Search

The authors explore the role of social-emotional learning in developing positive behaviors in students and the related challenges faced by teachers in the United States and India.

Background In 2020, the American Society of Shoulder and Elbow Therapists (ASSET) published an evidence-based consensus statement outlining postoperative rehabilitation guidelines following anatomic total shoulder arthroplasty (TSA). Purpose The purpose of this study was to (1) quantify the variability in online anatomic TSA rehabilitation protocols, and (2) assess their congruence with the ASSET consensus guidelines. Methods This study was a cross-sectional investigation of publicly available, online rehabilitation protocols for anatomic TSA. A web-based search was conducted in April 2022 of publicly available rehabilitation protocols for TSA. Each collected protocol was independently reviewed by two authors to identify recommendations regarding immobilization, initiation, and progression of passive (PROM) and active range of motion (AROM), as well as the initiation and progression of strengthening and post-operative exercises and activities. The time to initiation of various components of rehabilitation was recorded as the time at which the activity or motion threshold was permitted by the protocol. Comparisons between ASSET start dates and mean start dates from included protocols were performed. Results Of the 191 academic institutions included, 46 (24.08%) had publicly available protocols online, and a total of 91 unique protocols were included in the final analysis. There were large variations seen among included protocols for the duration and type of immobilization post-operatively, as well as for the initiation of early stretching, PROM, AROM, resistance exercises, and return to sport. Of the 37 recommendations reported by both the ASSET and included protocols, 31 (83.78%) were found to be significantly different between groups (p<0.05). [ABSTRACT FROM AUTHOR]

Objective: To summarize the prevalence of ALS in all 50 states and Washington, DC in the United States from 2011 to 2018 using data collected and analyzed by the National ALS Registry. In October 2010, the federal Agency for Toxic Substances and Disease Registry (ATSDR) launched the congressionally mandated Registry to determine the incidence and prevalence of ALS within the USA, characterize the demographics of persons with ALS, and identify the potential risk factors for the disease. This is the first analysis of state-level ALS prevalence estimates. Methods: ALS is not a notifiable disease in the USA, so the Registry uses a two-pronged approach to identify cases. The first approach uses existing national administrative databases (Medicare, Veterans Health Administration, and Veterans Benefits Administration). The second method uses a secure web portal to gather voluntary participant data and identify cases not included in the national administrative databases. Results: State-level age-adjusted average prevalence from 2011–2018 ranged from 2.6 per 100,000 persons (Hawaii) to 7.8 per 100,000 persons (Vermont), with an average of 4.4 per 100,000 persons in the US. New England and Midwest regions had higher prevalence rates than the national average. Conclusions: These findings summarize the prevalence of ALS for all 50 states from 2011 to 2018. This is a continuing effort to identify ALS cases on a national population basis. The establishment of the National ALS Registry has allowed for epidemiological trends of this disease and the assessment of potential risk factors that could cause ALS. [ABSTRACT FROM AUTHOR]

South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations. [ABSTRACT FROM AUTHOR]

Chronic pain syndromes affect over one-third of the US adult population and often lead to significant disability and a reduced quality of life. Despite their high prevalence, causal links between chronic pain syndromes and anatomic abnormalities are often not apparent. Most current chronic pain treatments provide modest, if any, relief. Thus, there is a pressing need to understand the causal mechanisms implicated in chronic pain as a means to develop more targeted interventions for improvement in clinical outcomes and reduction in morbidity and financial burden. In the present manuscript, we summarize the current literature on treatment for chronic pain, and hypothesize that nonspecific chronic back pain (without a clear organic etiology, such as tumors, infections or fractures) is of psychophysiologic origin. Based on this hypothesis, we developed Psychophysiologic Symptom Relief Therapy (PSRT), a novel pain reduction intervention for understanding and treating chronic pain. In this manuscript, we provide the rationale for PSRT, which we have tested in a pilot trial with a subsequent larger randomized trial underway. In the proposed trial, we will evaluate whether non-specific chronic back pain can be treated by addressing the underlying stressors and psychological underpinnings without specific physical interventions. [ABSTRACT FROM AUTHOR]

Objective: Both psychosocial stress and gestational weight gain are independently associated with adverse maternal and fetal outcomes. Studies of the association between psychosocial stress and gestational weight gain (GWG) have yielded mixed results. The objective of this study was to evaluate the association between psychosocial stress and GWG in a large population-based cohort. Methods: Data from the nationally representative Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 questionnaire 2012–2015 was utilized. Maternal psychosocial stress was assessed through response to questions designed to examine four domains of psychosocial stress (i.e., traumatic, financial, emotional, partner-related) three months prior to or during pregnancy. GWG was categorized using pre-pregnancy BMI and total GWG into inadequate, adequate, or excessive according to the Institute of Medicine's GWG guidelines. Multinomial logistic regression was used to evaluate the association between psychosocial stressors and adequacy of GWG. Analyses took into account complex survey design. Results: All respondents who delivered ≥ 37 weeks gestation with GWG information available were included in the analysis (n = 119,183). After adjusting for confounders, patients who reported financial stress were more likely to experience excessive versus adequate GWG (RRR 1.09 [95%CI: 1.02–1.17]). Exposure to any of the stressor groups did not significantly increase the risk of inadequate GWG. Conclusions: This large, population-based study revealed that among pregnant people in the US, exposure to financial stress is associated with higher risk of excessive GWG. Understanding the role stress plays in GWG will help to inform initiatives targeting this important aspect of prenatal care. Significance: What is already known on this subject?: Excessive gestational weight gain (GWG) has been linked to postpartum weight retention and long-term adverse maternal and child health outcomes. Multiple studies have shown an association between psychosocial stress and adverse fetal outcomes. Risks of inadequate weight gain include low birthweight and failure to initiate breast-feeding whereas the risks of excessive weight gain include cesarean deliveries and postpartum weight retention for the mother and large-for-gestational-age infants, macrosomia, and childhood overweight or obesity for the offspring. What this study adds?: The 2012–2015 Pregnancy Risk Assessment Monitoring System (PRAMS) provides unique nationally representative data in which birth outcomes and maternal weight are linked to psychosocial stressors. Our study is the largest of its kind examining the link between stress and GWG and reveals that exposure to financial stress is associated with higher risk of excessive GWG in the US. [ABSTRACT FROM AUTHOR]

