Category: Nevin Manimala

Cereb Cortex. 2023 Nov 8:bhad410. doi: 10.1093/cercor/bhad410. Online ahead of print.

ABSTRACT

Personality traits are commonly regarded as relatively stable, whereas life satisfaction can fluctuate with time and circumstances, shaped by external influences and personal encounters. The correlation between personality traits and life satisfaction is well-established, yet the underlying neural mechanisms of the myelin-based microstructural brain network connecting them remain unclear. Here, we constructed individual-level whole-brain myelin microstructural networks from the MRI data of 1,043 healthy adults and performed correlation analysis to detect significant personality trait-related and life satisfaction-related subnetworks. A mediation analysis was used to verify whether the shared structural basis of personality traits and life satisfaction significantly mediated their association. The results showed that agreeableness positively correlated with life satisfaction. We identified a shared structural basis of the personality trait of agreeableness and life satisfaction. The regions comprising this overlapping network include the superior parietal lobule, inferior parietal lobule, and temporoparietal junction. Moreover, the shared microstructural connections mediate the association between the personality trait of agreeableness and life satisfaction. This large-scale neuroimaging investigation substantiates a mediation framework for understanding the microstructural connections between personality and life satisfaction, offering potential targets for assessment and interventions to promote human well-being.

PMID:37948663 | DOI:10.1093/cercor/bhad410

Am J Manag Care. 2023 Nov 1;29(11):e330-e338. doi: 10.37765/ajmc.2023.89459.

ABSTRACT

OBJECTIVES: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF).

STUDY DESIGN: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020.

METHODS: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim. Descriptive statistics summarized transaction journeys by type of formulary restriction. Multivariable regression assessed patient characteristics associated with not receiving an OAC within 60 days after initial rejection.

RESULTS: Among 18,434 patients in the analytic sample, QL was the most common reason for rejection (68.7%), followed by PA (21.2%) and FE (10.2%). Most patients received a paid OAC claim within 60 days after rejection (82.2%-85.5% across restriction types). Mean time from rejection to paid claim ranged from 5.2 to 10.7 days among patients with a paid OAC claim and 12.4 to 17.6 days among those with multiple attempts before OAC receipt. Characteristics associated with higher odds of not receiving OAC treatment included being male, beingAfrican American, having Medicaid coverage, possessing a high stroke risk score, exhibiting no evidence of prior apixaban treatment, and being prescribed a low dose of apixaban on the initial rejected claim.

CONCLUSIONS: Most patients with a claim rejection for apixaban received approval for apixaban within 60 days, suggesting that initial rejection merely created a delay in treatment. Vulnerable populations were at greater risk of not receiving a paid OAC claim.

PMID:37948653 | DOI:10.37765/ajmc.2023.89459

ACS Chem Biol. 2023 Nov 10. doi: 10.1021/acschembio.3c00440. Online ahead of print.

ABSTRACT

The ellagitannins vescalagin and vescalin, known as actin-dependent inhibitors of osteoclastic bone resorption, were mounted onto chemical probes to explore their interactions with bone cell proteins by means of affinity-based chemoproteomics and bioinformatics. The chemical reactivity of the pyrogallol units of these polyphenols toward oxidation into electrophilic ortho-quinones was exploited using NaIO₄ to promote the covalent capture of target proteins, notably those expressed at lower abundance and those interacting with polyphenols at low-to-moderate levels of affinity. Different assays revealed the multitarget nature of both ellagitannins, with 100-370 statistically significant proteins captured by their corresponding probes. A much higher number of proteins were captured from osteoclasts than from osteoblasts. Bioinformatic analyses unveiled a preference for the capture of proteins having phosphorylated ligands and GTPase regulators and enabled the identification of 33 potential target proteins with systemic relevance to osteoclast differentiation and activity, as well as to the regulation of actin dynamics.

PMID:37948120 | DOI:10.1021/acschembio.3c00440

JMIR Aging. 2023 Nov 10;6:e50345. doi: 10.2196/50345.

ABSTRACT

BACKGROUND: A number of real-world digital literacy training programs exist to support engagement with mobile devices, but these have been understudied.

OBJECTIVE: The purpose of this study was to examine the effectiveness and program acceptability of a digital skills training program among middle-aged and older adults (aged ≥50 years) and to gather participants’ recommendations for lifelong digital skills promotion.

