Virtual Scribes and Physician Time Spent on Electronic Health Records.

Importance: Time on the electronic health record (EHR) is associated with burnout among physicians. Newer virtual scribe models, which enable support from either a real-time or asynchronous scribe, have the potential to reduce the burden of the EHR and EHR-related documentation. Objective: To characterize the association of use of virtual scribes with changes in physicians' EHR time and note and order composition and to identify the physician, scribe, and scribe response factors associated with changes in EHR time upon virtual scribe use. Design, Setting, and Participants: Retrospective, pre-post quality improvement study of 144 physicians across specialties who had used a scribe for at least 3 months from January 2020 to September 2022, were affiliated with Brigham and Women's Hospital and Massachusetts General Hospital, and cared for patients in the outpatient setting. Data were analyzed from November 2022 to January 2024. Exposure: Use of either a real-time or asynchronous virtual scribe. Main Outcomes: Total EHR time, time on notes, and pajama time (5:30 pm to 7:00 am on weekdays and nonscheduled weekends and holidays), all per appointment; proportion of the note written by the physician and team contribution to orders. Results: The main study sample included 144 unique physicians who had used a virtual scribe for at least 3 months in 152 unique scribe participation episodes (134 [88.2%] had used an asynchronous scribe service). Nearly two-thirds of the physicians (91 physicians [63.2%]) were female and more than half (86 physicians [59.7%]) were in primary care specialties. Use of a virtual scribe was associated with significant decreases in total EHR time per appointment (mean [SD] of 5.6 [16.4] minutes; P < .001) in the 3 months after vs the 3 months prior to scribe use. Scribe use was also associated with significant decreases in note time per appointment and pajama time per appointment (mean [SD] of 1.3 [3.3] minutes; P < .001 and 1.1 [4.0] minutes; P = .004). In a multivariable linear regression model, the following factors were associated with significant decreases in total EHR time per appointment with a scribe use at 3 months: practicing in a medical specialty (-7.8; 95% CI, -13.4 to -2.2 minutes), greater baseline EHR time per appointment (-0.3; 95% CI, -0.4 to -0.2 minutes per additional minute of baseline EHR time), and decrease in the percentage of the note contributed by the physician (-9.1; 95% CI, -17.3 to -0.8 minutes for every percentage point decrease). Conclusions and Relevance: In 2 academic medical centers, use of virtual scribes was associated with significant decreases in total EHR time, time spent on notes, and pajama time, all per appointment. Virtual scribes may be particularly effective among medical specialists and those physicians with greater baseline EHR time.

Development of a Rapid Adeno-Associated Virus (AAV) Identity Testing Platform through Comprehensive Intact Mass Analysis of Full-Length AAV Capsid Proteins.

Adeno-associated viruses (AAVs) are commonly used as vectors for the delivery of gene therapy targets. Characterization of AAV capsid proteins (VPs) and their post-translational modifications (PTMs) have become a critical attribute monitored to evaluate product quality. Liquid chromatography-mass spectrometry (LC-MS) analysis of intact AAV VPs provides both quick and reliable serotype identification as well as proteoform information on each VP. Incorporating these analytical strategies into rapid good manufacturing practice (GMP)-compliant workflows containing robust, but simplified, data processing methods is necessary to ensure effective product quality control (QC) during production. Here, we present a GMP-compliant LC-MS workflow for the rapid identification and in-depth characterization of AAVs. Hydrophilic interaction liquid chromatography (HILIC) MS with difluoroacetic acid as a mobile phase modifier is utilized to achieve the intact separation and identification of AAV VPs and their potential proteoforms. Peptide mapping is performed to confirm PTMs identified during intact VP analysis and for in-depth PTM characterization. The intact separations platform is then incorporated into a data processing workflow developed using GMP-compliant software capable of rapid AAV serotype identification and, if desired, specific serotype PTM monitoring and characterization. Such a platform provides product QC capabilities that are easily accessible in a regulatory setting.

Universal ddPCR-based assay for the determination of lentivirus infectious titer and lenti-modified cell vector copy number.

