General Installation of (4H)-Imidazolone cis-Amide Bioisosteres Along the Peptide Backbone.

Imidazolones represent an important class of heterocycles present in a wide range of pharmaceuticals, metabolites, and bioactive natural products and serve as the active chromophore in green fluorescent protein. Recently, imidazolones have received attention for their ability to act as a nonaromatic amide bond bioisotere which improves pharmacological properties. Herein, we present a tandem amidine installation and cyclization with an adjacent ester to yield (4H)-imidazolone products. Using amino acid building blocks, we can access the first examples of α-chiral imidazolones that have been previously inaccessible. Additionally, our method is amenable to on-resin installation which can be seamlessly integrated into existing solid-phase peptide synthesis protocols. Finally, we show that peptide imidazolones are potent cis-amide bond surrogates that preorganize linear peptides for head-to-tail macrocyclization. This work represents the first general approach to the backbone and side-chain insertion of imidazolone bioisosteres at various positions in linear and cyclic peptides.

Racial Disparities in Low-Value Care in the Last Year of Life for Medicare Beneficiaries With Neurodegenerative Disease.

Background and Objectives: There are racial disparities in health care services received by patients with neurodegenerative diseases, but little is known about disparities in the last year of life, specifically in high-value and low-value care utilization. This study evaluated racial disparities in the utilization of high-value and low-value care in the last year of life among Medicare beneficiaries with dementia or Parkinson disease. Methods: This was a retrospective, population-based cohort analysis using data from North and South Carolina fee-for-service Medicare claims between 2013 and 2017. We created a decedent cohort of beneficiaries aged 50 years or older at diagnosis with dementia or Parkinson disease. Specific low-value utilization outcomes were selected from the Choosing Wisely initiative, including cancer screening, peripheral artery stenting, and feeding tube placement in the last year of life. Low-value outcomes included hospitalization, emergency department visits, neuroimaging services, and number of days receiving skilled nursing. High-value outcomes included receipt of occupational and physical therapy, hospice care, and medications indicated for dementia and/or Parkinson disease. Results: Among 70,650 decedents, 13,753 were Black, 55,765 were White, 93.1% had dementia, and 7.7% had Parkinson disease. Adjusting for age, sex, Medicaid dual enrollment status, rural vs urban location, state (NC and SC), and comorbidities, Black decedents were more likely to receive low-value care including colorectal cancer screening (adjusted hazard ratio [aHR] 1.46 [1.32-1.61]), peripheral artery stenting (aHR 1.72 [1.43-2.08]), and feeding tube placement (aHR 2.96 [2.70-3.24]) and less likely to receive physical therapy (aHR 0.73 [0.64-0.85)], dementia medications (aHR 0.90 [0.86-0.95]), or Parkinson disease medications (aHR 0.88 [0.75-1.02]) within the last year of life. Black decedents were more likely to be hospitalized (aHR 1.28 [1.25-1.32]), more likely to be admitted to skilled nursing (aHR 1.09 [1.05-1.13]), and less likely to be admitted to hospice (aHR 0.82 [0.79-0.85]) than White decedents. Discussion: We found racial disparities in care utilization among patients with neurodegenerative disease in the last year of life, such that Black decedents were more likely to receive specific low-value care services and less likely to receive high-value supportive care than White decedents, even after adjusting for health status and socioeconomic factors.

Elevated Amyloid-ß PET Scan and Cognitive and Functional Decline in Mild Cognitive Impairment and Dementia of Uncertain Etiology.

