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The effect of subthalamic stimulation (STN-DBS) on patients' personal satisfaction with life and their Parkinson's disease (PD) treatment is understudied, as is its correlation with quality of life (QoL). Therefore, we tested the hypothesis that STN-DBS for PD enhances satisfaction with life and treatment. In a prospective, multicenter study with a 6-month follow-up involving 121 patients, we measured the main outcomes using the Satisfaction with Life and Treatment Scale (SLTS-7). Secondary outcomes included the eight-item PD Questionnaire (PDQ-8), European QoL Questionnaire (EQ-5D-3L), EQ-Visual Analogue Scale (VAS), Non-Motor Symptom Scale (NMSS), Hospital Anxiety and Depression Scale (HADS), and Unified PD Rating Scale (UPDRS). Longitudinal outcome changes, effect sizes (Cohen's d), and correlations between outcome changes were analyzed. SLTS-7 scores improved at the 6-month follow-up, particularly in the domains of 'satisfaction with physical health' and 'satisfaction with treatment'. Change scores correlated strongly (EQ-VAS), moderately (PDQ-8 SI and HADS), and weakly (UPDRS-activities of daily living and EQ-5D-3L) with other scales. Satisfaction with physical health, psychosocial well-being, or treatment was not related to UPDRS-motor examination. This study provides evidence that STN-DBS enhances patients' personal satisfaction with life and treatment. This satisfaction is associated with improvements in the QoL, daily activities, and neuropsychiatric aspects of PD rather than its motor aspects.

Background: The shift toward virtualized care introduces challenges in assessing the motor severity of Parkinson's disease (PD). The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, the most used rating scale in PD, lacks validation for synchronous remote administration., Objective: Our goal was to validate the usability of a patient guide to allow an accurate video-based MDS-UDPRS part III remote examination., Methods: We conducted a multi-stage mixed methods study that included a team consensus for the concept of the guide, cognitive pretesting, and usability (system usability scale, [SUS]) testing in five sites (total n = 25 participants) with distinct linguistic and cultural contexts., Results: A multi-language (English, Portuguese, Spanish, and traditional Chinese) largely pictograph guide of the MDS-UPDRS part III remote examination reached benchmark for usability (SUS score ≥68) in 25 participants who completed the synchronous remote assessment., Conclusions: The MDS-UDPRS part III remote examination guide can be used remotely accurately, and facilitate clinical practice and research in a paradigm of telemedicine., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Importance: Safe integration of artificial intelligence (AI) into clinical settings often requires randomized clinical trials (RCT) to compare AI efficacy with conventional care. Diabetic retinopathy (DR) screening is at the forefront of clinical AI applications, marked by the first US Food and Drug Administration (FDA) De Novo authorization for an autonomous AI for such use., Objective: To determine the generalizability of the 7 ethical research principles for clinical trials endorsed by the National Institute of Health (NIH), and identify ethical concerns unique to clinical trials of AI., Design, Setting, and Participants: This qualitative study included semistructured interviews conducted with 11 investigators engaged in the design and implementation of clinical trials of AI for DR screening from November 11, 2022, to February 20, 2023. The study was a collaboration with the ACCESS (AI for Children's Diabetic Eye Exams) trial, the first clinical trial of autonomous AI in pediatrics. Participant recruitment initially utilized purposeful sampling, and later expanded with snowball sampling. Study methodology for analysis combined a deductive approach to explore investigators' perspectives of the 7 ethical principles for clinical research endorsed by the NIH and an inductive approach to uncover the broader ethical considerations implementing clinical trials of AI within care delivery., Results: A total of 11 participants (mean [SD] age, 47.5 [12.0] years; 7 male [64%], 4 female [36%]; 3 Asian [27%], 8 White [73%]) were included, with diverse expertise in ethics, ophthalmology, translational medicine, biostatistics, and AI development. Key themes revealed several ethical challenges unique to clinical trials of AI. These themes included difficulties in measuring social value, establishing scientific validity, ensuring fair participant selection, evaluating risk-benefit ratios across various patient subgroups, and addressing the complexities inherent in the data use terms of informed consent., Conclusions and Relevance: This qualitative study identified practical ethical challenges that investigators need to consider and negotiate when conducting AI clinical trials, exemplified by the DR screening use-case. These considerations call for further guidance on where to focus empirical and normative ethical efforts to best support conduct clinical trials of AI and minimize unintended harm to trial participants.

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis., (© 2024. The Author(s).)

Background: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD)., Objective: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL)., Patients and Methods: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL., Results: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (β = 0.073; P = 0.027; R 2  = 0.62) and to develop disabling LID at V5 (β = 0.088; P = 0.009; R 2  = 0.73) were independently associated with a higher score on the PDQ-39SI., Conclusion: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL., (© 2024 International Parkinson and Movement Disorder Society.)

