Impact of a Tranexamic Acid Dosing Practice Guideline in Reducing Blood Product Administration in Pediatric Scoliosis Surgery.

Pediatric patients who undergo spinal corrective surgery often require multiple blood product transfusions. The use of antifibrinolytics, especially tranexamic acid (TXA), to mitigate intraoperative blood loss has increased in popularity. The goal of this quality improvement project was to evaluate provider compliance with a TXA dosing protocol during pediatric corrective spine procedures. A retrospective chart review was conducted to compare pre- and postimplementation data on cell saver and packed red blood cell (PRBC) administration and dose of antifibrinolytic administered. A total of 486 patients (68% idiopathic and 32% neuromuscular) were evaluated over a 9-year period. Following implementation of the protocol, patients of idiopathic origin experienced a 20% reduction in cell saver administration, a 10% reduction in PRBC administration, and a 37% increase in provider compliance with the dosing protocol. Patients of neuromuscular origin experienced a 53% increase in provider compliance with the recommended TXA dosing protocol; however, this patient population did not experience a statistically significant reduction in transfusion requirements. Implementation of an antifibrinolytic protocol can facilitate compliance with recommended TXA dosing parameters and potentially decrease intraoperative blood loss, reducing blood product transfusion requirements.

Pathways to maternal health inequities: Structural racism, sleep, and physiological stress.

Racial inequities in health are vast and well-documented, particularly regarding maternal and infant health. Sleep health, including but not limited to duration and quality, is central to overall health and well-being. However, research has not adequately addressed how racism embedded in structures and systems, in addition to individual experiences, may affect maternal health by impacting sleep. In this critical review, we aim to 1) synthesize findings, emphasizing collaborative studies within our group, 2) highlight gaps in knowledge, and 3) propose a theoretical framework and methodological approach for moving the field forward. Specifically, we focus on findings and future directions linking perinatal sleep, cardiovascular and immune function, and racial disparities in maternal health. Because too few studies look beyond individual-level determinants of sleep deficiencies among Black Americans, we assert a critical need for research that bridges multiple levels of analysis (e.g., individual, community, society) and provides recommendations for specific health parameters that researchers in this area can target. Although the need to understand and address perinatal health disparities is clear, the goal of identifying multilevel mechanisms underlying how racism in one's environment and daily life may interact to affect health extends far beyond pregnancy research.

Opioid Misuse by Adults with Chronic Pain: The Impact of Illness and Medication Beliefs.

BACKGROUND: Why do some adults with chronic pain misuse their prescription opioids when others do not? Based on the extended Common-Sense Model, the study evaluated whether adults' beliefs about their pain have an indirect effect on risk of opioid misuse through beliefs about opioids when controlling for depression. METHODS: The sample included 297 adult participants in the U.S. recruited from Prolific, an online crowdsourcing website. Study measures included the Illness Perception Questionnaire-Revised (IPQ-R; protective and threat-related illness beliefs about chronic pain), the Beliefs about Medicines Questionnaire-Specific subscale (BMQ-Specific; concern and necessity medication beliefs about prescription opioids), and the Current Opioid Misuse Measure (COMM; risk of current opioid misuse). This cross-sectional parallel mediation analysis was conducted using MPlus. RESULTS: After controlling for depression, the indirect effect of protective illness beliefs on opioid misuse risk through concern medication beliefs (b = -0.01, 95% CI (-0. 038, -0.001), and the indirect effect of threat-related illness beliefs on opioid misuse risk through necessity medication beliefs (b = 0.02, 95% CI (0.004, 0.036) were significant. The full model explained 35% of the variance of opioid misuse risk. CONCLUSIONS: Adults with chronic pain with stronger protective beliefs about pain were less likely to have concerns about their opioids and were at lower risk for opioid misuse, while those with greater threat-related beliefs about pain were more likely to believe that their opioids were necessary and be at greater risk for opioid misuse. Results have implications for medical and mental health providers and future research.

Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myeloma-reactive CD8+ T-cells are shared between blood and marrow.

Not available.

Improving TRansitions ANd outcomeS for heart FailurE patients in home health CaRe (I-TRANSFER-HF): a type 1 hybrid effectiveness-implementation trial: study protocol.