The translation of cell-based therapies from research to clinical setting requires robust analytical methods that successfully adhere to current good manufacturing practices and regulatory guidelines. Lentiviral vectors are commonly used for gene delivery to generate genetically modified therapeutic cell products. For some cell therapy products, standardized characterization assays for potency and safety have gained momentum. Translational applications benefit from assays that can be deployed broadly, such as for lentiviral vectors with various transgenes of interest. Development of a universal method to determine lentivirus infectious titer and vector copy number (VCN) of lenti-modified cells was performed using droplet digital PCR (ddPCR). Established methods relied on a ubiquitous lenti-specific target and a housekeeping gene that demonstrated comparability among flow cytometry-based methods. A linearized plasmid control was used to determine assay linearity/range, sensitivity, accuracy, and limits of quantification. Implementing this assay, infectious titer was assessed for various production runs that demonstrated comparability to the flow cytometry titer. The ddPCR assay described here also indicates suitability in the determination of VCN for genetically modified CAR-T cell products. Overall, the development of these universal assays supports the implementation of standardized characterization methods for quality control.

Modeling Phenological Phases across Olive Cultivars in the Mediterranean.

Modeling phenological phases in a Mediterranean environment often implies tangible challenges to reconstructing regional trends over heterogenous areas using limited and scattered observations. The present investigation aimed to project phenological phases (i.e., sprouting, blooming, and pit hardening) for early and mid-late olive cultivars in the Mediterranean, comparing two phenological modeling approaches. Phenoflex is a rather integrated but data-demanding model, while a combined model of chill and anti-chill days and growing degree days (CAC_GDD) offers a more parsimonious and general approach in terms of data requirements for parameterization. We gathered phenological observations from nine experimental sites in Italy and temperature timeseries from the European Centre for Medium-Range Weather Forecasts, Reanalysis v5. The best performances of the CAC_GDD (RMSE: 4 days) and PhenoFlex models (RMSE: 5-9.5 days) were identified for the blooming and sprouting phases of mid-late cultivars, respectively. The CAC_GDD model was better suited to our experimental conditions for projecting pit hardening and blooming dates (correlation: 0.80 and 0.70, normalized RMSE: 0.6 and 0.8, normalized standard deviation: 0.9 and 1.0). The optimization of the principal parameters confirmed that the mid-late cultivars were more adaptable to thermal variability. The spatial distribution illustrated the near synchrony of blooming dates between the early and mid-late cultivars compared to other phases.

Fine-scale population structure of the northern hard clam (Mercenaria mercenaria) revealed by genome-wide SNP markers.

Aquaculture is growing rapidly worldwide, and sustainability is dependent on an understanding of current genetic variation and levels of connectivity among populations. Genetic data are essential to mitigate the genetic and ecological impacts of aquaculture on wild populations and guard against unintended human-induced loss of intraspecific diversity in aquacultured lines. Impacts of disregarding genetics can include loss of diversity within and between populations and disruption of local adaptation patterns, which can lead to a decrease in fitness. The northern hard clam, Mercenaria mercenaria (Linnaeus, 1758), is an economically valuable aquaculture species along the North American Atlantic and Gulf coasts. Hard clams have a pelagic larval phase that allows for dispersal, but the level of genetic connectivity among geographic areas is not well understood. To better inform the establishment of site-appropriate aquaculture brood stocks, this study used DArTseq™ genotyping by sequencing to characterize the genetic stock structure of wild clams sampled along the east coast of North America and document genetic diversity within populations. Samples were collected from 15 locations from Prince Edward Island, Canada, to South Carolina, USA. Stringent data filtering resulted in 4960 single nucleotide polymorphisms from 448 individuals. Five genetic breaks separating six genetically distinct populations were identified: Canada, Maine, Massachusetts, Mid-Atlantic, Chesapeake Bay, and the Carolinas (F ST 0.003-0.046; p < 0.0001). This is the first study to assess population genetic structure of this economically important hard clam along a large portion of its native range with high-resolution genomic markers, enabling identification of previously unrecognized population structure. Results of this study not only broaden insight into the factors shaping the current distribution of M. mercenaria but also reveal the genetic population dynamics of a species with a long pelagic larval dispersal period along the North American Atlantic and Gulf coasts.

Assessing the suitability of cell counting methods during different stages of a cell processing workflow using an ISO 20391-2 guided study design and analysis.