BACKGROUND: Elevated amyloid-ß (Aß) on positron emission tomography (PET) scan is used to aid diagnosis of Alzheimer's disease (AD), but many prior studies have focused on patients with a typical AD phenotype such as amnestic mild cognitive impairment (MCI). Little is known about whether elevated Aß on PET scan predicts rate of cognitive and functional decline among those with MCI or dementia that is clinically less typical of early AD, thus leading to etiologic uncertainty. OBJECTIVE: We aimed to investigate whether elevated Aß on PET scan predicts cognitive and functional decline over an 18-month period in those with MCI or dementia of uncertain etiology. METHODS: In 1,028 individuals with MCI or dementia of uncertain etiology, we evaluated the association between elevated Aß on PET scan and change on a telephone cognitive status measure administered to the participant and change in everyday function as reported by their care partner. RESULTS: Individuals with either MCI or dementia and elevated Aß (66.6% of the sample) showed greater cognitive decline compared to those without elevated Aß on PET scan, whose cognition was relatively stable over 18 months. Those with either MCI or dementia and elevated Aß were also reported to have greater functional decline compared to those without elevated Aß, even though the latter group showed significant care partner-reported functional decline over time. CONCLUSIONS: Elevated Aß on PET scan can be helpful in predicting rates of both cognitive and functional decline, even among cognitively impaired individuals with atypical presentations of AD.

Factors associated with anxiety during the first two years of the COVID-19 pandemic in the United States: An analysis of the COVID-19 Citizen Science study.

COVID-19 increased the prevalence of clinically significant anxiety in the United States. To investigate contributing factors we analyzed anxiety, reported online via monthly Generalized Anxiety Disorders-7 (GAD-7) surveys between April 2020 and May 2022, in association with self-reported worry about the health effects of COVID-19, economic difficulty, personal COVID-19 experience, and subjective social status. 333,292 anxiety surveys from 50,172 participants (82% non-Hispanic white; 73% female; median age 55, IQR 42-66) showed high levels of anxiety, especially early in the pandemic. Anxiety scores showed strong independent associations with worry about the health effects of COVID-19 for oneself or family members (GAD-7 score +3.28 for highest vs. lowest category; 95% confidence interval: 3.24, 3.33; p<0.0001 for trend) and with difficulty paying for basic living expenses (+2.06; 1.97, 2.15, p<0.0001) in multivariable regression models after adjusting for demographic characteristics, COVID-19 case rates and death rates, and personal COVID-19 experience. High levels of COVID-19 health worry and economic stress were each more common among participants reporting lower subjective social status, and median anxiety scores for those experiencing both were in the range considered indicative of moderate to severe clinical anxiety disorders. In summary, health worry and economic difficulty both contributed to high rates of anxiety during the first two years of the COVID-19 pandemic in the US, especially in disadvantaged socioeconomic groups. Programs to address both health concerns and economic insecurity in vulnerable populations could help mitigate pandemic impacts on anxiety and mental health.

Fetal Metabolic Alkalosis Resulting from Maternal Vomiting.

We describe a pregnant patient with severe compulsive water ingestion and vomiting that lead to metabolic alkalosis and preterm delivery. A 21-year-old patient was hospitalized multiple times throughout pregnancy for symptoms initially thought to be related to hyperemesis gravidarum. Overtime, it became apparent that the patient induced vomiting by rapidly drinking large volumes of water. At 32 weeks' gestation, rapid ingestion of water caused 3 days of vomiting with findings of hyponatremia, hypokalemia, hypochloremia, metabolic alkalosis, and compensatory respiratory acidosis. Fetal monitoring showed minimal variability and recurrent decelerations; subsequent biophysical profile score of 2/10 prompted urgent cesarean section. A male newborn was delivered and cord blood gases reflected neonatal metabolic alkalosis and electrolyte imbalances identical to those of the mother. Compensatory hypoventilation in both mother and fetus were treated with assisted ventilation. With saline administration and repletion of electrolytes, metabolic alkalosis resolved for both patients within days. Metabolic alkalosis was transplacentally acquired by the fetus. This case demonstrates the development of metabolic alkalosis in a pregnant woman caused by vomiting severe enough to prompt preterm delivery for nonreassuring fetal status. It also demonstrates fetal dependence on both placenta and mother to maintain physiologic acid-base and electrolyte balance.

