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High-precision monitoring of and feedback control over drug concentrations in the brains of freely moving rats

Sci Adv. 2023 May 19;9(20):eadg3254. doi: 10.1126/sciadv.adg3254. Epub 2023 May 17.

ABSTRACT

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 μM limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (±10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.

PMID:37196087 | DOI:10.1126/sciadv.adg3254

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Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results

Oncologist. 2023 May 17:oyad095. doi: 10.1093/oncolo/oyad095. Online ahead of print.

ABSTRACT

BACKGROUND: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.

METHODS: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected.

RESULTS: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only.

CONCLUSION: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).

PMID:37196069 | DOI:10.1093/oncolo/oyad095

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Biomechanical behavior of a 3D-printed denture base material

Int J Prosthodont. 2023 May 17. doi: 10.11607/ijp.8295. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate relevant material properties (flexural strength (σf), elastic modulus (E), water sorption (Wsp) and solubility (Wsl), and biocompatibility) of a 3D-printed resin (3D) and a heat cured acrylic resin (AR-control) used for complete denture manufacturing, testing the hypothesis that constructs from both materials would present acceptable material properties for clinical use.

MATERIALS AND METHODS: The σf, E, Wsp and Wsl were evaluated according to the ISO 20795-1:2013 standard, and the biocompatibility was evaluated using 3-4,5-dimethyl-thiazol-2-yl-2.5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Disk-shaped specimens were fabricated and used for Wsp (n = 5), Wsl (n = 5), and biocompatibility (n = 3). Bar-shaped specimens (n = 30) were fabricated and stored in 37⁰ C distilled water for 48 hours and 6 months before flexural testing in a universal testing machine with constant displacement rate (5 ± 1 mm/min) until fracture. Data from σf, E, Wsp, Wsl and biocompatibility were statistically analyzed using Student t test (α= 0.05), Weibull analysis was also used for σf and E data.

RESULTS: Significant differences between the two polymers were found for the evaluated material properties. Water storage for 6 months did not affect the flexural strength of 3D. Yet, the additive manufactured polymer showed inadequate flexural strength and water solubility values.

CONCLUSION: Despite adequate biocompatibility and strength stability after 6 months of water storage, the additive manufactured polymer recommended for complete denture needs further development to improve the remaining material properties evaluated in this study.

PMID:37196039 | DOI:10.11607/ijp.8295

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Selective extended dissection for pancreaticoduodenectomy is associated with better survival in pancreatic cancer patients: retrospective cohort study

Int J Surg. 2023 May 17. doi: 10.1097/JS9.0000000000000437. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with relatively poor survival. Surgery is the first choice for treating patients with early pancreatic cancer. However, the surgical approach and the extent of resection for patients with pancreatic cancer are currently controversial.

METHODS: We optimized the procedure of standard pancreaticoduodenectomy to selective extended dissection (SED), which is based on the extra-pancreatic nerve plexus (PLX) potentially invaded by the tumor. We retrospectively analyzed the clinicopathological data of patients with pancreatic adenocarcinoma who underwent radical surgery in our center from 2011 to 2020. Patients who underwent standard dissection (SD) were matched 2:1 to those who underwent SED using propensity score matching (PSM). The log-rank test and cox regression model were used to analyze survival data. In addition, statistical analyses were performed for the perioperative complications, postoperative pathology and recurrence pattern.

RESULTS: A total of 520 patients were included in the analysis. Among patients with extra-pancreatic perineural invasion (EPNI), disease-free survival (DFS) was significantly longer in those who received SED than in those who received SD (14.5 mo vs. 10 mo, P<0.05). The incidence of metastasis in No.9 and No.14 lymph nodes was significantly higher in patients with EPNI. In addition, there was no significant difference in the incidence rate of perioperative complications between the two surgical procedures.

CONCLUSION: Compared with SD, SED exhibits significant prognostic benefit for patients with EPNI. The SED procedure aiming at specific nerve plexus dissection displayed particular efficacy and safety in resectable PDAC patients.