METHODS: The Gluu Essentials digital skills training program includes learning resources to support tablet use. Through pre-post surveys, this study assessed mobile device proficiency, confidence in going online and in avoiding frauds and scams, the frequency of engaging in online activities, program engagement, acceptability, and suggestions for continued support.

RESULTS: A total of 270 middle-aged and older adults completed baseline surveys. Of these 270 participants, 145 (53.7%) completed follow-up surveys. Our findings indicate that mobile device proficiency increased (P<.001), whereas confidence was unchanged. Participants also reported going online more frequently to shop (P=.01) and access government services (P=.02) at follow-up. Program engagement varied considerably, but program acceptability was high. Participants’ recommendations included the need for providing ongoing programs for support and training because technology constantly changes, reducing costs for technology and internet access, and keeping learning resources simple and easy to access.

CONCLUSIONS: The Gluu Essentials digital skills training program increased mobile device proficiency and frequency of web-based activities (shopping and accessing government services) among middle-aged and older adults.

PMID:37948115 | DOI:10.2196/50345

JMIR Res Protoc. 2023 Nov 10;12:e49956. doi: 10.2196/49956.

ABSTRACT

BACKGROUND: Dental fear and anxiety (DFA) is a condition that affects approximately one-quarter of children and adolescents. It is a significant cause for pediatric patients to avoid dental care later in adulthood. Lack of patient cooperation due to DFA can create an environment of stress, often obligating dentists to end appointments prematurely and consider alternative pharmacological treatment options. Virtual reality (VR) use during dental care, providing an immersive experience through sensory stimuli, is potentially an additional nonpharmacologic tool to better manage DFA in children with special health care needs (SHCN) undergoing dental procedures.

OBJECTIVE: This pilot study aims to assess the feasibility and acceptability of VR immersion as a tool to reduce DFA in pediatric special needs patients undergoing dental procedures. The study also aims to gain insight on parent and health care provider perspectives on the use of VR during dental appointments.

METHODS: This pilot randomized controlled trial study will follow a parallel design including 2 groups: a control group (clinic’s standard care using a wall TV) and an experimental group (using a VR game). We will randomize 20 participants to either group. Recruitment will be carried out at the dental clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary-quaternary care center that mostly serves pediatric patients with SHCN. The primary outcome will be patient recruitment rates and completion rates of planned procedures. DFA in children will be assessed using both an observation-based proxy assessment with the Venham Anxiety and Behavior Rating Scale and physiological assessments using parameters such as change in heart rate and levels of salivary alpha-amylase as a stress biomarker before and 10 minutes after the procedure. Sociodemographic characteristics, measures of the levels of parent and health care professional satisfaction, occurrence of side effects, and any deviation from normal procedure length will also be collected. Descriptive statistics, nonparametric tests, and effect sizes will be used for demographic and clinical variables and to present parent and health care professional satisfaction levels as well as procedural time.

RESULTS: This study will be conducted from May 2023 to May 2024, with results expected to be available in December 2024.

CONCLUSIONS: The pilot study will provide insight on the feasibility and acceptability of VR use in clinical dentistry to reduce DFA for pediatric patients with SHCN. This study will guide future research on VR use in pediatric dentistry and can serve as a framework for a larger randomized clinical trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05898100; https://classic.clinicaltrials.gov/ct2/show/NCT05898100.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49956.

PMID:37948113 | DOI:10.2196/49956

JMIR Form Res. 2023 Nov 10;7:e45725. doi: 10.2196/45725.

ABSTRACT

BACKGROUND: Transitioning to adulthood and challenges in university life can result in increased stress levels among university students. Chronic and severe stress is associated with deleterious psychological and physiological effects. Digital interventions could succeed in approaching and helping university students who might be at risk; however, the experiences of students with internet-based stress management interventions are insufficiently understood.

OBJECTIVE: This study aims to explore the feasibility; acceptability; and changes in perceived stress, depressive symptoms, and quality of life from baseline to posttest assessment of a 5-session, internet-based stress management intervention guided by an e-coach, developed for university students experiencing high levels of stress.