Association between results of an amyloid PET scan and healthcare utilization in individuals with cognitive impairment.

BACKGROUND: The Imaging Dementia Evidence for Amyloid Scanning (IDEAS) study reports that amyloid PET scans help providers diagnose and manage Alzheimer's disease and related dementias (ADRD). Using CARE-IDEAS, an IDEAS supplemental study, we examined the association between amyloid PET scan result (elevated or non-elevated amyloid), patient characteristics, and participant healthcare utilization. METHODS: We linked respondents in CARE-IDEAS study to their Medicare fee-for-service records (n = 1333). We examined participants' cognitive impairment-related, outpatient, emergency department (ED), and inpatient encounters in the year before compared with the 2 years after the amyloid PET scan. RESULTS: Individuals with a non-elevated amyloid scan had more healthcare encounters throughout the overall study period than those with an elevated amyloid scan. Regardless of the amyloid scan result, cognitive impairment-related and outpatient encounters overall decreased, but ED and inpatient encounters increased in the 2 years after the scan compared with the year prior. There was minimal evidence of differences in healthcare utilization between participants with an elevated and non-elevated amyloid scan. CONCLUSIONS: There is no difference in change in healthcare utilization between people with scans showing elevated and non-elevated beta-amyloid.

Collecting patient-reported outcome measures in the electronic health record: Lessons from the NIH pragmatic trials Collaboratory.

The NIH Pragmatic Trials Collaboratory supports the design and conduct of 27 embedded pragmatic clinical trials, and many of the studies collect patient reported outcome measures as primary or secondary outcomes. Study teams have encountered challenges in the collection of these measures, including challenges related to competing health care system priorities, clinician's buy-in for adoption of patient-reported outcome measures, low adoption and reach of technology in low resource settings, and lack of consensus and standardization of patient-reported outcome measure selection and administration in the electronic health record. In this article, we share case examples and lessons learned, and suggest that, when using patient-reported outcome measures for embedded pragmatic clinical trials, investigators must make important decisions about whether to use data collected from the participating health system's electronic health record, integrate externally collected patient-reported outcome data into the electronic health record, or collect these data in separate systems for their studies.

Amplitude Integrated Electroencephalography: Simulated Assessment of Neonatal Seizure Detection in PICU Patients.

OBJECTIVES: Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital. DESIGN: Retrospective study. SETTING: PICU/Neurophysiology Department in Dublin. PATIENTS: One hundred twenty patients (2 mo to 16 yr old) were chosen from a database of formal 10-20 system, 21-lead electroencephalography recordings (2012-2020), comprising 30 studies with seizures, 90 without. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalography studies containing electrographic seizures (ESzs) were annotated to describe number, duration, distribution, and spread. Two-channel aEEG (using leads C3-P3, C4-P4) recordings were generated and independently reviewed by a professional specialist in clinical neurophysiology blinded to outcome and without reference to the raw electroencephalography trace. Logistic regression was used to identify factors associated with correct seizure identification on aEEG. Median patient age was 6.1 years. Abnormal recordings featured 123 seizures. Status epilepticus (SE) was evident by electroencephalography in 10 cases. Using neonatal criteria, aEEG had a sensitivity of 70% and negative predictive value of 90% for identifying any ESz. Accurate detection of individual seizures was diminished when seizures were very short or occurred during waking. Sensitivity for individual seizures was 81% when seizures less than 1 minute were excluded. aEEG correctly identified SE in 70% of the 10 cases, although ESz were confirmed to be present in 80% of this subpopulation. CONCLUSIONS: aEEG criteria for neonatal seizure identification can be applied with caution to older children and should be supplemented by formal electroencephalography. Seizure identification is better for longer seizures and those arising from sleep. SE is not always recognized by aEEG among older children.

Atrial fibrillation as a novel risk factor for retinal stroke: A protocol for a population-based retrospective cohort study.