PMID:37195787 | DOI:10.1097/JS9.0000000000000437

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Cybervictimization of Adults With Long-term Conditions: Cross-sectional Study

J Med Internet Res. 2023 May 17;25:e39933. doi: 10.2196/39933.

ABSTRACT

BACKGROUND: People living with chronic conditions and disabilities experience harassment both offline and on the web. Cybervictimization is an umbrella term for negative web-based experiences. It has distressing consequences on physical health, mental well-being, and social relationships. These experiences have mostly been documented among children and adolescents. However, the scope of such experiences is not well documented among adults with long-term conditions, and the potential impact has not been examined from a public health perspective.

OBJECTIVE: This study aimed to examine the scope of cybervictimization among adults living with long-term conditions in the United Kingdom and the perceived impact on self-management of chronic conditions.

METHODS: This paper reports the findings of the quantitative phase of a mixed methods study in the United Kingdom. This cross-sectional study targeted adults aged ≥18 years with long-term conditions. Using a web-based link, the survey was shared on the web via 55 victim support groups, health support organizations, and social media accounts of nongovernmental organizations and activists such as journalists and disability campaigners. People with long-term conditions were asked about their health conditions, comorbidities, self-management, negative web-based experiences, their impact on them, and support sought to mitigate the experiences. The perceived impact of cybervictimization was measured using a set of questions on a Likert scale, frequency tables, and the Stanford Self-Efficacy for Managing Chronic Diseases Scale. Demographic data and the impact on self-management were cross-tabulated to identify the demographic characteristics of the targeted individuals and potential conditions with complications and highlight directions for future research.

RESULTS: Data from 152 participants showed that almost 1 in every 2 adults with chronic conditions was cybervictimized (69/152, 45.4%). Most victims (53/69, 77%) had disabilities; the relationship between cybervictimization and disability was statistically significant (P=.03). The most common means of contacting the victims was Facebook (43/68, 63%), followed by personal email or SMS text messaging, each accounting for 40% (27/68). Some participants (9/68, 13%) were victimized in web-based health forums. Furthermore, 61% (33/54) of victims reported that experiencing cybervictimization had affected their health condition self-management plan. The highest impact was on lifestyle changes such as exercise, diet, avoiding triggers, and avoiding excessive smoking and alcohol consumption. This was followed by changes to medications and follow-ups with health care professionals. Most victims (38/55, 69%) perceived a worsened self-efficacy on the Self-Efficacy for Managing Chronic Diseases Scale. Formal support was generally rated as poor, with only 25% (13/53) of victims having disclosed this experience to their physicians.

CONCLUSIONS: Cybervictimization of people with chronic conditions is a public health issue with worrying consequences. This triggered considerable fear and negatively influenced the self-management of different health conditions. Further context- and condition-specific research is needed. Global collaborations to address inconsistencies in research are recommended.

PMID:37195761 | DOI:10.2196/39933

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Exploring the Behavior of Users With Attention-Deficit/Hyperactivity Disorder on Twitter: Comparative Analysis of Tweet Content and User Interactions

J Med Internet Res. 2023 May 17;25:e43439. doi: 10.2196/43439.

ABSTRACT

BACKGROUND: With the widespread use of social media, people share their real-time thoughts and feelings via interactions on these platforms, including those revolving around mental health problems. This can provide a new opportunity for researchers to collect health-related data to study and analyze mental disorders. However, as one of the most common mental disorders, there are few studies regarding the manifestations of attention-deficit/hyperactivity disorder (ADHD) on social media.

OBJECTIVE: This study aims to examine and identify the different behavioral patterns and interactions of users with ADHD on Twitter through the text content and metadata of their posted tweets.

METHODS: First, we built 2 data sets: an ADHD user data set containing 3135 users who explicitly reported having ADHD on Twitter and a control data set made up of 3223 randomly selected Twitter users without ADHD. All historical tweets of users in both data sets were collected. We applied mixed methods in this study. We performed Top2Vec topic modeling to extract topics frequently mentioned by users with ADHD and those without ADHD and used thematic analysis to further compare the differences in contents that were discussed by the 2 groups under these topics. We used a distillBERT sentiment analysis model to calculate the sentiment scores for the emotion categories and compared the sentiment intensity and frequency. Finally, we extracted users’ posting time, tweet categories, and the number of followers and followings from the metadata of tweets and compared the statistical distribution of these features between ADHD and non-ADHD groups.

