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We describe the clinical, laboratory, and radiographic characteristics of 15 cases of eastern equine encephalitis in children during 1970-2010. The most common clinical and laboratory features were fever, headache, seizures, peripheral leukocytosis, and cerebrospinal fluid neutrophilic pleocytosis. Radiographic lesions were found in the basal ganglia, thalami, and cerebral cortex. Clinical outcomes included severe neurologic deficits in 5 (33%) patients, death of 4 (27%), full recovery of 4 (27%), and mild neurologic deficits in 2 (13%). We identify an association between a short prodrome and an increased risk for death or for severe disease. [ABSTRACT FROM AUTHOR]

Fear of engendering addiction is frequently reported as both a provider and a patient barrier to effective pain management. In this study, a clinical scenario ascertained nursing staff members' usual practice in addressing addiction fears for patients with concerns about the addictive potential of pain medication. One hundred forty-five Veterans Health Administration nursing staff members from eight ambulatory care sites were queried to identify variables associated with proclivity to address patient fears about addiction risks in a population where pain is prevalent and the risk for substance abuse is high. Regarding addressing addiction concerns, 66% of nursing staff were very likely, 16% somewhat likely, 9% unsure, 6% somewhat unlikely, and 2% very unlikely to take action. Health technicians were less likely to address addiction concerns than registered or licensed vocational nurses (odds ratio [OR] 0.116; p=.004). Nursing staff with more years' experience (OR 1.070; p=.005) and higher levels of self-efficacy/confidence (OR 1.380; p=.001) were more likely to engage in discussions related to addiction risks. Targeted efforts to improve pain management activities should focus on retaining experienced nursing staff in initial assessment positions and improving the skills and confidence of less experienced and less skilled staff. © 2010 by the American Society for Pain Management Nursing. [ABSTRACT FROM AUTHOR]

Background: The Institute of Medicine's 2001 report Crossing the Quality Chasm argued for fundamental redesign of the U.S. health care system. Six years later, many health care organizations have embraced the report's goals, but few have succeeded in making the substantial transformations needed to achieve those aims.Purposes: This article offers a model for moving organizations from short-term, isolated performance improvements to sustained, reliable, organization-wide, and evidence-based improvements in patient care.Methodology: Longitudinal comparative case studies were conducted in 12 health care systems using a mixed-methods evaluation design based on semistructured interviews and document review. Participating health care systems included seven systems funded through the Robert Wood Johnson Foundation's Pursuing Perfection Program and five systems with long-standing commitments to improvement and high-quality care.Findings: Five interactive elements appear critical to successful transformation of patient care: (1) Impetus to transform; (2) Leadership commitment to quality; (3) Improvement initiatives that actively engage staff in meaningful problem solving; (4) Alignment to achieve consistency of organization goals with resource allocation and actions at all levels of the organization; and (5) Integration to bridge traditional intra-organizational boundaries among individual components. These elements drive change by affecting the components of the complex health care organization in which they operate: (1) Mission, vision, and strategies that set its direction and priorities; (2) Culture that reflects its informal values and norms; (3) Operational functions and processes that embody the work done in patient care; and (4) Infrastructure such as information technology and human resources that support the delivery of patient care. Transformation occurs over time with iterative changes being sustained and spread across the organization.Practice Implications: The conceptual model holds promise for guiding health care organizations in their efforts to pursue the Institute of Medicine aims of fundamental system redesign to achieve dramatically improved patient care. [ABSTRACT FROM AUTHOR]