Cell counting is a fundamental measurement for determining viable cell numbers in biomanufacturing processes. The properties of different cell types and the range of intended uses for cell counts within a biomanufacturing process can lead to challenges in identifying suitable counting methods for each potential application. This is further amplified by user subjectivity in identifying the cells of interest and further identifying viable cells. Replacement of traditionally used manual counting methods with automated systems has alleviated some of these issues. However, a single cell type can exhibit different physical properties at various stages of cell processing which is further compounded by process impurities such as cell debris or magnetic beads. These factors make it challenging to develop a robust cell counting method that offers a high level of confidence in the results. Several initiatives from standards development organizations have attempted to address this critical need for standardization in cell counting. This study utilizes flow-based and image-based methods for the quantitative measurement of cell concentration and viability in the absence of a reference material, based on the tools and guidance provided by the International of Standards (ISO) and the US National Institute of Standards and Technology (NIST). Primary cells were examined at different stages of cell processing in a cell therapy workflow. Results from this study define a systematic approach that enables the identification of counting methods and parameters that are best suited for specific cell types and workflows to ensure accuracy and consistency. Cell counting is a foundational method used extensively along various steps of cell and gene therapy. The standard used in this study may be applied to other cell and gene therapy processes to enable accurate measurement of parameters required to guide critical decisions throughout the development and production process. Using a framework that confirms the suitability of the cell counting method used can minimize variability in the process and final product.

SP3-based host cell protein monitoring in AAV-based gene therapy products using LC-MS/MS.

Residual host cell proteins (HCPs) represent a critical quality attribute of biotherapeutic drug products. Workflows enabling reliable HCP detection in monoclonal antibodies and recombinant proteins have been developed, which facilitated process optimization to improve product stability and safety, and allowed setting of acceptance limits for HCP content. However, the detection of HCPs in gene therapy products such as adeno-associated viral (AAV) vectors has been limited. Here, the use of SP3 sample preparation followed by liquid chromatography-mass spectrometry (LC-MS) analysis for HCP profiling in various AAV samples is reported. Suitability of the workflow is demonstrated and provided data constitutes an important reference for future work aiming towards a knowledge-driven improvement of manufacturing conditions and characterization of AAV vector products.

Mini-review: Equipment evaluation for process scalability and readiness for current Good Manufacturing Practices in cell therapy workflows.

Cell therapies present a promising treatment for a variety of diseases and are a rapidly growing market. This facilitates the need for robust biomanufacturing processes that can be implemented early during process establishment which enables scalable and reproducible manufacturing. Historically, cell therapy has used equipment originally repurposed from biologics, where the supernatant is harvested at the end of production and not the cells. Unlike biologics, cell therapy requires the preservation of cell phenotype and potency, as well as the functional recovery of the cells for the final formulation. These traditional equipment platforms have been widely adopted and, in many cases, successfully. However, given that cell therapy processes are complex, equipment specifically designed for the intended application will add immense value by producing products that are pure, potent and stable. New equipment better suited for cell therapy is being introduced to improve efficiency and product quality compared with current systems, fill key gaps that exist in current workflows or address an emerging need in new paradigms. Integration of these new instruments in laboratories using current Good Manufacturing Practices to produce cell-based drug products and drug substances requires a risk-based approach to evaluate features based on suitability and compliance with regulatory requirements. The speed at which new equipment is evaluated and implemented into new workflows is critical to match the speed of therapeutic product innovations and manufacturing capabilities. Here, we outline a framework to evaluate new equipment and de-risk implementation based on a series of features, namely, hardware, software, consumables, and workflow compatibility for the intended use. A hypothetical evaluation of three cell processing workflows is used as an example to inform equipment deployment for early process establishment and translational use for current Good Manufacturing Practices-destined workflows.

Historical evaluation of the in vivo adventitious virus test and its potential for replacement with next generation sequencing (NGS).

The Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) collected historical data from 20 biopharmaceutical industry members on their experience with the in vivo adventitious virus test, the in vitro virus test, and the use of next generation sequencing (NGS) for viral safety. Over the past 20 years, only three positive in vivo adventitious virus test results were reported, and all were also detected in another concurrent assay. In more than three cases, data collected as a part of this study also found that the in vivo adventitious virus test had given a negative result for a sample that was later found to contain virus. Additionally, the in vivo adventitious virus test had experienced at least 21 false positives and had to be repeated an additional 21 times all while using more than 84,000 animals. These data support the consideration and need for alternative broad spectrum viral detection tests that are faster, more sensitive, more accurate, more specific, and more humane. NGS is one technology that may meet this need. Eighty one percent of survey respondents are either already actively using or exploring the use of NGS for viral safety. The risks and challenges of replacing in vivo adventitious virus testing with NGS are discussed. It is proposed to update the overall virus safety program for new biopharmaceutical products by replacing in vivo adventitious virus testing approaches with modern methodologies, such as NGS, that maintain or even improve the final safety of the product.

Meteorological driving forces of reference evapotranspiration and their trends in California.

Reference evapotranspiration (ETo) is a variable that helps determine atmospheric pressure on living (reference) grass to release water into the atmosphere. For this purpose, four main driving forces: air temperature, air humidity, solar radiation, and wind speed need to be measured over the well-watered reference grass. The relative influence of these driving forces is region and climate-specific, with daily and seasonal variations. A clear understanding of the dynamic interactions of ETo's driving factors can illuminate the water and energy cycles of the earth and assist modelers with more accurate predictions of ETo. In this study, Pearson correlation, mutual information, and random forest feature importance analyses have been used to evaluate the relative importance of meteorological driving forces of ETo in California. To better understand the interrelations of these variables, 1,365,823 daily data samples from 237 standardized weather stations for 36 years have been clustered into homogeneous climatic zones and analyzed. To compensate for the effects of seasonality, feature importance analysis is also conducted on seasonal and monthly clustered data. Moreover, seasonal and annual trends of ETo and its driving factors are investigated for California and homogeneous zones using the Mann-Kendall test. Our findings reveal that for annually clustered data, solar radiation is the most influential driving factor of ETo in California. However, analysis of seasonal and monthly clustered data shows that vapor pressure deficit is the most informative factor during the summer and spring, while solar radiation is more important during the colder seasons. Results of trend analysis don't suggest a consistent monotonic trend for ETo and other variables for different seasons and zones. However, it is shown that agricultural regions with heavy irrigation dependence like the Central Valley are getting warmer and drier, especially during the irrigation season. This can adversely affect the water resources, agriculture industry, and food production of California, and modeling efforts like this can be very informative for future water resources management.

Incidence and Severity of Depression Among Recovered African Americans with COVID-19-Associated Respiratory Failure.

BACKGROUND: Coronavirus disease (COVID-19) disproportionately affects African Americans, and they tend to experience more severe course and adverse outcomes. Using a simple and validated instrument of depression screening, we evaluated the incidence and severity of major depression among African American patients within 90 days of recovery from severe COVID-19-associated respiratory failure. METHODS: African American patients hospitalized and treated with invasive mechanical ventilation for COVID-19-associated respiratory failure in the intensive care unit (ICU) of Grady Memorial Hospital, Atlanta, between April 1, 2020, and June 30, 2020, were screened for depression within 90 days of hospital discharge using the validated patient health questionnaires (PHQ-2) and PHQ-9. RESULTS: A total of 73 patients completed the questionnaire. The median age was 52.5 years [IQR 44-65] and 65% were males. The most common comorbidities were hypertension (66%) and diabetes mellitus (51%). Forty-four percent of the patients had a diagnosis of major depressive disorder (MDD) based on their PHQ-9 questionnaire responses. The incidence of MDD was higher among females (69%, n=18/26) compared to males (29%, n=14/47), in patients > 75 years (66%) and those with multiple comorbidities (45%). Eighteen percent of the patients had moderate depression, while 15% and 22% had moderately severe and severe depression, respectively. Only 26% (n=7/27) of eligible patients were receiving treatment for depression at the time of this survey. CONCLUSION: The incidence of depression in a cohort of African American patients without prior psychiatric conditions who recovered from severe COVID-19 infection was 44%. More than 70% of these patients were not receiving treatment for depression.

Association between race and risk of ICU mortality in mechanically ventilated COVID-19 patients at a safety net hospital.

