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OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of −40.7% (95% confidence interval [CI]: −47.7 to −33.7) in A&E attendances, −25.8% (95% CI: −31.1 to −20.4) in emergency hospital admissions and −60.9% (95% CI: −66.1 to −55.7) in planned hospital admissions, in comparison to the 2018–2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

Key Points Question Are results of universal and selective screening for suicide risk implemented in a pediatric emergency department associated with future suicidal behaviors? Findings In this cohort study of 15 003 youths aged 8 to 18 years, positive screens were significantly associated with subsequent suicide-related hospital visits compared with standard emergency department procedures. Screening also more than doubled the detection of suicide risk compared with treatment as usual. Meaning These findings suggest that screening for suicide risk in pediatric emergency departments is an effective approach to identify risk for subsequent suicide-related emergency department visits., This cohort study examines the association between results of universal and selective screening for suicide risk in a pediatric emergency department using the Ask Suicide-Screening Questions (ASQ) instrument and subsequent suicide-related outcomes., Importance According to National Patient Safety Goal 15.01.01, all individuals being treated or evaluated for behavioral health conditions as their primary reason for care in hospitals and behavioral health care organizations accredited by The Joint Commission should be screened for suicide risk using a validated tool. Existing suicide risk screens have minimal or no high-quality evidence of association with future suicide-related outcomes. Objective To test the association between results of the Ask Suicide-Screening Questions (ASQ) instrument in a pediatric emergency department (ED), implemented through selective and universal screening approaches, and subsequent suicide-related outcomes. Design, Setting, and Participants In this retrospective cohort study at an urban pediatric ED in the United States, the ASQ was administered to youths aged 8 to 18 years with behavioral and psychiatric presenting problems from March 18, 2013, to December 31, 2016 (selective condition), and then to youths aged 10 to 18 years with medical presenting problems (in addition to those aged 8-18 years with behavioral and psychiatric presenting problems) from January 1, 2017, to December 31, 2018 (universal condition). Exposure Positive ASQ screen at baseline ED visit. Main Outcomes and Measures The main outcomes were subsequent ED visits with suicide-related presenting problems (ie, ideation or attempts) based on electronic health records and death by suicide identified through state medical examiner records. Association with suicide-related outcomes was calculated over the entire study period using survival analyses and at 3-month follow-up for both conditions using relative risk. Results The complete sample was 15 003 youths (7044 [47.0%] male; 10 209 [68.0%] black; mean [SD] age, 14.5 [3.1] years at baseline). The follow-up for the selective condition was a mean (SD) of 1133.7 (433.3) days; for the universal condition, it was 366.2 (209.2) days. In the selective condition, there were 275 suicide-related ED visits and 3 deaths by suicide. In the universal condition, there were 118 suicide-related ED visits and no deaths during the follow-up period. Adjusting for demographic characteristics and baseline presenting problem, positive ASQ screens were associated with greater risk of suicide-related outcomes among both the universal sample (hazard ratio, 6.8 [95% CI, 4.2-11.1]) and the selective sample (hazard ratio, 4.8 [95% CI, 3.5-6.5]). Conclusions and Relevance Positive results of both selective and universal screening for suicide risk in pediatric EDs appear to be associated with subsequent suicidal behavior. Screening may be a particularly effective way to detect suicide risk among those who did not present with ideation or attempt. Future studies should examine the impact of screening in combination with other policies and procedures aimed at reducing suicide risk.

Objective Pregnant women are at increased risk of serious complications from influenza and are recommended to receive an influenza vaccination during pregnancy. The objective of this study was to assess trends, timing patterns, and associated factors of influenza vaccination among pregnant women. Methods We used 2010-2018 MarketScan data on 1 286 749 pregnant women aged 15-49 who were privately insured to examine trends and timing patterns of influenza vaccination coverage. We examined descriptive statistics and identified factors associated with vaccination uptake by using multivariate log-binomial and Cox proportional hazard models. Results In-plan influenza vaccination coverage before delivery increased from 22.0% during the 2010-2011 influenza season to 33.2% during the 2017-2018 influenza season. About two-thirds of vaccinated women received the vaccine in September or October during each influenza season. For women who delivered in September through May, influenza vaccination coverage increased rapidly at the beginning of influenza season and flattened after October. For women who delivered in June through August, influenza vaccination coverage increased gradually until February and flattened thereafter. Most vaccinated women who delivered before January received the vaccine in the third trimester. Increased likelihood of being vaccinated was associated with age 31-40, living in a metropolitan statistical area, living outside the South, enrollment in a consumer-driven or high-deductible health plan, being spouses or dependents of policy holders, and delivery in November through January. Conclusions Despite increases during the past several years, vaccination uptake is still suboptimal, particularly after October. Health care provider education on timing of vaccination and recommendations throughout influenza seasons are needed to improve influenza vaccination coverage among pregnant women.

Key Points Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131 415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers., Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131 415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131 415 participants (mean [SD] age, 43.0 [10.4] years; 80 344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96 591 participants with data on loss of consciousness, 10 004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (, This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia.

Objectives Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. Methods We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. Results White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 μg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. Conclusions We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated.

Objectives Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. Methods We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. Results We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. Conclusions Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.

Background In the UK, about 14% of community-dwelling adults aged 65 and over are estimated to be at risk of malnutrition. Screening older adults in primary care and treating those at risk may help to reduce malnutrition risk, reduce the resulting need for healthcare use and improve quality of life. Interventions are needed to raise older adults’ risk awareness, offer relevant and meaningful strategies to address risk and support general practices to deliver treatment and support. Methods Using the Person-based Approach and input from Patient and Public Involvement representatives, we developed the ‘Eat well, feel well, stay well’ intervention. The intervention was optimised using qualitative data from think aloud and semi-structured process evaluation interviews with 23 and 18 older adults respectively. Positive and negative comments were extracted to inform rapid iterative modifications to support engagement with the intervention. Data were then analysed thematically and final adjustments made, to optimise the meaningfulness of the intervention for the target population. Results Participants’ comments were generally positive. This paper focuses predominantly on participants’ negative reactions, to illustrate the changes needed to ensure that intervention materials were optimally relevant and meaningful to older adults. Key factors that undermined engagement included: resistance to the recommended nutritional intake among those with reduced appetite or eating difficulties, particularly frequent eating and high energy options; reluctance to gain weight; and a perception that advice did not align with participants’ specific personal preferences and eating difficulties. We addressed these issues by adjusting the communication of eating goals to be more closely aligned with older adults’ beliefs about good nutrition, and acceptable and feasible eating patterns. We also adjusted the suggested tips and strategies to fit better with older adults’ everyday activities, values and beliefs. Conclusions Using iterative qualitative methods facilitated the identification of key behavioural and contextual elements that supported engagement, and issues that undermined older adults’ engagement with intervention content. This informed crucial revisions to the intervention content that enabled us to maximise the meaningfulness, relevance and feasibility of the key messages and suggested strategies to address malnutrition risk, and therefore optimise engagement with the intervention and the behavioural advice it provided.