The effects of subthalamic nucleus deep brain stimulation (STN-DBS) on anxiety in Parkinson's disease (PD) are understudied. We identified clinical predictors of STN-DBS effects on anxiety in this study. In this prospective, open-label, multicentre study, we assessed patients with anxiety undergoing STN-DBS for PD preoperatively and at 6-month follow-up postoperatively. We assessed the Hospital Anxiety and Depression Scale (HADS-anxiety and depression subscales), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-motor (SCOPA-M)-activities of daily living (ADL) and -motor complications, Non-Motor Symptom Scale (NMSS), PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose. We tested changes at follow-up with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We identified patients with a clinically relevant anxiety improvement of anxiety based on a designated threshold of ½ standard deviation of baseline HADS-anxiety. Moreover, we investigated predictors of HADS-anxiety changes with correlations and linear regressions. We included 50 patients with clinically relevant baseline anxiety (i.e., HADS-anxiety ≥ 8) aged 63.1 years ± 8.3 with 10.4 years ± 4.5 PD duration. HADS-anxiety improved significantly at 6-month follow-up as 80% of our cohort experienced clinically relevant anxiety improvement. In predictor analyses, worse baseline SCOPA-ADL and NMSS-urinary domain were associated with greater HADS-anxiety improvements. HADS-anxiety and PDQ-8 changes correlated moderately. Worse preoperative ADL and urinary symptoms predicted favourable postoperative anxiety outcome, which in turn was directly proportionate to greater QoL improvement. This study highlights the importance of detailed anxiety assessments alongside other non-motor and motor symptoms when advising and monitoring patients undergoing STN-DBS for PD., (© 2024. The Author(s).)

Background and Objectives : This retrospective cohort study analyzes mechanical complications in hip fracture surgery using the Trochanteric Fixation Nail-Advanced (TFNA) implant. It investigates the correlation of these complications with demographic, intraoperative, and radiological factors, aiming to identify associated risk factors and suggest improvements in clinical surveillance and treatment strategies. Materials and Methods : We enrolled 253 patients diagnosed with pertrochanteric hip fractures treated between 2017 and 2021, with 126 meeting the criteria for a minimum 6-month follow-up. Data on demographics, American Anesthesia Association Classification (ASA), comorbidities, AO/OTA [AO (Arbeitsgemeinschaft für Osteosynthesefragen)/OTA (Orthopedic Trauma Association)] fracture classification, procedural details, and time to failure were collected. Radiographs were evaluated for reduction quality, the tip-apex distance (TAD), progressive varus deviation, and identification of mechanical complications. Statistical analysis was performed using SPSS software. Results : The predominant AO/OTA fracture classification was 31A2 in 67 cases (52.7%). Reduction quality was deemed good or acceptable in 123 cases (97.6%). The mean time to failure was 4.5 months (range: 2.2-6). The average TAD was 18 mm (range: 1.2-36), with a mean progressive varus deviation of 2.44° (range: 1.30-4.14). A good or acceptable reduction quality was observed in 97.6% of cases. Mechanical complications occurred in 21.4% of patients, with significant associations found with the lateral cortex fracture, use of a TFNA implant with a 130° angle, open reduction, and absence of prior osteoporosis treatment. Conclusions : The study provides insights into mechanical complications in proximal femur fractures treated with the TFNA nail, emphasizing the need for enhanced clinical and radiographic surveillance, especially in patients without osteoporosis treatment. Our findings support the necessity for further clinical studies comparing these outcomes with other implant designs and underscore the importance of personalized treatment strategies to reduce complication rates., Competing Interests: The authors declare no conflicts of interest.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson's disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling., (© 2024. The Author(s).)

Background: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers., Objective: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions., Methods: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan., Results: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs., Conclusions: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs., (© 2024. The Author(s).)

Background: Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive., Objective: This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included., Methods: From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways., Results: Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments., Conclusion: The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.