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

Post-traumatic stress disorder symptoms among healthcare workers during the COVID-19 pandemic: Analysis of the HERO Registry.

Little is known about the mental health consequences of the COVID-19 pandemic in healthcare workers (HCWs). Past literature has shown that chronic strain caused by pandemics can adversely impact a variety of mental health outcomes in HCWs. There is growing recognition of the risk of stress and loss of resilience to HCWs during the COVID-19 pandemic, although the risk of post-traumatic stress disorder (PTSD) symptoms in HCWs during the COVID-19 pandemic remains poorly understood. We wanted to understand the relationship between the COVID-19 pandemic and the risk of PTDS symptoms in HCWs during the COVID-19 pandemic. We surveyed 2038 health care workers enrolled in the Healthcare Worker Exposure Response & Outcomes (HERO) study, which is a large standardized national registry of health care workers. Participants answered questions about demographics, COVID-19 exposure, job burnout, and PTSD symptoms. We characterize the burden of PTSD symptoms among HCWs, and determined the association between high PTSD symptoms and race, gender, professional role, work setting, and geographic region using multivariable regression. In a fully adjusted model, we found that older HCWs were less likely to report high PTSD symptoms compared with younger HCWs. Additionally, we found that physicians were less likely to report high PTSD symptoms compared with nurses. These data add to the growing literature on increased risks of mental health challenges to healthcare workers during the COVID-19 pandemic.

Social Networks and Cardiovascular Disease Events in the Jackson Heart Study.

Background Cardiovascular disease (CVD) disproportionately affects Black adults. Greater social networks (SNs), or social connectedness, may lower the risk of CVD events. This study determined the association of SNs and incident CVD and tested mediation by depressive symptoms, hypertension control, and diabetes control. Methods and Results We used the Social Network Index at exam 1 (2000-2004) to develop a continuous standardized SN score and binary categories (high versus low) among participants in the Jackson Heart Study (n=4686; mean age, 54.8 years). Surveillance of coronary heart disease, stroke, and heart failure events occurred after exam 1 (2005 for HF) until 2016. Using Cox proportional hazards regression, we estimated the association of SNs and CVD events by sex and tested the mediation of depressive symptoms, hypertension control, and diabetes control. Models adjusted for age, education, health behaviors, CVD comorbidities, and depressive symptoms. Among women, the SN score was associated with a lower hazard of stroke, coronary heart disease, and heart failure after full adjustment (hazard ratio [HR], 0.78 [95% CI, 0.64-0.95]; HR, 0.79 [95% CI, 0.71-0.88]; and HR, 0.78 [95% CI, 0.66-0.92], respectively). SN scores were also associated with a lower hazard of coronary heart disease in men (HR, 0.84 [95% CI, 0.75-0.94]) after full adjustment. High versus low SNs were associated with a lower hazard of coronary heart disease and heart failure among women after full adjustment. There was no evidence of mediation by depressive symptoms, diabetes control, and hypertension control. Conclusions Higher SNs may lower the risk of CVD events, especially in women.

Dementia and Parkinson's disease diagnoses in electronic health records vs. Medicare claims data: a study of 101,980 linked patients.

