Clinical Protocols Research Articles

Addressing barriers to implementing and scaling PrEP in carceral settings: Applying insights from implementation science.

Within the United States, individuals experiencing incarceration are at higher risk for HIV acquisition compared to the general population, yet may face additional difficulty engaging in HIV prevention clinical services. HIV pre-exposure prophylaxis (PrEP) is an effective approach to preventing HIV transmission, and the Centers for Disease Control (CDC) recommends that PrEP be offered in carceral settings, particularly during the vulnerable community re-entry period. However, there have been few efforts to scale PrEP in this setting. Based on our experience implementing PrEP in Rhode Island's state carceral system, we have identified potential approaches to overcoming barriers to PrEP use in this unique practice environment by utilizing the implementation research logic model (IRLM). We then evaluated specific implementation determinants and barriers as well as strategies used to overcome those barriers to effectively scale PrEP in this setting. We developed a "toolkit," or 14-step guide, for others in the field to use for implementing PrEP in carceral settings including the development and use of clinical protocols as well as community linkage strategies. Our experiences with barriers in the carceral setting, identifying and leveraging implementation strategies, allowed us to develop a "toolkit" to guide other PrEP implementation projects in carceral settings. We encourage others to scale-out our work to other carceral settings to better reach and engage a group of individuals both at elevated risk for HIV and currently underserved by HIV prevention strategies, including PrEP.

A study method using early dynamic acquisition of [18F]fluorodopa positron emission tomography for the differential diagnosis between progression and radionecrosis of brain metastases after radiotherapy

BackgroundIt is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion’s voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean).ResultsSeven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%.ConclusionThe 18F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.

Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients: The TELESCOPE Randomized Clinical Trial.

Despite its implementation in several countries, there has not been a randomized clinical trial to assess whether telemedicine in intensive care units (ICUs) could improve clinical outcomes of critically ill patients. To determine whether an intervention comprising daily multidisciplinary rounds and monthly audit and feedback meetings performed by a remote board-certified intensivist reduces ICU length of stay (LOS) compared with usual care. A parallel cluster randomized clinical trial with a baseline period in 30 general ICUs in Brazil in which daily multidisciplinary rounds performed by board-certified intensivists were not routinely available. All consecutive adult patients (aged ≥18 years) admitted to the participating ICUs, excluding those admitted due to justice-related issues, were enrolled between June 1, 2019, and April 7, 2021, with last follow-up on July 6, 2021. Remote daily multidisciplinary rounds led by a board-certified intensivist through telemedicine, monthly audit and feedback meetings for discussion of ICU performance indicators, and provision of evidence-based clinical protocols. The primary outcome was ICU LOS at the patient level. Secondary outcomes included ICU efficiency, in-hospital mortality, incidence of central line-associated bloodstream infections, ventilator-associated events, catheter-associated urinary tract infections, ventilator-free days at 28 days, patient-days receiving oral or enteral feeding, patient-days under light sedation, and rate of patients with oxygen saturation values under that of normoxemia, assessed using generalized linear mixed models. Among 17 024 patients (1794 in the baseline period and 15 230 in the intervention period), the mean (SD) age was 61 (18) years, 44.7% were female, the median (IQR) Sequential Organ Failure Assessment score was 6 (2-9), and 45.5% were invasively mechanically ventilated at admission. The median (IQR) time under intervention was 20 (16-21) months. Mean (SD) ICU LOS, adjusted for baseline assessment, did not differ significantly between the tele-critical care and usual care groups (8.1 [10.0] and 7.1 [9.0] days; percentage change, 8.2% [95% CI, -5.4% to 23.8%]; P = .24). Results were similar in sensitivity analyses and prespecified subgroups. There were no statistically significant differences in any other secondary or exploratory outcomes. Daily multidisciplinary rounds conducted by a board-certified intensivist through telemedicine did not reduce ICU LOS in critically ill adult patients. ClinicalTrials.gov Identifier: NCT03920501.

Ultra-High-Resolution Photon-Counting Detector CTA of the Head and Neck: Image Quality Assessment and Vascular Kernel Optimization.

