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Objective: Examine social media experiences of the suicidal adolescent presenting to the emergency department with an acute mental health crisis., Methods: We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders., Results: Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory., Conclusions: Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Hypertension complicates 2% to 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality globally. Given the prognostic role that angiogenic markers play in evaluation of patients with "suspected preeclampsia," the International Society for the Study of Hypertension in Pregnancy incorporated angiogenic imbalance into the 2021 definition of preeclampsia. As women with "suspected preeclampsia" are a heterogeneous group, with some already meeting the diagnostic criteria for preeclampsia, we evaluated whether the soluble fms-like tyrosine kinase-1/placental growth factor ratio adds prognostic value among these women., Objective: This study aimed to assess the additive value of soluble fms-like tyrosine kinase-1/placental growth factor ratio when the diagnostic criteria for preeclampsia have already been met., Study Design: This was a secondary analysis of a prospective cohort study of patients presenting to obstetrical triage with suspected preeclampsia at ≥20 +0 weeks' gestation from July 2009 to June 2012 in Boston, United States. Clinicians were masked to soluble fms-like tyrosine kinase-1/placental growth factor ratio results. Clinical records were reviewed for maternal and neonatal care and outcomes. The value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio (≤38, >38, or >85) was assessed for identifying women at low or high risk of evolving into preeclampsia with severe features within 2 weeks of the triage visit, with preeclampsia with severe features being defined by the American College of Obstetricians and Gynecologists (2013 definition). Based on information in obstetrical triage, preeclampsia among triage patients was defined either by: (1) The International Society for the Study of Hypertension in Pregnancy "restrictive" criteria (ie, new-onset hypertension and proteinuria at ≥20 weeks), or (2) The International Society for the Study of Hypertension in Pregnancy "broad" maternal criteria (ie, new-onset hypertension with proteinuria or one/more relevant maternal end-organ complications)., Results: Of 1043 patients included, 459 presented at 20 +0 to 34 +6 weeks and 584 at ≥35 +0 weeks. In triage, 25.8% of women with "suspected preeclampsia" already met the preeclampsia criteria based on the International Society for the Study of Hypertension in Pregnancy broad criteria and 22.0% based on the restrictive criteria. In separate multivariable analyses adjusted for gestational age, a soluble fms-like tyrosine kinase-1/placental growth factor ratio >38 was independently associated with preeclampsia with severe features within 2 weeks even after adjusting for preeclampsia diagnosis in obstetrical triage, whether that preeclampsia were defined restrictively (odds ratio, 15.62; 95% confidence interval, 8.91-27.40) or broadly (odds ratio, 14.56; 95% confidence interval, 8.30-25.56). A soluble fms-like tyrosine kinase-1/placental growth factor ratio ≤38 was good at ruling out development of preeclampsia with severe features within 2 weeks among all patients and among those meeting the restrictive or broad definitions of preeclampsia (negative likelihood ratios, ≤0.16), driven by performance of the ratio before 35 weeks (ie, negative likelihood ratio ≤0.12). A soluble fms-like tyrosine kinase-1/placental growth factor ratio >85 was good at ruling-in preeclampsia with severe features within 2 weeks among women with suspected preeclampsia, either before (positive likelihood ratio, 8.20) or after 35 weeks (positive likelihood ratio, 6.00) and fair at ruling-in preeclampsia with severe features within 2 weeks when preeclampsia had already been confirmed in patients at <35 weeks (restrictively positive likelihood ratio, 3.48, or broadly positive likelihood ratio, 3.40)., Conclusion: Our findings support the prognostic value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio among patients with confirmed preeclampsia, particularly to identify those both likely and unlikely to progress toward the development of severe features in the next 2 weeks and those who may be most appropriate for expectant and potentially outpatient care. Our findings support the incorporation of angiogenic imbalance into the definition of preeclampsia, particularly at 20-34 +0 weeks., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Post radical prostatectomy (RP) erectile dysfunction and incontinence impacts quality of life for patients. In an objective to hasten the recovery of these functional outcomes, human placental derived allografts laid on neurovascular bundles (NVB) have been investigated. These grafts include amniotic membranes (AM) chorionic membranes (CM) or umbilical cord (UC) allografts. A literature review performed using the MeSH terms "AMNION" OR "CHORION" OR "AMNIOTIC MEMBRANE" OR "UMBILICAL CORD" AND "PROSTATE CANCER" from no specified start date, to April 2022. 