BACKGROUND: Medicare claims and electronic health record data are both commonly used for research and clinical practice improvement; however, it is not known how concordant diagnoses of neurodegenerative diseases (NDD, comprising dementia and Parkinson's disease) are in these data types. Therefore, our objective was to determine the sensitivity and specificity of neurodegenerative disease (NDD) diagnoses contained in structured electronic health record (EHR) data compared to Medicare claims data. METHODS: This was a retrospective cohort study of 101,980 unique patients seen at a large North Carolina health system between 2013-2017, which were linked to 100% North and South Carolina Medicare claims data, to evaluate the accuracy of diagnoses of neurodegenerative diseases in EHRs compared to Medicare claims data. Patients age > 50 who were enrolled in fee-for-service Medicare were included in the study. Patients were classified as having or not having NDD based on the presence of validated ICD-CM-9 or ICD-CM-10 codes associated with NDD or claims for prescription drugs used to treat NDD. EHR diagnoses were compared to Medicare claims diagnoses. RESULTS: The specificity of any EHR diagnosis of NDD was 99.0%; sensitivity was 61.3%. Positive predictive value and negative predictive value were 90.8% and 94.1% respectively. Specificity of an EHR diagnosis of dementia was 99.0%, and sensitivity was 56.1%. Specificity of an EHR diagnosis of PD was 99.7%, while sensitivity was 76.1%. CONCLUSIONS: More research is needed to investigate under-documentation of NDD in electronic health records relative to Medicare claims data, which has major implications for clinical practice (particularly patient safety) and research using real-world data.

Optimizing data integration in trials that use EHR data: lessons learned from a multi-center randomized clinical trial.

BACKGROUND: Despite great promise, trials that ascertain patient clinical data from electronic health records (EHR), referred to here as "EHR-sourced" trials, are limited by uncertainty about how existing trial sites and infrastructure can be best used to operationalize study goals. Evidence is needed to support the practical use of EHRs in contemporary clinical trial settings. MAIN TEXT: We describe a demonstration project that used EHR data to complement data collected for a contemporary multi-center pharmaceutical industry outcomes trial, and how a central coordinating center supported participating sites through the technical, governance, and operational aspects of this type of activity. We discuss operational considerations related to site selection, data extraction, site performance, and data transfer and quality review, and we outline challenges and lessons learned. We surveyed potential sites and used their responses to assess feasibility, determine the potential capabilities of sites and choose an appropriate data extraction strategy. We designed a flexible, multimodal approach for data extraction, enabling each site to either leverage an existing data source, create a new research datamart, or send all data to the central coordinating center to produce the requisite data elements. We evaluated site performance, as reflected by the speed of contracting and IRB approval, total patients enrolled, enrollment yield, data quality, and compared performance by data collection strategy. CONCLUSION: While broadening the type of sites able to participate in EHR-sourced trials may lead to greater generalizability and improved enrollment, sites with fewer technical resources may require additional support to participate. Central coordinating center support is essential to facilitate the execution of operational processes. Future work should focus on sharing lessons learned and creating reusable tools to facilitate participation of heterogeneous trial sites.

Comparing Natural Language Processing and Structured Medical Data to Develop a Computable Phenotype for Patients Hospitalized Due to COVID-19: Retrospective Analysis.

Background: Throughout the COVID-19 pandemic, many hospitals conducted routine testing of hospitalized patients for SARS-CoV-2 infection upon admission. Some of these patients are admitted for reasons unrelated to COVID-19 and incidentally test positive for the virus. Because COVID-19-related hospitalizations have become a critical public health indicator, it is important to identify patients who are hospitalized because of COVID-19 as opposed to those who are admitted for other indications. Objective: We compared the performance of different computable phenotype definitions for COVID-19 hospitalizations that use different types of data from electronic health records (EHRs), including structured EHR data elements, clinical notes, or a combination of both data types. Methods: We conducted a retrospective data analysis, using clinician chart review-based validation at a large academic medical center. We reviewed and analyzed the charts of 586 hospitalized individuals who tested positive for SARS-CoV-2 in January 2022. We used LASSO (least absolute shrinkage and selection operator) regression and random forests to fit classification algorithms that incorporated structured EHR data elements, clinical notes, or a combination of structured data and clinical notes. We used natural language processing to incorporate data from clinical notes. The performance of each model was evaluated based on the area under the receiver operator characteristic curve (AUROC) and an associated decision rule based on sensitivity and positive predictive value. We also identified top words and clinical indicators of COVID-19-specific hospitalization and assessed the impact of different phenotyping strategies on estimated hospital outcome metrics. Results: Based on a chart review, 38.2% (224/586) of patients were determined to have been hospitalized for reasons other than COVID-19, despite having tested positive for SARS-CoV-2. A computable phenotype that used clinical notes had significantly better discrimination than one that used structured EHR data elements (AUROC: 0.894 vs 0.841; P<.001) and performed similarly to a model that combined clinical notes with structured data elements (AUROC: 0.894 vs 0.893; P=.91). Assessments of hospital outcome metrics significantly differed based on whether the population included all hospitalized patients who tested positive for SARS-CoV-2 or those who were determined to have been hospitalized due to COVID-19. Conclusions: These findings highlight the importance of cause-specific phenotyping for COVID-19 hospitalizations. More generally, this work demonstrates the utility of natural language processing approaches for deriving information related to patient hospitalizations in cases where there may be multiple conditions that could serve as the primary indication for hospitalization.