BACKGROUND: Some of the most promising strategies to reduce hospital readmissions in heart failure (HF) is through the timely receipt of home health care (HHC), delivered by Medicare-certified home health agencies (HHAs), and outpatient medical follow-up after hospital discharge. Yet national data show that only 12% of Medicare beneficiaries receive these evidence-based practices, representing an implementation gap. To advance the science and improve outcomes in HF, we will test the effectiveness and implementation of an intervention called Improving TRansitions ANd OutcomeS for Heart FailurE Patients in Home Health CaRe (I-TRANSFER-HF), comprised of early and intensive HHC nurse visits combined with an early outpatient medical visit post-discharge, among HF patients receiving HHC. METHODS: This study will use a Hybrid Type 1, stepped wedge randomized trial design, to test the effectiveness and implementation of I-TRANSFER-HF in partnership with four geographically diverse dyads of hospitals and HHAs ("hospital-HHA" dyads) across the US. Aim 1 will test the effectiveness of I-TRANSFER-HF to reduce 30-day readmissions (primary outcome) and ED visits (secondary outcome), and increase days at home (secondary outcome) among HF patients who receive timely follow-up compared to usual care. Hospital-HHA dyads will be randomized to cross over from a baseline period of no intervention to the intervention in a randomized sequential order. Medicare claims data from each dyad and from comparison dyads selected within the national dataset will be used to ascertain outcomes. Hypotheses will be tested with generalized mixed models. Aim 2 will assess the determinants of I-TRANSFER-HF's implementation using a mixed-methods approach and is guided by the Consolidated Framework for Implementation Research 2.0 (CFIR 2.0). Qualitative interviews will be conducted with key stakeholders across the hospital-HHA dyads to assess acceptability, barriers, and facilitators of implementation; feasibility and process measures will be assessed with Medicare claims data. DISCUSSION: As the first pragmatic trial of promoting timely HHC and outpatient follow-up in HF, this study has the potential to dramatically improve care and outcomes for HF patients and produce novel insights for the implementation of HHC nationally. TRIAL REGISTRATION: This trial has been registered on ClinicalTrials.Gov (#NCT06118983). Registered on 10/31/2023, https://clinicaltrials.gov/study/NCT06118983?id=NCT06118983&rank=1 .

Use of multiple micronutrient supplementation integrated into routine antenatal care: A discussion of research priorities.

Optimal maternal nutrition, including adequate intake and status of essential micronutrients, is important for the health of women and developing infants. Currently, the World Health Organization (WHO) Antenatal care recommendations for a positive pregnancy experience recommend daily iron and folic acid (IFA) supplementation as the standard of care. The use of multiple micronutrient supplements (MMSs) is recommended in the context of rigorous research as more evidence was needed regarding the impact of switching from IFA supplements to MMS, including evaluation of critical clinical maternal and perinatal outcomes, acceptability, feasibility, sustainability, equity and cost-effectiveness. WHO convened a technical consultation of key stakeholders to discuss research priorities with the objective of providing guidance and clarity to donors, implementers and researchers about this recommendation. The overarching principles of the research agenda include the use of clinical indicators and impact measures that are applicable across studies and settings and the inclusion of outcomes that are important to women. Future studies should consider using standardized protocols based on current best practices to measure critical outcomes such as gestational age (GA) and birthweight (BW) in studies. As GA and BW are influenced by multiple factors, more research is needed to understand the biological impact pathways, and how initiation and considerations for timing of MMS influence these outcomes. A set of core clinical indicators was agreed upon during the technical consultation. For implementation research, the Evidence-to-Decision framework was used as a resource for discussing components of implementation research. The implementation research questions, key indicators and performance measures will depend on country-specific context and bottlenecks that require further research and improved solutions to enable the successful implementation of iron-containing supplements.

Covalent Labeling Automated Data Analysis Platform for High Throughput in R (coADAPTr): A Proteome-Wide Data Analysis Platform for Covalent Labeling Experiments.

Covalent labeling methods coupled to mass spectrometry have emerged in recent years for studying the higher order structure of proteins. Quantifying the extent of modification of proteins in multiple states (i.e., ligand free vs ligand-bound) can provide information on protein interaction sites and regions of conformational change. Though there are several software platforms that are used to quantify the extent of modification, the process can still be time-consuming, particularly for proteome-wide studies. Here, we present an open-source software for quantitation called Covalent labeling Automated Data Analysis Platform for high Throughput in R (coADAPTr). coADAPTr tackles the need for more efficient data analysis in covalent labeling mass spectrometry for techniques such as hydroxyl radical protein footprinting (HRPF). Traditional methods like Excel's Power Pivot (PP) are cumbersome and time-intensive, posing challenges for large-scale analyses. coADAPTr simplifies analysis by mimicking the functions used in the previous quantitation platform using PowerPivot in Microsoft Excel but with fewer steps, offering proteome-wide insights with enhanced graphical interpretations. Several features have been added to improve the fidelity and throughput compared to those of PowerPivot. These include filters to remove any duplicate data and the use of the arithmetic mean rather than the geometric mean for quantitation of the extent of modification. Validation studies confirm coADAPTr's accuracy and efficiency while processing data up to 200 times faster than conventional methods. Its open-source design and user-friendly interface make it accessible for researchers exploring intricate biological phenomena via HRPF and other covalent labeling MS methods. coADAPTr marks a significant leap in structural proteomics, providing a versatile and efficient platform for data interpretation. Its potential to transform the field lies in its seamless handling of proteome-wide data analyses, empowering researchers with a robust tool for deciphering complex structural biology data.