Key Points Question By decreasing impaired driving, are rideshare services associated with changes in motor vehicle trauma rates? Findings This multicenter cohort study obtained hospital data at both major trauma centers in Houston, Texas; convictions for impaired driving from the Harris County, Texas, District Attorney’s office; and rideshare use data from Uber and Google for Houston. Rideshare volume had a significant negative correlation with the incidence of motor vehicle–associated trauma, and this was most evident in those younger than 30 years; a significant decrease in convictions for impaired driving was associated with the introduction of rideshare services. Meaning By using rideshares to avoid impaired driving, young people may aid in decreasing motor vehicle trauma., This multicenter cohort study seeks to determine if there was an association between rideshare use, motor vehicle crash traumas, and impaired driving convictions in Houston, Texas, by comparing traumas and convictions before and after the introduction of Uber., Importance Motor vehicle crashes (MVCs) are an important public health concern. Recent trends suggest that introducing rideshare services has decreased the incidence of MVCs. However, detailed analyses linking rideshare volume, convictions for impaired driving, and nonfatal MVC traumas remain inconclusive. Objective To determine if there is an association between rideshare use and MVC traumas and convictions for impaired driving in Houston, Texas. Design, Setting, and Participants This multicenter cohort study was conducted between January 2007 and November 2019 with hospital data from the Red Duke Trauma Institute within the Memorial Hermann Hospital–Texas Medical Center and Ben Taub General Hospital. Rideshare data from Uber and Google covered trips taken within Houston, Texas, from February 2014 (the date of deployment of Uber to Houston) to December 2018. Impaired driving convictions included all indictments made by the Harris County, Texas, District Attorney’s office from January 2007 to December 2018. All adults with MVC traumas evaluated at both centers in the study population (individuals >16 years with a mechanism of injury classified under “motor vehicle collision”) were included. Impaired driving incidents were included only if the final legal outcome was conviction. Main Outcomes and Measures The primary study outcomes were the incident rate ratios for hourly MVC traumas and daily impaired driving convictions. Results A total of 23 491 MVC traumas (involving patients with a mean [SD] age of 37.9 [17.8] years and 14 603 male individuals [62.1%]), 93 742 impaired driving convictions, and more than 24 million Uber rides were analyzed. Following the introduction of Uber in February 2014, MVC traumas decreased by 23.8% (from a mean [SD] of 0.26 [0.04] to 0.21 [0.06] trauma incidents per hour) during peak trauma periods (Friday and Saturday nights). The incident rate ratio of MVC traumas following Uber deployment was 0.33 (95% CI, 0.17-0.67) per 1000 indexed rides (P = .002). Furthermore, rideshare use was associated with a significant, geographically linked reduction in impaired driving convictions between January 2014 to December 2019 (incidence rate ratio, 0.76 [95% CI, 0.73-0.78]; P

Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of side effects, a high rate of paradoxical responses, and frequent treatment resistance. Therefore, new treatment options for insomnia in children with NDDs are needed. Dual orexin receptor antagonists (DORAs) are a relatively new class of pharmacotherapeutics that induce sleep by inhibiting the orexin signaling pathway. To date, there is little safety or efficacy data on the use of DORAs in children with NDDs. We present four patients with NDDs and insomnia that we treated with the DORA, suvorexant. We found that patients had a wide range of responses, with one patient displaying a robust improvement in sleep onset and maintenance, while another had significant improvement in insomnia symptoms on combination therapy with trazodone. Our final two patients had mild or no benefit from suvorexant therapy. Further research is necessary to establish the safety and efficacy of DORAs in this population and to identify predictive factors, such as specific neurogenetic diagnoses or clinical features, of a positive treatment response.

Purpose Information regarding the views of patients, on visual field testing is limited, and no information exists regarding their preferences for test developments. This study aimed to increase knowledge of patients’ experiences of visual field assessment and to explore their opinions and priorities regarding current areas of research and development. Design Online questionnaire with purposive sampling design. Participants Adults who regularly undergo visual field tests in Australia who report having glaucoma or being at glaucomatous risk. Methods An anonymous survey, implemented using the Qualtrics webtool, with both closed- and-open ended questions designed to explore opinions regarding visual field testing, visit attendance for perimetry, as well as priorities for developments. Main Outcome Measures The survey assessed 3 domains: (1) opinions regarding test duration and visit frequency, (2) subjective experience, and (3) perspectives on future developments. Results One hundred fifty-two complete survey responses were obtained. The median age of participants was 66 years (interquartile range [IQR], 60–72 years). Most participants (70%) had experience of undergoing more than 11 visual field tests. Participants recalled that they completed visual field tests in median of 6 minutes (IQR, 5–8 minutes) and were willing to accept additional time (median, 5 minutes; IQR, 3–6 minutes) to obtain more information. Participants were prepared to increase both the number of visual field tests per eye and the frequency of visual field tests (median, 3 visits per year; IQR, 2–4 visits per year) to gain more information about their visual status. Regarding future developments, the most preferred option was “similar test times but an increase in the level of information about my visual field,” which ranked significantly higher than all other options, including “shorter test times that maintain the currently available level of information about my visual field.” Conclusions Our study confirms, in a different population and health care system, previous research reporting patient perspectives on visual field assessment. We further revealed that health care consumers show a strong preference for accurate information about their vision and report being prepared to undergo longer visual field tests or more visual field tests to achieve that outcome.