Objectives: Natural language processing (NLP) represents one of the adjunct technologies within artificial intelligence and machine learning, creating structure out of unstructured data. This study aims to assess the performance of employing NLP to identify and categorize unstructured data within the emergency medicine (EM) setting. Methods: We systematically searched publications related to EM research and NLP across databases including MEDLINE, Embase, Scopus, CENTRAL, and ProQuest Dissertations & Theses Global. Independent reviewers screened, reviewed, and evaluated article quality and bias. NLP usage was categorized into syndromic surveillance, radiologic interpretation, and identification of specific diseases/events/syndromes, with respective sensitivity analysis reported. Performance metrics for NLP usage were calculated and the overall area under the summary of receiver operating characteristic curve (SROC) was determined. Results: A total of 27 studies underwent meta‐analysis. Findings indicated an overall mean sensitivity (recall) of 82%–87%, specificity of 95%, with the area under the SROC at 0.96 (95% CI 0.94–0.98). Optimal performance using NLP was observed in radiologic interpretation, demonstrating an overall mean sensitivity of 93% and specificity of 96%. Conclusions: Our analysis revealed a generally favorable performance accuracy in using NLP within EM research, particularly in the realm of radiologic interpretation. Consequently, we advocate for the adoption of NLP‐based research to augment EM health care management. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to pilot test a well-being curriculum for KL2 scholars to be used across the Clinical and Translational Science Award consortium. Methods: Between November 2022, and May 2023, 36 KL2 scholars from 25 hubs participated in the program. The General Well-Being Index for U.S. Workers and the Patient Reported Outcomes Measurement Information System (PROMIS-29) were completed by scholars before and after the program. Results: Postparticipation, there was a trend of improvement in the domains of well-being, sleep, anxiety, and fatigue. Conclusion: Implementing a virtual synchronous well-being curriculum allowed the scholars to connect across the consortium and improve their well-being. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic fractures can be devastating complications after total joint arthroplasty (TJA). The management of periprosthetic fractures is complex, spanning expertise in arthroplasty and trauma. The purpose of this study was to examine and project trends in the operative treatment of periprosthetic fractures in the United States. Methods: A large, public and private payer database was queried to capture all International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes for periprosthetic femoral and tibial fractures. Statistical models were created to assess trends in treatment for periprosthetic fractures and to predict future surgical rates. An alpha value of 0.05 was used to assess significance. A Bonferroni correction was applied where applicable to account for multiple comparisons. Results: In this study, from 2016 to 2021, 121,298 patients underwent surgical treatment for periprosthetic fractures. There was a significant increase in the total number of periprosthetic fractures. The incidence of periprosthetic hip fractures rose by 38% and that for periprosthetic knee fractures rose by 73%. The number of periprosthetic fractures is predicted to rise 212% from 2016 to 2032. There was a relative increase in open reduction and internal fixation (ORIF) compared with revision arthroplasty for both periprosthetic hip fractures and periprosthetic knee fractures. Conclusions: Periprosthetic fractures are anticipated to impose a substantial health-care burden in the coming decades. Periprosthetic knee fractures are predominantly treated with ORIF rather than revision total knee arthroplasty (TKA), whereas periprosthetic hip fractures are predominantly treated with revision total hip arthroplasty (THA) rather than ORIF. Both periprosthetic knee fractures and periprosthetic hip fractures demonstrated increasing trends in this study. The proportion of periprosthetic hip fractures treated with ORIF relative to revision THA has been increasing. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The retina is one of the most complex and extraordinary human organs affected by genetic, metabolic, and degenerative diseases, resulting in blindness for ∼1.3 million people in the United States and over 40 million people worldwide. This translates into a huge loss of productivity, especially among younger patients with inherited retinal diseases (IRDs) and diabetic retinopathy. Age-related macular degeneration accounts for 90% of all blindness cases worldwide. The prevalence of this condition is projected to reach over 5 million individuals over the next 3 decades. There are also >20 IRD phenotypes, affecting >2 million people worldwide. Nanobiotechnology uses nanotechnology for biological applications, making use of biological materials either conceptually or directly in the fabrication of new materials. Bionanotechnology, on the other hand, uses molecular biology for the purpose of creating nanostructures (ie, structures with at least 1 dimension <100 nm). Retinal applications of these technologies are developing at a rapid pace. This review includes the most current nanotechnological applications in retinal diagnostics, theranostics, drug delivery, and targeting, including the potential for nonviral vehicles such as liposomes, micelles, and dendrimers, which pose advantages over viral vectors in retinal drug delivery. Furthermore, we discuss current and future applications as surgical adjuncts and in regenerative medicine as they pertain to retinal disease. Structure and function of nanoparticles such as carbon nanotubules, quantum dots, and magnetic nanoparticles, as well as diagnostic technologies such as next-generation DNA sequencing and single-molecule bionanosensing, will also be discussed. [ABSTRACT FROM AUTHOR]

More than 25 million Americans have limited English-language proficiency (LEP) according to the U.S. Census Bureau. This population experiences challenges accessing health care and is least likely to receive preventive health care, including screening mammogram. In a setting where the breast radiologist does not speak the language of their patient, using certified medical interpreter services is fundamental. Medical interpreter use is associated with improved clinical care and patient satisfaction and can potentially increase adherence to screening mammograms and follow-up in patients with LEP. Title VI of the Civil Rights Act requires interpreter services for patients with LEP who are receiving federal financial assistance. Failure to provide interpretative services when necessary is considered discriminatory and illegal. The use of untrained medical interpreters, including ad hoc interpreters (eg, family, friends, or untrained staff), is associated with more medical errors, violation of confidentiality, and poor health outcomes. Types of medical interpretation services available to address language barriers include in-person interpretation, telephone and video remote interpretation, and qualified bilingual staff. Proper training and certification of medical interpreters is essential to prevent misinterpretations and ensure patient safety. When using an interpreter service, speak to and maintain eye contact with the patient, address the patient directly and seat the interpreter next to or slightly behind the patient, use visual aids whenever possible, and have the patient repeat the information to verify comprehension. Breast radiologists can address disparities in breast cancer screening and treatment by promoting effective communication. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) causes 5% of cancers and is the main cause of oropharyngeal cancer in the United States and of cervical cancer worldwide. HPV proteins induce DNA damage and exploit and hijack the host DNA damage response. The HPV oncoproteins E6 and E7 induce chromosomal instability (CIN), or chromosome missegregation during mitosis, which also causes DNA damage and can lead to profound genetic alterations in the host cell. Though these features are known to contribute to HPV-induced carcinogenesis, how this affects tumor cell response to DNA damaging treatments is not well understood. Here, we review how HPV induces DNA damage and activates the DNA damage response and how the HPV-induced CIN likely exacerbates this. We then discuss how this viral protein-mediated DNA damage may affect the efficacy of chemoradiation therapy. High-risk human papillomaviruses (HPVs) are the main cause of cervical, oropharyngeal, and anogenital cancers, which are all treated with definitive chemoradiation therapy when locally advanced. HPV proteins are known to exploit the host DNA damage response to enable viral replication and the epithelial differentiation protocol. This has far-reaching consequences for the host genome, as the DNA damage response is critical for the maintenance of genomic stability. HPV+ cells therefore have increased DNA damage, leading to widespread genomic instability, a hallmark of cancer, which can contribute to tumorigenesis. Following transformation, high-risk HPV oncoproteins induce chromosomal instability, or chromosome missegregation during mitosis, which is associated with a further increase in DNA damage, particularly due to micronuclei and double-strand break formation. Thus, HPV induces significant DNA damage and activation of the DNA damage response in multiple contexts, which likely affects radiation sensitivity and efficacy. Here, we review how HPV activates the DNA damage response, how it induces chromosome missegregation and micronuclei formation, and discuss how these factors may affect radiation response. Understanding how HPV affects the DNA damage response in the context of radiation therapy may help determine potential mechanisms to improve therapeutic response. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. Methods: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. Results: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. Conclusions: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival. [ABSTRACT FROM AUTHOR]