In early neurodevelopment, the central nervous system is established through the coordination of various neural organizers directing tissue patterning and cell differentiation. Better recapitulation of morphogen gradient production and signaling will be crucial for establishing improved developmental models of the brain in vitro. Here, we developed a method by assembling polydimethylsiloxane devices capable of generating a sustained chemical gradient to produce patterned brain organoids, which we termed morphogen-gradient-induced brain organoids (MIBOs). At 3.5 weeks, MIBOs replicated dorsal-ventral patterning observed in the ganglionic eminences (GE). Analysis of mature MIBOs through single-cell RNA sequencing revealed distinct dorsal GE-derived CALB2 + interneurons, medium spiny neurons, and medial GE-derived cell types. Finally, we demonstrate long-term culturing capabilities with MIBOs maintaining stable neural activity in cultures grown up to 5.5 months. MIBOs demonstrate a versatile approach for generating spatially patterned brain organoids for embryonic development and disease modeling., Competing Interests: Declaration of interests The authors listed (Y.S., C.P., F.Y., and N.P. ) have filed a provisionary patent related to this work (Docket Number: UMA 23-023, Title: “A chemical gradient inducing device and methods for developing patterned organoids.”)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The International Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is widely used in the assessment of the severity of Parkinson's disease (PD). This study aimed to validate the Kazakh version of the MDS-UPDRS, explore its dimensionality, and compare it to the original English version., Methods: The validation was conducted in three phases: first, the English version of the MDS-UPDRS was translated into Kazakh and thereafter back-translated into English by two independent teams; second, the Kazakh version underwent a cognitive pretesting; third, the Kazakh version was tested in 360 native Kazakh-speaking PD patients. Both confirmatory and exploratory factor analyses were performed to validate the scale. We calculated the comparative fit index (CFI) for confirmatory factor analysis and used unweighted least squares for exploratory factor analysis., Results: The CFI was higher than 0.90 for all parts of the scale, thereby meeting the pre-set threshold for the official designation of a validated translation. Exploratory factor analysis also showed that the Kazakh MDS-UPDRS has the analogous factors structure in each part as the English version., Conclusions: The Kazakh MDS-UPDRS had a consistent overall structure as the English MDS-UPDRS, and it was designated as the official Kazakh MDS-UPDRS, which can reliably be used in the Kazakh-speaking populations. Presently, Kazakhstan stands as the sole country in both Central Asia and Transcaucasia with an MDS-approved translated version of the MDS-UPDRS. We expect that other Central Asian and Transcaucasian countries will embark on the MDS Translation Program for MDS-UPDRS in the near future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Importance: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking., Objective: To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED)., Design, Setting, and Participants: In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023., Exposure: Treatment for PD of STN-DBS or MED., Main Outcomes and Measures: Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed., Results: The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001)., Conclusions and Relevance: This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments., Trial Registration: German ClinicalTrials Registry: DRKS00006735.

The following sections are included:Workshop DescriptionLearning ObjectivesPresenter InformationAbout the Workshop OrganizersPresentationsSpeaker Presentations.

Background: The prevalence of type 2 diabetes is increasing with the burden disproportionately falling on older adults and racial/ethnic minorities. Older adults with diabetes show greater cognitive decline and there are disparities in cognitive function by race/ethnicity that can be explained by social determinants such as wealth., Objective: To understand whether there is a differential relationship between wealth and cognitive function by race/ethnicity among older U.S. adults with diabetes., Methods: Data on 9,006 adults aged 50+ with diabetes from the Health and Retirement Study (2006-2016) were analyzed. The primary outcome, cognitive function, was a score ranging from range 0-27 categorized as: normal [12-27], mild cognitive impairment (MCI) [7-11], and dementia including Alzheimer's disease [0-6]. Three modeled outcomes were: 1) normal versus MCI, 2) normal versus dementia, 3) MCI versus dementia. Wealth was log transformed and used as continuous and binary (≥median,