Moral foundations theory proposes five domains of morality-harm, fairness, loyalty, purity, and authority. Endorsement of these moral domains is assessed by the Moral Foundations Questionnaire (MFQ), a 30-item scale that has undergone intense measurement scrutiny. Across five samples ( N = 464,229), we show greatly improved model fit using a Bifactor model that accounts for two kinds of items in the MFQ: judgment and relevance. We add to this space by demonstrating how using this improved measurement structure changes the strength of correlations of the moral foundations with numerous attitudes, cognitive styles, and moral decision-making. Future research should continue to identify what, if anything, the relevance and judgment factors might substantively capture over and above the substantive domains of moral foundations. In the meantime, we recommend that researchers use the Bifactor model for its improved model structure, rather than dropping the relevant items as some have proposed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: While not entirely understood, nocturnal enuresis (NE) has been considered pathophysiologically distinct from other non-neurogenic voiding disorders. We believe that a significant component of the pathology is due to bladder overactivity. Intravesical Onabotulinumtoxin A (OBTA) injections are utilized in overactive bladder management. We hypothesized that OBTA injections would be efficacious for NE management in pediatric patients with symptoms refractory to conventional therapies., Materials and Methods: A retrospective cohort analysis of patients <18-years-old with primary NE who underwent OBTA injections was performed. Injections were performed by a single surgeon at a single tertiary referral center per standardized protocol. Treatment response was defined as no improvement, greater than 50 % improvement in nightly accidents, or complete resolution of accidents. The primary outcome was treatment success, defined as greater than 50 % improvement in nightly accidents or complete resolution. Secondary outcomes included treatment response duration and complication data. Descriptive and bivariate statistics were performed as indicated. A Kaplan Meier analysis was performed to assess failure free survival following OBTA injection., Results: Fifty patients met inclusion criteria for this analysis. All patients had trialed at least one lifestyle modification, a bowel regimen, and at least two medications with symptom persistence. The median post-procedure follow-up time was 9.5 months (range 2-82). Improvement in incontinence symptoms compared to pre-operative baseline was seen in 94.0 % of patients, with 58.0 % demonstrating complete resolution of incontinence through most recent follow up. There was no difference in improvement rates or resolution rates in male vs female gender. The median failure free survival identified on Kaplan Meier analysis was 12.5 months (Figure 1) Minor post-operative complications (4 urinary tract infections; 1 retentive episode necessitating catheterization) were identified in five patients. There were no major post-operative complications., Discussion: Efficacy of OBTA injections was high, with treatment success demonstrated in 94 % of patients and failure free survival of 12.5 months. This procedure also demonstrated a favorable safety profile, with few minor post-operative complications identified. These results indicate that this procedure may be a beneficial therapeutic option for patients with NE refractory to multiple lines of conventional therapy. This study is limited by its retrospective design with short median follow up and potential for recall bias. It is strengthened by its large sample size and novelty., Conclusions: To our knowledge, this is the first analysis of the efficacy of OBTA injections for management of primary NE. A follow up clinical trial is essential to further understand this association., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

AAPM Task Group Report 135.B covers new technology components that have been added to an established radiosurgery platform and updates the components that were not well covered in the previous report. Considering the current state of the platform, this task group (TG) is a combination of a foundational task group to establish the basis for new processes/technology and an educational task group updating guidelines on the established components of the platform. Because the technology discussed in this document has a relatively small user base compared to C-arm isocentric linacs, the authors chose to emphasize the educational components to assist medical physicists who are new to the technology and have not had the opportunity to receive in-depth vendor training at the time of reading this report. The TG has developed codes of practice, introduced QA, and developed guidelines which are generally expected to become enduring practice. This report makes prescriptive recommendations as there has not been enough longitudinal experience with some of the new technical components to develop a data-based risk analysis., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice., Patients and Methods: This retrospective study used real-world data from the Flatiron Health electronic health record-derived deidentified longitudinal database. Patients with HR+/HER2- mBC aged ≥18 years at mBC diagnosis started 1L CDK4/6i therapy (index treatment) between February 2015 and November 2023, with a potential ≥6-month follow-up. OS was defined as months from start of index treatment to death. Stabilized inverse probability of treatment weighting (sIPTW; primary analysis) was used to balance baseline patient characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis., Results: Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib plus AI, ribociclib plus AI, or abemaciclib plus AI, respectively. After sIPTW, baseline characteristics were balanced between treatment groups. After sIPTW, no significant OS differences were found between treatment groups [ribociclib versus palbociclib: adjusted hazard ratio (aHR) 0.98, 95% confidence interval (CI) 0.87-1.10, P = 0.7531; abemaciclib versus palbociclib: aHR 0.95, 95% CI 0.84-1.08, P = 0.4292; abemaciclib versus ribociclib: aHR 0.97, 95% CI 0.82-1.14, P = 0.6956]. Sensitivity analysis including a subanalysis of patients who started index treatment in 2017 or later also showed no significant OS differences between treatment groups., Conclusions: This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2- mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2- mBC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Palliative care clinicians often help facilitate coordination of care, complex serious illness, and end-of-life medical decision-making. However, the clinical and legal issues related to guardianship can complicate the decision-making process, care delivery, outcomes, and the role of the palliative care clinician. Adult patients who have a guardian have been found by a court to be unable to make some or all decisions for themselves. Providing care for patients under guardianship is where medicine overlaps with legal rights. It is crucial to be familiar with the patients' rights and the guardians' responsibilities to clarify medical decision-making processes and identify necessary authorities. This article uses an interprofessional approach to leverage the expertise of physicians, nurses, lawyers, and guardians and to guide palliative care clinicians to optimally support patients under guardianship.