Background: Head and neck CTA requires fine detail evaluation, including characterization of potentially very small vessels and intrastent lumens. Blooming artifacts also hinder evaluation. Objectives: To evaluate image quality of ultra-high-resolution (UHR) photon-counting detector (PCD) CTA of the head and neck and to explore variation of such quality across reconstruction kernels. Methods: This prospective study included patients who underwent clinically indicated head and neck CTA from September 2023 to December 2023. Participants underwent PCD CTA in UHR mode. Reconstructions for each examination included a reference reconstruction (reflecting clinical protocols) using 0.8-mm slice thickness and Bv40 kernel, and six UHR reconstructions using 0.2-mm slice thickness and kernels of varying sharpness (Bv48-Bv80). Quantitative measures were recorded. Two radiologists independently evaluated qualitative measures using Likert scales (1=lowest quality; 5=highest quality). Results: The analysis included 103 participants (mean age, 61.3±13.0 years; 56 male, 48 female). Median vessel sharpness (in HU/mm) was 100.9 for reference reconstruction, and for UHR varied from 110.0 for Bv46 to 121.6 for Bv76 and 134.7 for Bv80. Median right internal carotid artery C2 luminal diameter was 3.8 mm for reference reconstruction, and for UHR increased from 4.1 mm for Bv48 to 4.9 mm for Bv80. For both readers, median overall image quality for reference reconstruction was 3, and for UHR was highest for Bv64 (5); calcified plaque blooming artifact for reference reconstruction was 1, and for UHR was highest for Bv72 (5) and Bv76 (5); stent blooming artifact for reference reconstruction was 1, and for UHR was highest for Bv76 (5) and Bv80 (5); soft-plaque delineation for reference reconstruction was 1, and for UHR was highest for Bv76 (5) or Bv80 (5); small-vessel visualization for reference reconstruction was 1, and for UHR was highest for Bv76 (5) or Bv80 (5). Conclusion: UHR-PCD CTA yielded reduced blooming artifact from calcified plaques or stents, and improved softplaque and small-vessel visualization. These advantages were more pronounced for strongest kernels, although subjective image quality was better for a weaker kernel. Clinical impact: The findings indicate benefits from use of UHR-PCD CTA for head and neck evaluation and may help guide such examinations' kernel selection.

6519 BCG Clinical Trial Programs in Advanced Type 1 Diabetes - 2024 Update

Abstract Disclosure: W.M. Kühtreiber: None. B. Thach: None. H. Hayashi: None. L. Adams: None. N. Hullavarad: None. D.A. Mounier: None. K. Le: None. E. Bulczynski: None. J.L. Dorsey: None. N. Kartsounis: None. J. Braley: None. H. Zheng: None. D.L. Faustman: None. The bacillus Calmette-Guerin (BCG) vaccine, originally developed a century ago to prevent tuberculosis infection, has today advanced in multiple clinical trials for the treatment of the type 1 diabetes (T1D), other forms of autoimmunity and infectious disease. At our institution, over 500 individuals with type 1 diabetes have been enrolled in ongoing BCG clinical protocols to test BCG’s ability to lower HbA1c, reduce insulin requirements and stabilize day-to-day fluctuations in blood sugars; 300 have been treated with BCG. In a completed randomized, placebo-controlled Phase I trial in adults with established T1D, long-term follow up continues to show that HbA1c values are durably lowered for 8+ years after multi-dose BCG treatment. In two open-label clinical trials in adults with juvenile-onset diabetes, a 10-15% reduction of HbA1c was observed after multi-dose BCG treatment. A randomized, double-blinded Phase II trial in adults with longstanding T1D has followed all patients in the BCG-treated (n=100) and placebo groups (n=50) for five years and is pending read-out. The primary outcome of all the trials is HbA1c lowering. Two new, randomized, double-blinded pediatric trials are testing the potential benefits of BCG vaccination with active enrollment ongoing. One is testing BCG in children ages 12 to 18 with more than 2 years since T1D diagnosis. The other is enrolling children ages 8 to 18 with less than 1 year since T1D diagnosis. BCG vaccine therapy may provide a safe and affordable medical intervention in individuals with longstanding T1D and works decades after disease onset by changing glucose metabolism within lymphocytes, independently of the pancreas. Presentation: 6/3/2024

Adaptive designs in clinical trials: a systematic review-part I

BackgroundAdaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community.MethodsPublished studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical s (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein.ResultsOut of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials.ConclusionThis review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials.Study protocol registrationhttps://doi.org/10.1186/s13063-018-2934-7.