Background: Hospitalized people with amyotrophic lateral sclerosis (ALS) may benefit from specialty palliative care services (sPCS). Objective: To describe access to in-hospital sPCS for people with ALS (pALS). Methods: We compared years 2010–2011 to 2018–2019, and conducted trend analyses of sPCS from 2010 to 2019 stratified by race. Results: Of 103,193 pALS admitted during the study period, 13,885 (13.4%) received sPCS. Rates of sPCS increased over time (2010–2011: 8.9% vs. 2018–2019: 16.6%; p < 0.01). From 2010 to 2019, there was an increase in sPCS (p-trend<0.01) for all studied racial groups. Conclusions: Access to palliative care has increased over time for pALS admitted to hospitals in the United States. [ABSTRACT FROM AUTHOR]

For many in the United States, emerging adulthood is a highly exploratory phase of life characterized by experimentations in love, work, and ideology. While research has highlighted significant differences in these trends among various sub-groups and cultures, we know little about how people's experiences of established adulthood build upon and connect with the experiences and opportunities of emerging adulthood. In this study, we qualitatively investigated the lived experience of established adult women from LDS backgrounds, for whom the transition from youth to adulthood is typically highly structured. Twenty-one LDS women aged 30–45 (mean age = 38.6) participated in semi-structured interviews lasting one to two hours. Participants described experiencing a period of retrospective reevaluation of their early adulthood wherein personal alignment with cultured gender norms over individualized exploration had been encouraged. Participants contrasted these early experiences with a variety of more recent life transitions characterized by increased personal exploration, introspection, and shifting family responsibilities. Our research suggests that for women from conservative religious US-subcultures, limited exploration during emerging adulthood may lead to a period of increased identity, career, and ideology exploration during established adulthood, resulting in an increased sense of autonomy and personal authority. [ABSTRACT FROM AUTHOR]

Objective: To provide an updated characterization of breast imaging fellowship programs in the United States to identify opportunities for improvement and standardization. Methods: An anonymous survey was e-mailed to program directors of breast imaging fellowship programs listed on the Society of Breast Imaging website. The survey was open from April 23, 2021, through May 27, 2021. The survey was deemed exempt by the IRB. Results: Forty-seven of 80 (59%) program directors responded, of which 36/47 (77%) represented programs dedicated 100% to breast imaging, and 11/47 (23%) represented programs dedicated 50%-75% to breast imaging. Common elements to most programs include tumor boards (47/47, 100%), journal clubs (39/47, 83%), case-based teaching sessions (35/47, 74%), didactic lectures (40/47, 85%), and participation in radiology-pathology conferences (29/47, 62%). Mammography Quality and Standards Act audit training (22/47, 47%), mammography quality control training (22/47, 47%), and formal communication training (19/47, 40%) were less common. Most programs provide exposure to wire (42/47, 89%) and wire-free localization procedures (45/47, 96%), but exposure to contrast-enhanced mammography (13/47, 28%) and molecular breast imaging (4/47, 9%) was limited. A small majority of programs (25/47, 53%) do not require weekday call; however, more (31/47, 66%) have weekend call responsibilities. Many programs (29/47, 62%) offer at least 3 weeks of elective time, which may be clinical or nonclinical. Conclusion: Breast imaging fellowship programs vary in curricula, modality exposure, and academic policies. The results of this survey can help guide further efforts to standardize and optimize fellowship training. [ABSTRACT FROM AUTHOR]

Rationale: Outcomes for people with respiratory failure in the United States vary by patient race and ethnicity. Invasive ventilation is an important treatment initiated based on expert opinion. It is unknown whether the use of invasive ventilation varies by patient race and ethnicity. Objectives: To measure 1) the association between patient race and ethnicity and the use of invasive ventilation; and 2) the change in 28-day mortality mediated by any association. Methods: We performed a multicenter cohort study of nonintubated adults receiving oxygen within 24 hours of intensive care admission using the Medical Information Mart for Intensive Care IV (MIMIC-IV, 2008--2019) and Phillips eICU (eICU, 2014--2015) databases from the United States. We modeled the association between patient race and ethnicity (Asian, Black, Hispanic, White) and invasive ventilation rate using a Bayesian multistate model that adjusted for baseline and time-varying covariates, calculated hazard ratios (HRs), and estimated 28-day hospital mortality changes mediated by differential invasive ventilation use. We reported posterior means and 95% credible intervals (CrIs). Results: We studied 38,258 patients, 52% (20,032) from MIMIC-IV and 48% (18,226) from eICU: 2% Asian (892), 11% Black (4,289), 5% Hispanic (1,964), and 81% White (31,113). Invasive ventilation occurred in 9.2% (3,511), and 7.5% (2,869) died. The adjusted rate of invasive ventilation was lower in Asian (HR, 0.82; CrI, 0.70--0.95), Black (HR, 0.78; CrI, 0.71--0.86), and Hispanic (HR, 0.70; CrI, 0.61--0.79) patients compared with White patients. For the average patient, lower rates of invasive ventilation did not mediate differences in 28-day mortality. For a patient on high-flow nasal cannula with inspired oxygen fraction of 1.0, the odds ratios for mortality if invasive ventilation rates were equal to the rate for White patients were 0.97 (CrI, 0.91--1.03) for Asian patients, 0.96 (CrI, 0.91--1.03) for Black patients, and 0.94 (CrI, 0.89--1.01) for Hispanic patients. Conclusions: Asian, Black, and Hispanic patients had lower rates of invasive ventilation than White patients. These decreases did not mediate harm for the average patient, but we could not rule out harm for patients with more severe hypoxemia. [ABSTRACT FROM AUTHOR]

Introduction: Many patients with human epidermal growth factor receptor-2-positive metastatic breast cancer (HER2+ mBC) require subsequent lines of therapy (LOTs) after being treated with pertuzumab and trastuzumab-based regimens in the first line (1L). Although the efficacy of the second-line (2L) therapies has been demonstrated in clinical trials, the real-world effectiveness of these treatments is understudied. This retrospective cohort study assessed the real-world treatment patterns and outcomes for patients with HER2+ mBC following 1L therapy with pertuzumab and trastuzumab-based regimens in the United States (US) during 2015–2019. Methods: Adults with HER2+ mBC in the US who initiated 1L pertuzumab and trastuzumab-based regimens between 01/01/2015 and 09/30/2019 and had ≥ 60 days of follow-up after 1L initiation were identified from the IQVIA Oncology Electronic Medical Records database. The regimens utilized in 2L following 1L pertuzumab and trastuzumab-based regimens were described. Median treatment duration and time to treatment failure were reported for 2L based on Kaplan–Meier analyses. Results: Of the 710 eligible patients who received pertuzumab and trastuzumab-based regimens in 1L (median age: 57.0 years [interquartile range: 48.0–65.0]; median follow-up: 20.3 months; median 1L duration: 15.3 months), 222 (31.3%) initiated 2L. The most common regimens in 2L were ado-trastuzumab emtansine (T-DM1)-based regimens (n = 159 [71.6%]), followed by lapatinib-based (n = 21 [9.5%]) and neratinib-based (n = 18 [8.1%]) regimens. The median treatment duration and time to treatment failure were 5.9 (95% CI: 5.0, 8.7) and 8.6 (7.3, 11.5) months, respectively, among patients initiating 2L, and 5.7 (4.7, 7.8) and 7.9 (6.5, 10.0) months among those receiving 2L T-DM1. Conclusions: Most patients with HER2+ mBC requiring additional treatments after 1L pertuzumab and trastuzumab-based regimens utilized T-DM1 in 2L during 2015–2019. The short median treatment duration and time to treatment failure highlight an unmet need that can potentially be fulfilled by recently approved treatment options. [ABSTRACT FROM AUTHOR]