Although Jewish people in the US are often racialized (i.e., perceived by others) as White, Jewish Americans vary in the extent to which they consider themselves White, and in how strongly they identify with being Jewish. Based on prior findings that identifying with a White ethnic subgroup (e.g., Irish, Italian) can reduce prejudice toward racial and ethnic minorities, we predicted that strongly identified Jewish Americans would exhibit less intergroup bias than weakly identified Jewish Americans. For the present research, we recruited participants whose religious affiliation was Jewish but who self-identified as racially White. In a preregistered correlational study, Jewish identification was associated with lower bias, whereas White identification was associated with greater bias, toward Whites relative to racial/ethnic minorities. The relationship between Jewish identification and intergroup bias was accounted for by high Jewish identifiers' perceptions that they could personally contribute to diversity in groups and organizations. Across three meta-analyzed experiments, participants whose religious minority (Jewish) identity was made salient exhibited less intergroup bias than did control participants, and in one preregistered experiment, perceived personal contributions to diversity mediated the effect of condition on intergroup bias. Implications for the forms of ethnic identity that predict more versus less intergroup bias in an increasingly multicultural society are discussed., (© 2024. The Author(s).)

Spermatogenesis produces male gametes from spermatogonial stem cells (SSC), beginning at puberty. Modern-day laboratory techniques allow for the long-term culture of SSC and in vitro spermatogenesis. The specific biochemical processes that occur during spermatogenesis remain poorly understood. One particular element of spermatogenesis that has yet to be characterized is the role of microRNAs (miRNA), short, non-transcribed RNAs that act as post-translational regulators of gene activity. In this study, we seek to describe the presence of miRNA in a two-dimensional (2D) SSC culture and a 3D human testis organoid (HTO) system. Testicular cells were isolated from the frozen tissue of three brain-dead subjects, propagated in cultures for four to five weeks, and used to form 3D HTOs. Following organoid formation, differentiation of testicular cells was induced. RNA was isolated from the whole testis tissue (WT) showing in vivo conditions, HTO Day Zero (2D SSC culture), Day 2 HTOs, and Day 23 differentiated HTOs, then analyzed for changes in miRNA expression using the Nanostring nCounter miRNA panel. One hundred ninety-five miRNAs met the criteria for expression in WT, 186 in 2D culture, 190 in Day 2 HTOs, and 187 in differentiated HTOs. One hundred thirty-three miRNAs were common across all conditions, and 41, 17, 6, and 11 miRNAs were unique for WT, 2D culture, Day 2 HTOs, and differentiated HTOs, respectively. Twenty-two miRNAs were similar between WT and differentiated HTOS. We evaluated the miRNA expression profiles of progressively complex stages of testicular cell culture, culminating in a 3D organoid model capable of meiotic differentiation, and compared these to WT. We identified a great variance between the native tissue and the culture system; however, some miRNAs are preserved. These data may provide avenues for deeper understanding of spermatogenesis and the ability to improve this process in the laboratory. Research on miRNA continues to be an essential avenue for understanding human spermatogenesis.