RESULTS: In contrast to the control group of the non-ADHD data set, users with ADHD tweeted about the inability to concentrate and manage time, sleep disturbance, and drug abuse. Users with ADHD felt confusion and annoyance more frequently, while they felt less excitement, caring, and curiosity (all P<.001). Users with ADHD were more sensitive to emotions and felt more intense feelings of nervousness, sadness, confusion, anger, and amusement (all P<.001). As for the posting characteristics, compared with controls, users with ADHD were more active in posting tweets (P=.04), especially at night between midnight and 6 AM (P<.001); posting more tweets with original content (P<.001); and following fewer people on Twitter (P<.001).

CONCLUSIONS: This study revealed how users with ADHD behave and interact differently on Twitter compared with those without ADHD. On the basis of these differences, researchers, psychiatrists, and clinicians can use Twitter as a potentially powerful platform to monitor and study people with ADHD, provide additional health care support to them, improve the diagnostic criteria of ADHD, and design complementary tools for automatic ADHD detection.

PMID:37195757 | DOI:10.2196/43439

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Factors Influencing Admission Decisions in Skilled Nursing Facilities: Retrospective Quantitative Study

J Med Internet Res. 2023 May 17;25:e43518. doi: 10.2196/43518.

ABSTRACT

BACKGROUND: Occupancy rates within skilled nursing facilities (SNFs) in the United States have reached a record low. Understanding drivers of occupancy, including admission decisions, is critical for assessing the recovery of the long-term care sector as a whole. We provide the first comprehensive analysis of financial, clinical, and operational factors that impact whether a patient referral to an SNF is accepted or denied, using a large health informatics database.

OBJECTIVE: Our key objectives were to describe the distribution of referrals sent to SNFs in terms of key referral- and facility-level features; analyze key financial, clinical, and operational variables and their relationship to admission decisions; and identify the key potential reasons behind referral decisions in the context of learning health systems.

METHODS: We extracted and cleaned referral data from 627 SNFs from January 2020 to March 2022, including information on SNF daily operations (occupancy and nursing hours), referral-level factors (insurance type and primary diagnosis), and facility-level factors (overall 5-star rating and urban versus rural status). We computed descriptive statistics and applied regression modeling to identify and describe the relationships between these factors and referral decisions, considering them individually and controlling for other factors to understand their impact on the decision-making process.

RESULTS: When analyzing daily operation values, no significant relationship between SNF occupancy or nursing hours and referral acceptance was observed (P>.05). By analyzing referral-level factors, we found that the primary diagnosis category and insurance type of the patient were significantly related to referral acceptance (P<.05). Referrals with primary diagnoses within the category “Diseases of the Musculoskeletal System” are least often denied whereas those with diagnoses within the “Mental Illness” category are most often denied (compared with other diagnosis categories). Furthermore, private insurance holders are least often denied whereas “medicaid” holders are most often denied (compared with other insurance types). When analyzing facility-level factors, we found that the overall 5-star rating and urban versus rural status of an SNF are significantly related to referral acceptance (P<.05). We found a positive but nonmonotonic relationship between the 5-star rating and referral acceptance rates, with the highest acceptance rates found among 5-star facilities. In addition, we found that SNFs in urban areas have lower acceptance rates than their rural counterparts.

CONCLUSIONS: While many factors may influence a referral acceptance, care challenges associated with individual diagnoses and financial challenges associated with different remuneration types were found to be the strongest drivers. Understanding these drivers is essential in being more intentional in the process of accepting or denying referrals. We have interpreted our results using an adaptive leadership framework and suggested how SNFs can be more purposeful with their decisions while striving to achieve appropriate occupancy levels in ways that meet their goals and patients’ needs.

