•The application is used in a regular clinical setting and has proven to be effective and very easy to use.•The application is user-friendly and is available either online or as a standalone mobile ...application.•The application can replace tedious and error prone levodopa equivalent dose conversion of the antiparkinsonian drugs efficiently.•In comparison to other solutions, our application provides much more functionality, reduces the risk of errors and can be run on a variety of devices.
Levodopa/carbidopa intestinal gel infusion is a treatment option for patients of advanced stage of Parkinson's disease. This treatment requires the time-consuming and error-prone conversion of orally taken antiparkinson drugs into an equivalent replacing dose of levodopa/carbidopa, which is delivered via pump. In order to facilitate and speed up this conversion process, we developed a specific user-friendly application that would be available online or as a standalone mobile application. Such an application has now been written and designed in collaboration with a computer scientist and physician, who is also intended to be the final user.
The levodopa equivalent dose calculations are based on previous studies and data reported in the literature. Two related on-line conversion applications were analyzed and evaluated. The primary objectives of the application were determined, and basic functionalities were outlined. The application was implemented using modern development tools and frameworks.
The application has proven to be effective and easy to use in our clinical setting. It can serve as a control for manual calculations made by medical staff. It can also be applied as a useful tool in levodopa/carbidopa intestinal gel infusion courses for the advanced treatment of Parkinson's disease.
The presented application could replace the tedious and error-prone levodopa equivalent dose conversion of antiparkinson drugs efficiently. In comparison to related on-line conversion applications, this specific application provides more functionality, reduces the risk of user errors, and can be run on a variety of devices. The conversion value provided by the application is only an estimate. The effect of the drugs is specific for each individual patient, which could not be considered in the calculations. Therefore, the responsibility of using the results of the application rests with the clinical judgment of the user. Nevertheless, the application can give us a good starting point for the initial pump setting, which would be adjusted further during the titration period, according to the patient's response.
Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for ...the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment.
In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson's disease' risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations.
We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson's disease (OR = 0.59; 95%CI = 0.38-0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15-0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events.
Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment.
Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of ...dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one
rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16-0.72;
= 0.004), while carriers of at least one
rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00-3.54;
= 0.049 and OR = 3.31; 95% CI = 1.37-8.03;
= 0.008, respectively). Carriers of at least one
rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07-3.23;
= 0.028 and OR = 2.30; 95% CI = 1.26-4.20;
= 0.007, respectively). Heterozygotes for
rs3837091 and
rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07-3.51;
= 0.028 and OR = 2.57; 95% CI = 1.11-5.95;
= 0.028, respectively). Carriers of the
rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62-9.88;
= 0.003 and OR = 3.16; 95% CI = 1.03-9.72;
= 0.045, respectively). Finally, heterozygotes for
rs628031 and carriers of at least one
rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24-0.98,
= 0.043 and OR = 0.48; 95% CI = 0.25-0.92;
= 0.027, respectively). Gene-gene interactions, more specifically
, and
, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of
and
were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16-0.72;
= 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01-6.07;
= 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization.
Abstract
Parkinson’s disease (PD) guidelines lack clear criteria for genetic evaluation. We assessed the yield and rationale of genetic testing for PD in a routine clinical setting on a multicenter ...cohort of 149 early-onset and familial patients by exome sequencing and semi-quantitative multiplex ligation-dependent probe amplification of evidence-based PD-associated gene panel. We show that genetic testing for PD should be considered for both early-onset and familial patients alike, and a clinical yield of about 10% in the Caucasian population can be expected.
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