Importance: Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization., Objective: To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19., Design, Setting, and Participants: This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024., Exposure: Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU., Main Outcomes and Measures: Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score <22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome., Results: The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization., Conclusions and Relevance: In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.

Objective: For nursing home residents with severe dementia, high-intensity medical treatment offers little possibility of benefit but has the potential to cause significant distress. Nevertheless, mechanical ventilation and intensive care unit (ICU) transfers have increased in this population. We sought to understand how and why such care is occurring., Design: Mixed methods study, with retrospective collection of qualitative and quantitative data., Setting: Department of Veterans Affairs (VA) hospitals., Methods: Using the Minimum Data Set, we identified veterans aged ≥65 years who had severe dementia, lived in nursing homes, and died in 2013. We selected those who underwent mechanical ventilation or ICU transfer in the last 30 days of life. We restricted our sample to patients receiving care at VA hospitals because these hospitals share an electronic medical record, from which we collected structured information and constructed detailed narratives of how medical decisions were made. We used qualitative content analysis to identify distinct paths to high-intensity treatment in these narratives., Results: Among 163 veterans, 41 (25.2%) underwent mechanical ventilation or ICU transfer. Their median age was 85 (IQR, 80-94), 97.6% were male, and 67.5% were non-Hispanic white. More than a quarter had living wills declining some or all treatment. There were 5 paths to high-intensity care. The most common (18 of 41 patients) involved families who struggled with decisions. Other patients (15 of 41) received high-intensity care reflexively, before discussion with a surrogate. Four patients had families who advocated repeatedly for aggressive treatment, against clinical recommendations. In 2 cases, information about the patient's preferences was erroneous or unavailable. In 2 cases, there was difficulty identifying a surrogate., Conclusions and Implications: Our findings highlight the role of surrogates' difficulty with decision making and of health system-level factors in end-of-life ICU transfers and mechanical ventilation among nursing home residents with severe dementia., Competing Interests: Disclosure The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Background: Despite significant support system disruptions during the coronavirus 2019 (COVID-19) pandemic, little is known about the relationship between social support and symptom burden among older adults following COVID-19 hospitalization., Methods: From a prospective cohort of 341 community-living persons aged ≥60 years hospitalized with COVID-19 between June 2020 and June 2021 who underwent follow-up at 1, 3, and 6 months after discharge, we identified 311 participants with ≥1 follow-up assessment. Social support prehospitalization was ascertained using a 5-item version of the Medical Outcomes Study Social Support Survey (range, 5-25), with low social support defined as a score ≤15. At hospitalization and each follow-up assessment, 14 physical symptoms were assessed using a modified Edmonton Symptom Assessment System inclusive of COVID-19-relevant symptoms. Mental health symptoms were assessed using Patient Health Questionnaire-4. Longitudinal associations between social support and physical and mental health symptoms, respectively, were evaluated through multivariable regression., Results: Participants' mean age was 71.3 years (standard deviation, 8.5), 52.4% were female, and 34.2% were of Black race or Hispanic ethnicity. 11.8% reported low social support. Over the 6-month follow-up period, low social support was independently associated with higher burden of physical symptoms (adjusted rate ratio [aRR], 1.26; 95% confidence interval [CI], 1.05-1.52), but not mental health symptoms (aRR, 1.14; 95% CI, 0.85-1.53)., Conclusions: Low social support is associated with greater physical, but not mental health, symptom burden among older survivors of COVID-19 hospitalization. Our findings suggest a potential need for social support screening and interventions to improve post-COVID-19 symptom management in this vulnerable group., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Evaluating infection in home-based primary care is challenging, and these challenges may impact antibiotic prescribing. A refined understanding of antibiotic decision-making in this setting can inform strategies to promote antibiotic stewardship. This study investigated antibiotic decision-making by exploring the perspectives of clinicians in home-based primary care., Methods: Clinicians from the Department of Veterans Affairs Home-Based Primary Care Program were recruited. Semi-structured interviews were conducted from June 2022 through September 2022 using a discussion guide. Transcripts were analyzed using grounded theory. The constant comparative method was used to develop a coding structure and to identify themes., Results: Theoretical saturation was reached after 22 clinicians (physicians, n = 7; physician assistants, n = 2, advanced practice registered nurses, n = 13) from 19 programs were interviewed. Mean age was 48.5 ± 9.3 years, 91% were female, and 59% had ≥6 years of experience in home-based primary care. Participants reported uncertainty about the diagnosis of infection due to the characteristics of homebound patients (atypical presentations of disease, presence of multiple chronic conditions, presence of cognitive impairment) and the challenges of delivering medical care in the home (limited access to diagnostic testing, suboptimal quality of microbiological specimens, barriers to establishing remote access to the electronic health record). When faced with diagnostic uncertainty about infection, participants described many factors that influenced the decision to prescribe antibiotics, including those that promoted prescribing (desire to avoid hospitalization, pressure from caregivers, unreliable plans for follow-up) and those that inhibited prescribing (perceptions of antibiotic-associated harms, willingness to trial non-pharmacological interventions first, presence of caregivers who were trusted by clinicians to monitor symptoms)., Conclusions: Clinicians face the difficult task of balancing diagnostic uncertainty with many competing considerations during the treatment of infection in home-based primary care. Recognizing these issues provides insight into strategies to promote antibiotic stewardship in home care settings., (© 2024 The American Geriatrics Society.)

