Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.

BACKGROUND: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. OBJECTIVES: Our goal was to investigate the effects of genetic variants on risk and time to LID. METHODS: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. RESULTS: We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21-2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09-1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile = 1.27; 95% CI, 1.03-1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile = 1.38; 95% CI, 1.07-1.79; P = 0.0128; HRfourth_quartile = 1.38; 95% CI = 1.06-1.78; P = 0.0147). CONCLUSIONS: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effect of Virtual Versus In Person Interpreting on Diabetes Outcomes in Non-English Language Preference Patients: A Pilot Study.

OBJECTIVE: The objective of this pilot study was to explore the impact of interpreter format (virtual vs in person) on clinical outcomes in patients with non-English language preference (NELP) and type 2 diabetes mellitus (T2DM) in a primary care setting. We hypothesized that NELP patients utilizing in person interpreters would have improved HbA1c values, better follow-up rate, and more complex care plans compared to patients utilizing virtual interpreters. METHODS: We completed a retrospective chart review of 137 NELP patients with T2DM who required a medical interpreter (February to June 2021). We calculated univariate and bivariate statistics to characterize the sample and assess the extent to which measures of continuity (follow-up visit rate and time to follow-up visit), quality (change in HbA1c), and complexity (medication intervention complexity) were associated with interpreter type. RESULTS: There was no statistically significant difference in follow-up rate or average days to follow-up visit for NELP patients with in person as opposed to virtual interpreters. Patients with virtual interpreters demonstrated a non-statistically significant decrease in HbA1c compared to those with in person interpreters. Finally, there was no statistically significant association between interpreter format and intervention complexity. CONCLUSIONS: Quality medical interpretation contributes to optimal health outcomes in NELP patients with diabetes. Our study suggests that both in person and virtual interpreters can be effective in providing care for NELP patients, especially for chronic disease management in the context of a primary care relationship. It also highlights the importance of pursuing additional qualitative and mixed method studies to better understand the benefits of various interpreter formats across different visit types.

Five Years of Extreme Risk Protection Orders in Oregon: A Descriptive Analysis.

Extreme Risk Protection Order (ERPO) laws have received increasing attention as a tool to prevent firearm suicide and homicide, including mass shootings. However, important gaps remain in our understanding of ERPO usage and implementation. Using the Oregon Judicial Case Information Network database, we abstracted data from all ERPO petitions filed in Oregon from 2018 to 2022, the first five years after the law took effect (N = 649). ERPO petitions were filed in 29 of 36 counties (81%, range 0-105 per county, median 11), against respondents 17-96 years of age (median: 42). Of ERPOs filed, 78% were initially granted. While only 22% of respondents in initially-granted ERPOs requested a hearing, when a hearing was held, nearly half (44%) of ERPOs were dismissed. The majority of ERPO petitions were motivated by threats of harm to respondents and others (n = 327, 50%), followed by threats of harm to others-only (n = 220, 34%) or respondents-only (n = 81, 12%). During the 5-year period, 72 (11%) ERPO petitions cited threats of mass violence as a motivating factor, including 24 (4%) petitions citing threats to schools or college campuses. The majority of ERPOs were filed by law enforcement officers (60%), and these petitions were significantly more often granted than those filed by family/household members (96% vs. 67%, p < .0001). We also found evidence of important gaps in documentation, including of respondent race (unavailable for 191 respondents, 29%) and of weapon removal or disposition after the ERPO was granted (unavailable in 350 cases, 69%). This study of long-term patterns of ERPO petitions highlights trends in usage and suggests areas where improvement may be possible, with implications for other states that have adopted or are considering similar ERPO laws.

Antecedents of major depressive, bipolar, and psychotic disorders: A systematic review and meta-analysis of prospective studies.

Major depressive, bipolar, or psychotic disorders are preceded by earlier manifestations in behaviours and experiences. We present a synthesis of evidence on associations between person-level antecedents (behaviour, performance, psychopathology) in childhood, adolescence, or early adulthood and later onsets of major depressive disorder, bipolar disorder, or psychotic disorder based on prospective studies published up to September 16, 2022. We screened 11,342 records, identified 460 eligible publications, and extracted 570 risk ratios quantifying the relationships between 52 antecedents and onsets in 198 unique samples with prospective follow-up of 122,766 individuals from a mean age of 12.4 to a mean age of 24.8 for 1522,426 person years of follow-up. We completed meta-analyses of 12 antecedents with adequate data. Psychotic symptoms, depressive symptoms, anxiety, disruptive behaviors, affective lability, and sleep problems were transdiagnostic antecedents associated with onsets of depressive, bipolar, and psychotic disorders. Attention-deficit/hyperactivity and hypomanic symptoms specifically predicted bipolar disorder. While transdiagnostic and diagnosis-specific antecedents inform targeted prevention and help understand pathogenic mechanisms, extensive gaps in evidence indicate potential for improving early risk identification.

Preferences for virtual versus in-person mental and physical healthcare in Canada: a descriptive study from a cohort of youth and their parents enriched for severe mental illness.