Sepsis is a major health problem in the United States (US), constituting a leading contributor to mortality among critically ill patients. Despite advances in treatment the underlying pathophysiology of sepsis remains elusive. Reactive oxygen species (ROS) have a significant role in antimicrobial host defense and inflammation and its dysregulation leads to maladaptive responses because of excessive inflammation. There is growing evidence for crosstalk between the central nervous system and the immune system in response to infection. The hypothalamic-pituitary and adrenal axis and the sympathetic nervous system are the two major pathways that mediate this interaction. Epinephrine (Epi) and norepinephrine (NE), respectively are the effectors of these interactions. Upon stimulation, NE is released from sympathetic nerve terminals locally within lymphoid organs and activate adrenoreceptors expressed on immune cells. Similarly, epinephrine secreted from the adrenal gland which is released systemically also exerts influence on immune cells. However, understanding the specific impact of neuroimmunity is still in its infancy. In this review, we focus on the sympathetic nervous system, specifically the role the neurotransmitter norepinephrine has on immune cells. Norepinephrine has been shown to modulate immune cell responses leading to increased anti-inflammatory and blunting of pro-inflammatory effects. Furthermore, there is evidence to suggest that norepinephrine is involved in regulating oxidative metabolism in immune cells. This review attempts to summarize the known effects of norepinephrine on immune cell response and oxidative metabolism in response to infection. [ABSTRACT FROM AUTHOR]

To estimate prevalent ALS cases in the United States for calendar year 2018. The National ALS Registry (Registry) compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and enrollment data voluntarily submitted through a web portal (). We used log-linear capture-recapture (CRC) model-based methodology to estimate the number of cases not ascertained by the Registry. The Registry identified 21,655 cases of ALS in 2018, with an age-adjusted prevalence of 6.6 per 100,000 U.S. population. When CRC methods were used, an estimated 29,824 cases were identified, for an adjusted prevalence of 9.1 per 100,000 U.S. population. The demographics of cases of ALS did not change from previous year's reports. ALS continues to impact Whites, males, and persons over 50 years of age more so than other comparison groups. The results from the present report suggest case ascertainment for the Registry has improved, with the estimate of missing prevalent cases decreasing from 44% in 2017 to 27% in in 2018. Consistent with previous estimates that used CRC, ALS prevalence in the United States is about 29,824 cases per year. [ABSTRACT FROM AUTHOR]

Technological developments in laboratory and epidemiologic methods, combined with increasing computing power, have synergistically increased our understanding of the epidemiology of infectious disease. Using historical examples from the first 100 years of the American Journal of Epidemiology , we illustrate how these developments provided the foundation for the rapid detection of the agent causing coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from its transmission efficiency and modalities, risk factors, and natural history to the evaluation of new vaccines and treatments to control its spread and impact. Comparisons with timelines for elucidation of the epidemiology, natural history, and control of other infectious diseases, including viral hepatitis, humbly remind us of how much past discoveries have paved the way for more rapid discovery of and response to new pathogens. We close with some comments on a potential future role of the Journal in infectious disease epidemiology. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative condition of the central nervous system, with distinct challenges due to its heterogeneous presentation, prognostic uncertainty, and variable clinical course of neurological and non-neurological symptoms and disability. Although there have been significant advances in management of MS, many patients experience disability progression. Despite MS being a frequent cause of neurological disability, particularly in young persons, involvement of palliative care physicians in the care of patients with MS has been limited. This article provides ten tips for palliative clinicians for caring for patients with MS and their care partners. [ABSTRACT FROM AUTHOR]

Transplantation is a high‐risk, high‐cost treatment for end‐stage diseases and is the most strictly regulated area of healthcare in the United States. Thus, achieving success for patients and the program requires skillful and collaborative leadership. Various factors, such as outcomes, volume, and financial health, may measure the success of a transplant program. Strong collaboration between clinical and administrative leaders is key to achieving and maintaining success in those three categories. Clinical leaders of adult programs, such as medical and surgical directors, bear the primary responsibility for a program's volume, outcomes, and patient safety, while administrative directors are focused on business intelligence and regulatory compliance. This paper aims to provide readers with insights into the critical role of collaborative leadership in running a successful program, with a focus on clinical, business, and regulatory perspectives. [ABSTRACT FROM AUTHOR]

Studies from more than 10 years ago showed epinephrine treatment of food-induced anaphylaxis in the emergency department (ED) was unacceptably low. We investigated whether epinephrine treatment of food-induced and other cause anaphylaxis in United States and Canadian EDs has changed over time. Guided by a health sciences librarian, we performed a systematic search in Medline, Embase, and Web of Science on 11 January 2023. We included observational studies that reported epinephrine use to treat anaphylaxis in the ED. We stratified by anaphylaxis etiology (food-, venom-, medication-induced, or any cause). Associations between year and epinephrine use were tested using Spearman correlation and proportional meta-analysis. Of 2458 records identified in our initial search, 40 met inclusion criteria. Of these, 14 examined food-induced, 4 venom-induced, 0 medication-induced, and 24 any cause anaphylaxis. For epinephrine treatment of food-induced anaphylaxis in the ED, among studies using similar definition of anaphylaxis, meta-analysis showed a pooled value of 20.7% (95% CI 17.8, 23.8) for studies performed >10 years ago and 45.1% (95% CI 38.4, 52.0) from those in the last 10 years. For anaphylaxis of any cause, there was no change over time, with a pooled value of 45.0% (95% CI 39.8, 50.3) over the last 10 years. Epinephrine treatment of food-induced anaphylaxis in the ED has increased over time. There was no clear change for anaphylaxis of any cause. Over the last 10 years, approximately 45% of ED patients with anaphylaxis received epinephrine. A limitation of the evidence is heterogeneity in anaphylaxis definitions. [ABSTRACT FROM AUTHOR]

We build on Diana Leonard's work on gender and graduate education by qualitatively investigating the perceived advantages and disadvantages of being a female graduate student in the USA and the UK. We interviewed six female students (ages 22-30) pursuing master's degrees in psychology or social sciences in the USA and the UK. Students from both countries reported the advantages and disadvantages of being a woman in their graduate programmes. Advantages included being the majority in their fields and receiving more lenient treatment from faculty. Disadvantages included being viewed in terms of stereotypical gender roles and receiving unwanted sexual attention. Participants also discussed strategies for managing their gender as they pursued their graduate education. We consider these findings in light of Leonard's work on gender and graduate education and from an ambivalent sexism framework. (Contains 4 notes.)

