A Qualitative Study on Perspectives of Parkinson's Disease Medications: Insights from Patient Focus Groups.

Purpose: Medication is an important component of the management of Parkinson's disease (PD), yet few studies investigate factors that inform medication decision-making from the perspective of those who use these therapies. This qualitative study aimed to better understand the medication experiences and perspectives of people with PD (PwPD). Patients and Methods: Thirty-two PwPD recruited from five large movement disorder clinics from five US states participated in 1-hour on-line focus groups in 2022. Thematic analysis was used to analyze the data. Results: Four primary themes (subthemes in parentheses) emerged concerning PD medications: (1) medication effectiveness (uncertainty, inconsistent effects, adjusting expectations); (2) medication burden (morning doses, timing challenges, constant reminder); (3) side effects (toleration, treatment, confusion with disease symptoms); and (4) preferences/requests (important attributes, therapy advancement). Conclusion: This study identified four core dimensions associated with PD medications from the perspective of PwPD. Results indicate the need for enhanced communication between providers and patients regarding PD medication to reduce the uncertainties and burden associated with PD medication regimens and promote better health outcomes for PwPD.

Evaluating Changes in Adult Cochlear Implant Users' Brain and Behavior Following Auditory Training.

OBJECTIVES: To describe the effects of two types of auditory training on both behavioral and physiological measures of auditory function in cochlear implant (CI) users, and to examine whether a relationship exists between the behavioral and objective outcome measures. DESIGN: This study involved two experiments, both of which used a within-subject design. Outcome measures included behavioral and cortical electrophysiological measures of auditory processing. In Experiment I, 8 CI users participated in a music-based auditory training. The training program included both short training sessions completed in the laboratory as well as a set of 12 training sessions that participants completed at home over the course of a month. As part of the training program, study participants listened to a range of different musical stimuli and were asked to discriminate stimuli that differed in pitch or timbre and to identify melodic changes. Performance was assessed before training and at three intervals during and after training was completed. In Experiment II, 20 CI users participated in a more focused auditory training task: the detection of spectral ripple modulation depth. Training consisted of a single 40-minute session that took place in the laboratory under the supervision of the investigators. Behavioral and physiologic measures of spectral ripple modulation depth detection were obtained immediately pre- and post-training. Data from both experiments were analyzed using mixed linear regressions, paired t tests, correlations, and descriptive statistics. RESULTS: In Experiment I, there was a significant improvement in behavioral measures of pitch discrimination after the study participants completed the laboratory and home-based training sessions. There was no significant effect of training on electrophysiologic measures of the auditory N1-P2 onset response and acoustic change complex (ACC). There were no significant relationships between electrophysiologic measures and behavioral outcomes after the month-long training. In Experiment II, there was no significant effect of training on the ACC, although there was a small but significant improvement in behavioral spectral ripple modulation depth thresholds after the short-term training. CONCLUSIONS: This study demonstrates that auditory training improves spectral cue perception in CI users, with significant perceptual gains observed despite cortical electrophysiological responses like the ACC not reliably predicting training benefits across short- and long-term interventions. Future research should further explore individual factors that may lead to greater benefit from auditory training, in addition to optimization of training protocols and outcome measures, as well as demonstrate the generalizability of these findings.

Impact of a psychoeducational intervention on willingness to seek help for depression among African American young adults.

Despite the success of psychoeducational interventions at improving willingness to seek professional help for mental illness, limited research explores the effect of culturally tailored psychoeducational interventions on African American (AA) college students. The objective of this study was to determine if exposure to a culturally relevant psychoeducational intervention impacted AA young adult attitudes, subjective norms, perceived behavioral control, depression stigma, disclosure and willingness to seek help for depression. We conducted a one-group pre- and post-test intervention study of AA college students (N = 75). The 2.5-h intervention featured presentations, large-group discussions, videos, and active learning exercises and was guided by applying a cultural adaptation framework to an existing psychoeducational intervention. The self-administered surveys were created using the Theory of Planned Behavior as a guide. Data were analyzed using paired t-tests. A total of 70 participants completed both pre- and post-test surveys. Overall, willingness, attitude, and disclosure significantly increased after the intervention (p < .001). Additionally, depression stigma significantly decreased after the intervention, indicating fewer stigmatizing beliefs about depression (p < .001). Willingness to seek help for depression among AA college students can be improved through culturally relevant and interactive psychoeducational interventions. These interventions can also improve negative attitudes and perceived behavioral control toward seeking help and decrease stigmatizing beliefs. More research is needed to explore the longitudinal impact of culturally relevant psychoeducational interventions and how they may affect actual help-seeking behavior among AA college students.