BACKGROUND: Virtual care may improve access to healthcare and may be well suited to digitally connected youth, but experts caution that privacy and technology barriers could perpetuate access inequities. Success of virtual care will depend on its alignment with patient preferences. However, information on preferences for virtual and in-person healthcare is missing, especially for youth. We sought to quantify preferences for and barriers to virtual versus in-person mental and physical healthcare in youth and their parents, including in vulnerable segments of the population such as families with a parent with severe mental illness (SMI). METHODS: Participants were 219 youth and 326 parents from the Families Overcoming Risks and Building Opportunities for Wellbeing cohort from Canada, of which 61% of youth had at least one parent with SMI. Participants were interviewed about healthcare preferences and access to privacy/technology between October 2021 and December 2022. RESULTS: Overall, youth reported a preference for in-person mental (66.6%) and physical healthcare (74.7%) versus virtual care or no preference, and to a somewhat lesser degree, so did their parents (48.0% and 53.9%). Half of participants reported privacy/technology barriers to virtual care, with privacy being the most common barrier. Preferences and barriers varied as a function of parent SMI status, socioeconomic status and rural residence. CONCLUSIONS: The majority of youth and parents in this study prefer in-person healthcare, and the preference is stronger in youth and in vulnerable segments of the population. Lack of privacy may be a greater barrier to virtual care than access to technology.

Dopamine pathway and Parkinson's risk variants are associated with levodopa-induced dyskinesia.

Background: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. Objectives: To investigate the effects of genetic variants on risk and time to LID. Methods: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1,612 PD patients with and 3,175 without LID. Results: We found that GBA1 variants were associated with LID risk (OR=1.65, 95% CI=1.21-2.26, p=0.0017) and LRRK2 variants with reduced time to LID onset (HR=1.42, 95% CI=1.09-1.84, p=0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile=1.27, 95% CI=1.03-1.56, p=0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile=1.38, 95% CI=1.07-1.79, p=0.0128; HRfourth_quartile=1.38, 95% CI=1.06-1.78, p=0.0147). Conclusions: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care.

Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects.

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.

Knowledge Retention Using "Relay": A Novel Active-Learning Technique.

Introduction: Many residency programs utilize passive didactic lectures despite mixed evidence for knowledge retention. This prospective study investigated the efficacy of "relay," an active-learning technique, as measured by residents' knowledge retention and attitudes compared to traditional format. Methods: Faculty presented lectures to four family medicine residency programs on a randomized schedule. Lectures were followed by a 15-minute question-and-answer (Q&A) session or relay session. A relay is a collaborative, question-based game. The primary outcome was knowledge retention at 3 months, comparing Q&A to relay sessions as measured by a multiple-choice assessment. Responses were only included if a given resident completed knowledge assessments for both Q&A and relay sessions, to allow for intraresident adjustments, in addition to program, training year, and lecturer/topic. Secondary outcomes included residents' self-perceived knowledge and engagement as surveyed by an ordinal scale immediately following the learning session. Results: The primary analysis included 51 responses from 18 unique residents. The adjusted mean knowledge assessment score at 3 months was not statistically different after the relay sessions compared to Q&A (67% vs 60%, respectively; 7% difference, 95% CI: -4 to 18%, P=.20). For the secondary outcomes of learner attitudes (n=143 responses), learners reported greater engagement after the relay sessions compared to Q&A (51% vs 28% "very engaged"; overall P=.003), but self-perceived knowledge was not significantly different (overall P=.05, rounded down). Conclusions: The relay technique did not show significant difference in 3-month knowledge retention, nor immediate self-perceived knowledge, despite greater learner self-perceived engagement.

Rate of bacteremia in the hemodialysis patient presenting to the emergency department with fever: a retrospective chart review.

BACKGROUND: Infectious disease is the second most common cause of death in patients receiving hemodialysis (HD). When presenting to the emergency department (ED) with fever, it remains a diagnostic challenge to distinguish patients with potentially life-threatening bacterial infections from those with less significant causes of fever. The primary goal of this study was to determine the rate of bacteremia in HD patients presenting to the ED with fever. The secondary goal of this study was to identify any independent risk factors associated with bacteremia in the febrile HD patient. METHODS: This is a retrospective medical record review of all HD patients who presented to the ED with either subjective fever as primary complaint or with a documented triage temperature of 38 °C or higher during the 3-year period between September 1, 2014, and September 1, 2017. Patient visits were included in the study if blood cultures were ordered in the ED. Data related to demographic information, clinical parameters, diagnostic test results in the ER, final diagnosis, and results of microbiology cultures were collected from each patient encounter. Univariate analysis was performed to identify risk factors associated with bacteremia. RESULTS: We identified 353 patient visits from 138 unique patients that met inclusion criteria. Fifty-eight percent of these were women, and the average age was 54.6 years. The rate of bacteremia was 31.7%, and the main microorganisms isolated in blood culture were non-MRSA Staphylococcus aureus (40.7%), MRSA (13.3%), Pseudomonas aeruginosa (11.5%), and Enterobacter spp. (11.5%). Independent prognostic factors associated with bacteremia were use of dialysis catheter, prior history of bacteremia, and > 5% neutrophilic band cells (OR 6.55 [95% CI 3.96-10.8; p < 0.0001]; OR 8.87 [95% CI 5.32-14.8; p < 0.0001]; OR 3.32 [95% CI 1.90-5.80; p < 0.0001] respectively). CONCLUSION: HD patients presenting to the ED with fever have high rates of bacteremia, with a significantly higher rate in patients using dialysis catheters or those with a history of bacteremia. Other clinical data available in the ED is minimally useful in predicting bacteremia.