PURPOSE: To determine racial differences in intensive care unit (ICU) mortality outcomes among mechanically ventilated patients with severe coronavirus disease 2019 (COVID-19) infection in a safety net hospital. METHODS: We retrospectively analyzed a cohort of patients ≥ 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease associated respiratory failure who were treated with invasive mechanical ventilation and admitted to the ICU from May 1, 2020 - July 30 -2020 at Grady Memorial Hospital, Atlanta, Georgia - a safety net hospital. We evaluated the association between mortality and demographics, co-morbidities, inpatient laboratory, and radiological parameters. RESULTS: Among 181 critically ill mechanically ventilated African American patients treated at a safety net hospital, the mortality rate was 33%. On stratified analysis by race (Table 2), mortality rates were significantly higher in African Americans (39%) and Hispanics (26.3%), compared to Whites (18.9%). On multivariate regression, African Americans were 3 times more likely to die in the ICU compared to Whites (OR 3.1 95% CI 1.6 -5.5). Likewise, the likelihood of mortality was higher in Hispanics compared to Whites (OR 1.3 95% CI 1.0 -3.9). CONCLUSIONS: Our study demonstrated a high ICU mortality rate in a cohort of mechanically ventilated patients with severe COVID-19 infection treated at a safety net hospital. African Americans and Hispanics had significantly higher risks of ICU mortality compared to Whites. These study findings further elucidate the disproportionately higher burden of COVID-19 infection in African Americans and Hispanics.

Sudden Cardiac Arrest During the Immediate Revascularization Period in Patients With Non-ST Elevation Myocardial Infarction: A Case Series.

INTRODUCTION: The timing of sudden cardiac arrest (SCA) after myocardial infarction (MI) has been a subject of research because of the impact on preventive strategies. Currently, there is limited data on the risk of SCA in the immediate post revascularization period (≤48 h) in non-ST segment elevation myocardial infarction (NSTEMI). METHODS: We retrospectively reviewed the electronic medical record system and identified patients who underwent revascularization for NSTEMI at Grady Memorial Hospital, Atlanta, Georgia between January 1st, 2014-December 31st, 2019. We selected patients who had SCA within 48 h of revascularization and evaluated their socio-demographic and inpatient characteristics and outcomes. RESULTS: Sixteen (16) cases of SCA in the immediate post revascularization period (within 48 h) were identified and analyzed which corresponds to an incidence rate of 1.8% (n = 16/869). The mean age (SD) was 69 years (14.6) and 75% were males. On angiography, more than 80% of the patients had hemodynamically significant lesions in the left anterior descending arteries and its territories and 50% had multivessel disease. All 16 patients had at least one coronary artery with hemodynamically significant lesion and successfully underwent revascularization. Three-quarter of the patients had a shockable rhythm. The etiology of SCA was in-stent thrombosis in 25% of the patients, cardiogenic shock in 19%, acute respiratory failure in 13% and unknown in 44% of the cases. The 30-day mortality rate was 38%. CONCLUSION: The rate of SCA is high in the first 48 h after MI even with revascularization. Risk stratification for SCA during this critical period may improve outcomes.

Intensive care unit hospitalizations and outcomes in patients with severe COVID-19 during summer and fall surges in Georgia.

BACKGROUND: There is limited data on the difference in the clinical characteristics and outcomes of patients with severe coronavirus disease 2019 (COVID-19) infection in the summer compared to the fall surge. AIM: To compare the sociodemographic, clinical characteristics, and outcomes among mechanically ventilated patients with severe COVID-19 infection admitted to the intensive care unit (ICU) during the summer and fall surges in the year 2020. METHODS: We included patients admitted to the ICU and treated with invasive mechanical ventilation for COVID-19 associated respiratory failure between April 1 and December 31, 2020. Patients were categorized into summer surge for ICU admissions between June 15, 2020, and August 15, 2020, and fall surge between October 15, 2020, and December 31, 2020. We compared patients' characteristics and outcomes using descriptive and inferential statistics. RESULTS: A total of 220 patients were admitted to the Grady Memorial Hospital ICU and mechanically ventilated for COVID-19 associated hypoxemic respiratory failure during the period considered (125 during the summer surge and 95 during the fall surge). More women were admitted in the fall compared to summer (41.1% vs 36.8%, difference, 4.3%; 95%CI: 1.2, 7.5). Patients admitted in the fall had fewer comorbidities (chronic obstructive pulmonary disease, stroke, diabetes mellitus, obstructive sleep apnea and body mass index ≥ 35 kg/m2). Overall, patients in the fall had a lower ICU mortality rate (27.4% vs 38.4%, difference, -11.0; 95%CI: -6.4, -18.2), shorter length of stay on the mechanical ventilator (7 d vs 11 d, difference, 4 d; 95%CI: 2.1, 6.6) and shorter ICU length of stay (9 d vs 14 d, difference, 5 d; 95%CI: 2.7, 9.4). CONCLUSION: Patients admitted with severe COVID-19 infection requiring mechanical ventilation had better outcomes in the fall than summer. This difference observed is likely attributable to a better understanding of the condition and advances in treatment strategies.