PurposeA disconnect often exists between those with the expertise to manage and analyze complex, multi-source data sets, and the clinical, social services, advocacy, and public health professionals who can pose the most relevant questions and best apply the answers. We describe development and implementation of a cancer informatics infrastructure aimed at broadening the usability of community cancer data to inform cancer control research and practice; and we share lessons learned. MethodsWe built a multi-level database known as The Ohio Cancer Assessment and Surveillance Engine (OH-CASE) to link data from Ohio’s cancer registry with community data from the U.S. Census and other sources. Space- and place-based characteristics were assigned to individuals according to residential address. Stakeholder input informed development of an interface for generating queries based on geographic, demographic, and disease inputs and for outputting results aggregated at the state, county, municipality, or zip code levels. ResultsOH-CASE contains 723,410 patient records for Ohioans diagnosed with cancer from 1/1/2006 – 12/31/2017 across 88 counties containing 1215 municipalities and 1197 zip codes. Stakeholder feedback from cancer center community outreach teams, advocacy organizations, public health, and researchers suggests a broad range of uses of such multi-level data resources accessible via a user interface. ConclusionOH-CASE represents a prototype of a transportable model for curating and synthesizing data to understand cancer burden across communities. Beyond supporting collaborative research, this infrastructure can serve the clinical, social services, public health, and advocacy communities by enabling targeting of outreach, funding, and interventions to narrow cancer disparities.

Purpose: Involvement of adolescent and young adult (AYAs) cancer survivors as consumers in research is increasingly encouraged, yet few studies have identified the feasibility and acceptability of ...

Introduction Establishing intravenous access is essential but may be difficult to achieve for patients requiring isolation for SARS-CoV-2 infection. This study aimed to investigate the effectiveness of infrared vein visualizer on the peripheral intravenous catheter therapy in COVID-19 patients. Methods A nonrandomized clinical trial was performed. One-hundred and twenty-two COVID-19 patients that required peripheral intravenous cannulation were divided into two groups with 60 in the control group and 62 in the intervention group. Conventional venipuncture method was applied to the control group while infrared vein imaging device was applied in the intervention group. The first attempt success rate, total procedure time and patients’ satisfaction score were compared between two groups using chi-square, t-test, and z-test (also known as Mann-Whitney U test) statistics. Results The first attempt success rate in the intervention group was significantly higher than that of control group (91.94% vs 76.67%, ꭓ2=5.41, P=0.02). The procedure time was shorter in the intervention group (M=211.44, SD=68.58 seconds vs M=388.27, SD=88.97 seconds, t=12.27, P

Setting Nonoptimized medication therapies (NOMTs) are associated with likely avoidable illnesses and mortality affecting millions of people and costing an estimated $528 billion per year in excess health spending in the United States. The coronavirus disease 2019 (COVID-19) pandemic brought into focus barriers limiting the ability of U.S. pharmacists and pharmacies to provide services that can reduce NOMTs and improve U.S. population health. Objectives This National Science Foundation Center for Health Organization Transformation study explored potential strategies that U.S. pharmacists, pharmacies, and their partners could implement to reduce NOMTs while also delivering other forms of value to U.S. populations from 2021 to 2025 (during and after the COVID-19 pandemic). Design A panel of senior leaders representing the U.S. pharmacist and pharmacy sector participated in a 4-round Delphi process to identify unmet needs, barriers, change drivers, and priority strategies for meeting those needs. Data were gathered and analyzed by public health researchers, most of whom are outside the pharmacist and pharmacy sector. Results A comprehensive set of evidence-based strategies with potential to reduce NOMTs, protect and improve population health and well-being, and strengthen the sector were identified. Four transformational strategies were recommended: comprehensive payment and practice transformation, strengthening pharmacy data interoperability infrastructure, development of unifying measurement and management mechanisms, and development of a more robust national research infrastructure. Strengthening health equity was a cross-cutting strategy affecting all areas. Conclusion The results may be of interest to policy makers, pharmacists, pharmacies, physicians, nurses and other clinicians, pharmaceutical firms, plan sponsors, plans, health systems, clinics, aging care, digital technology companies, and others interested in optimizing outcomes from medications and related therapies for U.S. populations.

Background Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. Objective We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. Methods We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. Results The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. Conclusions We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

BackgroundTumor-associated macrophages (TAMs) are closely related to unfavorable prognosis of patients with clear cell renal cell carcinoma (ccRCC). However, the important molecules in the interaction between ccRCC and TAMs are unclear.MethodsTCGA-KIRC gene expression data of tumor tissues and normal tissues adjacent to tumor were compared to identify differentially expressed genes in ccRCC. TAMs related genes were discovered by analyzing the correlation between these differentially expressed genes and common macrophage biomarkers. Gene set enrichment analysis was performed to predict functions of TAMs related gene. The findings were further validated using RNA sequencing data obtained from the CheckMate 025 study and immunohistochemical analysis of samples from 350 patients with ccRCC. Kaplan–Meier survival curve, Cox regression analysis and Harrell’s concordance index analysis were used to determine the prognostic significance.ResultsIn this study, we applied bioinformatic analysis to explore TAMs related differentially expressed genes in ccRCC and identified 5 genes strongly correlated with all selected macrophage biomarkers:STAC3,LGALS9,TREM2,FCER1G, andPILRA. Among them,FCER1Gwas abundantly expressed in tumor tissues and showed prognostic importance in patients with ccRCC who received treatment with Nivolumab; however, it did not exhibit prognostic value in those treated with Everolimus. We also discovered that high expression levels ofFCER1Gare related to T cell suppression. Moreover, combination ofFCER1Gand macrophage biomarkerCD68can improve the prognostic stratification of patients with ccRCC from TCGA-KIRC. Based on the immunohistochemical analysis of samples from patients with ccRCC, we further validated that FCER1G and CD68 are both highly expressed in tumor tissue and correlate with each other. Higher expression of CD68 or FCER1G in ccRCC tissue indicates shorter overall survival and progression-free survival; patients with high expression of both CD68 and FCER1G have the worst outcome. Combining CD68 and FCER1G facilitates the screening of patients with a worse prognosis from the same TNM stage group.ConclusionsHigh expression ofFCER1Gin ccRCC is closely related to TAMs infiltration and suppression of T cell activation and proliferation. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC.

Background Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC. Results Data from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan–Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman’s correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT. Conclusion Our results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.

Background: Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden. Methods: Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation.Results: The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09–1.15) for >3–6 months’ duration, 0.21 (0.06–0.69) for >6–9 months and 0.16 (0.05–0.55) for >9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27–1.66), 0.80 (0.31–2.07), and 1.19 (0.47–3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation.Conclusion: The greatest benefit in reducing recurrent VTE risk was with >9 months anticoagulation for PE and >3–6 months for DVT. Risks of major bleeding were low not being substantially different to the risks after treatment cessation.

