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In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

Sci Adv. 2023 Jun 16;9(24):eadf8332. doi: 10.1126/sciadv.adf8332. Epub 2023 Jun 14.

ABSTRACT

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs’ effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain’s functional architecture.

PMID:37315149 | DOI:10.1126/sciadv.adf8332

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Intolerance-of-uncertainty therapy versus metacognitive therapy for generalized anxiety disorder in primary health care: A randomized controlled pilot trial

PLoS One. 2023 Jun 14;18(6):e0287171. doi: 10.1371/journal.pone.0287171. eCollection 2023.

ABSTRACT

OBJECTIVE: This randomized controlled pilot study investigated the feasibility of a future full-scale RCT to compare the effects of intolerance-of-uncertainty therapy (IUT) and metacognitive therapy (MCT) in primary health care patients with generalized anxiety disorder (GAD). Preliminary treatment effects were also evaluated.

MATERIALS AND METHODS: 64 patients with GAD at a large primary health care center in Stockholm, Sweden, were randomized to IUT or MCT. Feasibility outcomes included participant recruitment and retention, willingness to receive psychological treatment, and therapists’ competence in and adherence to treatment protocols. Self-reported scales were used to assess treatment outcomes, including worry, depression, functional impairment, and quality of life.

RESULTS: Recruitment was satisfactory, and dropout was low. On a scale from 0 to 6, participants were satisfied with participating in the study (M = 5.17, SD = 1.09). Following brief training, therapists’ competence was rated as moderate, and adherence was rated as weak to moderate. From pre- to post-treatment, reductions on the primary treatment outcome measure of worry were of a large effect size and statistically significant in both the IUT and MCT conditions (Cohen’s d for IUT = -2.69, 95% confidence interval [-3.63, -1.76] and d for MCT = -3.78 [-4.68, -2.90]). The between-group effect size from pre- to post-treatment was large and statistically significant (d = -2.03 [-3.31, -0.75]), in favor of the MCT condition.

CONCLUSION: It is feasible to carry out a full-scale RCT to compare the effects of IUT to MCT for patients with GAD in primary health care. Both protocols seem effective, and MCT seems superior to IUT, but a full-scale RCT is needed to confirm these conclusions.

TRIAL REGISTRATION: ClinicalTrials.gov (no. NCT03621371).

PMID:37315099 | DOI:10.1371/journal.pone.0287171

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The use of patient sitters at a Swiss hospital: A retrospective observational study

PLoS One. 2023 Jun 14;18(6):e0287317. doi: 10.1371/journal.pone.0287317. eCollection 2023.

ABSTRACT

OBJECTIVE: Patient sitters are frequently used in acute care hospitals to provide one-to-one care for agitated or disorientated patients to assure the safety and well-being of patients. However, there is still a lack of evidence on the use of patient sitters, especially in Switzerland. Therefore, the aim of this study was to describe and explore the use of patient sitters in a Swiss acute care hospital.

METHODS: In this retrospective, observational study we included all inpatients who were hospitalized between January and December 2018 in a Swiss acute care hospital and required a paid or volunteer patient sitter. Descriptive statistics were used to describe the extent of patient sitter use, patient characteristics, and organizational factors. For the subgroup analysis between internal medicine and surgical patients Mann-Whitney U tests and chi-square tests were used.

RESULTS: Of the total of 27’855 included inpatients, 631 (2.3%) needed a patient sitter. Of these, 37.5% had a volunteer patient sitter. The median patient sitter duration per patient per stay was 18.0 hours (IQR = 8.4-41.0h). The median age was 78 years (IQR = 65.0-86.0); 76.2% of patients were over the age of 64. Delirium was diagnosed in 41% of patients, and 15% had dementia. Most of the patients showed signs of disorientation (87.3%), inappropriate behavior (84.6%), and risk of falling (86.6%). Patient sitter uses varied during the year and between surgical and internal medicine units.

CONCLUSIONS: These results add to the limited body of evidence concerning patient sitter use in hospitals, supporting previous findings related to patient sitter use for delirious or geriatric patients. New findings include the subgroup analysis of internal medicine and surgical patients, as well as analysis of patient sitter use distribution throughout the year. These findings may contribute to the development of guidelines and policies regarding patient sitter use.