Changes in COVID-19 vaccine acceptance rate among recovered critically Ill patients: A 12-month follow-up study.

INTRODUCTION: We surveyed a cohort of patients who recovered from severe SARS-CoV-2 infection to determine the COVID-19 vaccination rate. We also compared the willingness to accept COVID-19 vaccine before and after its availability to assess changes in perception and attitude towards vaccination. MATERIALS AND METHODS: Recovered patients with severe hypoxemic respiratory failure from SARS-CoV-2 infection treated in the ICU at Grady Memorial Hospital, Atlanta, Georgia between April 1, 2020, and June 30, 2020 were followed up over a 1-year period to assess vaccine acceptability and acceptance rates, and changes in perception towards COVID-19 vaccination before and after vaccine availability. RESULTS: A total of 98 and 93 patients completed the initial and follow up surveys respectively. During the initial survey, 41% of the patients intended to receive vaccination, 46% responded they would not accept a vaccine against COVID-19 even if it were proven to be 'safe and effective 'and 13% undecided. During the follow up survey, 44% of the study cohort had received at least one dose of a COVID-19 vaccine. Major reasons provided by respondents for not accepting COVID-19 vaccine were lack of trust in the effectiveness of the vaccine, pharmaceutical companies, government, vaccine technology, fear of side effects and perceived immunity against COVID-19. Respondents were more likely to be vaccinated if recommended by their physicians (OR 6.4, 95% CI 2.8-8.3), employers (OR 2.5, 95% CI 1.9-5.8), and family and friends (OR 1.6, 95% CI 1.1-4.5). CONCLUSION: We found a suboptimal COVID-19 vaccination rate in a cohort of patients who recovered from severe infection. COVID-19 vaccine information and recommendation by healthcare providers, employers, and family and friends may improve vaccination uptake.

Anaphylactic Food Allergy After Roux-en-Y Gastric Bypass.

The prevalence of obesity in the United States is projected to increase as high as 85% by 2030. Weight loss is associated with improved morbidity and mortality outcomes. Roux-en-Y gastric bypass (RYGB) is an effective procedure recommended for individuals with morbid obesity for weight loss. We report the case of a patient who developed worsening food allergic reactions after RYGB surgery that progressed to an anaphylactic reaction. A 36-year-old female developed an anaphylactic reaction to an ingredient in guacamole eight years after RYGB surgery. Prior to the surgery, she had symptoms consistent with oral allergy syndrome. After the gastric bypass, however, she experienced worsening symptoms. On this occasion, she developed throat tightness prompting a visit to the emergency department where she required emergent intubation for airway protection. Blood testing to assess for an immunoglobin E-mediated allergy to common foods was negative. Despite the negative test, the allergist maintained a high suspicion for the progression of food-pollen syndrome following gastric bypass. Disruption of protein digestion from stomach bypass surgery may result in dietary proteins large enough to elicit immune responses being presented to the immune-rich intestinal mucosa. Additional consideration should be given to patients with a preexisting history of food allergic reactions undergoing RGYB surgery.

Infective Endocarditis Manifesting as Severe Elevation in Serum Aminotransferases in the Absence of Severe Tricuspid Regurgitation, Heart Failure, or Shock: A Diagnostic Challenge.