The Addis Ababa toxicology curriculum project: educational needs assessment for the toxicology modules of an emergency medicine training program.

BACKGROUND: The Toronto Addis Ababa Academic Collaboration in Emergency Medicine (TAAAC-EM) is a bi-institutional partnership between the University of Toronto (UofT) and Addis Ababa University (AAU) focused on addressing the need for emergency medicine (EM) postgraduate training and care in Ethiopia. Toxicology is a key competency in EM. EM physicians are often the first and sole clinicians to identify and treat patients presenting with a wide range of intoxications. The goal of this project was to conduct an educational needs assessment to inform the development of a context-specific toxicology curriculum for the AAU EM training program. METHODS: Our needs assessment employed a survey (available electronically and in paper format) and face-to-face interviews conducted with Ethiopian EM faculty (all graduates of the AAU EM residency training program) and current AAU EM residents. The survey was distributed in October 2018 and the interviews were conducted in November 2018. RESULTS: Of the 63 surveys distributed, we received 17 complete responses and completed 11 interviews with AAU EM faculty and residents. The survey conducted on toxicology training highlighted overall satisfaction with current training, with thematic analysis revealing key areas for growth. System-related themes focused on resource availability, healthcare access, and public health education. Provider-related themes emphasized the need for context-specific training, including common local toxins, and for advanced toxicology training such as poison center rotations. Patient-related themes centered on specific toxicological presentations in Ethiopia, highlighting the importance of public health advocacy, education on safe handling, and governmental regulation of toxic substances. Both survey and interview data highlighted challenges stemming from inconsistent availability of resources and underscored the need for tailored education to manage poisoned patients with locally available resources. CONCLUSIONS: Our findings indicate the need to focus on the most prevalent local toxicological presentations and practical management challenges in local contexts, including resource limitations and delayed presentations. Moreover, it emphasizes the importance of public health initiatives such as regulation of the sale and promotion of safe handling of toxic substances to mitigate toxicological risks. These findings are likely relevant to other resource-constrained settings outside of Ethiopia.

[Clinical Pathway for Suicide Risk Screening in Adult Primary Care Settings:Special Recommendations]. / Klinikai útvonal az öngyilkossági kockázat szurésére a felnott alapellátásban: Speciális ajánlások.

Suicide is a serious public health concern. On average, 80% of suicide decedents had contact with primary care within one year of their suicide. This and other research underscore the importance of screening for suicide risk within primary care settings, and implementation of suicide risk screening is already underway in many practices. However, while primary care practices may be familiar with screening for other mental health concerns (e.g., depression), many feel uncomfortable or unprepared for suicide risk screening. To meet the increasing demand for evidence-based suicide-risk screening guidance, we provide a clinical pathway for adult primary care practices (to include family medicine, internal medicine, women's health). The pathway was developed by experts with research, clinical expertise and experience in suicide risk screening and primary care. We also provide detailed guidance to aid primary care practices in their decisions about how to implement the clinical pathway.

Fracture Risk Prediction Using the Fracture Risk Assessment Tool in Individuals With Cancer.

Importance: The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain. Objective: To determine the performance of FRAX for predicting incident fractures in individuals with cancer. Design, Setting, and Participants: This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023. Main Outcomes and Measures: FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry. Results: This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P < .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures. Conclusions and Relevance: In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.

Medication errors and mitigation strategies in obstetric anesthesia.

