Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson\u27s disease study

\ua9 The Author(s) 2024. Estimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson’s disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 7 10−34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 7 10−35). Female patients were 22% more likely to have a positive PDGT (P = 3 7 10−4), and for individuals with FH+ this likelihood was 55% higher (P = 1 7 10−14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD

General dental practices with and without a dental therapist: a survey of appointment activities and patient satisfaction with their care.

Introduction Policy changes regarding the role of Dental Hygienist-Therapists (DTs) have been implemented in recent years with a view to promoting delivery of oral health-care through a more preventive-focused, team work approach. Aims To explore i) treatments led by dentists and DTs, and ii) patients' satisfaction with the care they received. Materials and methods Six case-studies of general dental practices in Wales, UK: three with, and three without a DT. For each participant, a patient-satisfaction questionnaire and a staff-member-completed appointment record form were completed. We sought to recruit 150 patients seeing a dentist and 100 patients seeing a DT, per case-study practice. Results 1,224 patients were recruited in total (314 DT and 910 dentist appointments). Preventive work accounted for nearly half of all treatments. Dentists, in practices with a DT, undertook significantly less preventive and restorative work, and significantly more extractions and advanced treatment (p <0.005, χ² = 15.352). Patient satisfaction and confidence in dentists' or DTs' ability was uniformly high (97% and 99% each group respectively). Conclusion Practices with DTs provided a more preventive-focused approach to oral health-care delivery; dentists in these practices performed more complex work. Positive patient satisfaction and confidence in practitioners' ability suggest patient acceptability of a preventive model

Philip Ball: The Music Instinct. How music works and why we can't do without it

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How A.I. people think

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