A Comparative Effectiveness Study of Speech and Surgical Outcomes: Study Overview.

To provide an overview of the Cleft Outcomes Research NETwork (CORNET) and the CORNET Speech and Surgery study. The study is (1) comparing speech outcomes and fistula rate between two common palate repair techniques, straight-line closure with intra-velar veloplasty (IVVP) and Furlow Double-Opposing Z-palatoplasty (Furlow Z-plasty); (2) summarizing practice variation in the utilization of early intervention speech-language (EI-SL) services; and (3) exploring the association between EI-SL services and speech outcomes. Prospective, longitudinal, observational, comparative effectiveness, multi-center. Twenty sites across the United States. One thousand two hundred forty-seven children with cleft palate with or without cleft lip (CP ± L). Children with submucous cleft palate or bilateral sensorineural severe to profound hearing loss were excluded from participation. Straight-line closure with IVVP or Furlow Z-plasty based on each surgeon's standard clinical protocol. The primary study outcome is perceptual ratings of hypernasality judged from speech samples collected at 3 years of age. Secondary outcomes are fistula rate, measures of speech production, and quality of life. The statistical analyses will include generalized estimating equations with propensity score weighting to address potential confounders. Recruitment was completed in February 2023; 80% of children have been retained to date. Five hundred sixty two children have completed their final 3-year speech assessment. Final study activities will end in early 2025. This study addresses long-standing questions related to the effectiveness of the two most common palatoplasty approaches and describes CORNET which provides an infrastructure that will streamline future studies in all areas of cleft care.

Calcium carbonate supplementation for the prevention of preeclampsia in high-risk pregnant women: a randomized clinical trial protocol

BackgroundPreeclampsia (PE) is a significant cause of maternal mortality worldwide, affecting 2% to 8% of pregnancies. The World Health Organization recommends the use of low-dose acetylsalicylic acid (100 mg of aspirin) and 1.5 to 2 g of calcium carbonate during pregnancy to prevent PE. However, robust evidence supporting the efficacy of calcium supplementation is still needed. This study aims to assess the efficacy of calcium carbonate in preventing preeclampsia in high-risk pregnant women.MethodsA triple-blind, randomized clinical trial will be conducted at an outpatient clinic in Brazil between May 2024 and March 2026. Pregnant women at high risk of developing preeclampsia and with low dietary calcium intake will be randomly assigned to one of three groups: one group will receive calcium carbonate capsules (commercially available in Brazil) along with 100 mg of aspirin; the second group will receive calcium carbonate derived from Crassostrea sp. along with 100 mg of aspirin; and the control group will receive a placebo alongside 100 mg of aspirin. The primary outcome is the diagnosis of preeclampsia during pregnancy, while secondary outcomes evaluate maternal and fetal health indicators.DiscussionThis trial seeks to generate evidence on the efficacy of calcium carbonate in preeclampsia prevention, with a focus on comparing industrial calcium carbonate with calcium carbonate sourced from Crassostrea sp., a more sustainable alternative.Trial registrationThe study was approved by the Research Ethics Committee of the Federal University of Sergipe and registered in the Brazilian Registry of Clinical Trials (ReBEC), under the ID RBR-7hqhj3y. Registered on November 16, 2023.

A dynamic approach for MR T2-weighted pelvic imaging.