PURPOSE OF REVIEW: Medication administration errors represent a significant yet preventable cause of patient harm in the peripartum period. Implementation of best practices contained in this manuscript can significantly reduce medication errors and associated patient harm. RECENT FINDINGS: Cases of medication errors involving unintended intrathecal administration of tranexamic acid highlight the need to improve medication safety in peripartum patients and obstetric anesthesia. SUMMARY: In obstetric anesthesia, medication errors can include wrong medication, dose, route, time, patient, or infusion setting. These errors are often underreported, have the potential to be catastrophic, and most can be prevented. Implementation of various types of best practice cost effective mitigation strategies include recommendations to improve drug labeling, optimize storage, determine correct medication prior to administration, use non-Luer epidural and intravenous connection ports, follow patient monitoring guidelines, use smart pumps and protocols for all infusions, disseminate medication safety educational material, and optimize staffing models. Vigilance in patient care and implementation of improved patient safety measures are urgently needed to decrease harm to mothers and newborns worldwide.

The impact of cohort inclusion/exclusion criteria on pregnancy weight gain chart percentiles.

Pregnancy weight gain standards are charts describing percentiles of weight gain among participants with no risk factors that could adversely affect weight gain. This detailed information is burdensome to collect. We investigated the extent to which exclusion of various pre-pregnancy, pregnancy and postpartum factors impacted the values of pregnancy weight gain percentiles. We examined pregnancy weight gain (kg) among 3178 participants of the US nuMoM2b-Heart Health Study (HHS). We identified five groups of potential exclusion criteria for pregnancy weight gain standards: socio-economic characteristics (group 1), maternal morbidities (group 2), lifestyle/behaviour factors (group 3), adverse neonatal outcomes (group 4) and longer-term adverse outcomes (group 5). We established the impact of different exclusion criteria by comparing the median, 25th and 75th percentiles of weight gain in the full cohort with the values after applying each of the five exclusion criteria groups. Differences > 0·75 kg were considered meaningful. Excluding participants with group 1, 2, 3 or 4 exclusion criteria had no impact on the 25th, median or 75th percentiles of pregnancy weight gain. Percentiles were only meaningfully different after excluding participants in group 5 (longer-term adverse outcomes), which shifted the upper end of the weight gain distribution to lower values (e.g. 75th percentile decreased from 19·6 kg to 17·8 kg). This shift was due to exclusion of participants with excess postpartum weight retention > 5 kg or > 10 kg. Except for excess postpartum weight retention, most potential exclusion criteria for pregnancy weight gain standards did not meaningfully impact chart percentiles.

Marked variation in disease acuity and outcomes on the liver transplant waiting list by sociodemographic characteristics.

Understanding the association of social determinants of health (SDOH) with liver transplant listing and wait list outcomes can inform healthcare policy and interventions aimed at improving access to care. We analyzed the Scientific Registry of Transplant Recipients database merged with the Social Deprivation Index (SDI) to evaluate if area of residence is associated with Model for End-Stage Liver Disease incorporating sodium (MELD-NA) at time of wait list placement and outcomes following wait listing, and if this varied based on sociodemographic variables. Compared to candidates residing in areas of low SDI), those residing in areas of high SDI (most socioeconomic disadvantage) had 11% higher adjusted likelihood [aOR (95% CI)=1.11(CI 1.05,1.17)] of being listed for transplant with a MELD-NA score ≥30; this was not statistically significant when also adjusted for race/ethnicity [aOR=1.02(0.97,1.08)]. When stratified by race/ethnicity, residing in an area of high SDI was associated with a MELD-NA score ≥30 at time of wait listing among Hispanic White candidates (aOR=1.24, 95% CI: 1.04, 1.49). Candidates residing in areas of high SDI had 8% lower chance [aHR=0.92 (0.88,0.96)] of undergoing a liver transplant, 6% higher risk of death [aHR=1.06(1.002,1.13)], and 20% higher risk [aHR=1.20(1.13,1.28)] of removal on the wait list independent of race, ethnicity, insurance status, or sex. In the US, residence in areas of high socioeconomic disadvantage is significantly associated with higher MELD-NA at the time of wait listing among Hispanic White candidates. In addition, residence in areas of high socioeconomic disadvantage was associated with a higher risk of death or removal from the wait list and lower chances of receiving a liver transplant after wait list placement, particularly among Non-Hispanic White candidates and older candidates.

Shell-by-Shell functionalized nanoparticles as radiosensitizers and radioprotectors in radiation therapy of cancer cells and tumor spheroids.