Background Respiratory motion may introduce errors during radiotherapy. This study aims to assess and validate internal gross tumour volume (IGTV) margins in proximal and distal borders of gastroesophageal junction (GEJ) tumours during simultaneous integrated boost radiotherapy. Methods We enrolled 10 patients in group A and 9 patients in group B. For all patients, two markers were placed at the upper and lower borders of the tumour before treatment. In group A, within the simulation and every 5 fractions of radiotherapy, we used 4-dimensional computed tomography (4DCT) to record the intrafractional displacement of the proximal and distal markers. By fusing the average image of each repeated 4DCT with the simulation image based on the lumbar vertebra, the interfractional displacement could be obtained. We calculated the IGTV margin in the proximal and distal borders of the GEJ tumour. In group B, by referring to the simulation images and cone-beam computed tomography (CBCT) images, the range of tumour displacement in proximal and distal borders of GEJ tumour was estimated. We calculated the proportion of marker displacement range in group B lay within the IGTV margin calculated based on the data obtained in group A to estimate the accuracy of the IGTV margin. Results The intrafractional displacement in the cranial–caudal (CC) direction was significantly larger than that in the anterior–posterior (AP) and left–right (LR) directions for both the proximal and distal markers of the tumour. The interfractional displacement in the AP and LR directions was larger than that in the CC direction (p = 0.001, p = 0.017) based on the distal marker. The IGTV margins in the LR, AP and CC directions were 9 mm, 8.5 mm and 12.1 mm for the proximal marker and 15.8 mm, 12.7 mm and 11.5 mm for the distal marker, respectively. In group B, the proportions of markers that located within the IGTV margin in the LR, AP and CC directions were 96.5%, 91.3% and 96.5% for the proximal marker and 100%, 96.5%, 93.1% for the distal marker, respectively. Conclusions Our study proposed individualized IGTV margins for proximal and distal borders of GEJ tumours during neoadjuvant radiotherapy. The IGTV margin determined in this study was acceptable. This margin could be a reference in clinical practice.

Background The present study aimed to evaluate the elimination of three common pollutants (dimethoate, benzo(a)pyrene (BaP) and bisphenol A (BPA) by different physical exercises and to assess the possible factors which could affect the pollutants elimination. Methods A total of 200 individuals who chose different kinds of exercises in accordance to their own wish were recruited. The levels of urinary pollutants were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography tandem mass spectrometry-based method. Results Totally, the levels of dimethoate, BaP and BPA were reduced after physical exercises. However, the elimination of BaP in male was higher than that in female but the elimination of BPA in female was higher than that in male. Multivariate logistic regression showed that the degree of heart rate (HR) change was a protective factor affecting the improvement effect of dimethoate, BaP and BPA while BMI (body mass index) was a risk factor. Nevertheless, sex was a risk factor affecting the improvement of dimethoate and BaP but had a lower efficacy on BPA improvement. Conclusion The present findings indicate that physical exercises can be considered as a novel approach to eliminate pollutants level in human body and can also give suggestions for choosing specific physical exercises to male and female individuals. Moreover, those who are with higher BMI need to lose weight before eliminating pollutant level through physical exercises.

Background B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. Even though significant progresses have been made in the treatment of B-ALL, some pediatric B-ALL have still poor prognosis. The identification of tumor autoantibodies may have utility in early cancer diagnosis and immunotherapy. In this study, we used serological proteome analysis (SERPA) to screen serum autoantibodies of pediatric B-ALL, aiming to contribute to the early detection of B-ALL in children. Methods The total proteins from three pooled B-ALL cell lines (NALM-6, REH and BALL-1 cells) were separated using two-dimensional gel electrophoresis (2-DE), which was followed by Western blot by mixed serum samples from children with B-ALL (n=20) or healthy controls (n=20). We analyzed the images of 2-D gel and Western blot by PDQuest software, and then identified the spots of immune responses in B-ALL samples compared with those in control samples. The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against alpha-enolase (α-enolase) and voltage-dependent anion-selective channel protein 1 (VDAC1) were further validated in sera from another 30 children with B-ALL and 25 normal individuals by the use of enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis. Results Utilizing the SERPA approach, α-enolase and VDAC1 were identified as candidate autoantigens in children with B-ALL. The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23% by using ELISA analysis, respectively, which were significantly higher than those in normal controls (4% and 0, p Conclusions This study incidated that α-enolase and VDAC1 may be the autoantigens associated with B-ALL. Therefore, α-enolase and VDAC1 autoantibodies may be the potential serological markers for children with B-ALL.

Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

Background Few semi-quantitative food frequency questionnaires (SFFQ)s has yet been developed to assess sodium intake in Middle East region. This study was performed to validate a SFFQ for assessment of sodium consumption and food groups΄ contribution to sodium intake. Methods This study was performed on 219 healthy participants including 113 adults aged ≥19 years and 106 children aged 6–18 years in Isfahan, Iran. They were administered two SFFQ at the beginning and after 1 year to evaluate the reproducibility. The validity of SFFQ for assessment of sodium intake was compared with 24-h urine sodium and twelve 24-h dietary recalls which were completed monthly during a year as two standard methods. Results Correlation coefficient between the contribution of food groups to sodium intake based on SFFQ and 24-h dietary recalls varied from 0.04 for legumes (P = 0.667) to 0.47 for added salt (P P Conclusions The SFFQ was a relatively valid and reproducible method for estimating sodium intake. Combination of this SFFQ with a valid prediction of 24-h urinary sodium excretion can be useful in achieving more accurate results.

Background Fractures are a great health issue associated with morbidity, quality of life, life span, and health care expenditure. Fractures are correlated with cardiovascular disease, type 2 diabetes mellitus, cerebrovascular disease, and some psychiatric disorders. However, representative national data are few, and longitudinal cohort studies on the association between schizophrenia and the subsequent fracture risk are scant. We designed a nationwide population-based cohort study to investigate the association of schizophrenia with hip, vertebral, and wrist fractures over a 10-year follow-up. Methods Data of patients with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification code 295) and matched over January 2000–December 2009) were extracted from Taiwan National Health Insurance Research Database. A Cox proportional-hazards regression model was constructed to calculate hazard ratios (HRs) for fractures between the schizophrenia and control cohorts. Results Of 2028 people with schizophrenia (mean age: 36.3 years, 49.4% female), 89 (4.4%) reported newly diagnosed fractures—significantly higher than the proportion in the control population (257, 3.2%; P = 0.007). The incidences of hip (1.2%, P = 0.009) and vertebral (2.6%, P = 0.011) fractures were significantly higher in the schizophrenia cohort than in the control cohort. In Cox regression analysis, hip (adjusted HR: 1.78, 95% confidence interval [CI]: 1.08–2.93) and vertebral (adjusted HR: 1.40, 95% CI: 1.01–1.95) fracture risks were significantly higher in patients with schizophrenia. Furthermore, a sex-based subgroup analysis revealed that the risk of hip fracture remained significantly higher in female patients with schizophrenia (HR: 2.68, 95% CI: 1.32–5.44) than in female controls. On the other hand, there was no significant interaction between effects of sex and schizophrenia on the risk of fractures. Conclusions Over a 10-year follow-up, hip and vertebral fracture risks were higher in the people with schizophrenia than in the controls. The risk of fractures in patients with schizophrenia does not differ between female and male.