PMID:37315098 | DOI:10.1371/journal.pone.0287317

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Demand segmentation and sociodemographic aspects of food festivals: A study in Bahrain

PLoS One. 2023 Jun 14;18(6):e0287113. doi: 10.1371/journal.pone.0287113. eCollection 2023.

ABSTRACT

Food festivals have been a growing tourism sector in recent years due to their contributions to a region’s economic, marketing, brand, and social growth. This study analyses the demand for the Bahrain food festival. The stated objectives were: i) To identify the motivational dimensions of the demand for the food festival, (ii) To determine the segments of the demand for the food festival, and (iii) To establish the relationship between the demand segments and socio-demographic aspects. The food festival investigated was the Bahrain Food Festival held in Bahrain, located on the east coast of the Persian Gulf. The sample consisted of 380 valid questionnaires and was taken using social networks from those attending the event. The statistical techniques used were factorial analysis and the K-means grouping method. The results show five motivational dimensions: Local food, Art, Entertainment, Socialization, and Escape and novelty. In addition, two segments were found; the first, Entertainment and novelties, is related to attendees who seek to enjoy the festive atmosphere and discover new restaurants. The second is Multiple motives, formed by attendees with several motivations simultaneously. This segment has the highest income and expenses, making it the most important group for developing plans and strategies. The results will contribute to the academic literature and the organizers of food festivals.

PMID:37315091 | DOI:10.1371/journal.pone.0287113

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Increasing multimonth dispensing of antiretrovirals and assessing the effect on viral load suppression among children and adolescents receiving HIV services in Nigeria

PLoS One. 2023 Jun 14;18(6):e0286303. doi: 10.1371/journal.pone.0286303. eCollection 2023.

ABSTRACT

INTRODUCTION: Multimonth dispensing (MMD) enables less frequent clinic visits and improved outcomes for people living with HIV, but few children and adolescents living with HIV (CALHIV) are on MMD. At the end of the October-December 2019 quarter, only 23% of CALHIV receiving antiretroviral therapy (ART) through SIDHAS project sites in Akwa Ibom and Cross River states, Nigeria, were receiving MMD. In March 2020, during COVID-19, the government expanded MMD eligibility to include children and recommended rapid implementation to minimize clinic visits. SIDHAS provided technical assistance to 36 “high-volume” facilities-≥5 CALHIV on treatment-in Akwa Ibom and Cross River to increase MMD and viral load suppression (VLS) among CALHIV, toward PEPFAR’s 80% benchmark for people currently on ART. We present change in MMD, viral load (VL) testing coverage, VLS, optimized regimen coverage, and community-based ART group enrollment among CALHIV from the October-December 2019 quarter (baseline) to January-March 2021 (endline) based on retrospective analysis of routinely collected program data.

MATERIALS AND METHODS: We compared MMD coverage (primary objective), and optimized regimen coverage, community-based ART group enrollment, VL testing coverage, and VLS (secondary objectives), among CALHIV 18 years and younger pre-/post-intervention (baseline/endline) at the 36 facilities. We excluded children younger than two years, who are not recommended for or routinely offered MMD. The extracted data included age, sex, ART regimen, months of ART dispensed at last refill, most recent VL test results, and community ART group enrollment. Data on MMD-three or more months of ARVs dispensed at one time-were disaggregated into three to five months (3-5-MMD) vs. six or more months (6-MMD). VLS was defined as ≤1,000 copies. We documented MMD coverage by site, optimized regimen, and VL testing and suppression. Using descriptive statistics, we summarized the characteristics of CALHIV on MMD and non-MMD, number of CALHIV on optimized regimens, and proportion enrolled in differentiated service delivery models and community-based ART refill groups. For the intervention, SIDHAS technical assistance was data driven: weekly data analysis/review, site-prioritization scoring, provider mentoring, line listing eligible CALHIV, pediatric regimen calculator, child-optimized regimen transitioning, and community ART models.