The underlying genetic defect in most cases of dilated cardiomyopathy (DCM), a common inherited heart disease, remains unknown. Intriguingly, many patients carry single missense variants of uncertain pathogenicity targeting the giant protein titin, a fundamental sarcomere component. To explore the deleterious potential of these variants, we first solved the wild-type and mutant crystal structures of I21, the titin domain targeted by pathogenic variant p.C3575S. Although both structures are remarkably similar, the reduced hydrophobicity of deeply buried position 3575 strongly destabilizes the mutant domain, a scenario supported by molecular dynamics simulations and by biochemical assays that show no disulfide involving C3575. Prompted by these observations, we have found that thousands of similar hydrophobicity-reducing variants associate specifically with DCM. Hence, our results imply that titin domain destabilization causes DCM, a conceptual framework that not only informs pathogenicity assessment of gene variants but also points to therapeutic strategies counterbalancing protein destabilization., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status., Patients and Methods: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8)., Results: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers., Conclusion: Staging PD according to the MNCD classification is correlated with caregivers' strain and burden., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Aims: Blood glucose control is central to the management of diabetes, and continuous glucose monitoring (CGM) improves glycemic control. We aimed to describe the perspectives of people with diabetes using CGM., Materials and Methods: We performed a systematic review of qualitative studies., Results: Fifty-four studies involving 1845 participants were included. Six themes were identified: gaining control and convenience (reducing pain and time, safeguarding against complications, achieving stricter glucose levels, and sharing responsibility with family); motivating self-management (fostering ownership, and increasing awareness of glycemic control); providing reassurance and freedom (attaining peace of mind, and restoring social participation); developing confidence (encouraged by the endorsement of others, gaining operational skills, customizing settings for ease of use, and trust in the device); burdened with device complexities (bewildered by unfamiliar technology, reluctant to rely on algorithms, overwhelmed by data, frustrated with malfunctioning and inaccuracy, distressed by alerts, and bulkiness of machines interfering with lifestyle); and excluded by barriers to access (constrained by cost, lack of suppliers)., Conclusions: CGM can improve self-management and confidence in patients managing diabetes. However, the technical issues, uncertainty in readings, and cost may limit the uptake. Education and training from the health professionals may help to reduce the practical and psychological burden for better patient outcomes., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Objective: Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls., Patients and Methods: Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI)., Results: One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R 2  = 0.61; OR = 0.965; p = 0.029)., Conclusion: Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Numerous ethics guidelines have been handed down over the last few years on the ethical applications of machine learning models. Virtually every one of them mentions the importance of "fairness" in the development and use of these models. Unfortunately, though, these ethics documents omit providing a consensually adopted definition or characterization of fairness. As one group of authors observed, these documents treat fairness as an "afterthought" whose importance is undeniable but whose essence seems strikingly elusive. In this essay, which offers a distinctly American treatment of "fairness," we comment on a number of fairness formulations and on qualitative or statistical methods that have been encouraged to achieve fairness. We argue that none of them, at least from an American moral perspective, provides a one-size-fits-all definition of or methodology for securing fairness that could inform or standardize fairness over the universe of use cases witnessing machine learning applications. Instead, we argue that because fairness comprehensions and applications reflect a vast range of use contexts, model developers and clinician users will need to engage in thoughtful collaborations that examine how fairness should be conceived and operationalized in the use case at issue. Part II of this paper illustrates key moments in these collaborations, especially when inter and intra disagreement occurs among model developer and clinician user groups over whether a model is fair or unfair. We conclude by noting that these collaborations will likely occur over the lifetime of a model if its claim to fairness is to advance beyond "afterthought" status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Banja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Facial expression is the best evidence of our emotions. Its automatic detection and recognition are key for robotics, medicine, healthcare, education, psychology, sociology, marketing, security, entertainment, and many other areas. Experiments in the lab environments achieve high performance. However, in real-world scenarios, it is challenging. Deep learning techniques based on convolutional neural networks (CNNs) have shown great potential. Most of the research is exclusively model-centric, searching for better algorithms to improve recognition. However, progress is insufficient. Despite being the main resource for automatic learning, few works focus on improving the quality of datasets. We propose a novel data-centric method to tackle misclassification, a problem commonly encountered in facial image datasets. The strategy is to progressively refine the dataset by successive training of a CNN model that is fixed. Each training uses the facial images corresponding to the correct predictions of the previous training, allowing the model to capture more distinctive features of each class of facial expression. After the last training, the model performs automatic reclassification of the whole dataset. Unlike other similar work, our method avoids modifying, deleting, or augmenting facial images. Experimental results on three representative datasets proved the effectiveness of the proposed method, improving the validation accuracy by 20.45%, 14.47%, and 39.66%, for FER2013, NHFI, and AffectNet, respectively. The recognition rates on the reclassified versions of these datasets are 86.71%, 70.44%, and 89.17% and become state-of-the-art performance., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Christian Mejia-Escobar et al.)

Background and Objective: A good response to levodopa is a key factor to indicate device-aided therapies in people with Parkinson's disease (PwPD). The aim of the present study was to analyze the response to levodopa in PwPD with motor fluctuations followed for 4 years., Patients and Methods: PwPD with motor fluctuations recruited from January 2016 to November 2017 from the COPPADIS cohort and assessed annually (from baseline to 4-year follow-up) during the OFF and ON states were included in this analysis. At each visit, the Unified Parkinson's Disease Rating Scale - part III (UPDRS-III) was applied during the OFF state (without medication during the last 12 h) and during the ON state. General linear model repeated measures were used to test for changes in the mean UPDRS-III-OFF, UPDRS-III-ON, and ΔUPDRS-III (UPDRS-III-OFF - UPDRS-III-ON) between visits. Levodopa equivalent daily dose (LEDD) was included as covariate., Results: Sixty-three patients (63.94 ± 8.42 years old; 68.3% males) were included. Mean disease duration was 7.81 ± 3.64 years. From baseline to 4-year follow-up visit, a significant increase in both the UPDRS-III-OFF (from 27.98 ± 9.58 to 31.75 ± 12.39; p = 0.003) and the UPDRS-III-ON (from 15.92 ± 7.93 to 18.84 ± 8.17; p = 0.006) was observed despite the significant increase in the LEDD (from 896.35 ± 355.65 to 1085.51 ± 488.29; p = 0.003). However, no significant differences were detected between visits in the ΔUPDRS-III., Conclusion: In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up., Competing Interests: Declaration of competing interest Diego Santos-García has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, Merz, and grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”). Teresa de Deus Fonticoba: None. Carlos Cores Bartolomé has received honoraria for educational presentations and advice service by Lundbeck and UCB Pharma. María J. Feal Painceiras: None. Iago García Díaz has received support for educational activity from Bial. María Cristina Íñiguez Alvarado: None. Jose Manuel Paz has received honoraria/support for educational presentations and attending meetings from UCB, AbbVie, Zambon, Bial and KRKA. Silvia Jesús has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and holds the competitive contract “Juan Rodés" supported by the Instituto de Salud Carlos III. She has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) and the Consejería de Salud de la Junta de Andalucía (PI-0459-2018). Marina Cosgaya: None. Juan García Caldentey has received honoraria for educational presentations and advice service by Qualigen, Nutricia, Abbvie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial, and Teva. Nuria Caballol has received honoraria from Bial, Italfármaco, Qualigen, Zambon, UCB, Teva and KRKA and sponsorship from Zambon, TEVA and Abbvie for attending medical conferences. Ines Legarda has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Isabel González Aramburu: None. Maria A. Ávila Rivera has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva, and sponsorship from Zambon and Teva for attending conferences. Víctor Gómez Mayordomo has received honoraria from Bial, Merz and Zambon for educational lectures. Lydia Vela has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Sonia Escalante has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. Zebenzui Mendoza: None. Juan C. Martínez Castrillo has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and AbbVie. He has received speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. Pilar Sánchez Alonso has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Maria G. Alonso Losada has received honoraria for educational presentations and advice service by Zambon and Bial. Nuria López Ariztegui has received honoraria for educational presentations and advice service by Abbvie, Italfarmaco, Zambon, and Bial. Darrian McAfee: None. Pablo Martinez-Martin has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Pablo Mir has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [ PI16/01575] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [ PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib., Case Report: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer., Management and Outcome: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE., Discussion: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated., Competing Interests: Authors’ contributionsVirginia Martinez Martin and Pilar Zamora Auñon designed the study. Victoria Lucia Collada Sánchez and Javier Álvarez Criado collected the date an performed the analysis. Inmaculada Nacher Jimenez Enrique Espinosa Arranz, Ander Mayor Ibarguren and Alicia Herrero Ambrosio drafted the manuscript. Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Big data and AI have enabled digital simulation for prediction of future health states or behaviors of specific individuals, populations or humans in general. "Digital simulacra" use multimodal datasets to develop computational models that are virtual representations of people or groups, generating predictions of how systems evolve and react to interventions over time. These include digital twins and virtual patients for in silico clinical trials, both of which seek to transform research and health care by speeding innovation and bridging the epistemic gap between population-based research findings and their application to the individual. Nevertheless, digital simulacra mark a major milestone on a trajectory to embrace the epistemic culture of data science and a potential abandonment of medical epistemological concepts of causality and representation. In doing so, "data first" approaches potentially shift moral attention from actual patients and principles, such as equity, to simulated patients and patient data.