T2-weighted 2D fast spin echo sequence serves as the standard sequence in
clinical pelvic MR imaging protocols. However, motion artifacts and blurring caused
by peristalsis present significant challenges. Patient preparation such as administering
antiperistaltic agents is often required before examination to reduce artifacts, which
discomfort the patients. This work introduce a novel dynamic approach for T2
weighted pelvic imaging to address peristalsis-induced motion issue without any patient
preparation.
Approach: A rapid dynamic data acquisition strategy with complementary sampling
trajectory is designed to enable highly undersampled motion-resistant data sampling,
and an unrolling method based on deep equilibrium model is leveraged to reconstruct
images from the dynamic sampled k-space data. Moreover, the fix-point convergence of
the equilibrium model ensures the stability of the reconstruction. The high acceleration
factor in each temporal phase, which is much higher than that in traditional static
imaging, has the potential to effectively freeze pelvic motion, thereby transforming
the imaging problem from conventional motion prevention or removal to motion
reconstruction.
Main results: Experiments on both retrospective and prospective data have
demonstrated the superior performance of the proposed dynamic approach in reducing
motion artifacts and accurately depicting structural details compared to standard static
imaging.
Significance: The proposed dynamic approach effectively captures motion states
through dynamic data acquisition and deep learning-based reconstruction, addressing
motion-related challenges in pelvic imaging.

HLA-G neo-expression modifies genetic programs governing tumor cell lines

The development of immunotherapies has proved to be clinically encouraging to re-establish the immune function modified by the expression of immune inhibitory molecules in tumors. However, there are still patients with poor survival rates following treatment. The elucidation of molecular mechanisms triggered by the neo-expression of particular IC in tumors would constitute a major step toward better understanding tumor evolution and would help to design future clinical protocols. To this end, we investigate the modifications triggered by the neo-expression of the immune checkpoints HLA-G in ccRCC tumor cells. We demonstrate, for the first time, that HLA-G modifies key genes implicated mainly in tumor development, angiogenesis, calcium flow and mitochondria dynamics. The involvement of HLA-G on the expression of genes belonging to these pathways such as ADAM-12, NCAM1 and NRP1 was confirmed by the CRISPR/Cas9-mediated edition of HLA-G. The data reveal multifaceted roles of HLA-G in tumor cells which are far beyond the well-known function of HLA-G in the immune anti-tumor response. This warrants further investigation of HLA-G and these new partners in tumors of different origin so as to propose future new treatments to improve health patient’s outcome.

Real-time automated quality control for quantitative MRI.

This work presents an automated quality control (QC) system within quantitative MRI (qMRI) workflows. By leveraging the ISMRM/NIST quantitative MRI system phantom, we establish an open-source pipeline for rapid, repeatable, and accurate validation and stability tracking of sequence quantification performance across diverse clinical settings. A microservice-based QC system for automated vial segmentation from quantitative maps was developed and tested across various MRF acquisition and protocol designs, with reports generated and returned to the scanner in real time. The system demonstrated consistent and repeatable value segmentation and reporting, successfully extracted all 252 T1 and T2 vial samples tested. Values extracted from the same sequence were found to be repeatable with 0.09% ± 1.23% and -0.26% ± 2.68% intersession error, respectively. By providing real-time quantification performance assessment, this easily deployable automated QC approach streamlines sequence validation and long-term performance monitoring, vital for the broader acceptance of qMRI as a standard component of clinical protocols.

Matrix Support: interface between Specialty Dental Centers and primary oral health care in Brazil

BackgroundMatrix Support (MS) is a strategy that can be used to improve integration between Primary Health Care (PHC) and other levels of care.ObjectiveThe aim of this study was to investigate the association between MS carried out in Brazilian Dental Specialty Centers (CEOs) (secondary level of oral health care) and aspects of the integrated work process with PHC, as well as contextual variables.MethodsA quantitative cross-sectional study was conducted using data from the Program for Quality Improvement and Access to CEOs (PMAQ-CEO). Secondary data from the External Evaluation of the second cycle of PMAQ-CEO were analyzed, including contextual variables obtained from sources such as the Unified Health System (SUS) and official research institutions. Descriptive analyses were performed, and four multiple models were adjusted to investigate the association between the variables.ResultsThe results showed that about half of the CEOs did not carry out therapeutic projects developed with the oral health teams of PHC. It was found that the lack of therapeutic projects developed with the teams was associated with the lack of discussion of complex cases by the team, lack of discussion of individual therapeutic project, absence of joint continuing education activities, lack of construction and discussion of clinical protocols, and lack of belief in the importance of planning and periodic evaluation. The results suggest that the articulation between PHC and secondary oral health care still presents weaknesses within the scope of SUS. Comprehensive care needs to be strengthened, requiring greater intervention from management.ConclusionIt was concluded that the individual factors of CEOs, related to the work process, have a greater influence on the lack of integration with oral health teams of PHC, compared to the contextual variables of municipalities.