Development of a comprehensive cardiovascular disease genetic risk assessment test.

Background: Despite monogenic and polygenic contributions to cardiovascular disease (CVD), genetic testing is not widely adopted, and current tests are limited by the breadth of surveyed conditions and interpretation burden. Methods: We developed a comprehensive clinical genome CVD test with semi-automated interpretation. Monogenic conditions and risk alleles were selected based on the strength of disease association and evidence for increased disease risk, respectively. Non-CVD secondary findings genes, pharmacogenomic (PGx) variants and CVD polygenic risk scores (PRS) were assessed for inclusion. Test performance was modeled using 2,594 genomes from the 1000 Genomes Project, and further investigated in 20 previously tested individuals. Results: The CVD genome test is composed of a panel of 215 CVD gene-disease pairs, 35 non-CVD secondary findings genes, 4 risk alleles or genotypes, 10 PGx genes and a PRS for coronary artery disease. Modeling of test performance using samples from the 1000 Genomes Project revealed ~6% of individuals with a monogenic finding in a CVD-associated gene, 6% with a risk allele finding, ~1% with a non-CVD secondary finding, and 93% with CVD-associated PGx variants. Assessment of blinded clinical samples showed complete concordance with prior testing. An average of 4 variants were reviewed per case, with interpretation and reporting time ranging from 9-96 min. Conclusions: A genome sequencing based CVD genetic risk assessment can provide comprehensive genetic disease and genetic risk information to patients with CVD. The semi-automated and limited interpretation burden suggest that this testing approach could be scaled to support population-level initiatives.

Provider perceptions of barriers to biosimilar utilization in community oncology practices.

BACKGROUND: Biosimilars reduce the burden of cost on patients and payers, and so doing, increase access to life-saving care. However, biosimilar uptake in the US has been inconsistent. OBJECTIVES: This study assessed provider perceptions of barriers to biosimilar use and their relationships to utilization rates in a large, national oncology network and examined if perceptions differed by demographic and practice characteristics. METHODS: A 28-item survey was administered to 400 network physicians, pharmacists, nurses, and administrators, spanning 25 provider groups, and measured 1) barriers to use categorized into 4 subscales-payer-related, provider-related, operational, and patient-related, using a Likert scale ranging from Never (1) to Always (5); and 2) demographic and practice characteristics. Utilization rates were assessed using aggregated patient-level drug administration data found in the electronic health record system. Descriptive and inferential statistics were used to describe responses and assess relationships between variables. RESULTS: A total of 46 responses were analyzed, with a response rate of 11.5%. Most respondents were female (55.6%), physicians (52.2%), with over 6 years of experience (67%). A majority worked in practices participating in the Oncology Care Model (86.7%) and received continuing education on biosimilars (84.8%). Overall scale score was moderately low (mean=2.31), indicating low levels of perceived barriers. The lowest subscale score was operational barriers (mean=2.21), while payer-related barriers was the highest (mean=2.78). Perceptions of barriers did not differ based on demographic and practice characteristics. The average biosimilar utilization rate was 66.2%, with practices in the West administering biosimilars most frequently (71.8%). Utilization was not impacted by perceptions of barriers. CONCLUSION: Perceived barriers to biosimilar utilization were not common and not associated with utilization. Infrequent impediments to utilization may be associated with network-wide emphasis on continuing education and a value-based care environment. Future research should consider other practice- and patient-level factors that may impact biosimilar utilization.

A framework for the evaluation and reporting of incidental findings in clinical genomic testing.