Background: The ascomycete fungus Anisogramma anomala causes Eastern Filbert Blight (EFB) on hazelnut (Corylus spp.) trees. It is a minor disease on its native host, the American hazelnut (C. americana), but is highly destructive on the commercially important European hazelnut (C. avellana). In North America, EFB has historically limited commercial production of hazelnut to west of the Rocky Mountains. A. anomala is an obligately biotrophic fungus that has not been grown in continuous culture, rendering its study challenging. There is a 15-month latency before symptoms appear on infected hazelnut trees, and only a sexual reproductive stage has been observed. Here we report the sequencing, annotation, and characterization of its genome., Results: The genome of A. anomala was assembled into 108 scaffolds totaling 342,498,352 nt with a GC content of 34.46%. Scaffold N50 was 33.3 Mb and L50 was 5. Nineteen scaffolds with lengths over 1 Mb constituted 99% of the assembly. Telomere sequences were identified on both ends of two scaffolds and on one end of another 10 scaffolds. Flow cytometry estimated the genome size of A. anomala at 370 Mb. The genome exhibits two-speed evolution, with 93% of the assembly as AT-rich regions (32.9% GC) and the other 7% as GC-rich (57.1% GC). The AT-rich regions consist predominantly of repeats with low gene content, while 90% of predicted protein coding genes were identified in GC-rich regions. Copia-like retrotransposons accounted for more than half of the genome. Evidence of repeat-induced point mutation (RIP) was identified throughout the AT-rich regions, and two copies of the rid gene and one of dim-2, the key genes in the RIP mutation pathway, were identified in the genome. Consistent with its homothallic sexual reproduction cycle, both MAT1-1 and MAT1-2 idiomorphs were found. We identified a large suite of genes likely involved in pathogenicity, including 614 carbohydrate active enzymes, 762 secreted proteins and 165 effectors., Conclusions: This study reveals the genomic structure, composition, and putative gene function of the important pathogen A. anomala. It provides insight into the molecular basis of the pathogen's life cycle and a solid foundation for studying EFB., (© 2024. The Author(s).)