Trogocytosis is an active process whereby fragments of plasma membrane proteins and cytoplasm are transferred from one cell to another in a cell-cell contact-dependent manner. T cells trogocytose pieces of the cells presenting antigen to them at the site of the immunological synapse. Fragments of the antigen-presenting cell membrane rich in antigen/major histocompatibility (MHC) complexes are internalized by the T cell. Those complexes are redirected to the plasma membrane of the T cell, which subsequently becomes an antigen-presenting cell to other T cells. Removing antigen/MHC complexes from professional and tumoral cells has consequences for the intensity and duration of the immune response. However, the acquired capacity of T cells to present the trogocytosed cognate antigen/MHC complexes also affects the properties of the trogocytotic T cells. Acting as antigen-presenting cells, trogocytotic CD4 T cells influence both the differentiation of cytotoxic T cells and the differentiation of other CD4 T cells into pro-inflammatory effector T cells. Furthermore, trogocytosis of antigen/MHC complexes promotes the differentiation of the trogocytotic CD4 T cells towards regulatory T cells and Th2 effector cells. Trogoctyosis is, therefore, a parallel mechanism to signal transduction by membrane receptors, including the T cell antigen receptor, at the plane of the plasma membrane., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed., Objectives: To update LED conversion formulae based on a systematic review., Methods: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency., Results: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon., Conclusions: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Purpose: Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC)., Methods: Patients with PD-NC (total score of >80 on the Parkinson's Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as "with SCC" and "with VH," respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81., Results: At V0 ( n =376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p <0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05-6.83, p =0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36-10.17, p =0.011)., Conclusions: VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC., Competing Interests: Santos-García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva., (Copyright © 2023 Korean Neurological Association.)