Currently, there are no widely accepted recommendations in the genomics field guiding the return of incidental findings (IFs), defined here as unexpected results that are unrelated to the indication for testing. Consequently, reporting policies for IFs among laboratories offering genomic testing are variable and may lack transparency. Herein we describe a framework developed to guide the evaluation and return of IFs encountered in probands undergoing clinical genome sequencing (cGS). The framework prioritizes clinical significance and actionability of IFs and follows a stepwise approach with stopping points at which IFs may be recommended for return or not. Over 18 months, implementation of the framework in a clinical laboratory facilitated the return of actionable IFs in 37 of 720 (5.1%) individuals referred for cGS, which is reduced to 3.1% if glucose-6-phosphate dehydrogenase (G6PD) deficiency is excluded. This framework can serve as a model to standardize reporting of IFs identified during genomic testing.

Determinants of Human Papillomavirus (HPV) vaccination intentions among young adult college students using the theory of planned behavior.

Purpose: To determine college students' intentions to be Human Papillomavirus (HPV) vaccinated. Methods: The study was comprised of college students aged 18-45 years. A survey was developed based on the Theory of Planned Behavior (TPB). The significance of the TPB constructs-attitude, subjective norms, and perceived behavioral control-and an additional construct-knowledge-in predicting intention were assessed. Results: The regression model containing attitude, subjective norms and perceived behavioral control accounted for 40% of the variance in intention. Attitude and subjective norms were significant predictors, while perceived behavioral control was not. Provider recommendation was the only significant covariate. Knowledge did not significantly contribute to the model. Discussion: The TPB was useful in predicting HPV vaccination intentions. A focus on attitude, subjective norms and provider recommendation may be useful in creating new or enhancing existing interventions.

Studying CaMKII: Tools and standards.

The Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a ubiquitous mediator of cellular Ca2+ signals with both enzymatic and structural functions. Here, we briefly introduce the complex regulation of CaMKII and then provide a comprehensive overview of the expanding toolbox to study CaMKII. Beyond a variety of distinct mutants, these tools now include optical methods for measurement and manipulation, with the latter including light-induced inhibition, stimulation, and sequestration. Perhaps most importantly, there are now three mechanistically distinct classes of specific CaMKII inhibitors, and their combined use enables the interrogation of CaMKII functions in a manner that is powerful and sophisticated yet also accessible. This review aims to provide guidelines for the interpretation of the results obtained with these tools, with careful consideration of their direct and indirect effects.

Pregnancy-related risk factors and receipt of postpartum care among Texas Medicaid pregnant enrollees: Opportunities for pharmacist services.

BACKGROUND: The United States (US) experiences the highest rate of maternal mortality of similar countries. Postpartum care (PPC) focused on chronic disease management is potentially lifesaving, especially among pregnancies complicated by risk factors such as diabetes, hypertension, and mental health conditions (MHCs), which are conditions in which pharmacists can have an impact. OBJECTIVE: To evaluate the prevalence of maternal mortality risk factors and their relationships with receipt of PPC among Texas Medicaid enrollees. METHODS: A retrospective study included women with a delivery between 3/25/2014-11/1/2019 who were continuously enrolled in Texas Medicaid during the study period from 84 days pre-delivery to 60 days post-delivery. PPC was defined as ≥1 visit associated with postpartum follow-up services. Maternal mortality risk factors (diabetes, hypertension, and MHCs) during and after pregnancy were identified using diagnoses and medication utilization. Age, race/ethnicity, cesarean delivery, and preterm birth served as covariates. Multivariable logistic regression was used to address the study objective. RESULTS: The sample (N = 617,010) was 26.5±5.7 years, primarily (52.8%) Hispanic, and 33.0% had cesarean deliveries and 9.3% had preterm births. Risk factor prevalence included: diabetes (14.0%), hypertension (14.3%), and MHCs during (6.3%) and after (9.1%) pregnancy. A majority (77.9%) had a PPC visit within 60 days of delivery. The odds of receiving PPC were 1.2 times higher for patients with diabetes (OR = 1.183; 95% CI = 1.161-1.206; P < 0.0001), 1.1 times higher for patients with hypertension (OR = 1.109; 95% CI= 1.089-1.130; P < 0.0001), and 1.1 times higher for patients with MHCs (OR=1.138; 95% CI = 1.108-1.170; P < 0.0001) than patients without, respectively. CONCLUSION: Over three-quarters of Texas Medicaid pregnant enrollees received PPC within 60 days of delivery and risk factors were prevalent and predictive of receipt of PPC. Pharmacists can have a positive impact on maternal health by addressing hypertension, diabetes, and MHC risk factors.