Investigating different dimensions of women’s childbirth experiences and its predictors among postnatal women: findings from a cross sectional study

Background and aimsChildbirth experience is an event in a woman’s life with short- and long-term effects on her physical and mental health. This study aimed to investigate different dimensions of women’s childbirth experiences and its predictors.MethodsThis cross-sectional study was conducted on 430 postnatal women with vaginal delivery in 2021 in Northern Iran. Data were collected using the Iranian women’s childbirth experience questionnaire (IWCEQ) and demographic and pregnancy-related characteristics questionnaire. Principal component analysis using Amos 24 and backward multiple linear regression using SPSS 22 were employed to analyze the data.ResultsThe mean score of childbirth experiences was 48.48 ± 19.09% out of 100 (95% CI: 46.68–50.28). The Principal Component Analysis revealed that the preparation (β = 0.84), positive perception (β = 0.78), and fear dimensions (β= -0.72) were the most important dimensions of women’s childbirth experiences. Moreover, education (B = -7.14, p = 0.001), spouse’s education (B = 7.40, p = 0.001), history of previous childbirth (B = 4.88, p = 0.001), obstetric problems of previous childbirth (B = − 7.73, p = 0.038), mother’s preferred type of delivery (B = 9.34, p = 0.001), the simultaneous delivery of another baby in the delivery room (B = -3.39, p = 0.017), and birth weight (B = -5.79, p = 0.005) explained 40% of the variance of the childbirth experience score.ConclusionChildbirth experience is a unique experience that influenced by positive and negative issues. More studies to identify related factors to dimensions of childbirth experience may have some insights for developing national and local- level health policies and clinical protocols.

The effect of intra- and inter-fractional motion on target coverage and margins in proton therapy for uveal melanoma.


This study aims to assess the effective lateral margin requirements for target coverage in ocular proton therapy (OPT), considering the unique challenges posed by eye motion and hypofractionation. It specifically addresses the previously unaccounted-for uncertainty contribution of intra-fractional motion, in conjunction with setup uncertainties, on dosimetric determination of lateral margin requirements. 


Method: 
The methodology integrates dose calculations from the in-house developed treatment planning system OCULARIS with measured intra-fractional motion, patient models from EyePlan and Monte Carlo (MC) sampling of setup uncertainties. The study is conducted on 16 uveal melanoma patients previously treated in the OPTIS2 treatment room at the Paul Scherrer Institute (PSI).


Results:
The retrospective simulation analysis highlights a significant impact of non-systematic factors on lateral margin requirements in OPT. Simulations indicate that reducing the 2.5 mm clinical lateral margin, represented by a 2.1 mm margin in this work, would have resulted in inadequate target coverage for two patients, revealing a greater impact of non-systematic factors on lateral margin requirements. 


Conclusions:
This work characterizes intra-fractional motion in 16 OPT patients and identifies limitations of clinical margin selection protocols for OPT applications. A novel framework was introduced to assess margin sufficiency for target coverage. The findings suggest that prior research underestimated non-systematic factors and overestimated systematic contributions to lateral margin components. This re-evaluation highlights the critical need to prioritize the management of non-systematic uncertainty contributions in OPT.

Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol

BackgroundPost-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation.MethodsThis 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex.DiscussionOur hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach.Trial registrationChictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Exploring the Intersection of Blood Transfusion and Same-Day Computed Tomography Imaging: An Overview of Clinical Risks and Practices

The use of transfusions, whether involving whole blood or specific blood components, is essential for managing various clinical conditions. Many cases are acute, often requiring post-transfusion imaging evaluation. While there is no absolute contraindication for chest imaging following blood transfusion, it should be approached cautiously. We conducted a comprehensive search across multiple databases and registries. Research studies were limited to full-text original articles, reviews, and case reports published in English, involved human subjects, and focused on the interplay between blood transfusions and contrast-enhanced imaging. Scientific analyses were excluded if they did not focus on transfusion practices in the context of imaging or failed to address issues such as hemoglobin thresholds, transfusion reactions, or the clinical implications of contrast agents. Our research fills this gap by emphasizing the need for a cautious, multidisciplinary approach to post-transfusion computed tomography (CT) scans, especially in the presence of contrast agents. This study calls for increased awareness of the heightened risk of complications, such as autoimmune hemolysis, when both procedures are performed together. New insights from our research recommend individualized assessments and close patient monitoring when combining these interventions. Nevertheless, patients need to be hemodynamically and clinically stable before undergoing CT. Discussions. Symptoms that develop within the first 24 h post-transfusion are classified as secondary post-transfusion reactions unless proven otherwise. The prevalence of side effects from same-day CT scans and blood transfusions is challenging to quantify, as few studies focus on this combination. Transfusions and contrast-enhanced CT scans share overlapping adverse reactions and carry significant risks. Acute hemolytic red blood cell transfusion reactions are among the most frequent side effects, with a prevalence of 1:12,000–38,000. Conclusion. Our study contributes new insights to the literature by filling the gap concerning the interplay between transfusions and contrast media, paving the way for more informed clinical protocols to enhance patient safety.

Paucity of Published Data and Protocols for Hypoglycemia Management in Long-term Care.

Background: Older people with diabetes are at high risk for hypoglycemia. Implementing a hypoglycemia treatment protocol in long-term care (LTC) settings may positively affect patient-related outcomes and health care resource utilization and costs. Anecdotal experience indicates little has been studied and published regarding this clinical practice. Objective: To identify hypoglycemia treatment protocols established for LTC settings and assess their effects on patient-related outcomes and health care resource use. Data Sources: The authors performed a systematic literature search of English-language articles and abstracts published between January 1, 2003 (PubMed), or 2018 (Google Scholar) and May 10, 2023. Search terms were "hypoglycemia," "diabetes mellitus," "longterm care," "nursing facilities," "assisted living facilities," "geriatrics," "elderly," "aged," "disabled," "disease management," "evidence-based medicine," "clinical protocols," "guideline," "glucagon," and/or "blood glucose." Included were publications with hypoglycemia treatment and management protocols or hypoglycemia-specific recommendations for LTC settings. DATA SYNTHESIS: The authors identified 405 articles and abstracts, removed 36 duplicates, screened 369 titles/ abstracts, and analyzed the full text for 93. Five met the inclusion criteria. Two originated from the American Diabetes Association: 2016 position statement regarding the management of diabetes in LTC and skilled nursing facilities, and 2023 standard-of-care guideline for managing older people with diabetes. One included the results after implementing an overall diabetes clinical care management algorithm in LTC facilities. A 2020 abstract and 2019 article were the only 2 publications involving specific hypoglycemia treatment protocols in LTC settings. Conclusion: This systematic literature search identified lack of published hypoglycemia treatment protocols in LTC settings and their effects on patient outcomes.

Blue-button: A tool for institution-agnostic, EHR-integrated regional clinical trial matching.

