Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia—Literature Review

Levodopa remains the primary drug for controlling motor symptoms in Parkinson’s disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

Current Knowledge on the Background, Pathophysiology, and Treatment of Levodopa-Induced Dyskinesia – Literature Review.

Levodopa remains the primary drug for controlling motor symptoms in Parkinson's disease through the whole course, but over time complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mostly characteristic of the ON phase and reflect an excess of exogenous levodopa. They may also occur during OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English-language literature published since 2010. Based on the selected papers, the current state of knowledge on morphological, functional, genetic, and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation are described.

Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

The acquired EGFR C797X mutation has been identified as the most notable resistance to osimertinib, and novel secondary mutations of EGFR L718 and L792 residues have also been demonstrated to confer osimertinib resistance, making the choice of medication after osimertinib treatment a quandary. Dacomitinib has been reported to have potential impact on patients acquiring rare compound mutations after osimertinib resistance; however, little evidence is available to date. In five lung adenocarcinoma patients resistant to later-line osimertinib, recurrent mutations at EGFR L792 and/or L718 were identified using targeted next-generation sequencing of tissue or cell-free DNA from plasma or pleural effusion. Dacomitinib was initiated after osimertinib resistance; however, all patients progressed within 2 months. Molecular structural simulation revealed that L792H + T790M and L718Q mutations could interfere with the binding of dacomitinib to EGFR and potentially cause primary drug resistance. Our case series study, to our knowledge, is the first to report the clinical efficacy of dacomitinib in patients harboring rare complex mutations after later-line osimertinib resistance.

A new way to optimize primary prevention of bleeding from varicose veins of esophagus

Objective. To establish the possibility of optimization of drug prevention of bleeding from varicose veins of the esophagus based on the influence of meteorological factors on the development of the disease. Materials and methods. The results of examination and treatment of 86 patients diagnosed bleeding from varicose veins of the esophagus, who were treated at the Emergency Hospital of Ryazan in 2016-2018, were analyzed. Results. A significant dependence of the incidence of bleeding from varicose veins of the esophagus on meteorological factors, in particular, on changes in atmospheric pressure, was revealed. Based on the analysis of the weather data archive, the safest periods for temporary interruption of the courses of drug primary prevention were established. Conclusions. A break in the course of primary drug prevention of bleeding from varicose veins of the esophagus, necessary to increase its effectiveness, will be the safest in February and July.

The relationship between severity of drug problems and perceived interdependence of drug use and sexual intercourse among adult males in drug addiction rehabilitation centers in Japan

Background Consuming drugs in conjunction with sexual intercourse may shape the perceived interdependence of drug use and sexual intercourse (PIDS). Additionally, the severity of drug problems may have a significant impact on PIDS. However, this relationship remains unverified. Therefore, this study investigates whether the severity of drug problems is associated with PIDS among adult males in drug addiction rehabilitation centers (DARC) in Japan. Methods This study was a secondary analysis of the “DARC Follow-Up Study in Japan” conducted by the National Center of Neurology and Psychiatry in 2016, in which participants from 46 facilities completed a self-report questionnaire. A total of 440 males with drug dependence were included in the analysis. We analyzed participants’ demographic characteristics, history of sexually transmitted disease diagnoses, and responses to questions related to drug use (e.g., primary drug use and PIDS). Additionally, we measured the severity of drug problems using the Japanese version of the Drug Abuse Screening Test-20 (DAST-20). Results The median age of the participants was 42 years. The median DAST-20 score was 14.0, the primary drug was methamphetamine (61.4%) and new psychoactive substances (NPS: 13.6%). Multivariate analysis indicated that participants’ experiences with unprotected sexual intercourse (“mostly a non-condom user”: adjusted odds ratio (AOR) = 4.410), methamphetamine use (AOR = 3.220), new psychoactive substances use (AOR = 2.744), and the DAST-20 score (AOR = 1.093) were associated with PIDS. Conclusions This study indicated that the frequency of unprotected sexual intercourse under the influence of drugs, methamphetamine and NPS use were strongly associated with PIDS. The severity of drug problems was also significantly associated with PIDS. It is necessary to develop culturally appropriate treatment programs adapted to the needs of patients who experience strong PIDS.