A narrative review of the well-being and burnout of U.S. community pharmacists.

OBJECTIVES: The purpose of this narrative review is to summarize the literature on well-being and burnout among community pharmacists in the U.S. and provide recommendations for future research. METHODS: Relevant literature was identified by searching PubMed for combinations of keywords such as "burnout" and "well-being" combined with "pharmacists." Titles and abstracts were reviewed for relevancy, and full text articles were reviewed when applicable. RESULTS: While burnout is defined by its 3 core symptoms of emotional exhaustion, depersonalization, and low personal accomplishment, well-being is more challenging to define and measure, which has led to it being less studied. Community pharmacists faced high rates of burnout, low quality of life (QOL), and extreme fatigue prior to the COVID-19 pandemic, a situation that has likely only worsened. Factors such as workload, the type of community pharmacy, the level of education or training of the pharmacist, and stress may be some of the contributors to high rates of burnout. Clinician burnout may be related to high rates of mental health disorders seen in pharmacists, may impact patient safety and satisfaction, and may affect productivity and costs to employers and the healthcare system overall. There has been no research into interventions or strategies to support well-being and reduce burnout among community pharmacists, but having a workplace that is perceived as supporting well-being may have some impact. Recommendations for future research include the following: (1) define well-being, (2) explore why various factors support well-being or contribute to burnout, (3) determine the impact of community pharmacists experiencing well-being or burnout, and (4) develop strategies to support well-being and reduce burnout that are specific to community pharmacy. CONCLUSION: There is a sparsity of evidence regarding community pharmacist well-being and burnout. Further research is needed to generate the evidence needed to support interventions that are specific to the unique work setting of community pharmacists.

Examination of recent hydroelectric dam projects in Canada for alignment of baseline studies, predictive modeling, and postdevelopment monitoring phases of aquatic environmental impact assessments.

Environmental impact assessment (EIA) has been widely criticized by the aquatic science community for poorly aligned approaches when selecting endpoints and collecting data during the baseline, predictive modeling, and postdevelopment monitoring phases. If these critical phases of the EIA process are not aligned properly, it can be difficult to evaluate the presence of postdevelopment effects. Examples of the misalignment of these phases include baseline studies failing to measure indicators that are monitored postdevelopment; predictive assessments that do not quantitatively predict conditions or potential impacts postdevelopment; and the failure to identify relevant indicators that may detect effects postdevelopment. For aquatic assessments, understanding how to protect critical ecosystem attributes to satisfy regulatory concerns could help to better align aquatic science monitoring activities across EIA phases. In this article we investigate recent Canadian hydroelectric dam EIAs to evaluate how well recent assessment approaches are meeting these necessary conditions of good aquatic EIA practice through the lens of ecosystem services from a fish's perspective. We found that larger facilities generally had baseline studies and modeling that better supported postdevelopment monitoring, but improvements in structure, linkages, and expectations would better align EIA phases in a manner that would improve assessments and environmental protection. Integr Environ Assess Manag 2024;20:616-644. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Out of the Silence: Insights into How Genes Escape X-Chromosome Inactivation.

The silencing of all but one X chromosome in mammalian cells is a remarkable epigenetic process leading to near dosage equivalence in X-linked gene products between the sexes. However, equally remarkable is the ability of a subset of genes to continue to be expressed from the otherwise inactive X chromosome-in some cases constitutively, while other genes are variable between individuals, tissues or cells. In this review we discuss the advantages and disadvantages of the approaches that have been used to identify escapees. The identity of escapees provides important clues to mechanisms underlying escape from XCI, an arena of study now moving from correlation to functional studies. As most escapees show greater expression in females, the not-so-inactive X chromosome is a substantial contributor to sex differences in humans, and we highlight some examples of such impact.