PMID:37195755 | DOI:10.2196/43518

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Using Human-Centered Design and Cocreation to Create the Live 5-2-1-0 Mobile App to Promote Healthy Behaviors in Children: App Design and Development

JMIR Pediatr Parent. 2023 May 17;6:e44792. doi: 10.2196/44792.

ABSTRACT

BACKGROUND: The prevalence of obesity among Canadian children is rising, partly because of increasingly obesogenic environments that limit opportunities for physical activity and healthy nutrition. Live 5-2-1-0 is a community-based multisectoral childhood obesity prevention initiative that engages stakeholders to promote and support the message of consuming ≥5 servings of vegetables and fruits, having <2 hours of recreational screen time, participating in ≥1 hour of active play, and consuming 0 sugary drinks every day. A Live 5-2-1-0 Toolkit for health care providers (HCPs) was previously developed and piloted in 2 pediatric clinics at British Columbia Children’s Hospital.

OBJECTIVE: This study aimed to co-create, in partnership with children, parents, and HCPs, a Live 5-2-1-0 mobile app that supports healthy behavior change and could be used as part of the Live 5-2-1-0 Toolkit for HCPs.

METHODS: Three focus groups (FGs) were conducted using human-centered design and participatory approaches. In FG 1, children (separately) and parents and HCPs (together) participated in sessions on app conceptualization and design. Researchers and app developers analyzed and interpreted qualitative data from FG 1 in an ideation session, and key themes were subsequently presented separately to parents, children, and HCPs in FG-2 (co-creation) sessions to identify desired app features. Parents and children tested a prototype in FG 3, provided feedback on usability and content, and completed questionnaires. Thematic analysis and descriptive statistics were used for the qualitative and quantitative data, respectively.

RESULTS: In total, 14 children (mean age 10.2, SD 1.3 years; 5/14, 36% male; 5/14, 36% White), 12 parents (9/12, 75% aged 40-49 years; 2/12, 17% male; 7/12, 58% White), and 18 HCPs participated; most parents and children (20/26, 77%) participated in ≥2 FGs. Parents wanted an app that empowered children to adopt healthy behaviors using internal motivation and accountability, whereas children described challenge-oriented goals and family-based activities as motivating. Parents and children identified gamification, goal setting, daily steps, family-based rewards, and daily notifications as desired features; HCPs wanted baseline behavior assessments and to track users’ behavior change progress. Following prototype testing, parents and children reported ease in completing tasks, with a median score of 7 (IQR 6-7) on a 7-point Likert scale (1=very difficult; 7=very easy). Children liked most suggested rewards (28/37, 76%) and found 79% (76/96) of suggested daily challenges (healthy behavior activities that users complete to achieve their goal) realistic to achieve. Participant suggestions included strategies to maintain users’ interest and content that further motivates healthy behavior change.

CONCLUSIONS: Co-creating a mobile health app with children, parents, and HCPs was feasible. Stakeholders desired an app that facilitated shared decision-making with children as active agents in behavior change. Future research will involve clinical implementation and assessment of the usability and effectiveness of the Live 5-2-1-0 app.

PMID:37195754 | DOI:10.2196/44792

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Empowering Health Care Education Through Learning Analytics: In-depth Scoping Review

J Med Internet Res. 2023 May 17;25:e41671. doi: 10.2196/41671.

ABSTRACT

BACKGROUND: Digital education has expanded since the COVID-19 pandemic began. A substantial amount of recent data on how students learn has become available for learning analytics (LA). LA denotes the “measurement, collection, analysis, and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs.”

OBJECTIVE: This scoping review aimed to examine the use of LA in health care professions education and propose a framework for the LA life cycle.

METHODS: We performed a comprehensive literature search of 10 databases: MEDLINE, Embase, Web of Science, ERIC, Cochrane Library, PsycINFO, CINAHL, ICTP, Scopus, and IEEE Explore. In total, 6 reviewers worked in pairs and performed title, abstract, and full-text screening. We resolved disagreements on study selection by consensus and discussion with other reviewers. We included papers if they met the following criteria: papers on health care professions education, papers on digital education, and papers that collected LA data from any type of digital education platform.