METHODS: A single-arm study was conducted. Students were recruited from different channels, mainly from a web survey. Students were eligible if they (1) scored ≥20 on the Perceived Stress Scale-10, (2) were aged ≥18 years, and (3) were studying at one of the participating universities. Feasibility and acceptability of the intervention were investigated using several indications, including satisfaction (Client Satisfaction Questionnaire-8) and usability (System Usability Scale-10). We also investigated the indicators of intervention adherence using use metrics (eg, the number of completed sessions). Our secondary goal was to explore the changes in perceived stress (Perceived Stress Scale-10), depressive symptoms (Patient Health Questionnaire-9), and quality of life (EQ-5D-5L scale) from baseline to posttest assessment. In addition, we conducted semistructured interviews with intervention completers and noncompleters to understand user experiences in depth. For all primary outcomes, descriptive statistics were calculated. Changes from baseline to posttest assessment were examined using 2-tailed paired sample t tests or the Wilcoxon signed rank test. Qualitative data were analyzed using thematic analysis.

RESULTS: Of 436 eligible students, 307 (70.4%) students started using the intervention. Overall, 25.7% (79/307) completed the core sessions (ie, sessions 1-3) and posttest assessment. A substantial proportion of the students (228/307, 74.3%) did not complete the core sessions or the posttest assessment. Students who completed the core sessions reported high satisfaction (mean 25.78, SD 3.30) and high usability of the intervention (mean 86.01, SD 10.25). Moreover, this group showed large reductions in perceived stress (Cohen d=0.80) and moderate improvements in depression score (Cohen d=0.47) and quality of life (Cohen d=-0.35) from baseline to posttest assessment. Qualitative findings highlight that several personal and intervention-related factors play a role in user experience.

CONCLUSIONS: The internet-based stress management intervention seems to be feasible, acceptable, and possibly effective for some university students with elevated stress levels. However, given the high dropout rate and qualitative findings, several adjustments in the content and features of the intervention are needed to maximize the user experience and the impact of the intervention.

TRIAL REGISTRATION: Netherlands Trial Register 8686; https://onderzoekmetmensen.nl/nl/trial/20889.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.invent.2021.100369.

PMID:37948106 | DOI:10.2196/45725

Exp Physiol. 2023 Nov 10. doi: 10.1113/EP091339. Online ahead of print.

ABSTRACT

NEW FINDINGS: What is the central question of this study? Genetic variations in the GSTT1 and GSTM1 enzymes that detoxify cigarette smoke products might be correlated to chronic obstructive pulmonary disease (COPD) development: do GSTT1 and GSTM1 polymorphisms modulate the risk for COPD in North Indians and what is the relationship with associated clinical parameters? What is the main finding and its importance? The GSTT1(-) null genotype was strongly correlated with COPD development, and GSTT1 deletion was also linked with higher Global Strategy for Obstructive Lung Disease (GOLD) grading. At the same time, no association was observed in the GSTM1(-) null genotype in the North Indian COPD patients.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30-3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43-5.87, P = 0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

PMID:37948104 | DOI:10.1113/EP091339

JAMA Netw Open. 2023 Nov 1;6(11):e2342475. doi: 10.1001/jamanetworkopen.2023.42475.

ABSTRACT

IMPORTANCE: Infants younger than 6 months are at risk of severe SARS-CoV-2 infection. Data are lacking on the optimum timing for maternal vaccination and estimated effectiveness against Omicron variants, including XBB, for infants.

OBJECTIVE: To investigate maternal vaccination against Omicron variants, including XBB, and the association of vaccination timing during pregnancy vs prior to pregnancy and risks of SARS-CoV-2 infection among infants aged 6 months or younger.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted between January 1, 2022, and March 31, 2023. Singapore’s national dataset was used to study infants born at greater than 32 weeks’ gestation between January 1, 2022, and September 30, 2022. The study included infants whose parents had a confirmed SARS-CoV-2 infection from the date of birth up to 6 months of age. Of 21 609 infants born during this period, 7292 (33.7%) had at least 1 parent infected with SARS-CoV-2 before the age of 7 months. Statistical analysis was performed from April to July 2023.

EXPOSURE: Infants’ mothers were unvaccinated, vaccinated prior to pregnancy, or vaccinated with a messenger RNA (mRNA) SARS-CoV-2 vaccine during pregnancy.

MAIN OUTCOME AND MEASURE: Infants were considered infected if they had a positive polymerase chain reaction test.