A 20-year population study of peripartum cardiomyopathy.

BACKGROUND AND AIMS: The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted. METHODS: Women hospitalized with presumed de novo left ventricular systolic dysfunction around the time of pregnancy and no clear alternative cause were included. Each case was matched to 10 controls. Incidence and risk factors were identified. Morbidity and mortality were examined in mothers and children. RESULTS: The incidence of PPCM was 1 in 4950 deliveries. Among 225 women with PPCM, obesity, gestational hypertensive disorders, and multi-gestation were found to be associated with having the condition. Over a median of 8.3 years (9.7 years for echocardiographic outcomes), 8% of women with PPCM died and 75% were rehospitalized for any cause at least once. Mortality and rehospitalization rates in women with PPCM were ∼12- and ∼3-times that of controls, respectively. The composite of all-cause death, mechanical circulatory support, or cardiac transplantation occurred in 14%. LV recovery occurred in 76% and, of those who recovered, 13% went on to have a decline in LV systolic function despite initial recovery. The mortality rate for children born to women with PPCM was ∼5-times that of children born to controls and they had an ∼3-times greater incidence of cardiovascular disease over a median of 8.8 years. CONCLUSIONS: PPCM affected 1 in 4950 women around the time of pregnancy. The condition is associated with considerable morbidity and mortality for the mother and child. There should be a low threshold for investigating at-risk women. Long term follow-up, despite apparent recovery, should be considered.

LTP induction by structural rather than enzymatic functions of CaMKII.

Learning and memory are thought to require hippocampal long-term potentiation (LTP), and one of the few central dogmas of molecular neuroscience that has stood undisputed for more than three decades is that LTP induction requires enzymatic activity of the Ca2+/calmodulin-dependent protein kinase II (CaMKII)1-3. However, as we delineate here, the experimental evidence is surprisingly far from conclusive. All previous interventions inhibiting enzymatic CaMKII activity and LTP4-8 also interfere with structural CaMKII roles, in particular binding to the NMDA-type glutamate receptor subunit GluN2B9-14. Thus, we here characterized and utilized complementary sets of new opto-/pharmaco-genetic tools to distinguish between enzymatic and structural CaMKII functions. Several independent lines of evidence demonstrated LTP induction by a structural function of CaMKII rather than by its enzymatic activity. The sole contribution of kinase activity was autoregulation of this structural role via T286 autophosphorylation, which explains why this distinction has been elusive for decades. Directly initiating the structural function in a manner that circumvented this T286 role was sufficient to elicit robust LTP, even when enzymatic CaMKII activity was blocked.

The smallest likely pathogenic duplication of a SOX9 enhancer identified to date in a family with 46,XX testicular differences of sex development.

Copy number variants that duplicate distal upstream enhancer elements of the SOX9 gene cause 46,XX testicular differences of sex development (DSD) which is characterized by a 46,XX karyotype in an individual presenting with either ambiguous genitalia or genitalia with varying degrees of virilization, including those resembling typical male genitalia. Reported duplications in this region range in size from 24 to 780 kilobases (kb). Here we report a family with two affected individuals, the proband and his maternal uncle, harboring a 3.7 kb duplication of a SOX9 enhancer identified by clinical genome sequencing. Prior fluorescence in situ hybridization (FISH) for SRY and a multi-gene panel for ambiguous genitalia were non-diagnostic. The unaffected mother also carries this duplication, consistent with previously described incomplete penetrance. To our knowledge, this is the smallest duplication identified to-date, most of which resides in a 5.2 kb region that has been previously shown to possess enhancer activity that promotes the expression of SOX9. The duplication was confirmed by quantitative-PCR and shown to be in tandem by bidirectional Sanger sequencing breakpoint analysis. This finding highlights the importance of non-coding variant interrogation in suspected genetic disorders.