This review describes the relationship between the coronavirus-related pandemic and health inequities. The latter are linked to pre-existing social and economic discriminations in terms of access to healthcare for people affected by chronic diseases. We believe that we are living in a "syndemic pandemic". The term "syndemic" was originally developed by the medical anthropologist Merrill Singer in the 1990s in order to recognize the correlation between HIV/AIDS, illicit drug use, and violence in the United States. This complex interplay exacerbated the burden of the disease and the prognosis of the patient. Similarly, in COVID-19 infection, socio-economic, ethnic, and racial inequities result in higher morbidity and mortality in certain sections of society. Unfortunately, such differences are becoming too common during the COVID-19 pandemic, in terms of the incidence and prevalence of the disease, as well as inequal access to new medical advances and life-saving therapeutics for those with COVID-19, such as vaccines and monoclonal antibody treatment. Lockdown measures, imposed internationally as a response to the COVID-19 pandemic, are causing economic inequities, which complicate the issue even further. An appropriate syndemic anthropological approach is necessary to ensure that this pandemic does not increase health inequities in access to appropriate treatments. [ABSTRACT FROM AUTHOR]

Background: Physical medicine and rehabilitation (PM&R) clinicians commonly care for patients with serious illness/injury and would benefit from primary palliative care (PC) training. Objective: To assess current practices, attitudes, and barriers toward PC education among U.S. PM&R residencies. Design: This is a cross-sectional study utilizing an electronic 23-question survey. Setting/Subjects: Subjects were program leaders from U.S. PM&R residency programs. Results: Twenty-one programs responded (23% response). Only 14 (67%) offered PC education through lectures, elective rotations, or self-directed reading. Pain management, communication, and nonpain symptom management were identified as the most important PC domains for residents. Nineteen respondents (91%) felt residents would benefit from more PC education, but only five (24%) reported undergoing curricular change. Lack of faculty availability/expertise and teaching time were the most endorsed barriers. Conclusion: PC education is heterogeneous across PM&R programs despite its perceived value. PC and PM&R educators can collaborate to build faculty expertise and integrate PC principles into existing curricula. [ABSTRACT FROM AUTHOR]

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC–MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities. [ABSTRACT FROM AUTHOR]

To evaluate the impact of 1) updating the existing algorithm to improve case-finding sensitivity and 2) reclassifying the Registry's diagnostic status nomenclature into four new categories ("confirmed ALS," "likely ALS," "undetermined ALS," or "not ALS") versus the current three ("definite ALS," "possible ALS," or "not ALS") to be more inclusive and descriptive of cases and individuals. A retrospective analysis of Registry data from 2011–2017 was conducted to follow "possible ALS" individuals over time to determine what qualifier caused them to convert, if at all and when, to Registry-eligible cases (i.e. "confirmed ALS" or "likely ALS"). In 2011, 720 individuals were classified by the Registry algorithm as having "possible ALS". By 2017, 42% of these had converted to Registry-eligible ALS cases. Approximately 14% of those who were identified solely based on an ALS prescription drug never converted to Registry-eligible cases. This analysis indicates that "possible ALS" individuals with a single prescription for an ALS drug should be converted to Registry-eligible cases which would add between 300–500 cases per year on average. The Registry's existing algorithm likely results in the under-ascertainment of ALS cases. However, updating the algorithm with the inclusion of patients having been prescribed ALS-specific drugs, even with a single prescription, leads to improved epidemiologic estimates of ALS in the US. This and future algorithmic updates will help the Registry more accurately depict the true disease burden of ALS in the US. [ABSTRACT FROM AUTHOR]

Objective: To report multiple cause of death (MCOD) occurrence among patients in the United States with amyotrophic lateral sclerosis (ALS). Methods: Using death certificate data for all ALS deaths from 50 U.S. states and the District of Columbia, 2011–2014, we tabulated MCOD, used association rules mining (ARM) to determine if MCOD occurred together, and calculated standardized mortality odds ratios (SMOR) for select causes, comparing ALS with other U.S. decedents. Results: Among 24,328 death certificates, there were 25,704 MCOD, excluding ALS. ALS was listed as the sole cause of death in n = 11,263 (46%). The most frequent causes of death co‐occurring with ALS were respiratory failure (n = 6503; 25.3%), cardiovascular disease (n = 6077; 12.6%), pneumonia (n = 1345; 5.2%), and pneumonitis (n = 856; 3.3%). The SMORs among ALS decedents compared with non‐ALS decedents for falls and accidents were 3.4 (95% CI 2.6, 4.3) and 3.0 (95% CI 2.2, 4.2), respectively. From ARM analysis, falls and accidents were both associated with injuries. The most common causes identified were weakly to very strongly associated with being an ALS decedent compared with other U.S. deaths, with SMOR point estimates ranging from 1.3 to 51.1. Interpretation: This study provides information about the natural history of ALS. With knowledge that some causes of death may be preventable, healthcare providers may be able to optimize patient care and possibly postpone mortality and reduce morbidity. Moreover, this study located gaps in data; medical certifiers completing death certificates for ALS decedents should ensure all MCOD data are recorded. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The objectives of this study are (1) to assess practice patterns among urogynecology/female pelvic medicine and reconstructive surgery (FPMRS) providers regarding the use of bladder diaries (BD) and (2) to review the literature regarding BD. Methods: For the first objective, a survey was emailed to United States-based urogynecology providers in 2019 querying frequency of use of bladder diaries (FBD), indications, problems, patient education methods, and perception of utility. Chi-square tests and multiple logistic regression were performed. For the second objective, we reviewed literature published in English by searching the terms "voiding," "bladder," or "incontinence," in combination with "diary," "log," or "questionnaire." Results: A total of 371 of 851 (43.5%) contacted providers responded. Nearly 80% were attending physicians, 75.5% of whom completed the FPMRS fellowship; 20.8% of all respondents and nearly 25% of fellowship-trained attendings reported FBD <20% in the last year. FPMRS providers were more likely to report FBD >80%. A total of 97.5% of respondents cited difficulty in using BD. Most (71.6%) taught patients to use BD themselves or shared responsibility with a nonphysician staff member (53.4%). BD is a validated and valuable instrument; however, there are obstacles to its use. Despite recent innovations including electronic and automated BD, there is a paucity of data regarding the provider-viewed challenges in implementing BD. Conclusions: The literature supports the use of BD; however, many survey respondents, including fellowship-trained attendings, never or rarely use BD. Most respondents reported difficulty in using BD. More research is needed to improve the ease, accuracy, and widespread adaptation of BD use in clinical practice. [ABSTRACT FROM AUTHOR]

In the United States, established adulthood (ages 30–45) often represents the most intense and demanding years of adult life. During this time, most individuals settle into adult roles and responsibilities, negotiating the intersecting demands of work and family obligations. While discrete topics relevant to this period have been investigated by developmental scientists, the subjective experience of established adulthood as a whole remains largely overlooked. In the present study, we aim to provide the foundation for a more comprehensive and integrated understanding of established adulthood by interviewing participants (n = 127) aged 30–45 from across the United States about the nature of their current lived experience. In general, participants described the Experience of Established Adulthood as a time of establishing their adulthood, stability, changes in priorities, and shifting perceptions of time. They also noted a number of Responsibilities and Commitments, describing an increase in obligations, and feeling a "career and care crunch. Participants also reported experiencing Evolution, noting that they continued to grow and learn, explore their beliefs and values, and make course corrections as needed. Finally, participants described Actualization in terms of gained wisdom, self-understanding, self- confidence, and life satisfaction. Taken together, our results suggest that established adults in the USA face challenges and opportunities distinct from those faced during emerging adulthood or midlife. [ABSTRACT FROM AUTHOR]