65 Background: Research indicates that most people with cancer are willing to enroll in clinical trials when offered the chance, but only 7% actually participate in cancer treatment trials. Barriers to screening and enrollment include time and effort for providers to screen patients for trials, and lack of awareness of available regional trials. Stakeholders recommended creation of free, automated screening tools and processes integrated into provider workflows, directly interfacing with site electronic health records (EHRs), that would search for regional trial eligibility. The need for such tools was independently identified in a large national survey of oncology providers. Methods: The Blue-button tool was developed to automatically identify relevant, regional clinical trials. A collaboration between ACS CAN and MITRE, a not-for-profit organization working in the public interest, created the tool’s functionality. Clinical workflow and research protocol were developed in collaboration with University of Texas Southwestern Simmons Comprehensive Cancer Center. This SMART-on-FHIR application works within existing EHR systems by automatically extracting and sending limited, deidentified patient data elements to third-party trial matching services via the FHIR mCODE standard, a core set of non-proprietary, open-source structured data elements that establishes minimum standards for the structure and content of oncology data in health records. Potential trial matches within a specified radius of the practice are returned in a standard format using the FHIR Research Study resource. Results: Blue-button extracts limited patient data from EHR and provides it in an interface allowing users to update data before sending to trial matching services. Only non-identifiable information is sent to the external clinical trial matching services, which then return prescreen trial matches for manual review to confirm patient eligibility. Thus, with a few clicks in a medical record, the tool quickly identifies comprehensive trial availability within a specified distance of the patient’s location. When used by providers, Blue-button reduces the manual burden that often prevents consideration of clinical trials and identifies regional opportunities beyond the treating institution. Conclusions: Successful feasibility testing demonstrated the effectiveness of automated regional trial screening as a model. We have launched a clinical trial at two sites to assess the effectiveness of the Blue-button tool with patients in healthcare settings. We expect patient enrollment to continue through part or all of 2025. This trial of the Blue-button tool will provide additional information on provider accessibility and uptake and will demonstrate whether EHR-integrated regional trial screening leads to increased opportunities and enrollment in cancer clinical trials. Clinical trial information: NCT05885880 .

Neurologic Care for Transgender and Gender-Diverse People: A Review of Current Evidence and Clinical Implications.

To summarize the literature on neurologic care for transgender and gender-diverse (TGD) people and provide implications for clinical practice. There are limited data on the frequency and management of neurologic conditions among TGD people. TGD people have a higher prevalence of various neurologic conditions compared with cisgender or general population cohorts, including migraine, subjective cognitive decline, sleep disturbances, functional disorders, and cerebrovascular disease. Gender-affirming hormone therapy interacts with commonly prescribed neurologic medications and increases stroke risk among transfeminine people. Sex hormones and sex chromosomes may play a role in neurodegeneration and disability progression in neuroimmunologic diseases. Clitoral reduction surgeries on intersex children can cause neurologic disability and sexual dysfunction in adulthood. Socioeconomic disparities among TGD people contribute to health care barriers. Neurologists should consider the unique experiences and health care needs of TGD people in their clinical practice and research protocols.

Behavioral exposure for interoceptive tolerance (BE-FIT): A stage II randomized clinical trial protocol

BackgroundExercise anxiety is a novel mechanism related to non-adherence to exercise and lifestyle physical activity. We developed a cognitive-behavioral treatment, Behavioral Exposure For Interoceptive Tolerance (BE-FIT), which is a manualized, values-based exposure intervention developed to target exercise anxiety that is delivered as a supplement to outpatient cardiac rehabilitation (CR). MethodWe describe a Stage II randomized controlled trial (RCT) that is designed to test BE-FIT, compared to a Health Education Control (HEC) intervention on exercise and physical activity outcomes at end-of-treatment (EOT) and follow-ups (Weeks 12, 18, and 24), and evaluate mechanisms of change (i.e., reductions in exercise anxiety). Adults (N = 146) who are ≥40 years of age, cleared for outpatient exercise-based CR, low active and have elevated exercise anxiety will be recruited. The primary study hypothesis is that BE-FIT compared to HEC will result in higher levels of overall exercise and lifestyle physical activity at EOT and follow-ups. The second hypothesis is that BE-FIT vs HEC will produce greater reductions in exercise anxiety at EOT and Week 12. The third hypothesis is that reductions in exercise anxiety at EOT and Weeks 12 will mediate the effect of BE-FIT on activity outcomes at Weeks 18 and 24. DiscussionWe expect the results of this study will produce knowledge regarding BE-FIT's efficacy and mechanisms of action. Our goal is to better understand “how and why” the intervention is (or is not) effective and for whom, and increase collective knowledge and reproducibility of behavior change research.