Background Lactation consultants frequently advise adjustments to fit and hold (or positioning and attachment) with the aim of optimising intra-oral nipple placement. However, approaches to fit and hold vary widely, with limited evidence of benefits, and effects of fit and hold on infant tongue movement have not been examined. The aim of this preliminary study was to investigate whether a gestalt breastfeeding intervention alters tongue movement, using measurements from ultrasound imaging to determine nipple placement and intra-oral nipple and breast tissue dimensions. Methods Ultrasound measurements were conducted in five breastfeeding dyads, infants aged 4–20 weeks, while feeding in their usual or ‘standard’ position and again after brief application of gestalt principles of fit and hold. Four of the mother-baby pairs, who had received comprehensive lactation support, reported persisting nipple pain. Three of these infants had difficulty latching and fussed at the breast; three had been diagnosed with oral ties. A fifth pair was breastfeeding successfully. Results Ultrasound demonstrated that the distance from nipple tip to junction of the hard and soft palate decreased, intra-oral nipple and breast tissue dimensions increased, and nipple slide decreased after a brief gestalt intervention. Conclusion These preliminary findings suggest that changes in fit and hold impact on infant tongue movement and contour. Further research investigating short- and long-term outcomes of a gestalt breastfeeding intervention in larger cohorts is required.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease’s clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Research mentoring programs are limited in many low- and middle-income countries (LMICs). The TDR Global initiated a global crowdsourcing open call soliciting proposals on how to improve research mentorship in LMICs. The purpose of this study is to examine ideas submitted to this open call to identify the ways to improve research mentorship in LMICs. Open calls have a group of individuals solve all or part of a problem and then share solutions. A WHO/TDR/SESH crowdsourcing guide was used to structure the open call. Each submission was judged by three independent individuals on a 1-10 scale. Textual submissions were extracted from eligible proposals and qualitatively analyzed via inductive and deductive coding techniques to identify themes. The open call received 123 submissions from 40 countries in Asia (49), Africa (38), Latin America (26), and Europe (10). Among all participants, 108 (87%) had research experience. A total of 21 submissions received a mean score of 7/10 or higher. Our thematic analysis identified three overarching themes related to prementoring, facilitation, and evaluation. Prementoring establishes mentor-mentee compatibility to lay foundations for mentorship. Facilitation involves iterative cycles of planning, communication, and skill improvement. Evaluation creates commitment and accountability within a framework of monitoring. This global crowdsourcing open call generated numerous mentorship ideas, including LMIC-contextualized facilitation tools. The open call demonstrates a need for greater focus on mentorship. Our data may inform the development of formal and informal mentoring programs in LMIC settings. Published version This study received support from the Special Programme for Research and Training in Tropical Diseases (TDR) and the US NIH (NIAID K24AI143471).

Background Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. Methods We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. Results During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). Conclusions The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Background Arthroscopy is a minimally invasive diagnostic tool and treatment strategy in patients suffering from temporomandibular disorders (TMD) when conservative treatment fails. This study aimed to find specific variables on pre-operative MRI or during arthroscopy that could predict success of arthroscopic lysis and lavage. Methods This retrospective analysis compared pre-operative maximum interincisal opening (MIO), pain and main complaint (pain, limited MIO or joint sounds) with results at short-term and medium-term follow-up (ST and MT respectively). Different variables scored on MRI or arthroscopy were used to make a stepwise regression model, subsequently a combined analysis was conducted using variables from both MRI and arthroscopy. Results A total of 47 patients (50 joints) met the inclusion criteria. The main complaint improved by 62 and 53% at ST and MT respectively. The absolute or probable absence of a crumpled disc scored on MRI predicted success at ST and MT (p = 0.0112 and p = 0.0054), and remained significant at MT in the combined analysis (p = 0.0078). Arthroscopic findings of degenerative joint disease predicted success at ST (p = 0.0178), absolute or probable absence of discal reduction scored during arthroscopy significantly predicted success in the combined analysis at ST (p = 0.0474). Conclusion To improve selection criteria for patients undergoing an arthroscopic lysis and lavage of the TMJ, future research might focus on variables visualized on MRI. Although more research is needed, disc shape and in particular the absolute or probable absence of a crumpled disc might be used as predictive variable for success.

Background Hematopoietic stem cell transplantation (HSCT) is an aggressive medical procedure which significantly impacts the shared emotional well-being of patients and family caregivers (FC). Prior work has highlighted the significant overlap in well-being among patients and FCs; however, how this interdependence may change over the course of HSCT has received less attention. Methods We conducted secondary analyses of a supportive intervention delivered to 154 FCs of HSCT patients and examined relationships at baseline, 6 weeks, 3 and 6 months post-HSCT. Actor Partner Interdependence Modeling examined patient quality of life (QOL) and FC anxiety/depression. Results The data did not fit a multigroup approach limiting our ability to test intervention effects; however, bivariate analyses indicated FC depression significantly correlated to patient QOL at baseline (r = − .32), 6 weeks (r = − .22) and 6 months post-HSCT (r = − .34; p’s p’s lower FC depression at 3-months (B = .193; p = .026) and changed direction with patient QOL at 3-months being related to more FC depression at 6-months (B = − .187; p = .001). Conclusions These findings highlight the significant, yet nuanced, interdependence of patient QOL and FC well-being during HSCT. Specifically, greater interdependence was observed between patient QOL and FC depression compared to FC anxiety, suggesting potential treatment targets for patients and their families. Trial was registered at ClinicalTrials.gov Identifier: NCT02037568; first registered: January 16, 2014; https://clinicaltrials.gov/ct2/show/NCT02037568

Background Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient’s condition. Methods APAP patients numbering 151 were enrolled in this study. All patients’ severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1–2 and 3–5 through receiving operating characteristics (ROC) curve. Results Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1–2 and 3–5) showed an optimal cutoff of LDH of over 203 U/L ( 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748–0.882], sensitivity: 0.606, specificity: 0.877). Conclusion Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. Methods PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Results The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p P P P Conclusion Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