The problem of unaffordable prescription medications in the United States is complex and can result in poor patient adherence to therapy, worse clinical outcomes, and high costs to the healthcare system. While providers are aware of the financial burden of healthcare for patients, there is a lack of actionable price transparency at the point of prescribing. Real-time prescription benefit (RTPB) tools are new electronic clinical decision support tools that retrieve patient- and medication-specific out-of-pocket cost information and display it to clinicians at the point of prescribing. The rise in US healthcare costs has been a major driver for efforts to increase medication price transparency, and mandates from the Centers for Medicare & Medicaid Services for Medicare Part D sponsors to adopt RTPB tools may spur integration of such tools into electronic health records. Although multiple factors affect the implementation of RTPB tools, there is limited evidence on outcomes. Further research will be needed to understand the impact of RTPB tools on end results such as prescribing behavior, out-of-pocket medication costs for patients, and adherence to pharmacologic treatment. We review the terminology and concepts essential in understanding the landscape of RTPB tools, implementation considerations, barriers to adoption, and directions for future research that will be important to patients, prescribers, health systems, and insurers. [ABSTRACT FROM AUTHOR]

Alexithymia is a key transdiagnostic risk factor for emotion-based psychopathologies. Conceptual models specify that this is because alexithymia impairs emotion regulation. However, the extent of these putative emotion regulation impairments remains underexplored. Our aim in this study was to begin to address this gap by examining whether people with high, average, or low levels of alexithymia differ in the types of emotion regulation strategies they typically use. General community adults from the United States (N = 501) completed a battery of alexithymia and emotion regulation measures. Participants were grouped into high, average, and low alexithymia quantiles. After controlling for demographics and current levels of distress, the high, average, and low alexithymia groups differed in their use of cognitive and behavioral emotion regulation strategies. Compared to the other groups, the high alexithymia group reported lesser use of generally adaptive regulation strategies (cognitive reappraisal, approaching problems, and seeking social support) and greater use of generally maladaptive regulation strategies (expressive suppression, behavioral withdrawal, ignoring). Our data were cross-sectional and from self-report questionnaires. Future work in other cultural groups would be beneficial. Our results support the view that alexithymia is associated with impaired emotion regulation. In particular, people with high alexithymia seem to exhibit a less adaptive profile of emotion regulation strategies. Direct targeting of these emotion regulation patterns in psychotherapy may therefore be a useful pathway for the treatment of emotional disorder symptoms in people with high alexithymia. • The process model predicts that alexithymia should impair emotion regulation • We examined the emotion regulation strategy use profiles characterizing alexithymia • Alexithymia was characterized by a less adaptive emotion regulation profile: • Less use of cognitive reappraisal, approaching problems, and seeking social support. • More use of expressive suppression, behavioural withdrawal, and ignoring. [ABSTRACT FROM AUTHOR]

Since 2010, US life expectancy growth has stagnated. Much research on US mortality has focused on working-age adults given adverse trends in drug overdose deaths, other external causes of death, and cardiometabolic deaths in midlife. We show that the adverse mortality trend at retirement ages (65+ y) has in fact been more consequential to the US life expectancy stagnation since 2010, as well as excess deaths and years of life lost in 2019, than adverse mortality trends at working ages. These results reveal that the United States is experiencing a "double jeopardy" that is driven by both mid-life and older-age mortality trends, but more so by older-age mortality. Understanding and addressing the causes behind the worsening mortality trend in older ages will be essential to returning to the pace of life expectancy improvements that the United States had experienced for decades. [ABSTRACT FROM AUTHOR]

Background: Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the '$10 Challenge'. Methods: We conducted a cross-sectional study of DARE alumni over five consecutive years (2015–2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software. Results: DARE Medical students were 31.2 years (range 24–35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p < 0.001 for all). Qualitative key themes included: increased confidence, a deepening of research inquiry and linkage to a research network. Conclusions: Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration. [ABSTRACT FROM AUTHOR]

Background: Celiac disease has an increasing incidence worldwide and is treated with lifelong adherence to a gluten-free diet. We aimed to describe gluten-free diet adherence rates in children with screening-identified celiac disease, determine adherence-related factors, and compare adherence to food records in a multinational prospective birth cohort study. Methods: Children in The Environmental Determinants of Diabetes in the Young study with celiac disease were included. Subjects had at least annual measurement of adherence (parent-report) and completed 3-day food records. Descriptive statistics, t-tests, Kruskal-Wallis tests and multivariable logistic and linear regression were employed. Results: Two hundred ninety (73%) and 199 (67%) of subjects were always adherent to a gluten-free diet at 2 and 5 years post celiac disease diagnosis respectively. The percentage of children with variable adherence increased from 1% at 2 years to 15% at 5 years. Children with a first-degree relative with celiac disease were more likely to be adherent to the gluten-free diet. Gluten intake on food records could not differentiate adherent from nonadherent subjects. Adherent children from the United States had more gluten intake based on food records than European children (P <.001 and P =.007 at 2 and 5 years respectively). Conclusion: Approximately three-quarters of children with screening-identified celiac disease remain strictly adherent to a gluten-free diet over time. There are no identifiable features associated with adherence aside from having a first-degree relative with celiac disease. Despite good parent-reported adherence, children from the United States have more gluten intake when assessed by food records. Studies on markers of gluten-free diet adherence, sources of gluten exposure (particularly in the United States), and effects of adherence on mucosal healing are needed. [ABSTRACT FROM AUTHOR]

The decision to treat advanced gastroesophageal cancers (GECs) with targeted therapy and immunotherapy is based on key biomarker expression (human epidermal growth factor receptor 2 (HER2), programmed cell death-ligand 1 (PD-L1), microsatellite instability (MSI), and/or mismatch repair (MMR)). Real-world data on testing, results, and treatment patterns are limited. This retrospective observational study used a nationwide electronic health record-derived de-identified database of patients from the United States. The analysis included adult patients with advanced GECs who initiated systemic treatment between 2017 and 2020. Biomarker testing patterns, timing, assays, tissue collection site, results, and treatment sequences were assessed. Of 1142 eligible patients, adenocarcinoma was the most prevalent histology (83% of patients). Overall, 571 (50%) patients were tested for PD-L1, 582 (51%) were tested for MMR/MSI, and 857 (75%) were tested for HER2. Between 2017 and 2020, the PD-L1 testing rate increased from 39% to 58%, and the MMR/MSI testing rate increased from 41% to 58%; the median time from initial diagnosis to first test decreased for both biomarkers. Programmed cell death receptor-1 inhibitor use was observed among patients with positive PD-L1 or MMR-deficient/MSI-High results. These results supplement data reported in key clinical trials and may inform decision-making as treatment options for advanced GECs evolve. [ABSTRACT FROM AUTHOR]

Objective:To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2017 using data from the National ALS Registry (Registry) as well as capture–recapture methodology to account for under-ascertainment. Established in 2010, the Registry collects and examines data on ALS patients in the US to better describe the epidemiology of ALS (i.e. risk factor exposures, demographics). Methods: The Registry compiled data from national administrative databases (from the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration) and a voluntary enrollment data through a web portal (). To estimate the number of missing cases, capture–recapture methodology was utilized. Results: The Registry conservatively identified 17,800 adult persons (lower-bound estimate) who met the Registry definition of ALS for an age-adjusted prevalence of 5.5 per 100,000 US population. Using capture–recapture methodology, we obtained a "mean case count" of 24,821 ALS cases (prevalence of 7.7 per 100,000 U.S. population) and estimated the upper-bound estimate to be 31,843 cases (prevalence of 9.9 per 100,000 U.S. population). The pattern of patient characteristics (e.g. age, sex, and race/ethnicity) remained unchanged from previous Registry reports. Overall, ALS was most common among whites, males, and persons aged 60–69 years. The age groups with the lowest number of cases were persons aged 18–39 years. Males had a higher prevalence than females overall and across all data sources. Conclusions: Existing Registry methodology, along with capture-recapture methodology, are being used to better describe the epidemiology and demographics of ALS in the US. [ABSTRACT FROM AUTHOR]