Shell-by-Shell (SbS)-functionalized NPs can be tailor-made by combining a metal oxide NP core of choice with any desired phosphonic acids and amphiphiles as 1st or 2nd ligand shell building blocks. The complementary composition of such highly hierarchical structures makes them interesting candidates for various biomedical applications, as certain active ingredients can be incorporated into the structure. Here, we used TiO2 and CoFe2O4 NPs as drug delivery tools and coated them with a hexadecylphosphonic acid and with hexadecyl ammonium phenolates (caffeate, p-coumarate, ferulate), that possess anticancer as well as antioxidant properties. These architectures were then incubated in 2D and 3D cell cultures of non-tumorigenic and tumorigenic breast cells and irradiated to study their anticancer effect. It was found that both, the functionalized TiO2 and CoFe2O4 NPs acted as strong protective agents in non-tumorigenic spheroids. In contrast, the functionalized CoFe2O4 NPs induce a higher damage in irradiated tumor spheroids compared to the functionalized TiO2 NPs. CoFe3O4 NPs act additionally as radiosensitizing agents to the tumor spheroids. The radio-enhancement of the CoFe2O4 NPs is due to the generation of highly toxic hydroxyl radicals during X-ray irradiation. The irradiation exposed the CoFe2O4 surface, releasing the anticancer drugs into the cytoplasm and making the surface Co2+ ions accessible. These surface ions catalyze the Fenton reaction. This combination of radiosensitizer and anticancer drug delivery proved to be a very effective nanotherapeutic in 2D and 3D cell cultures of breast cancer cells.

The inaccessible road to science for people with disabilities.

This article examines the contributions of disabled scientists and the barriers they face, including systemic ableism and lack of inclusivity. It offers recommendations to foster an inclusive STEM environment, underscoring the importance of supporting disabled scientists to boost innovation and equity.

Construction of Whole Cell Bacterial Biosensors as an Alternative Environmental Monitoring Technology to Detect Naphthenic Acids in Oil Sands Process-Affected Water.

After extraction of bitumen from oil sands deposits, the oil sand process-affected water (OSPW) is stored in tailings ponds. Naphthenic acids (NA) in tailings ponds have been identified as the primary contributor to toxicity to aquatic life. As an alternative to other analytical methods, here we identify bacterial genes induced after growth in naphthenic acids and use synthetic biology approaches to construct a panel of candidate biosensors for NA detection in water. The main promoters of interest were the atuAR promoters from a naphthenic acid degradation operon and upstream TetR regulator, the marR operon which includes a MarR regulator and downstream naphthenic acid resistance genes, and a hypothetical gene with a possible role in fatty acid biology. Promoters were printed and cloned as transcriptional lux reporter plasmids that were introduced into a tailings pond-derived Pseudomonas species. All candidate biosensor strains were tested for transcriptional responses to naphthenic acid mixtures and individual compounds. The three priority promoters respond in a dose-dependent manner to simple, acyclic, and complex NA mixtures, and each promoter has unique NA specificities. The limits of NA detection from the various NA mixtures ranged between 1.5 and 15 mg/L. The atuA and marR promoters also detected NA in small volumes of OSPW samples and were induced by extracts of the panel of OSPW samples. While biosensors have been constructed for other hydrocarbons, here we describe a biosensor approach that could be employed in environmental monitoring of naphthenic acids in oil sands mining wastewater.

The chromatin remodeler DEK promotes proliferation of mammary epithelium and is associated with H3K27me3 epigenetic modifications.

The DEK chromatin remodeling protein was previously shown to confer oncogenic phenotypes to human and mouse mammary epithelial cells using in vitro and knockout mouse models. However, its functional role in normal mammary gland epithelium remained unexplored. We developed two novel mouse models to study the role of Dek in normal mammary gland biology in vivo . Mammary gland-specific Dek over-expression in mice resulted in hyperproliferation of cells that visually resembled alveolar cells, and a transcriptional profile that indicated increased expression of cell cycle, mammary stem/progenitor, and lactation-associated genes. Conversely, Dek knockout mice exhibited an alveologenesis or lactation defect, resulting in dramatically reduced pup survival. Analysis of previously published single-cell RNA-sequencing of mouse mammary glands revealed that Dek is most highly expressed in mammary stem cells and alveolar progenitor cells, and to a lesser extent in basal epithelial cells, supporting the observed phenotypes. Mechanistically, we discovered that Dek is a modifier of Ezh2 methyltransferase activity, upregulating the levels of histone H3 trimethylation on lysine 27 (H3K27me3) to control gene transcription. Combined, this work indicates that Dek promotes proliferation of mammary epithelial cells via cell cycle deregulation. Furthermore, we report a novel function for Dek in alveologenesis and histone H3 K27 trimethylation.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.