Biological processes in the Proterozoic Ocean are often inferred from modern oxygen-deficient environments (MODEs) or from stable isotopes in preserved sediment. To date, few MODE studies have simultaneously quantified carbon fixation genes and attendant stable isotopic signatures. Consequently, how carbon isotope patterns reflect these pathways has not been thoroughly vetted. Addressing this, we profiled planktonic productivity and quantified carbon fixation pathway genes and associated organic carbon isotope values (δ 13 C POC ) of size-fractionated (0.2-2.7 and >2.7 μm) particulate matter from meromictic Fayetteville Green Lake, NY, USA. The high-O 2 Calvin-Benson-Bassham (CBB) gene (cbbL) was most abundant in the <2.7 μm size fraction in shallow oxic and deep hypoxic waters, corresponding with cyanobacterial and eukaryote algal populations. The low-O 2 CBB gene (cbbM) was most abundant near the lower oxycline boundary in the larger size fraction, coincident with purple sulfur bacteria populations. The reverse citric acid cycle gene (aclB) was equally abundant in both size fractions in the deepest photic zone, coinciding with green sulfur bacteria populations. Methane coenzyme reductase A (mcrA), of anaerobic methane cyclers, was most abundant at the lower oxycline boundary in both size fractions, coinciding with Methanoregula populations. δ 13 C POC values overlapped with the high-O 2 CBB fixation range except for two negative excursions near the lower oxycline boundary, likely reflecting assimilation of isotopically-depleted groundwater-derived carbon by autotrophs and sulfate-reducers. Throughout aphotic waters, δ 13 C POC values of the large size fraction became 13 C-enriched, likely reflecting abundant purple sulfur bacterial aggregates. Eukaryote algae- or cyanobacteria-like isotopic signatures corresponded with increases in cbbL, cbbM, and aclB, and enrichment of exopolymer-rich prokaryotic photoautotrophs aggregates. Results suggest that δ 13 C POC values of preserved sediments from areas of the Proterozoic Ocean with sulfidic photic zones may reflect a mixture of alternate carbon-fixing populations exported from the deep photic zone, challenging the paradigm that sedimentary stable carbon isotope values predominantly reflect oxygenic photosynthesis from surface waters., (© 2024 John Wiley & Sons Ltd.)

Abstract: Digital health tools extend well beyond telemedicine, holding great potential to advance oncological care. We survey digital health and provide recommendations across the health continuum, tailoring them to oncology, including prevention, detection and diagnosis, and treatment and monitoring. Within the prevention realm, we review wellness technologies, cancer screening, mental health solutions, and digital biomarkers. For detection and diagnosis, we describe existing and emerging solutions for remote patient monitoring and various means to capture digital biomarkers, the "digital exam," and "digital outcomes." Treatment and monitoring solutions include telemedicine, chatbots, and digital therapeutics, which are also explored. We also discuss a host of technology enablers that are required for successful implementation and sustainment of digital health-enabled care. Our recommendations pertain to health care systems as well as companies that work with these systems or provide care to patients directly., Competing Interests: Conflicts of Interest and Source of Funding: A.B.C. is advisor to Thirty Madison. L.H.S. reports the following relationships relevant to research grants or companies: scientific consultant regarding trial design and conduct on late-window thrombolysis and member of steering committee for Genentech (TIMELESS NCT03785678); user interface design and usability to LifeImage (privately held teleradiology company); member of a Data Safety Monitoring Board (DSMB) for Penumbra (MIND NCT03342664); principal investigator, Multicenter Trial of Stroke Prevention for Medtronic (Stroke AF NCT02700945); principal investigator, StrokeNet Network NINDS (New England Regional Coordinating Center U24NS107243); coinvestigator, The Impact of Telestroke on Patterns of Care and Long-Term Outcomes, NINDS (R01NS111952); coinvestigator, REACH-PC Telepalliative Care Trial, PCORI (NCT03375489, R-1609-35995)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI's ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability. Methods: We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (e.g., clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (i.e. not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information. Results: We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates. Conclusion: NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer., Competing Interests: Authors BA, MW, AB, JK, KK, SN, JG, JR, KH, GH, RL, TB, SW, GA, EE, CB, EF, ME, WS, and AB are employees of Flatiron Health, Inc., which is an independent member of the Roche group, and own stock in Roche., (Copyright © 2023 Adamson, Waskom, Blarre, Kelly, Krismer, Nemeth, Gippetti, Ritten, Harrison, Ho, Linzmayer, Bansal, Wilkinson, Amster, Estola, Benedum, Fidyk, Estévez, Shapiro and Cohen.)