RESULTS: Among 7292 infants included in this study, 4522 (62.0%) had mothers who were Chinese, 527 (7.2%) had mothers who were Indian, 2007 (27.5%) had mothers who were Malay, and 236 (3.2%) had mothers who were other ethnicity; 6809 infants (93.4%) were born at full term, and 1272 infants (17.4%) were infected during the study period. There were 7120 infants (97.6%) born to mothers who had been fully vaccinated or boosted as of 14 days prior to delivery. The crude incidence rate was 174.3 per 100 000 person-days among infants born to mothers who were unvaccinated, 122.2 per 100 000 person-days among infants born to mothers who were vaccinated before pregnancy, and 128.5 per 100 000 person-days among infants born to mothers who were vaccinated during pregnancy. The estimated vaccine effectiveness (VE) was 41.5% (95% CI, 22.8% to 55.7%) among infants born to mothers vaccinated during pregnancy. Infants of mothers who received vaccination prior to pregnancy did not have a lower risk for infection (estimated VE, 15.4% [95% CI, -17.6% to 39.1%]). A lower risk for Omicron XBB infection was only observed among mothers vaccinated with the third (booster) dose antenatally (estimated VE, 76.7% [95% CI, 12.8% to 93.8%]).

CONCLUSIONS AND RELEVANCE: In this population-based cohort study, maternal mRNA vaccination was associated with a lower risk of Omicron SARS-CoV-2 infection among infants up to 6 months of age only if the vaccine was given during the antenatal period. These findings suggest that mRNA vaccination during pregnancy may be needed for lower risk of SARS-CoV-2 infection among newborns.

PMID:37948079 | DOI:10.1001/jamanetworkopen.2023.42475

JAMA Netw Open. 2023 Nov 1;6(11):e2342681. doi: 10.1001/jamanetworkopen.2023.42681.

ABSTRACT

IMPORTANCE: Interception therapy requires individuals to undergo treatment to prevent a future medical event, but little is known about preferences of individuals at high risk for lung cancer and whether they would be interested in this type of treatment.

OBJECTIVE: To explore preferences of individuals at high risk for lung cancer for potential interception therapies to reduce this risk.

DESIGN, SETTING, AND PARTICIPANTS: This survey study used a discrete-choice experiment and included hypothetical lung cancer interception treatments with 4 attributes: reduction in lung cancer risk over 3 years, injection site reaction severity, nonfatal serious infection, and death from serious infection. Respondents were assigned to a baseline lung cancer risk of 6%, 10%, or 16% over 3 years. The discrete-choice experiment was administered online (July 13 to September 6, 2022) to US respondents eligible for lung cancer screening according to US Preventive Services Task Force guidelines. Participants included adults aged 50 to 80 years with at least a 20 pack-year smoking history. Statistical analysis was performed from September to December 2022.

MAIN OUTCOMES AND MEASURES: Attribute-level preference weights were estimated, and conditional relative attribute importance, maximum acceptable risks, and minimum acceptable benefits were calculated. Characteristics of respondents who always selected no treatment were also explored.

RESULTS: Of the 803 survey respondents, 495 (61.6%) were female, 138 (17.2%) were African American or Black, 55 (6.8%) were Alaska Native, American Indian, or Native American, 44 (5.5%) were Asian or Native Hawaiian or Other Pacific Islander, 104 (13.0%) were Hispanic, Latin American, or Latinx, and 462 (57.5%) were White, Middle Eastern or North African, or a race or ethnicity not listed; and mean (SD) age was 63.0 (7.5) years. Most respondents were willing to accept interception therapy and viewed reduction in lung cancer risk as the most important attribute. Respondents would accept a greater than or equal to a 12.0 percentage point increase in risk of nonfatal serious infection if lung cancer risk was reduced by at least 20.0 percentage points; and a greater than or equal to 1.2 percentage point increase in risk of fatal serious infection if lung cancer risk was reduced by at least 30.0 percentage points. Respondents would require at least a 15.4 (95% CI, 10.6-20.2) percentage point decrease in lung cancer risk to accept a 12.0 percentage point increase in risk of nonfatal serious infection; and at least a 23.1 (95% CI, 16.4-29.8) percentage point decrease in lung cancer risk to accept a 1.2 percentage point increase in risk of death from serious infection. Respondents who were unwilling to accept interception therapy in any question (129 [16.1%]) were more likely to be older and to currently smoke with no prior cessation attempt, and less likely to have been vaccinated against COVID-19 or examined for skin cancer.