Background We have here assessed the impact of demographic, clinical, and treatment compliance characteristics on health-related quality of life (HRQoL) of Venezuelan patients with systemic lupus erythematosus (SLE). We have used a disease-specific questionnaire, the Lupus Quality of Life (LupusQoL), validated in our patient population, to measure HRQoL. Methods A cross-sectional study was conducted among 100 patients with SLE from outpatient clinics. Patients completed a form with demographic, clinical, and treatment compliance data, and the LupusQoL questionnaire. HRQoL was classified as better or worse according to previously established cut-off points for this patient population. Spearman’s r test was used to determine the correlations between age, years of education, disease duration, SLEDAI, and SLICC-DI with the eight domains of the LupusQoL. Mann–Whitney U test was used to compare the HRQoL between the two groups of patients according to treatment compliance. Binomial logistic regression using the backward stepwise selection method was performed to identify the risk factors associated with each of the eight domains of the LupusQoL among patients with inactive (SLEDAI Results HRQoL of our patients was classified as better in all domains of the LupusQoL. Age correlated negatively with all domains of the LupusQoL, except with “burden to others”, and disease activity correlated negatively with all domains of the LupusQoL, except with “intimate relationships” and “burden to others” (p p worse “planning” and “intimate relationships” was advanced age, while having had SLE flare-ups in the previous six months was a risk factor associated with worse “physical health” (p Conclusion Age and disease activity were negatively correlated with almost all domains of the LupusQoL, and treatment compliance was associated with higher score in the “physical health” domain. Disease control and treatment compliance should be the main goals for a better HRQoL in our patients with SLE.

Background Bacteraemia is associated with high morbidity and mortality, with delayed antibiotic treatment associated with poorer outcomes. Early identification is challenging, but clinically important. Multiple scoring systems have been developed to identify individuals in the broader categories of sepsis. We designed this study to assess the performance of existing scoring systems and pathways—CEC SEPSIS KILLS pathway (an Australian sepsis care package), quick sequential organ failure score (qSOFA), systemic inflammatory response syndrome (SIRS) and the Shapiro criteria. Methods This was a retrospective cohort study performed in two metropolitan hospitals in NSW, consisting of adult patients (> 18 years) with positive blood cultures containing a true pathogen and patients matched by age without positive blood cultures. Performance (sensitivity, specificity, and mortality prediction) of recognised sepsis and bacteraemia criteria and pathways—qSOFA, SIRS, Shapiro criteria and CEC SEPSIS KILLS pathway in the first 4 h following ED triage was assessed. Results There were 251 patients in each cohort. Sepsis-related mortality was higher in the bacteraemic group (OR 0.4, p = 0.03). Of the criteria studied, the modified Shapiro criteria had the highest sensitivity (88%) with modest specificity (37.85%), and qSOFA had the highest specificity (83.67%) with poor sensitivity (19.82%). SIRS had reasonable sensitivity (82.07%), with poor sensitivity (20.72%). The CEC SEPSIS pathway sensitivity of 70.1% and specificity of 71.1%. The SEPSIS KILLS was activated on only 14% of bacteraemic patients. Conclusion The performance of all scoring systems and pathways was suboptimal in the identification of patients at risk of bacteraemia presenting to the emergency department.

Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Background This study was performed to identify the association between the total magnetic resonance imaging burden of small vessel disease and the occurrence of post-stroke dysphagia in patients with a single recent small subcortical infarct (RSSI). Methods We retrospectively identified all patients with a magnetic resonance imaging-confirmed single RSSI. The water-swallowing test and volume-viscosity swallow test were performed within the first 24 h following admission to assess swallowing. Demographic and clinical data were extracted from our stroke database. Based on brain magnetic resonance imaging, we independently rated the presence of cerebral microbleeds, lacunes, white matter hyperintensities and enlarged perivascular spaces. The presence of each small vessel disease feature was summed to determine the total small vessel disease burden, ranging from 0 to 4. Results In total, 308 patients with a single RSSI were enrolled. Overall, 54 (17.5%) were diagnosed with post-stroke dysphagia. The risk factors related to post-stroke dysphagia included the following: older age, higher National Institute of Health Stroke Scale scores, higher C-reactive protein level and higher fibrinogen level. Based on multiple logistic regression, National Institute of Health Stroke Scale scores and total small vessel disease burden were independent risk factors of post-stroke dysphagia in patients with a single RSSI, after adjusting for age, gender, history of hypertension, C-reactive protein level and fibrinogen level. Conclusions Dysphagia in patients with a single RSSI was associated with a more severe total small vessel disease burden as reflected by MRI. Total MRI of cerebral small vessel disease burden may predict dysphagia in these patients. Furthermore, more severe total small vessel disease burden was associated with systemic inflammation.

BackgroundGangliosides are glycosphingolipids highly enriched in the brain, with important roles in cell signaling, cell-to-cell communication, and immunomodulation. Genetic defects in the ganglioside biosynthetic pathway result in severe neurodegenerative diseases, while a partial decrease in the levels of specific gangliosides was reported in Parkinson’s disease and Huntington’s disease. In models of both diseases and other conditions, administration of GM1—one of the most abundant gangliosides in the brain—provides neuroprotection. Most studies have focused on the direct neuroprotective effects of gangliosides on neurons, but their role in other brain cells, in particular microglia, is not known. In this study we investigated the effects of exogenous ganglioside administration and modulation of endogenous ganglioside levels on the response of microglia to inflammatory stimuli, which often contributes to initiation or exacerbation of neurodegeneration.MethodsIn vitro studies were performed using BV2 cells, mouse, rat, and human primary microglia cultures. Modulation of microglial ganglioside levels was achieved by administration of exogenous gangliosides, or by treatment with GENZ-123346 and L–t-PDMP, an inhibitor and an activator of glycolipid biosynthesis, respectively. Response of microglia to inflammatory stimuli (LPS, IL-1β, phagocytosis of latex beads) was measured by analysis of gene expression and/or secretion of pro-inflammatory cytokines. The effects of GM1 administration on microglia activation were also assessed in vivo in C57Bl/6 mice, following intraperitoneal injection of LPS.ResultsGM1 decreased inflammatory microglia responses in vitro and in vivo, even when administered after microglia activation. These anti-inflammatory effects depended on the presence of the sialic acid residue in the GM1 glycan headgroup and the presence of a lipid tail. Other gangliosides shared similar anti-inflammatory effects in in vitro models, including GD3, GD1a, GD1b, and GT1b. Conversely, GM3 and GQ1b displayed pro-inflammatory activity. The anti-inflammatory effects of GM1 and other gangliosides were partially reproduced by increasing endogenous ganglioside levels with L–t-PDMP, whereas inhibition of glycolipid biosynthesis exacerbated microglial activation in response to LPS stimulation.ConclusionsOur data suggest that gangliosides are important modulators of microglia inflammatory responses and reveal that administration of GM1 and other complex gangliosides exerts anti-inflammatory effects on microglia that could be exploited therapeutically.