Hyperostosis Fronto-Parieto-Occipitalis: A Cadaveric Case Report.

Hyperostosis of the skull is a rare bone dysplasia described in disorders such as hyperostosis cranialis interna (HCI) and hyperostosis frontalis interna (HFI). Other syndromes presenting with hyperostosis include Morgagni-Stewart-Morel (MSM) and Troell-Junet. HCI is an abnormal hyperostosis of most endosteal skull and calvarium surface regions. A more specific hyperostosis, HFI, is an unusual bone growth based on its volume and porosity; it is primarily located bilaterally on the frontal portions of the calvarium. However, the hyperossification does not cross the superior sagittal sinus. Upon cadaveric dissection, we found hyperossification beyond the frontal area, extending to the parietal and occipital bones with the significant characteristic of no midline interference. Hyperossification results in gross indentations on the corresponding frontal, parietal, and occipital hemispheric brain tissues. This report discusses possible differentials for this rare cadaveric finding of frontal, parietal, and occipital bone hyperostosis. This case report includes some major characteristic features indicative of HCI and HFI with some interesting variations and features suggestive of MSM and Troell-Junet syndromes. Due to the lack of patient history and medical records, no further conclusions about clinical differentials, symptoms, or causative syndromes could be drawn; further research needs to be conducted on HCI, HFI, and related syndromes to understand their presentations better.

Comparative Outcomes of Sacubitril/Valsartan Use After Hospitalization for Heart Failure Among Medicare Beneficiaries Naïve to Renin-Angiotensin System Inhibitors.

Sacubitril/valsartan improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with angiotensin-converting enzyme inhibitors (ACEis). However, data on postdischarge outcomes in renin-angiotensin system inhibitor (RASi)-naïve patients are limited. We included Medicare beneficiaries aged ≥65 years who were hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry between October 2015 and June 2019, had part D prescription coverage, and were not on RASi therapy during the 6 months before hospital admission. We examined the associations between sacubitril/valsartan prescription at hospital discharge and outcomes at 30 days and 1 year after discharge using overlap-weighted median regression and Cox proportional hazards models. The end points included "home time" (defined as days alive and out of any health care institution), mortality, and rehospitalization. Among 3,572 patients with HFrEF and who are naïve to RASi therapy, at discharge, 290 (8.1%) were prescribed sacubitril/valsartan and 1,390 (38.9%) were prescribed ACEis and angiotensin receptor blockers. After adjusting for baseline characteristics, patients prescribed sacubitril/valsartan had a longer median home time (parameter estimate 27.0 days, 95% confidence interval [CI] 12.40 to 41.6, p <0.001) and lower all-cause mortality (hazard ratio [HR] 0.74, 95% CI 0.61 to 0.91, p = 0.004) at 1 year than patients not prescribed sacubitril/valsartan. The prescription of sacubitril/valsartan was not significantly associated with all-cause rehospitalization (HR 0.87, 95% CI 0.74 to 1.03, p = 0.10) or heart failure rehospitalization (HR 0.87, 95% CI 0.70 to 1.07, p = 0.19). In a restricted comparison of patients discharged on sacubitril/valsartan versus ACEis and angiotensin receptor blockers, there were no significant differences in the outcomes. In conclusion, in this contemporary population of RASi-naïve patients with HFrEF from routine clinical practice, compared with not initiating, the initiation of sacubitril/valsartan at discharge was associated with longer home time and improvements in overall survival.

Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

Gender and intention to leave healthcare during the COVID-19 pandemic among U.S. healthcare workers: A cross sectional analysis of the HERO registry.

IMPORTANCE: The COVID-19 pandemic stressed the healthcare field, resulting in a worker exodus at the onset and throughout the pandemic and straining healthcare systems. Female healthcare workers face unique challenges that may impact job satisfaction and retention. It is important to understand factors related to healthcare workers' intent to leave their current field. OBJECTIVE: To test the hypothesis that female healthcare workers were more likely than male counterparts to report intention to leave. DESIGN: Observational study of healthcare workers enrolled in the Healthcare Worker Exposure Response and Outcomes (HERO) registry. After baseline enrollment, two HERO 'hot topic' survey waves, in May 2021 and December 2021, ascertained intent to leave. Unique participants were included if they responded to at least one of these survey waves. SETTING: HERO registry, a large national registry that captures healthcare worker and community member experiences during the COVID-19 pandemic. PARTICIPANTS: Registry participants self-enrolled online and represent a convenience sample predominantly composed of adult healthcare workers. EXPOSURE(S): Self-reported gender (male, female). MAIN OUTCOME: Primary outcome was intention to leave (ITL), defined as having already left, actively making plans, or considering leaving healthcare or changing current healthcare field but with no active plans. Multivariable logistic regression models were performed to examine the odds of intention to leave with adjustment for key covariates. RESULTS: Among 4165 responses to either May or December surveys, female gender was associated with increased odds of ITL (42.2% males versus 51.4% females reported intent to leave; aOR 1.36 [1.13, 1.63]). Nurses had 74% higher odds of ITL compared to most other health professionals. Among those who expressed ITL, three quarters reported job-related burnout as a contributor, and one third reported experience of moral injury. CONCLUSIONS AND RELEVANCE: Female healthcare workers had higher odds of intent to leave their healthcare field than males. Additional research is needed to examine the role of family-related stressors. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04342806.

Self-esteem's impacts on intimacy-building: Pathways through self-disclosure and responsiveness.

Building intimate relationships is rewarding but entails risking rejection. Trait self-esteem-a person's overall self-evaluation-has important implications for how people behave in socially risky situations. Integrating established models of responsiveness and intimacy with theory and research on self-esteem, we present a model that highlights the ways in which self-esteem impacts intimacy-building. A review of relevant research reveals that compared to people with high self-esteem, people with low self-esteem exhibit interpersonal perceptions and behaviors that can hinder intimacy development-for example, disclosing less openly, and eliciting and perceiving less responsiveness from others. We identify important directions for future research and consider methods for encouraging intimacy-promoting processes among people with low self-esteem.

Potential bias and lack of generalizability in electronic health record data: reflections on health equity from the National Institutes of Health Pragmatic Trials Collaboratory.

Embedded pragmatic clinical trials (ePCTs) play a vital role in addressing current population health problems, and their use of electronic health record (EHR) systems promises efficiencies that will increase the speed and volume of relevant and generalizable research. However, as the number of ePCTs using EHR-derived data grows, so does the risk that research will become more vulnerable to biases due to differences in data capture and access to care for different subsets of the population, thereby propagating inequities in health and the healthcare system. We identify 3 challenges-incomplete and variable capture of data on social determinants of health, lack of representation of vulnerable populations that do not access or receive treatment, and data loss due to variable use of technology-that exacerbate bias when working with EHR data and offer recommendations and examples of ways to actively mitigate bias.