CONCLUSIONS AND RELEVANCE: In this survey study of individuals at high risk of lung cancer, most respondents were willing to consider interception therapy. These results suggest the importance of benefit-risk assessments for future lung cancer interception treatments.

PMID:37948077 | DOI:10.1001/jamanetworkopen.2023.42681

JAMA Netw Open. 2023 Nov 1;6(11):e2342781. doi: 10.1001/jamanetworkopen.2023.42781.

ABSTRACT

IMPORTANCE: HIV preexposure prophylaxis (PrEP) is a key component of the Ending the HIV Epidemic (EHE) Initiative to curb new HIV diagnoses. In October 2019, emtricitabine/tenofovir alafenamide was added as an approved formulation for PrEP in addition to emtricitabine/tenofovir disoproxil fumarate; despite availability of another formulation with a similar prevention indication, variations in coverage may limit access.

OBJECTIVE: To assess qualified health plan (QHP) coverage, prior authorization (PA) requirements, and specialty tiering for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide following emtricitabine/tenofovir alafenamide approval as a PrEP treatment.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed QHPs in the US that were compliant with the Patient Protection and Affordable Care Act from 2018 to 2020. QHPs were categorized by region and EHE priority jurisdictions. Data analysis occurred from March 2022 to March 2023.

EXPOSURES: Enrollment in a qualified health plan certified by the Patient Protection and Affordable Care Act.

MAIN OUTCOME AND MEASURES: Annual variation in QHP coverage and PA requirement for emtricitabine/tenofovir disoproxil fumarate and/or emtricitabine/tenofovir alafenamide. Descriptive statistics were reported for all outcomes. A secondary outcome was whether the PrEP formulation was determined by the QHP to be placed on a specialty drug tier.

RESULTS: A total of 58 087 QHPs (19 533 for 2018; 17 007 for 2019; and 21 547 for 2020) were analyzed. QHPs covered emtricitabine/tenofovir disoproxil fumarate (19 165 QHPs [98.1%] in 2018; 16 970 QHPs [99.8%] in 2019; 20 045 QHPs [94.8%] in 2020) at a higher rate than emtricitabine/tenofovir alafenamide (17 391 QHPs [91.9%] in 2018; 15 757 QHPs [92.7%] in 2019; 18 836 QHPs [87.4%] in 2020). QHPs in the South required exclusive PA (ie, PA for 1 of the formulations even if the QHP covered both) for emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide at the highest rates in all 3 years. In the South, the rate of PA for emtricitabine/tenofovir disoproxil fumarate increased from 806 of 8023 QHPs (10.0%) in 2018 to 3466 of 7401 QHPs (46.8%) in 2020. QHPs with exclusive PA requirement for emtricitabine/tenofovir disoproxil fumarate were higher in EHE jurisdictions than non-EHE jurisdictions (difference: 2018, 0.9 percentage points; 2019, 3.5 percentage points; 2020, 29.1 percentage points). QHPs were more likely to place emtricitabine/tenofovir disoproxil fumarate on a specialty tier compared with emtricitabine/tenofovir alafenamide (difference: 2018, 1.8 percentage points; 2019, 3.7 percentage points; 2020, 4.1 percentage points).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, despite similar indications for biomedical prevention, QHPs were more likely to cover emtricitabine/tenofovir disoproxil fumarate than emtricitabine/tenofovir alafenamide, and QHPs were also more likely to subject emtricitabine/tenofovir disoproxil fumarate to PA or place it on a specialty tier despite the broader clinical indication. QHP PA requirements of emtricitabine/tenofovir disoproxil fumarate following emtricitabine/tenofovir alafenamide approval does not reflect clinical guidelines. The requirements could reflect differences in clinical indication, manufacturer discounts, or anticipation of a changing regulations and emerging generics. High rates of exclusive PA for emtricitabine/tenofovir disoproxil fumarate in areas where rates of HIV diagnoses are highest and PrEP is most needed (eg, the South and EHE priority jurisdictions) is concerning; policy solutions to address the growing PrEP health equity crisis could include regulator actions and a national PrEP program.

PMID:37948076 | DOI:10.1001/jamanetworkopen.2023.42781