Infective endocarditis (IE) is a challenging condition to diagnose, given its protean clinical signs and symptoms, Elevation in serum aminotransferases in IE is associated with valvular regurgitation, acute heart failure, or congestive hepatopathy. Studies show co-existing liver failure portends worsening outcomes in IE and poses a challenge for successful surgical management. Here we report a diagnostic challenge in a 35-year-old man with IE presenting predominantly with gastrointestinal symptoms and severe elevation in serum aminotransferase. The degree of aminotransferase elevation in our patient prompted consideration of alternative causes like acetaminophen toxicity. Severe elevation in aminotransferases as an initial presentation in the absence of significant valvular regurgitation, acute right heart failure, or shock is uncommon. A high degree of suspicion is required to diagnose IE when patients present with atypical signs and symptoms to avoid delay in initiation of antibiotics and improve overall morbidity and mortality.

Renal Phosphate Wasting Due to Tumor-Induced (Oncogenic) Osteomalacia.

Osteomalacia is a widely prevalent bone disorder that is caused by an imbalance in body calcium and phosphate. Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia that is associated with mesenchymal tumors. It is caused by overproduction of fibroblast growth factor 23 (FGF-23), a hormone involved in phosphate regulation. A 59-year-old male with a history of factor V Leiden mutation, pulmonary embolism, and deep vein thrombosis was diagnosed with oncogenic osteomalacia in 2008 following laboratory findings significant for low phosphorus and elevated FGF-23 levels. He underwent a resection of a right suprascapular notch mass with the biopsy confirming a phosphaturic mesenchymal tumor. He was maintained on oral phosphorus and calcitriol replacements with a regular follow-up with oncology and nephrology. Eight years later, the patient's phosphorus levels started declining despite replacement. A repeat test showed FGF-23 levels once again elevated. A whole-body magnetic resonance imaging (MRI) scan showed no significant findings. The patient was continued on oral replacement therapy with a close follow-up. Two years later, urine phosphorus excretion was elevated at 2494 mg per 24 hours with low plasma phosphorus (1.2 mg/dL) and an elevated FGF-23 level of 1005 relative units (RU)/mL. A repeat MRI of the right shoulder revealed a mass in the supraspinatus muscle and another in the spinal glenoid notch. The masses were resected and the biopsy was consistent with a recurrence of the phosphaturic mesenchymal tumor. Follow-up serum phosphate levels remained in the normal range. FGF-23 plays a critical role in bone mineralization through the regulation of phosphate levels. Overproduction, as seen in mesenchymal tumors, results in hyperphosphaturia, hypophosphatemia, and low calcitriol levels. While the definitive treatment of TIO involves the resection of the mesenchymal tumor, localization of the tumor is often challenging given its small size and slow growth. This leads to delayed diagnosis and treatment. For individuals whose tumor cannot be resected or detected, burosumab is the preferred form of therapy. Interestingly, FGF-23 is shown to have a potential cardiovascular (CV) morbidity and mortality through various mechanisms like activation of myocardial FGF-23 receptors, endothelial dysfunction, inflammation, and altered phosphorus and vitamin D metabolisms. While studies have shown possible FGF-23 effects on CV outcomes in patients with chronic kidney disease, this has not been proven in cases of TIO.

Who Stays at Home? The Politics of Social Distancing in Brazil, Mexico, and the United States during the COVID-19 Pandemic.

CONTEXT: Reductions in population mobility can mitigate COVID-19 virus transmission and disease-related mortality. But do social distancing policies actually change population behavior and, if so, what factors condition policy effects? METHODS: We leverage subnational variation in the stringency and timing of state-issued social distancing policies to test their effects on mobility across 109 states in Brazil, Mexico, and the United States. We also explore how conventional predictors of compliance, including political trust, socioeconomic resources, health risks, and partisanship, modify these policy effects. FINDINGS: In Brazil and the United States, stay-at-home orders and workplace closures reduced mobility, especially early in the pandemic. In Mexico, where federal intervention created greater policy uniformity, workplace closures produced the most consistent mobility reductions. Conventional explanations of compliance perform well in the United States but not in Brazil or Mexico, apart from those emphasizing socioeconomic resources. CONCLUSIONS: In addition to new directions for research on the politics of compliance, the article offers insights for policy makers on which measures are likely to elicit compliance. Our finding that workplace closure effectiveness increases with socioeconomic development suggests that cash transfers, stimulus packages, and other policies that mitigate the financial burdens of the pandemic may help reduce population mobility.