When ethics committees are consulted about patients who have or need court-appointed guardians, they lack empirical evidence about several common issues, including the relationship between guardianship and prolonged, potentially medically unnecessary hospitalizations for patients. To provide information about this issue, we conducted quantitative and qualitative analyses using a retrospective cohort from Veterans Healthcare Administration. To examine the relationship between guardianship appointment and hospital length of stay, we first compared 116 persons hospitalized prior to guardianship appointment to a comparison group (n = 348) 3:1 matched for age, diagnosis, date of admission, and comorbidity. We then compared 91 persons hospitalized in the year following guardianship appointment to a second matched comparison group (n = 273). Mean length of stay was 30.75 days (SD = 46.70) amongst those admitted prior to guardianship, which was higher than the comparison group (M = 7.74, SD = 9.71, F = 20.75, p < .001). Length of stay was lower following guardianship appointment (11.65, SD = 12.02, t = 15.16, p < .001); while higher than the comparison group (M = 7.60, SD = 8.46), differences were not associated with guardianship status. In a separate analysis involving 35 individuals who were hospitalized both prior to and following guardianship, length of stay was longer in the year prior (M = 23.00, SD = 37.55) versus after guardianship (M = 10.37, SD = 10.89, F = 4.35, p = .045). In qualitative analyses, four themes associated with lengths of stay exceeding 45 days prior to guardianship appointment were: administrative issues, family conflict, neuropsychiatric comorbidity, and medical complications. Our results suggest that persons who are admitted to hospitals, and subsequently require a guardian, experience extended lengths of stay for multiple complex reasons. Once a guardian has been appointed, however, differences in hospital lengths of stay between patients with and without guardians are reduced., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Purpose: The Critical Care EEG Monitoring Research Consortium (CCEMRC) is an international research group focusing on critical care EEG and epilepsy. As CCEMRC grew to include 50+ institutions over the past decade, members met to establish research priorities., Methods: The authors used an analytical hierarchy process-based research prioritization method, adapted from an approach previously applied to a Department of Defense health-related research program. Forty-six CCEMRC members identified and scored a set of eight clinical problems (CPs) and 15 research topic areas (RTAs) at an annual CCEMRC meeting. Members scored CPs on three criteria using a five-point ordinal scale: Incidence, Impact, and Gap Size; and RTAs on four additional criteria: Niche, Feasibility, Scientific Importance, and Medical Importance, each of which was assigned a weight. The first three RTA criteria were scored using a five-point scale, and CPs were mapped to RTAs using a four-point scale. The Medical Importance score was a weighted average of its mapping scores and the CP score. Finally, a Priority score was calculated for each RTA as a product of the four RTA criteria scores., Results: The CPs with the highest scores were "Altered mental status" and "Long-term neurologic disability after hospital discharge." The RTAs with the highest priority scores were "Development of risk prediction tools," "Multicenter observational studies," and "Outcome prediction.", Conclusions: Research prioritization helped CCEMRC evaluate its current research trajectory, identify high-priority near-term research pursuits, and create a roadmap for future research plans aligned with its mission. This approach may be helpful to other academic consortia and research programs., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Wordle is a daily, online brainteaser. The widespread popularity of the game in the early months of 2022 has also led to widespread cheating. Here, we use data from Google Trends and Twitter to explore correlates of cheating on Wordle. We find that cheating behavior is negatively related to religiosity and cultural tightness. Although this is a benign example of cheating behavior, we discuss how popular trends can be used as case studies of group-level behavior.