Background: Self-monitoring of blood pressure is a key strategy in managing hypertension but may be challenging and burdensome for patients. The aim of the study was to describe the perspectives and experiences of self-monitoring of blood pressure in patients with hypertension., Methods: MEDLINE, Embase, PsycINFO, and CINAHL were searched from database inception to March 2022. We used thematic synthesis to analyze the data., Results: Thirty-five studies involving 872 patients aged 18-95 years were included. Four themes were identified: enabling autonomy and empowerment of own health (allowing access to comprehensive and accurate data, bolstering motivation for lifestyle changes, encouraging diligence in medication taking, gaining interest in self-management, and increasing awareness of health status); providing reassurance and convenience (instilling a sense of security, readiness for troubleshooting, and reducing the frequency of clinical appointments); triggering confusion and stress (anxiety and panic over "bad" numbers, constant reminder of illness identity, disregarded by clinicians, lack of confidence in interpreting and responding to results, redundancy of continuous monitoring, and uncertainties around targets and frequency of measures, concerns of unreliability); financial and operational burden of device (vulnerability preventing use, or unsustainable cost)., Conclusions: Inadequate knowledge about the benefits of lowering blood pressure, home blood pressure monitoring, blood pressure goals, and interpretation of blood pressure values, limited access to home blood pressure monitoring devices, and psychological burden with home blood pressure monitoring limit home blood pressure monitoring., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Objetivo: Presentar las prevalencias de adultos que acudieron a realizarse pruebas de detección de enfermedades crónicas no transmisibles (ECNT) en el año previo, las prevalencias por diagnóstico previo de algunas ECNT, así como la proporción de los que siguen tratamiento farmacológico. Material y métodos. Se analizó la información de los cuestionarios de 11 895 adultos participantes de la Encuesta Nacional de Salud y Nutrición de 2022. Se presentan prevalencias e intervalos de confianza al 95%., Resultados: En el año previo se realizaron pruebas de detección de diabetes 12.2%, de hipertensión 9.1% y de dislipidemias 9.0%. La prevalencia por diagnóstico previo de diabetes es de 10.9%, de hipertensión 15.9% y de hipercolesterolemia 30.6%; de éstos, siguen tratamiento farmacológico 89.5, 81.7 y 60.4%, respectivamente. Conclusión. Los porcentajes de quienes acudieron a realizarse pruebas de tamizaje siguen siendo bajas y aún son inferiores a los observados en 2012. Tanto las prevalencias por diagnóstico previo de diabetes y de hipercolesterolemia han aumentado, mientras que la de hipertensión disminuyó 0.17%. Es recomendable realizar la detección de factores de riesgo cardiovascular, incluyendo la diabetes, de manera integrada y se incrementen las tasas de tratamiento.

Objetivo: Estimar la prevalencia de prediabetes y diabetes en la población adulta mexicana. Material y métodos. Se utilizó información de la submuestra de adultos de la Encuesta Nacional de Salud y Nutrición 2022 con una muestra de sangre de 10 ml. Se excluyeron 150 individuos con ayuno menor a 8 horas y cuatro personas con diabetes gestacional. La muestra final fue de 1 945 adultos que expande a 78.3 millones de adultos., Resultados: La prevalencia de prediabetes fue de 22.1%, y de diabetes diagnosticada y no diagnosticada de 12.6 y 5.8%, respectivamente, lo que resulta en una prevalencia de diabetes total de 18.3%. Conclusión. La diabetes en México es muy prevalente e implica un reto importante para el sistema de salud. Se requieren acciones contundentes para prevenir la enfermedad, mejorar el tamizaje, el diagnóstico oportuno y el control de la enfermedad.

As the health-care industry emerges into a new era of digital health driven by cloud data storage, distributed computing, and machine learning, health-care data have become a premium commodity with value for private and public entities. Current frameworks of health data collection and distribution, whether from industry, academia, or government institutions, are imperfect and do not allow researchers to leverage the full potential of downstream analytical efforts. In this Health Policy paper, we review the current landscape of commercial health data vendors, with special emphasis on the sources of their data, challenges associated with data reproducibility and generalisability, and ethical considerations for data vending. We argue for sustainable approaches to curating open-source health data to enable global populations to be included in the biomedical research community. However, to fully implement these approaches, key stakeholders should come together to make health-care datasets increasingly accessible, inclusive, and representative, while balancing the privacy and rights of individuals whose data are being collected., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic required science to provide answers rapidly to combat the outbreak. Hence, the reproducibility and quality of conducting research may have been threatened, particularly regarding privacy and data protection, in varying ways around the globe. The objective was to investigate aspects of reporting informed consent and data handling as proxies for study quality conduct., Methods: A systematic scoping review was performed by searching PubMed and Embase. The search was performed on November 8th, 2020. Studies with hospitalised patients diagnosed with COVID-19 over 18 years old were eligible for inclusion. With a focus on informed consent, data were extracted on the study design, prestudy protocol registration, ethical approval, data anonymisation, data sharing and data transfer as proxies for study quality. For reasons of comparison, data regarding country income level, study location and journal impact factor were also collected., Results: 972 studies were included. 21.3% of studies reported informed consent, 42.6% reported waivers of consent, 31.4% did not report consent information and 4.7% mentioned other types of consent. Informed consent reporting was highest in clinical trials (94.6%) and lowest in retrospective cohort studies (15.0%). The reporting of consent versus no consent did not differ significantly by journal impact factor (p=0.159). 16.8% of studies reported a prestudy protocol registration or design. Ethical approval was described in 90.9% of studies. Information on anonymisation was provided in 17.0% of studies. In 257 multicentre studies, 1.2% reported on data sharing agreements, and none reported on Findable, Accessible, Interoperable and Reusable data principles. 1.2% reported on open data. Consent was most often reported in the Middle East (42.4%) and least often in North America (4.7%). Only one report originated from a low-income country., Discussion: Informed consent and aspects of data handling and sharing were under-reported in publications concerning COVID-19 and differed between countries, which strains study quality conduct when in dire need of answers., Competing Interests: Competing interests: LAC is funded by the National Institute of Health through the NIBIB R01 grant EB01720., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group., Methods: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI., Results: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041)., Conclusion: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI., (© 2023 John Wiley & Sons Ltd.)

Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods . PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls., Results: The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p  < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p  < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p  = 0.012), being male (OR = 2.333; p  < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p  < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p  < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p  = 0.007) as a predictor of drooling at V2., Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden., Competing Interests: Santos García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, and grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”). De Deus Fonticoba T.: None. Cores Bartolomé C. has received honoraria for educational presentations and advice service by Lundbeck and UCB Pharma. Feal Painceiras M. J.: None. Íñiguez Alvarado MC: None. Jesús S. has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and holds the competitive contract “Juan Rodés” supported by the Instituto de Salud Carlos III. She has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) and the Consejería de Salud de la Junta de Andalucía (PI-0459-2018). Buongiorno M. T.: Planellas LL.: None. Cosgaya M.: None. García Caldentey J. has received honoraria for educational presentations and advice service by Qualigen, Nutricia, Abbvie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial, and Teva. Caballol N. has received honoraria from Bial, Italfarmaco, Qualigen, Zambon, UCB, Teva, and KRKA and sponsorship from Zambon, TEVA, and Abbvie for attending medical conferences. Legarda I. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Hernández Vara J. has received travel bursaries and educational grants from Abbvie and has received honoraria for educational presentations from Abbvie, Teva, Bial, Zambon, Italfarmaco, and Sanofi-Genzyme. Cabo I. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. López Manzanares L.: Compensated advisory services, consulting, research grant support, or speaker honoraria: AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. González Aramburu I.: None. Ávila Rivera MA. has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva and sponsorship from Zambon and Teva for attending conferences. Gómez Mayordomo V.: None. Nogueira V.: None. Puente V. has served as consultant for Abbvie and Zambon; has received grant/research from Abbvie. Dotor García-Soto J.: Compensated advisory services, consulting, research grant support, or speaker honoraria: Merck, Sanofi-Genzyme, Allergan, Biogen, Roche, UCB, and Novartis. Borrué C.: None. Solano Vila B. has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, Abbvie, and Bial. Álvarez Sauco M. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Vela L. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Escalante S. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. Cubo E.: Travel grants: Abbvie, Allergan, Boston; Lecturing honoraria: Abbvie, International Parkinson´s disease Movement Disorder Society. Carrillo Padilla F. has received honoraria from Zambon (SEN Congress assistance). Martínez Castrillo JC. has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and Abbvie. He has received speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. Sánchez Alonso P. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Alonso Losada M. G. has received honoraria for educational presentations and advice service by Zambon and Bial. López Ariztegui N. has received honoraria for educational presentations and advice service by Abbvie, Italfarmaco, Zambon, and Bial. Gastón I. has received research support from Abbvie and Zambon and has served as a consultant for Abbvie, Exelts, and Zambon. Kulisevsky J.: (1) Consulting fees: Roche, Zambon; (2) Stock/allotment: No; (3) Patent royalties/licensing fees: No; (4) Honoraria (e.g. lecture fees): Zambon, Teva, Bial, UCB; (5) Fees for promotional materials: No; (6) Research funding: Roche, Zambon, Ciberned; Instituto de SaludCarlos III; FundacióLa Maratóde TV3; (7) Scholarship from corporation: No; (8) Corporate laboratory funding: No; (9) Others (e.g. trips, travel, or gifts): No. Blázquez Estrada M. has received honoraria for educational presentations and advice service by Abbvie, Abbott, UCB Pharma, Allergan, Zambon, Bial, and Qualigen. Seijo M. has received honoraria for educational services from KRKA, UCB, Zambon, Bial; travel grants from Daiichi and Roche. Ruiz Martínez J. has received honoraria for educational presentations, attending medical conferences, and advice service by Abbvie, UCB Pharma, Zambon, Italfarmaco, Bial, and Teva. Valero C. has received honoraria for educational services from Zambon, Abbvie, and UCB. Kurtis M. has received honoraria from Bial, the Spanish Neurology Society, and the International and Movement Disorders Society. de Fábregues O. has received honoraria for educational presentations and advice service by Bial, Zambon, Abbvie, KRKA, and Teva. González Ardura J. has recieved honoraria for speking from italofarma, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL and Ferrer, course grant from Teva and travel grant from Merck. Alonso Redondo R.: None. Ordás C.: None. López Díaz L. M. has received honoraria from UCB, Lundbeck, and KRKA. McAfee D.: None. Martínez-Martin P. has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña., (Copyright © 2023 Diego Santos-García et al.)

Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD., Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests., Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores., Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The prevalence of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) varies among geographical regions. Cultural differences in patient-based perceptions of LID have not been studied., Objective: We compared patient and clinician evaluations of LID severity across multiple cultures in patients with PD., Methods: The data set included the Unified Dyskinesia Rating (UDysRS) scores from 16 language translation programs (3566 patients). We defined the Perception Severity Index (PSI) as the ratio between normalized patient-based subjective ratings (UDysRS Part 1B) and normalized clinician examination (Parts 3 and 4) scores (Part 1B/Parts 3 + 4) and compared the PSI across languages., Results: The mean PSI for the Chinese language (2.16) was higher than those of all other languages, whereas the ratio for the Korean language (0.73) was lower than those for Japanese, German, Turkish, Greek, Polish, and Finnish languages (corrected P values <0.05)., Conclusions: Culture, as represented by language, affects the subjective perception of LID and needs to be considered in multinational clinical PD trials on dyskinesia. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: Caring for a partner or family member with Parkinson's disease (PD) negatively affects the caregiver's own physical and emotional well-being, especially those caring for people with advanced PD (APD). This study was designed to examine the impact of APD on caregiver perceived burden, quality of life (QoL), and health status., Methods: Dyads of people with PD and their primary caregivers were identified from the Adelphi Parkinson's Disease Specific Program (DSP™) using real-world data from the United States, Japan and five European countries. Questionnaires were used to capture measures of clinical burden (people with PD) and caregiver burden (caregivers)., Results: Data from 721 patient-caregiver dyads in seven countries were captured. Caregivers had a mean age 62.6 years, 71.6% were female, and 70.4% were a spouse. Caregivers for people with APD had a greater perceived burden, were more likely to take medication and had lower caregiver treatment satisfaction than those caring for people with early or intermediate PD; similar findings were observed for caregivers of people with intermediate versus early PD. Caregivers for people with intermediate PD were also less likely to be employed than those with early PD (25.3% vs 42.4%) and spent more time caring (6.6 vs 3.2 h/day)., Conclusions: This real-world study demonstrates that caregivers of people with APD experience a greater burden than those caring for people with early PD. This highlights the importance of including caregiver-centric measures in future studies, and emphasizes the need for implementing treatments that reduce caregiver burden in APD., Trial Registration: N/A., (© 2023. The Author(s).)

Background: Progressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease, with few studies done in Asian populations., Methods: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed., Results: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3 ± 7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (r s  = 0.45, P < 0.001) and weakly with caregiver burden (r s  = 0.22, P = 0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants., Conclusions: Significant heterogeneity in clinical features and disease burden, and high rates of RBD symptoms, visual hallucinations, and familial involvement were observed in this relatively large cohort. Our findings highlight important considerations when assessing Asian patients, and provide further support for the notion of overlapping neurobiology between PSP and Lewy body disorders., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD., Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used., Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression ( p < 0.0001), fatigue ( p < 0.0001), and pain ( p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia ( p < 0.0001), speech problems ( p < 0.0001), rigidity ( p < 0.0001), and hypersexuality ( p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose ( p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males ( p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females ( p = 0.001)., Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Smart toilets are a key tool for enabling precision health monitoring in the home, but such passive monitoring has ethical considerations.

Background: Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health-related quality of life and the CISI-PD., Objective: To analyze the association of CISI-PD scores with those of generic (EQ-5D-5L) and Parkinson's disease (PD) disease-specific (Parkinson's Disease Questionnaire-8 [PDQ-8]) health-related quality of life assessments., Methods: Persons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI-PD and EQ-5D-5L and/or PDQ-8 were included. Correlations with EQ-5D dimensions were analyzed. The relationships between the CISI-PD, EQ-5D-5L, and PDQ-8 were estimated by linear mixed models with random intercept., Results: In the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self-care, mobility, and usual activities correlated moderately with the CISI-PD ( r s  = 0.60, r s  = 0.54, r s  = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort ( r s  = 0.39, r s  = 0.29) ( P values < 0.001). The fitted model included the CISI-PD, age, sex, and time since diagnosis. The CISI-PD had a statistically significant impact on the EQ-5D and PDQ-8 ( P values < 0.001)., Conclusions: The CISI-PD provides a moderate correlation with the EQ-5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI-PD., (© 2022 International Parkinson and Movement Disorder Society.)

In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with <30 years of age and had a follow-up >5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p < 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The progress in pharmacotherapy that has been made in recent years, including the introduction of very effective and safe lipid-lowering and antihypertensive drugs, has not yet translated into the expected universal control of blood pressure, lipid disorders and diabetes. In the STRUGGLE FOR Italian- -Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023, experts from five countries recounted several points about the paradigms of cardiological and cardiometabolic care for better control of classical modifiable risk factors in the year 2023. It is believed herein, that the need to intensify treatment, actively search for patients with cardiovascular risk factors, especially with arterial hypertension, hypercholesterolemia and diabetes, should go hand in hand with the implementation of the latest therapy, based on single pill combinations including proven, effective antihypertensive, lipid-lowering and antidiabetic molecules, many of which are listed in the present document. There is a need to use both new technological concepts, completely new drugs, as well as novel treatment concepts such as metabolic treatment in coronary artery disease, try to intensify the fight against smoking in every way, including the available range of drugs and procedures reducing the harm. This approach will provide substantially better control of the underlying cardiovascular risk factors in countries as varied as Italy, Poland, Spain, Uzbekistan and Vietnam.