RESULTS: The proportion of CALHIV ages 2-18 receiving MMD increased from 23% (620/2,647; baseline) to 88% (3,992/4,541; endline), while the proportion of sites reporting suboptimal MMD coverage among CALHIV (<80%) decreased (100% to 28%). In March 2021, 49% of CALHIV were receiving 3-5-MMD and 39% 6-MMD. In October-December 2019, 17%-28% of CALHIV were receiving MMD; by January-March 2021, 99% of those 15-18 years, 94% 10-14 years, 79% 5-9 years, and 71% 2-4 years were on MMD. VL testing coverage remained high (90%), while VLS increased (64% to 92%). The proportion on pediatric-optimized regimens increased (58% to 79%).

CONCLUSIONS: MMD was feasible among CALHIV without compromising VLS. Expanded eligibility criteria, line listing eligible children, monitoring pediatric antiretroviral stock, and data use contributed to positive results. Future efforts should address low 6-MMD uptake related to stock limitations and synchronize antiretroviral refill pickup with VL sample collection.

PMID:37315075 | DOI:10.1371/journal.pone.0286303

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Optic Neuritis After COVID-19 Vaccination: An Analysis of the Vaccine Adverse Event Reporting System

J Neuroophthalmol. 2023 Jun 14. doi: 10.1097/WNO.0000000000001900. Online ahead of print.

ABSTRACT

BACKGROUND: To investigate the association of optic neuritis (ON) after the COVID-19 vaccines.

METHODS: Cases of ON from Vaccine Adverse Event Reporting System (VAERS) were collected and divided into the prepandemic, COVID-19 pandemic, and COVID-19 vaccine periods. Reporting rates were calculated based on estimates of vaccines administered. Proportion tests and Pearson χ2 test were used to determine significant differences in reporting rates of ON after vaccines within the 3 periods. Kruskal-Wallis testing with Bonferroni-corrected post hoc analysis and multivariable binary logistic regression was used to determine significant case factors such as age, sex, concurrent multiple sclerosis (MS) and vaccine manufacturer in predicting a worse outcome defined as permanent disability, emergency room (ER) or doctor visits, and hospitalizations.

RESULTS: A significant increase in the reporting rate of ON after COVID-19 vaccination compared with influenza vaccination and all other vaccinations (18.6 vs 0.2 vs 0.4 per 10 million, P < 0.0001) was observed. However, the reporting rate was within the incidence range of ON in the general population. Using self-controlled and case-centered analyses, there was a significant difference in the reporting rate of ON after COVID-19 vaccination between the risk period and control period (P < 0.0001). Multivariable binary regression with adjustment for confounding variables demonstrated that only male sex was significantly associated with permanent disability.

CONCLUSIONS: Some cases of ON may be temporally associated with the COVID-19 vaccines; however, there is no significant increase in the reporting rate compared with the incidence. Limitations of this study include those inherent to any passive surveillance system. Controlled studies are needed to establish a clear causal relationship.

PMID:37314860 | DOI:10.1097/WNO.0000000000001900

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Protein Biomarkers for the Identification of Forensically Relevant Human Hair from Different Body Parts in Intimate Contact Cases

J Proteome Res. 2023 Jun 14. doi: 10.1021/acs.jproteome.3c00129. Online ahead of print.

ABSTRACT

Correctly identifying the human hair anatomic location found at crime scenes can link biological sample donors with the actual crime event, thus providing significant insight into the crime scene reconstruction. Forensic proteomic studies on human hairs can facilitate the development of new biomarkers for hair identification while compensating for the limitations of the conventional morphologic hair comparison and DNA analysis. Herein, the LC-MS/MS platform was used to find differentially expressed protein biomarkers in hairs from different body sites. The findings indicated that a total of 296 protein biomarkers with statistically significant differences in body sites were initially identified, and hair samples from the scalp, pubic, and armpit parts were distinguished from each other, which were validated by multiple bioinformatic methods. Fewer differences in protein patterns between armpit and pubic hairs while larger differences between hair and armpit as well as pubic hairs provided reasonable evidence of sexual or close intimate contact in crimes. This study lays the foundation for the development of a more reliable strategy to distinguish human hairs of various body areas from Chinese and will also support microscopic hair comparison analysis and assist in the proper handling of legal proceedings in relative cases by judicial officers, deserving special attention and further in-depth investigation. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD038173.