Meaningful real-world evidence (RWE) generation requires unstructured data found in electronic health records (EHRs) which are often missing from administrative claims; however, obtaining relevant data from unstructured EHR sources is resource-intensive. In response, researchers are using natural language processing (NLP) with machine learning (ML) techniques (i.e., ML extraction ) to extract real-world data (RWD) at scale. This study assessed the quality and fitness-for-use of EHR-derived oncology data curated using NLP with ML as compared to the reference standard of expert abstraction. Using a sample of 186,313 patients with lung cancer from a nationwide EHR-derived de-identified database, we performed a series of replication analyses demonstrating some common analyses conducted in retrospective observational research with complex EHR-derived data to generate evidence. Eligible patients were selected into biomarker- and treatment-defined cohorts, first with expert-abstracted then with ML-extracted data. We utilized the biomarker- and treatment-defined cohorts to perform analyses related to biomarker-associated survival and treatment comparative effectiveness, respectively. Across all analyses, the results differed by less than 8% between the data curation methods, and similar conclusions were reached. These results highlight that high-performance ML-extracted variables trained on expert-abstracted data can achieve similar results as when using abstracted data, unlocking the ability to perform oncology research at scale.

Background: Most older adults hospitalized with COVID-19 survive their acute illness. The impact of COVID-19 hospitalization on patient-centered outcomes, including physical function, cognition, and symptoms, is not well understood. To address this knowledge gap, we collected longitudinal data about these issues from a cohort of older survivors of COVID-19 hospitalization., Methods: We undertook a prospective study of community-living persons age ≥ 60 years who were hospitalized with COVID-19 from June 2020-June 2021. A baseline interview was conducted during or up to 2 weeks after hospitalization. Follow-up interviews occurred at one, three, and six months post-discharge. Participants completed comprehensive assessments of physical and cognitive function, symptoms, and psychosocial factors. An abbreviated assessment could be performed with a proxy. Additional information was collected from the electronic health record., Results: Among 341 participants, the mean age was 71.4 (SD 8.4) years, 51% were women, and 37% were of Black race or Hispanic ethnicity. Median length of hospitalization was 8 (IQR 6-12) days. All but 4% of participants required supplemental oxygen, and 20% required care in an intensive care unit or stepdown unit. At enrollment, nearly half (47%) reported at least one preexisting disability in physical function, 45% demonstrated cognitive impairment, and 67% were pre-frail or frail. Participants reported a mean of 9 of 14 (SD 3) COVID-19-related symptoms. At the six-month follow-up interview, more than a third of participants experienced a decline from their pre-hospitalization function, nearly 20% had cognitive impairment, and burdensome symptoms remained highly prevalent., Conclusions: We enrolled a diverse cohort of older adults hospitalized with COVID-19 and followed them after discharge. Functional decline was common, and there were high rates of persistent cognitive impairment and symptoms. Future analyses of these data will advance our understanding of patient-centered outcomes among older COVID-19 survivors., (© 2022 The American Geriatrics Society.)

Objectives: Studies have separately examined the health impacts of the COVID-19 pandemic on persons with dementia and their caregivers. Less attention has been paid to the social and emotional impacts of the pandemic in this population or how these individuals are mutually coping with the pandemic. Guided by the social citizenship theory, this qualitative study sought to characterize how persons with dementia and their adult children are coping during this time with a focus on the strengths demonstrated by persons with dementia., Methods: Participants were 43 dyads of individuals aged 55 and older with early-stage dementia and their adult children. Discussions between parent-child dyads were recorded. Using reflexive thematic analysis, themes related to social and emotional impacts of the pandemic and coping strategies were identified., Results: Adult children shared with their parents how the pandemic resulted in reduced social engagement and challenging work arrangements. Dyads described how the pandemic positively impacted their relationship, allowing some of them to spend more time together. In coping with the pandemic, adult children provided instrumental support to their parents and parents reciprocated with emotional support. Participants also coped by making meaning of their situation during discussions., Conclusions: Findings characterize the resilience of persons with dementia and the mutuality of the relationship between both members of the care partner dyad, as both parents and adult children offered support to one another. Facilitating dyadic discussions may be a cost-effective way to sustain social connections and offer ongoing coping support through the pandemic or other challenging circumstances., (© 2023 John Wiley & Sons Ltd.)