RESULTS: We retrieved 1238 papers, of which 65 met the inclusion criteria. From those papers, we extracted some typical characteristics of the LA process and proposed a framework for the LA life cycle, including digital education content creation, data collection, data analytics, and the purposes of LA. Assignment materials were the most popular type of digital education content (47/65, 72%), whereas the most commonly collected data types were the number of connections to the learning materials (53/65, 82%). Descriptive statistics was mostly used in data analytics in 89% (58/65) of studies. Finally, among the purposes for LA, understanding learners’ interactions with the digital education platform was cited most often in 86% (56/65) of papers and understanding the relationship between interactions and student performance was cited in 63% (41/65) of papers. Far less common were the purposes of optimizing learning: the provision of at-risk intervention, feedback, and adaptive learning was found in 11, 5, and 3 papers, respectively.

CONCLUSIONS: We identified gaps for each of the 4 components of the LA life cycle, with the lack of an iterative approach while designing courses for health care professions being the most prevalent. We identified only 1 instance in which the authors used knowledge from a previous course to improve the next course. Only 2 studies reported that LA was used to detect at-risk students during the course’s run, compared with the overwhelming majority of other studies in which data analysis was performed only after the course was completed.

PMID:37195746 | DOI:10.2196/41671

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The Influence of Mass Media on the COVID-19 Vaccination Decision-making Process: Prospective Survey-Based Study

J Med Internet Res. 2023 May 17;25:e45417. doi: 10.2196/45417.

ABSTRACT

BACKGROUND: Vaccine hesitancy during the COVID-19 pandemic was exacerbated by an infodemic of conflating accurate and inaccurate information with divergent political messages, leading to varying adherence to health-related behaviors. In addition to the media, people received information about COVID-19 and the vaccine from their physicians and closest networks of family and friends.

OBJECTIVE: This study explored individuals’ decision-making processes in receiving the COVID-19 vaccine, focusing on the influence of specific media outlets, political orientation, personal networks, and the physician-patient relationship. We also evaluated the effect of other demographic data like age and employment status.

METHODS: An internet survey was disseminated through the Western Michigan University Homer Stryker MD School of Medicine Facebook account. The survey included questions on media sources for COVID-19 information, political affiliation, presidential candidate choice, and multiple Likert-type agreement scale questions on conceptions of the vaccine. Each respondent was assigned a media source score, which represented the political leaning of their media consumption. This was calculated using a model based on data from the Pew Research Center that assigned an ideological profile to various news outlets.

RESULTS: The sample consisted of 1757 respondents, with 89.58% (1574/1757) of them choosing to take the COVID-19 vaccine. Those employed part-time and the unemployed were at 1.94 (95% CI 1.15-3.27) and 2.48 (95% CI 1.43-4.39) greater odds of choosing the vaccine than those employed full-time. For every 1-year increase in age, there was a 1.04 (95% CI 1.02-1.06) multiplicative increase in odds of choosing to receive the vaccine. For every 1-point increase in media source score toward more Liberal or Democrat, there was a 1.06 (95% CI 1.04-1.07) multiplicative increase in odds of choosing to take the COVID-19 vaccine. The Likert-type agreement scale showed statistically significant differences (P<.001) between respondents; those who chose the vaccine agreed more strongly on their belief in the safety and efficacy of vaccines, the influence of their personal beliefs, and the encouragement and positive experiences of family and friends. Most respondents rated their personal relationship with their physician to be good, but this factor did not correlate with differences in vaccine decision.

CONCLUSIONS: Although multiple factors are involved, the role of mass media in shaping attitudes toward vaccines cannot be ignored, especially its ability to spread misinformation and foster division. Surprisingly, the effect of one’s personal physician may not weigh as heavily in one’s decision-making process, potentially indicating the need for physicians to alter their communication style, including involvement in social media. In the era of information overload, effective communication is critical in ensuring the dissemination of accurate and reliable information to optimize the vaccination decision-making process.

PMID:37195740 | DOI:10.2196/45417