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases. [ABSTRACT FROM AUTHOR]

Background: We investigate the impact of gender, race, and socioeconomic status on the diagnosis and management of bladder cancer in the United States. Methods: We utilized the National Cancer Database to stratify cases of urothelial cell carcinoma of the bladder as early (Tis, Ta, T1), muscle invasive (T2–T3, N0), locally advanced (T4, N1–3), and metastatic. Multivariate binomial and multinomial logistic regression analyses identified demographic characteristics associated with stage at diagnosis and receipt of cancer‐directed therapies. Odds ratios (OR) are reported with 95% confidence intervals. Results: After exclusions, we identified 331,714 early, 72,154 muscle invasive, 15,579 locally advanced, and 15,161 metastatic cases from 2004–2016. Relative to diagnosis at early stage, the strongest independent predictors of diagnosis at muscle invasive, locally advanced, and metastatic disease included Black race (OR = 1.19 [1.15–1.23], OR = 1.49 [1.40–1.59], OR = 1.66 [1.56–1.76], respectively), female gender (OR = 1.21 [1.18–1.21], OR = 1.16 [1.12–1.20], and OR = 1.34 [1.29–1.38], respectively), and uninsured status (OR = 1.22 [1.15–1.29], OR = 2.09 [1.94–2.25], OR = 2.57 [2.39–2.75], respectively). Additional demographic factors associated with delayed diagnosis included older age, treatment at an academic center, Medicaid insurance and patients from lower income/less educated/more rural areas (all p < 0.01). Treatment at a non‐academic center, older age, women, Hispanic and Black patients, lower income and rural areas were all less likely to receive cancer‐directed therapies in early stage disease (all p < 0.01). Women, older patients, and Black patients remained less likely to receive treatment in muscle invasive, locally advanced, and metastatic disease (all p < 0.01). Conclusion: Black race was the strongest independent predictor of delayed diagnosis and substandard treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

The associations between clinical phenotypes of coronavirus disease 2019 (COVID-19) and the host inflammatory response during the transition from peak illness to convalescence are not yet well understood. Blood plasma samples were collected from 129 adult SARS-CoV-2 positive inpatient and outpatient participants between April 2020 and January 2021, in a multi-center prospective cohort study at 8 military hospitals across the United States. Plasma inflammatory protein biomarkers were measured in samples from 15 to 28 days post symptom onset. Topological Data Analysis (TDA) was used to identify patterns of inflammation, and associations with peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated using logistic regression. The study population (n = 129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct inflammatory biomarker clusters were identified and were associated with significant differences in peak disease severity (p < 0.001), age (p < 0.001), BMI (p < 0.001), and CCI (p = 0.001). Host-biomarker profiles stratified a heterogeneous population of COVID-19 patients during the transition from peak illness to convalescence, and these distinct inflammatory patterns were associated with comorbid disease and severe illness due to COVID-19. [ABSTRACT FROM AUTHOR]

To investigate the association of the Affordable Care Act (ACA) with nationwide eye-related emergency department (ED) use. Retrospective, cross-sectional study. All patients who presented to the ED with an eye-related primary diagnosis were eligible for inclusion. Nationally representative data from the US Nationwide Emergency Department Sample were used to analyze eye-related ED visits before (2010–2013) and after (2014–2017) the ACA was mandated. All ED visits were categorized as emergent or nonemergent or could not be determined. The primary outcome was to compare the nationwide and regional incidence of eye-related ED visits per 100 000 US population before (2010–2013) and after (2014–2017) the ACA was mandated. Secondary outcome measures included change in payor status, proportion of urgent versus nonurgent visits, proportion of visits at teaching versus nonteaching hospitals, associated charges, and discharge disposition. A total of 16 808 343 eye-related ED visits occurred in the United States during the study period from 2010 to 2017. Of these, 8 088 203 ED visits occurred before the ACA was mandated (2010–2013), and 8 720 766 ED visits occurred after the ACA was mandated (2014–2017). After the ACA was mandated in 2014, there was an initial decline in incidence of eye-related ED visits from 652.4 per 100 000 population in 2013 to 593.0 per 100 000 population in 2014, followed by a rapid increase in incidence to 658.5 per 100 000 population in 2015, with a further increase to 746.6 per 100 000 population in 2016. The percentage of uninsured patients decreased from 19.0% to 14.3%. The increase in ED use was greatest for individuals in the lowest income quartile (895.1 per 100 000 population in 2013 to 964.0 per 100 000 in 2017). Overall, 44.8% of ED visits were due to nonemergent eye conditions. Although the ACA increased insurance coverage for Americans, theoretically increasing access to outpatient ophthalmic care, this did not decrease ED reliance for management of ophthalmic conditions. Additional measures beyond expanding insurance coverage may be necessary to provide high-quality, efficient, and equitable outpatient ophthalmic care to all Americans. [ABSTRACT FROM AUTHOR]

129 Background: As B/AA patients are underrepresented in clinical research, data is limited on survival outcomes of B/AA patients with HER2-neg aBC. This study compared survival outcomes of these patients against those of non-B/AA patients. Methods: This was a retrospective cohort study at Huntsman Cancer Institute, H. Lee Moffitt Cancer Centre and Research Institute, and Winthrop P. Rockefeller Cancer Institute. Adult patients diagnosed with HER2-neg aBC from 2010 to 2021 were eligible. Patient data were extracted via chart review, including self-reported race from clinical records. HER2-low status was defined as immunohistochemistry (IHC) scores 1+ or 2+ and negative fluorescence in situ hybridization test; HER2-neg comprised HER2-low and IHC 0. Overall survival (OS), i.e. time until death, and progression-free survival (PFS), i.e. time until death or disease progression, were estimated using Kaplan-Meier methods with treatment start as index date and censoring at date of last follow-up or 12/31/2021, whichever earlier. Association between B/AA race and survival was evaluated using multivariable Cox regression. Results: A total of 869 patients were HER2-neg, 95 were B/AA, and 64 (67%) were HER2-low while 31 (33%) had IHC 0 disease. Compared to non-B/AA patients (85% non-Hispanic White), fewer B/AA patients had stage IV disease (38% vs 57%, p=0.001), lobular histology (3% vs 14%, p=0.001) and positive hormone receptor status (HR) (60% vs 78%, p<0.001). B/AA patients showed shorter median OS and PFS than non-B/AA patients overall and in subgroups defined by stage and HR but 95% confidence intervals (CI) overlapped (Table). Controlling for stage and HR, B/AA patients had shorter OS (Hazards ratio: 1.4, 95% CI: 1.0-1.9) but no difference in PFS (Hazards ratio: 1.2, 95% CI: 0.9-1.6). Conclusions: OS of B/AA patients with HER2-neg aBC was shorter than that of non-B/AA patients controlling for staging and HR. A sizable proportion of B/AA patients have HER2-low disease and more studies are needed to confirm if this patient population has different outcomes compared to non-B/AA. Survival outcomes of B/AA patients vs non-B/AA patients. Overall Survival (months) Progression-free Survival (months) B/AA Non-B/AA B/AA Non-B/AA n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) n Mdn (95% CI) Overall 95 41.4 (28.3 to 69.4) 774 56.7 (50.0 to 66.2) 95 9.9 (8.0 to 20.3) 773 16.1 (13.9 to 18.3) Staging IIIB/IIIC 60 69.4 (39.1 to NR) 339 NR (110.1 to NR) 60 10.2 (8.0 to 23.8) 339 22.5 (15.0 to 37.8) IV 35 28.1 (18.2 to 40.9) 435 39.4 (35.5 to 44.0) 35 9.6 (7.3 to 25.7) 434 13.9 (11.6 to 17.0) Hormone receptor Positive 57 41.4 (27.8 to 69.4) 609 62.0 (55.1 to 69.7) 57 8.6 (7.8 to 20.3) 609 17.1 (14.1 to 19.7) Negative 38 40.9 (23.1 to NR) 162 41.6 (24.2 to 68.3) 38 10.2 (7.7 to NR) 161 11.8 (9.3 to 17.2) B/AA – Black/African American, Mdn – median, NR – not reached. [ABSTRACT FROM AUTHOR]