AANA Journal Course-Residual Neuromuscular Blockade: Evidence-Based Recommendations to Improve Patient Outcomes.

Neuromuscular blocking drugs are administered to facilitate endotracheal intubation and induce paralysis to allow surgeons access to their anatomical target. Traditionally, qualitative measures; such as tactile observation of fade by a peripheral nerve stimulator, are used to assess the extent of the patient's recovery after receiving the neuromuscular blocking agent. Use of these qualitative measures; however, can contribute to high rates of residual neuromuscular blockade (RNMB), placing patients at risk of serious postoperative adverse events. Such adverse events include the need for tracheal reintubation, impaired oxygen and ventilation, increased risk of aspiration and pneumonia, pharyngeal dysfunction, and delayed discharge from the postanesthesia care unit. This problem of RNMB is exacerbated by the use of traditional drugs to reverse the neuromuscular blockade, such as the acetylcholinesterase inhibitor neostigmine. This course will examine the current limitations of qualitative neuromuscular monitoring, introduce the reader to acceleromyography, and outline the advantages of monitoring neuromuscular blockade during the perioperative period. In addition, this course will review the contemporary neuromuscular antagonists, including the newer neuromuscular antagonist sugammadex.

Annual competencies through self-governance and evidence-based learning.

Meeting the constant demands for the educational needs of nurses is extremely challenging. The pressure from various stakeholders to meet these demands can lead to hasty programs in which learning is questionable. An example of evidence-based learning methods using a self-governance model is presented. Outcomes from this approach promoted real learning, improved performance, and improved teamwork.

Time of day is associated with postoperative morbidity: an analysis of the national surgical quality improvement program data.

OBJECTIVE: To examine the association between surgical start time and morbidity and mortality for nonemergent procedures. SUMMARY BACKGROUND DATA: Patients require medical services 24 hours a day. Several studies have demonstrated a difference in outcomes over the course of the day for anesthetic adverse events, death in the ICU, and dialysis care. The relationship between operation start time and patient outcomes is yet undefined. METHODS: We performed a retrospective cohort study of 144,740 nonemergent general and vascular surgical procedures performed within the VA Medical System 2000-2004 and entered into the National Surgical Quality Improvement Program Database. Operation start time was the independent variable of interest. Logistic regression was used to adjust for patient and procedural characteristics and to determine the association between start time and, in 2 independent models, mortality and morbidity. RESULTS: Unadjusted later start time was significantly associated with higher surgical morbidity and mortality. After adjustment for patient and procedure characteristics, mortality was not significantly associated with start time. However, after appropriate adjustment, operations starting between 4 pm and 6 pm were associated with an elevated risk of morbidity (OR = 1.25, P < or = 0.005) over those starting between 7 am and 4 pm as were operations starting between 6 pm and 11 pm (OR = 1.60, P < or = 0.005). CONCLUSIONS: When considering a nonemergent procedure, surgeons must bear in mind that cases that start after routine "business" hours within the VA System may face an elevated risk of complications that warrants further evaluation.

Frequencies of mutagen-induced coincident mitotic recombination at unlinked loci in Saccharomyces cerevisiae.

Frequencies of coincident genetic events were measured in strain D7 of Saccharomyces cerevisiae. This diploid strain permits the detection of mitotic gene conversion involving the trp5-12 and trp5-27 alleles, mitotic crossing-over and gene conversion leading to the expression of the ade2-40 and ade2-119 alleles as red and pink colonies, and reversion of the ilv1-92 allele. The three genes are on different chromosomes, and one might expect that coincident (simultaneous) genetic alterations at two loci would occur at frequencies predicted by those of the single alterations acting as independent events. Contrary to this expectation, we observed that ade2 recombinants induced by bleomycin, beta-propiolactone, and ultraviolet radiation occur more frequently among trp5 convertants than among total colonies. This excess among trp5 recombinants indicates that double recombinants are more common than expected for independent events. No similar enrichment was found among Ilv(+) revertants. The possibility of an artifact in which haploid yeasts that mimic mitotic recombinants are generated by a low frequency of cryptic meiosis has been excluded. Several hypotheses that can explain the elevated incidence of coincident mitotic recombination have been evaluated, but the cause remains uncertain. Most evidence suggests that the excess is ascribable to a subset of the population being in a recombination-prone state.