PMID:37314855 | DOI:10.1021/acs.jproteome.3c00129

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Developing a Culturally and Linguistically Congruent Digital Storytelling Intervention in Vietnamese and Korean American Mothers of Human Papillomavirus-Vaccinated Children: Feasibility and Acceptability Study

JMIR Form Res. 2023 Jun 14;7:e45696. doi: 10.2196/45696.

ABSTRACT

BACKGROUND: The high morbidity, mortality, and economic burden attributed to cancer-causing human papillomavirus (HPV) call for researchers to address this public health concern through HPV vaccination. Disparities of HPV-associated cancers in Vietnamese and Korean Americans exist, yet their vaccination rates remain low. Evidence points to the importance of developing culturally and linguistically congruent interventions to improve their HPV vaccination rates. We adopted digital storytelling (DST) that combines oral storytelling with computer-based technology (digital images, audio recording, and music) as a promising approach for facilitating the communication of culturally relevant health messages.

OBJECTIVE: This study aimed to (1) assess the feasibility and acceptability of intervention development through DST workshops, (2) conduct an in-depth analysis of the cultural experience that shapes HPV attitudes, and (3) explore aspects of the DST workshop experience that could inform future formative and intervention work.

METHODS: Through community partners, social media, and snowball sampling, we recruited 2 Vietnamese American and 6 Korean American mothers (mean age 41.4, SD 5.8 years) who had children vaccinated against HPV. Three virtual DST workshops were conducted between July 2021 and January 2022. Our team supported mothers to develop their own stories. Mothers completed web-based surveys before and after the workshop and provided feedback on each other’s story ideas and the workshop experience. We used descriptive statistics to summarize quantitative data and constant comparative analysis to analyze qualitative data collected in the workshop and field notes.

RESULTS: Eight digital stories were developed in the DST workshops. They were well accepted, and the mothers showed overall satisfaction and relevant indicators (eg, would recommend it to others, would attend a similar workshop, it was worth their time; mean 4.2-5, range 1-5). Mothers found the process rewarding and appreciated the opportunity to share their stories in group settings and learn from each other. The 6 major themes that emerged from the data reflect the mothers’ rich personal experiences, attitudes, and perceptions about their child’s HPV vaccination, which included (1) showing parents’ love and responsibility; (2) HPV and related knowledge, awareness, and attitudes; (3) factors influencing vaccine decision-making; (4) source of information and information sharing; (5) response to children’s being vaccinated; and (6) cultural perspectives on health care and HPV vaccination.

CONCLUSIONS: Our findings suggest that a virtual DST workshop is a highly feasible and acceptable approach to engaging Vietnamese American and Korean American immigrant mothers in developing culturally and linguistically congruent DST interventions. Further research is needed to test the efficacy and effectiveness of digital stories as an intervention for Vietnamese American and Korean American mothers of unvaccinated children. This process of developing an easy-to-deliver, culturally and linguistically aligned, and holistic web-based DST intervention can be implemented with other populations in other languages.

PMID:37314851 | DOI:10.2196/45696

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Rationale, Design, and Methods for the Sedentary Behavior Reduction in Pregnancy Intervention (SPRING): Protocol for a Pilot and Feasibility Randomized Controlled Trial

JMIR Res Protoc. 2023 Jun 14;12:e48228. doi: 10.2196/48228.

ABSTRACT

BACKGROUND: Adverse pregnancy outcomes (APOs) identify cardiovascular disease risk, but few effective interventions are available. High sedentary behavior (SED) has recently been associated with APOs, but very few randomized controlled trials (RCTs) have tested SED reduction in pregnancy.

OBJECTIVE: The Sedentary Behavior Reduction in Pregnancy Intervention (SPRING) pilot and feasibility RCT addresses this gap by testing the feasibility, acceptability, and preliminary pregnancy health effects of an intervention to reduce SED in pregnant women. The objective of this manuscript is to describe the rationale and design of SPRING.