In the United States, silicone and saline breast implants with their familiar radiologic appearance are the mainstays of breast augmentation. However, less well-known sequelae of unconventional injected materials introduced for cosmetic and noncosmetic purposes may also be encountered on breast imaging--for example, free silicone, paraffin and/or oil, polyacrylamide gel, autologous fat, and hyaluronic acid, which are encountered in the setting of breast augmentation. Breast injection of go-yak is not cosmetic but also results in characteristic imaging findings. Breast changes due to extravasation of chemotherapy or interstitial brachytherapy can mimic the appearance of injected noncosmetic materials. Because many of these materials can mimic or obscure imaging findings of breast cancer, it is important to recognize their varied appearances and the limitations of imaging alone in delineating breast injection material from cancer. Given the relatively uncommon incidence of injected materials into the breast, this article aims to review the imaging appearance in order to aid radiologists in maximizing cancer detection and ensuring optimal patient management. [ABSTRACT FROM AUTHOR]

The article reports that the accelerated approval pathway was created by the Food and Drug Administration in 1992 for drugs intended for serious and life-threatening diseases. Topics include considered this approval pathway aims to speed drug approval on the basis of a surrogate end point deemed reasonably likely to prediet clinical benefit or an intermediate clinical end point other than irreversible illness or death.

Background: Older adults have many comorbidities contributing to mortality.Objective: To develop a summary Elixhauser (S-Elixhauser) comorbidity score to predict 30-day, in-hospital, and 1-year mortality in older adults using the 38 comorbidities operationalized by the Agency for Healthcare Research and Quality (AHRQ).Design: Retrospective cohort study.Setting: Medicare beneficiaries from 2017 to 2019.Patients: Persons hospitalized in 2018 (n = 899 844) and 3 disease-specific hospitalized cohorts.Measurements: Weights were derived for 38 comorbidities to predict 30-day, in-hospital, and 1-year mortality. The S-Elixhauser score was internally validated and calibrated. Individual Elixhauser comorbidity indicators (38 comorbidities), the modified application of the AHRQ-derived Elixhauser summary score, the Charlson comorbidity indicators (17 comorbidities), and the Charlson summary score were externally validated. The c-statistic was used to evaluate discrimination of a comorbidity score model.Results: The S-Elixhauser score was well calibrated and internally validated, with a c-statistic of 0.705 (95% CI, 0.703 to 0.707) in predicting 30-day mortality, 0.654 (CI, 0.651 to 0.657) for in-hospital mortality, and 0.743 (CI, 0.741 to 0.744) for 1-year mortality. In external validation of other comorbidity indices for 30-day mortality, the c-statistic was 0.711 (CI, 0.709 to 0.713) for the individual Elixhauser comorbidity indicators, 0.688 (CI, 0.686 to 0.690) for the AHRQ Elixhauser score, 0.696 (CI, 0.694 to 0.698) for the Charlson comorbidity indicators, and 0.690 (CI, 0.688 to 0.693) for the Charlson summary score. In 3 disease-specific populations, the discrimination of the S-Elixhauser score in predicting 30-day mortality ranged from 0.657 to 0.732.Limitation: Validation of the S-Elixhauser comorbidity score and head-to-head comparison with other comorbidity scores in an external population are needed to evaluate comparative performance.Conclusion: The S-Elixhauser comorbidity score is well calibrated and internally validated but its advantage over the AHRQ Elixhauser and Charlson summary scores is unclear.Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the incidence of pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes, and their relationship in US Medicaid-funded women.Methods: Medicaid is a government-sponsored health insurance programme for low-income families in the USA. We report the incidence of pregnancy-related cardiometabolic conditions (hypertensive disorders and diabetes in, or complicated by, pregnancy) and severe cardiovascular outcomes (myocardial infarction, stroke, acute heart failure, cardiomyopathy, cardiac arrest, ventricular fibrillation, ventricular tachycardia, aortic dissection/aneurysm and peripheral vascular disease) among Medicaid-funded women with a birth (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code O80 or O82) over the period January 2015-June 2019, from the states of Georgia, Ohio and Indiana. In this cross-sectional cohort, we examined the relationship between pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes from pregnancy through to 60 days after birth using multivariable models.Results: Among 74 510 women, mean age 26.4 years (SD 5.5), the incidence per 1000 births of pregnancy-related cardiometabolic conditions was 224.3 (95% CI 221.3 to 227.3). The incidence per 1000 births of severe cardiovascular conditions was 10.8 (95% CI 10.1 to 11.6). Women with pregnancy-related cardiometabolic conditions were at greater risk of having a severe cardiovascular condition with an age-adjusted OR of 3.1 (95% CI 2.7 to 3.5).Conclusion: This US cohort of Medicaid-funded women have a high incidence of severe cardiovascular conditions during pregnancy. Cardiometabolic conditions of pregnancy conferred threefold higher odds of severe cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Clinical pharmacology is a branch of the field of pharmacology that evolved following the recognition that the nature, duration, and intensity of drug action depend on both the intrinsic properties of the drug and an interaction with the host to whom the drug is given. Advances in drug development have placed highly specific and extremely potent therapeutic agents in the marketplace. While these advances have progressed rapidly in adult medicine, pediatric clinical pharmacology has not kept pace and until very recently has lagged behind the research and attention paid to the proper use of therapeutic and diagnostic drugs in adults. Recognition that advances in the science of developmental pharmacology and pediatric clinical pharmacology were essential in the development of new drugs to treat children came in the 1950s and 1960s mostly through the work of 2 pioneering scientists in fetal and perinatal clinical pharmacology, Drs Sumner Yaffe and Bernard Mirkin. Here we pay a tribute to these most influential pioneers in the United States who were instrumental in paving the path for advancing the field of fetal and perinatal pharmacology concepts and their incorporation into pediatric drug development programs. [ABSTRACT FROM AUTHOR]