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

BackgroundHip fracture is highly associated with disability and consequently, mortality in the elderly population. Postoperative acute kidney injury (AKI) is not unusual and is associated with considerable morbidity and mortality. We aimed to determine the incidences and potential risk factors for postoperative AKI in elderly patients with femoral neck fracture.MethodsWe retrospectively evaluated patients over 65 years of age who had been subjected to surgery for femoral neck fracture at Peking University People's Hospital from January 2015 to December 2019. Demographic characteristics and potential risk factors were collected. AKI was defined according to the Kidney Disease Improving Global Outcomes Guidelines (KDIGO).ResultsA total of 308 elderly patients with femoral neck fracture were included in the study. The overall incidence of postoperative AKI was 12% (37 cases). Through binary logistic regression analysis, adjusted for age, intraoperative blood loss and BMI, we identified that early postoperative albumin levels, hemoglobin changes and intraoperative hypotension are independent risk factors for postoperative AKI. The model considering the three factors can improve accuracy of predicting the possibility of developing AKI. The patients with AKI had a significantly higher mortality of 40.5% than those without AKI (24.0%,p< 0.001)ConclusionThe incidence of postoperative AKI in elderly patients with femoral neck fracture was 12%. Independent risk factors for postoperative AKI included hemoglobin changes, early postoperative hypoalbuminemia and intraoperative hypotension. At the same time, postoperative AKI significantly increased mortality in elderly patients with femoral neck fracture. Taking multiple possible factors into consideration can better predict the possibility of elderly patients developing AKI after surgery.

Background Mirror therapy (MT) has been used for functional recovery of the affected hand by providing the mirrored image of the unaffected hand movement, which induces neural activation of the cortical hemisphere contralateral to the affected hand. Recently, many wearable robots assisting the movement of the hand have been developed, and several studies have proposed robotic mirror therapy (RMT) that uses a robot to provide mirrored movements of the unaffected hand to the affected hand with the robot controlled by measuring electromyography or posture of the unaffected hand. In some cases of RMT a mirror is placed to allow the person to observe only the unaffected hand but in others users simply observe the robotically assisted hand performing the mirrored movements, as was the case in this study. There have been limited evaluations of the cortical activity during RMT compared to MT and robotic therapy (RT) providing passive movements despite the difference in the modality of sensory feedback and the involvement of motor intention, respectively. Methods This paper analyzes bilateral motor cortex activation in nine healthy subjects and five chronic stroke survivors during a pinching task performed in MT, RT, and RMT conditions using functional near infrared spectroscopy (fNIRS). In the MT condition, the person moved the unaffected hand and observed it in a mirror while the affected hand remained still. In RT condition passive movements were provided to the affected hand with a cable-driven soft robotic glove, while, in RMT condition, the posture of the unaffected hand was measured by a sensing glove and the soft robotic glove mirrored its movement on the affected hand. Results For both groups, the RMT condition showed the greatest mean cortical activation on the motor cortex contralateral to the affected (non-dominant for the healthy group) hand compared to other conditions. Individual results indicate that RMT induces similar or greater neural activation on the motor cortex compared to MT and RT conditions. The interhemispheric activations of both groups were balanced in RMT condition. In MT condition, significantly greater activation was shown on the hemisphere ipsilateral to the affected (dominant for the healthy group) hand for both subject groups, while the contralateral side showed significantly greater activation for the healthy group in RT condition. Conclusion The experimental results indicate that combining visual feedback, somatosensory feedback, and motor intention are important for greater stimulation on the contralateral motor cortex of the affected hand. RMT that includes these factors is hypothesized to achieve a more effective functional rehabilitation due to greater and more balanced cortical activation.

Healthcare staff behaviour can impact on the performance of hospitals. Staff involvement in clinical research can have a wider positive effect on patients and hospital performance. The aim of this study was to further assess the putative positive effect of clinical research activity on patient feedback with a more recent dataset, and if staff's motivational engagement levels may impact on aspects of in-patient feedback.A retrospective cross-sectional study was conducted with (survey) data from 2019; the sample was 129 English National Health Service hospital Trusts. Sources were the national in-patient survey, national staff survey (for staff motivational engagement), and research activity (based on Trust size-corrected National Institute for Health Research records data). Spearman correlation analyses were conducted (minimum rho value 0.25, p-value0.005), followed by principal component analysis (score cut-off 0.2).Initial correlation analyses identified eleven in-patient survey questions where better in-patient feedback was associated with increased clinical research activity, and only three questions linked with higher degree of staff motivational engagement. Subsequent principal component analysis confirmed that increased staff engagement is mainly linked to overall Trust performance such as staff levels, whereas staff in research-active hospitals provided in-patients with sufficient information - including on medication - and did well answering patient questions.Staff involvement in clinical research is associated with better patient feedback. Clear and thorough information provision to patients, may be a mechanism for improved patient outcomes including mortality.

In September of 2020, the Iowa Department of Public Health released guidance stating that persons exposed to someone with coronavirus disease (COVID-19) need not quarantine if the case-patient and the contact wore face masks at the time of exposure. This guidance differed from that issued by the Centers for Disease Control and Prevention. To determine the best action, we matched exposure information from COVID-19 case investigations with reported test results and calculated the secondary attack rates (SARs) after masked and unmasked exposures. Mask use by both parties reduced the SAR by half, from 25.6% to 12.5%. Longer exposure duration significantly increased SARs. Masks significantly reduced virus transmission when worn by both the case-patient and the contact, but SARs for each group were higher than anticipated. This finding suggests that quarantine after COVID-19 exposure is beneficial even if parties wore masks.