METHODS: Pregnant participants (n=53) in their first trimester, who are at risk for high SED and APO and without contraindications, are randomized in a 2:1 ratio to an intervention or control group. SED (primary outcome) and standing durations, and steps per day, are measured objectively in each trimester for 1 week with a thigh-mounted activPAL3 accelerometer. SPRING also seeks to demonstrate feasibility and acceptability while estimating preliminary effects on maternal-fetal health outcomes assessed during study visits and abstracted from medical records. The pregnancy-customized intervention promotes daily behavioral targets of less than 9 hours of SED and at least 7500 steps, achieved via increased standing and incorporating light-intensity movement breaks each hour. The multicomponent intervention provides a height-adjustable workstation, a wearable activity monitor, behavioral counseling every 2 weeks (through videoconference), and membership in a private social media group. Herein, we review the rationale, describe recruitment and screening processes, and detail the intervention, assessment protocols, and planned statistical analyses.

RESULTS: This study was funded by the American Heart Association (20TPA3549099), with a funding period of January 1, 2021, and until December 31, 2023. Institutional review board approval was obtained on February 24, 2021. Participants were randomized between October 2021 and September 2022, with final data collection planned for May 2023. Analyses and submission of results are expected for winter of 2023.

CONCLUSIONS: The SPRING RCT will provide initial evidence on the feasibility and acceptability of an SED-reduction intervention to decrease SED in pregnant women. These data will inform the design of a large clinical trial testing SED reduction as a strategy to reduce APO risk.

TRIAL REGISTRATION: ClincialTrials.gov NCT05093842; https://clinicaltrials.gov/ct2/show/NCT05093842.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48228.

PMID:37314845 | DOI:10.2196/48228

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Implementing Active Assisted Living Technology in the Long-term Care of People Living With Dementia to Address Loneliness: European Survey

JMIR Aging. 2023 Jun 14;6:e45231. doi: 10.2196/45231.

ABSTRACT

BACKGROUND: In the lives of people with dementia, loneliness is an important issue with psychological and physical consequences. Active assisted living (AAL) technology has been gaining visibility in the care of persons living with dementia, including addressing loneliness. However, to the best of our knowledge, there is a lack of evidence concerning the factors influencing the implementation of AAL technology within the context of dementia, loneliness, and long-term care (LTC).

OBJECTIVE: We aimed to identify the familiarity with AAL technology that is promising for addressing loneliness in persons living with dementia in LTC in Europe and the factors influencing AAL technology implementation.

METHODS: A web-based survey was developed based on findings from our previous literature review. The Consolidated Framework for Implementation Research guided the development and analysis of the survey. Participants included 24 representatives of Alzheimer Europe member associations from 15 European countries. The data were analyzed using basic statistical methods (descriptive statistics).

RESULTS: The baby seal robot Paro was reported to be the most familiar AAL technology by 19 of 24 participants addressing loneliness in people with dementia living in LTC. Participants from Norway (n=2) reported familiarity with 14 AAL technologies, and participants from Serbia (n=1) reported zero familiarity. It seems that countries that invest less in LTC facilities are familiar with fewer AAL technologies. At the same time, these countries report a more positive attitude toward AAL technology, express a higher need for it, and see more advantages than disadvantages than those countries that invest more in LTC. However, a country’s investment in LTC facilities does not seem to be linked to other implementation aspects such as costs, planning, and the impact of infrastructure.

CONCLUSIONS: Implementation of AAL technology to address loneliness in dementia seems to be linked to familiarity with the technology in a country as well as national investment in LTC facilities. This survey confirms the literature on higher investment countries’ critical stance in regard to AAL technology implementation to address loneliness in persons living with dementia living in LTC. Further research is needed to clarify the potential reasons why familiarity with more AAL technology does not seem to be directly linked with acceptance, positive attitude, or satisfaction with AAL technology addressing loneliness in persons living with dementia.

PMID:37314840 | DOI:10.2196/45231