product, the long-term efficacy and safety of LECIG infusion remain to be established; however, real-world data will continue to be collected and analysed to provide this information and help inform future clinical decisions