Background The COVID-19 pandemic remains a public health priority, and vaccination is important for ending the pandemic. Racial and ethnic minorities are disproportionally affected by COVID-19 yet report high levels of vaccination hesitancy. Objective We conducted virtual Town Halls to address vaccine hesitancy among racial and ethnic minorities in South Florida. Methods Our approach used social influence and persuasion models. A formative phase gathered meeting preferences from our communities and developed and tested our approach. An implementation phase conducted six virtual Town Halls in partnership with minority community-based organizations. Results The Town Halls reached 383 participants (mean age 37.5 years; 63.4% female, 33.9% male, 2.7% nonbinary; 59% racial/ethnic minority), who completed pre- and post-meeting assessments. Among non-vaccinated participants, at the pre poll, 58% reported a high likelihood of seeking vaccination, rising to 63% at post-assessment. Unvaccinated “non-hesitant” and “hesitant” groups were compared on trusted information sources, and reasons and barriers for vaccination. Non-hesitant participants reported significantly greater trust in the COVID-19 Task Force (97.3% vs. 83.3%) as a source of vaccine information than did hesitant participants. Non-hesitant participants were significantly more likely to endorse family safety (82.5% vs. 63.2%), community safety (72.5% vs. 26.3%), personal safety (85% vs. 36.8%), and wanting to return to a normal life (70% vs. 31.6%), as reasons for vaccination than were hesitant participants. Hesitant participants were significantly more likely to endorse concerns about vaccine safety doubts (63.2% vs. 17.5%) and not believing the pandemic is as bad as people say it is (21.1% vs. 5%) as barriers to vaccination than were non-hesitant participants. Qualitative data revealed high consumer satisfaction with the Town Halls. Conclusion This study supports the feasibility, acceptability, and potential impact of virtual Town Halls for addressing vaccine hesitancy among racial/ethnic minorities; however, our approach was very resource intensive, required an extensive community-university collaborative infrastructure, and yielded a small effect.

Background The evidence-base underpinning treatment efficacy and effectiveness for hidradenitis suppurativa (HS) is limited, as has been highlighted in the wide-ranging research priorities established by a James Lind Alliance priority-setting partnership (PSP). Understanding the landscape of surgical practice is a key step towards tackling undesired variation in care and resolving treatment uncertainties. This survey of current surgical practice aimed to describe care pathways involving surgeons for the management of HS and surgical approaches to management. Methods In the development of the prospective cohort Treatment of Hidradenitis Suppurativa Evaluation Study (THESEUS), a bespoke electronic surgeon survey was conducted to describe variation in care pathways and surgical preferences in the management of HS. This was disseminated to a pre-defined denominator list of surgeons using local collaborators through the reconstructive surgery trials network (RSTN). Results Key results were small numbers of surgeons working in formal multidisciplinary teams (MDTs) (8/198, 4%), heterogeneity of first-line intervention, low rates of guideline endorsed treatments (laser and deroofing in particular), variation in wound closure methods and follow-up length, and that over half of respondents do not use well-validated outcome instruments to determine treatment success/failure (110/198, 56%). Conclusions This survey demonstrated variation in care, which is likely to be undesirable. Surgeons treating HS patients might consider developing MDTs or referring patients to those with an interest in HS and considering routine outcome measurement. Such steps might reduce variation, increase standardisation of care and improve access to specific treatments.

Background: The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease. Methods: In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed. Results: Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively. Conclusions: The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not., BMC Pulmonary Medicine, 22, art. no. 45; 2022

Objective The aim of this study was to evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas. Methods We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus–pituitary–thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.

Upadacitinib is an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA) and recently approved by the European Medicines Agency for the treatment of psoriatic arthritis (PsA). The efficacy and safety profile of upadacitinib in PsA have been established in the SELECT‐PsA program in two global phase III studies, which evaluated upadacitinib 15 and 30 mg q.d. The analyses described here characterized upadacitinib pharmacokinetics and exposure‐response relationships for efficacy and safety endpoints using data from the SELECT‐PsA studies. Upadacitinib pharmacokinetics in patients with PsA were characterized through a Bayesian population analysis approach and were comparable to pharmacokinetics in patients with RA. Exposure‐response relationships for key efficacy and safety endpoints were characterized using data from 1916 patients with PsA. The percentage of patients achieving efficacy endpoints at week 12 (American College of Rheumatology [ACR]50 and ACR70), 16 and 24 (sIGA0/1) increased with increasing upadacitinib average plasma concentration over a dosing interval, whereas no clear exposure‐response trend was observed for ACR20 at week 12 or ACR20/50/70 at week 24 within the range of plasma exposures evaluated in the phase III PsA studies. No clear trends for exposure‐response relationships were identified for experiencing pneumonia, herpes zoster infection, hemoglobin less than 8 g/dl, lymphopenia (grade ≥ 3), or neutropenia (grade ≥ 3) after 24 weeks of treatment. Shallow relationships with plasma exposures were observed for serious infections and hemoglobin decrease greater than 2 g/dl from baseline at week 24. Based on exposure‐response analyses, the upadacitinib 15 mg q.d. regimen is predicted to achieve robust efficacy in patients with PsA and to be associated with limited incidences of reductions in hemoglobin or occurrence of serious infections.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF‐κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre‐operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1–15 +/‐ 2); Debio 1143 (200 mg/day D1–15 +/‐ 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014‐004655‐31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP‐1 (cIAP‐1). Levels of cIAP‐1/‐2, X‐linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD‐1), PD‐ligand 1 (PD‐L1), and gene expression were also analyzed. Twenty‐three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18‐fold (maximum 55.2‐fold) greater than in plasma, exceeding the half‐maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000‐fold, with significant engagement/degradation of cIAP‐1 (p

Structural racism-the ways that institutional policies, practices, and other norms operate to create and sustain race-based inequities1-has historically been foundational to the operations of academic medical centers and research institutions. Since its inception, academic medicine has depended on the exploitation of vulnerable communities to achieve medical, educational, and research goals.2 Research practices have long ignored or taken advantage of the individuals purportedly benefiting from the research, a dynamic most manifestly true for Black, Indigenous, and People of Color (BIPOC) communities in the United States. Reflecting current practices in racial justice work, we intentionally use the term "BIPOC" to highlight shared experiences within racially and ethnically minoritized communities, given the history of white supremacy in the United States. We acknowledge limitations of this term, which collapses myriad unique communities and histories into 1 construct. Specifically, child and adolescent psychiatry has historically been driven by Eurocentric approaches, paradigms, and methodology. These nonparticipatory dominant research practices have contributed to a lack of culturally responsive interventions for BIPOC communities, a paucity of evidence-based practices with demonstrated effectiveness within BIPOC communities, and disparities in access and quality of care.3 Mental health research involving BIPOC communities has been replete with exploitation and inequality.2.