163 articles were retrieved, with 149 articles excluded. 14 articles were eligible and analysed. 5 articles were included in this review for an analysis on comparative outcomes. The average return to potency was statistically significant in the intervention groups. Positive surgical margin (PSM) rates showed a higher rate in the control groups. BCR was observed at a lower rate in the interventional group. This review reveals a benefit from human placental allograft's ability to hasten post RP functional recovery, without impacting oncological control., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: Carcinosarcoma of the salivary gland is a rare malignant biphasic tumor. The present study investigates the epidemiology and clinical behavior of carcinosarcoma of the major salivary glands using the National Cancer Database (NCDB)., Study Design: Historical cohort study., Setting: NCDB., Methods: All tumors were selected between 2004 and 2018. Patient demographics, tumor characteristics, treatments, and survival were analyzed. Cox regression analysis was performed in surgically treated patients., Results: We identified 154 patients in the NCDB with carcinosarcoma of the salivary gland. Median age at diagnosis was 66 years (interquartile range, 55-76). Most patients were male (n = 92, 60%). The majority of tumors were in the parotid (n = 122, 79%), followed by submandibular gland (n = 21, 14%). The majority were high grade (n = 93, 95%), and a significant portion had locally advanced disease (pT3-4; n = 65, 62%). Nodal disease was present in more than one-third (n = 35, 36%). The most common treatment was surgery with adjuvant radiotherapy (n = 75, 49%). With a median follow-up of 36 months, the 3-year overall survival was 57.6% (95% CI, 48.7%-68.0%). In univariable analysis, advanced pT stage, pN+ disease, and positive margins were associated with worse survival. In multivariable analysis, age (hazard ratio, 1.02; 95% CI, 1.01-1.04; P = .03) and pT stage (hazard ratio, 2.51; 95% CI, 1.27-4.95; P = .008) remained significant., Conclusion: Carcinosarcoma is a rare salivary gland tumor that frequently presents at a locally advanced stage. Despite multimodality treatments, the outcomes are poor. In the absence of clinical trial data, these data from the NCDB could guide clinicians in the management of this rare disease., (© 2022 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Although obesity is often associated with adverse outcomes in cardiovascular diseases, studies have demonstrated a beneficial effect on patients who underwent transcatheter aortic valve implantation (TAVI), coining the term "obesity paradox." We sought to determine if the obesity paradox is valid when patients are studied in body mass index (BMI) groups versus simplified classification of obese and nonobese. We examined the National Inpatient Sample database from 2016 to 2019 for all patients who underwent TAVI >18 years of age using the International Classification of Diseases, 10th edition procedure codes. Patients were grouped by BMI categories of underweight, overweight, obese, and morbidly obese. They were compared with normal-weight patients to assess the relative risk of in-hospital mortality, cardiogenic shock, ST-elevation myocardial infarction, bleeding complications requiring transfusions, and complete heart blocks requiring permanent pacemaker. A logistic regression model was constructed to account for potential confounders. Of the 221,000 patients who underwent TAVI, 42,315 patients with appropriate BMI designation were stratified into BMI groups. Compared to the normal-weight group, overweight, obese, and morbid-obese TAVI patients were associated with a lower risk of in-hospital mortality (relative risk [RR] 0.48, confidence interval [CI] 0.29 to 0.77, p <0.001), (RR 0.42, CI 0.28 to 0.63, p <0.001), (RR 0.49, CI 0.33 to 0.71, p <0.001 respectively), cardiogenic shock (RR 0.27, CI 0.20 to 0.38, p <0.001), (RR 0.21, CI 0.16 to 0.27, p <0.001), (RR 0.21, CI 0.16 to 0.26, p <0.001), and blood transfusions (RR 0.63, CI 0.50 to 0.79, p <0.001), (RR 0.47, CI 0.39 to 0.58, p <0.001), (RR 0.61, CI 0.51 to 0.74, p <0.001). This study indicated that obese patients were at a significantly lower risk of in-hospital mortality, cardiogenic shock, and bleeding complications requiring transfusions. In conclusion, our study supported the existence of the obesity paradox in TAVI patients., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The avoidance of infectious disease by widespread use of 'systems hygiene', defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this 'biota alteration' leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.35; p<0.0001). Thus, it is now apparent that 'biome reconstitution', defined as the artificial re-introduction of benign, symbiotic helminths or protists into the ecosystem of the human body, is important not only for alleviation of chronic immune disease, but likely also for pandemic preparedness., Competing Interests: Co-author W.P. is a founding member and CEO of XPara Mutualistic Helminths, LLC, which has a financial interest in helminth therapy. Co-author E.P. is currently a student at Duke University, which owns intellectual property related to helminth therapy. Co-authors E.P., K.J.P., and J.D.L. have no competing interests., (© 2023 The Author(s).)

Background: Preeclampsia is a disease with far-reaching consequences that extend beyond the immediate postpartum period and have a significant impact later in life. Preeclampsia exerts an effect on most organ systems in the body. These sequelae are mediated in part by the incompletely elucidated pathophysiology of preeclampsia and the associated vascular changes., Content: Current research focuses on unraveling the pathophysiology of preeclampsia with the goal of implementing accurate screening and treatment modalities based on disease development and progression. Preeclampsia causes significant short- and long-term maternal morbidity and mortality, not only in the cardiovascular system but also in other organ systems throughout the body. This impact persists beyond pregnancy and the immediate postpartum period., Summary: The goal of this review is to discuss the current understanding of the pathophysiology of preeclampsia as it relates to the adverse health consequences in patients impacted by this disease, along with a brief discussion of ways to improve overall outcomes., Competing Interests: SR reports serving as a consultant to Roche Diagnostics and Thermo Fisher Scientific and has received funding from Roche Diagnostics and Siemens for studies related to the use of angiogenic factors in pregnancy which is unrelated to work for this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bisson, Dautel, Patel, Suresh, Dauer and Rana.)

Importance: Emergency department (ED)-based initiation of buprenorphine has been shown to increase engagement in outpatient treatment and reduce the risk of subsequent opioid overdose; however, rates of buprenorphine treatment in the ED and follow-up care for opioid use disorder (OUD) remain low in the US. The Opioid Hospital Quality Improvement Program (O-HQIP), a statewide financial incentive program designed to increase engagement in OUD treatment for Medicaid-enrolled patients who have ED encounters, has the potential to increase ED-initiated buprenorphine treatment., Objective: To evaluate the association between hospitals attesting to an ED buprenorphine treatment O-HQIP pathway and patients' subsequent initiation of buprenorphine treatment., Design, Setting, and Participants: This cohort study included Pennsylvania patients aged 18 to 64 years with continuous Medicaid enrollment 6 months before their OUD ED encounter and at least 30 days after discharge between January 1, 2016, and December 31, 2020. Patients with a claim for medication for OUD 6 months before their index encounter were excluded., Exposures: Hospital implementation of an ED buprenorphine treatment O-HQIP pathway., Main Outcomes and Measures: The main outcome was patients' receipt of buprenorphine within 30 days of their index OUD ED visit. Between August 2021 and January 2023, data were analyzed using a difference-in-differences method to evaluate the association between hospitals' O-HQIP attestation status and patients' treatment with buprenorphine after ED discharge., Results: The analysis included 17 428 Medicaid-enrolled patients (female, 43.4%; male, 56.6%; mean [SD] age, 37.4 [10.8] years; Black, 17.5%; Hispanic, 7.9%; White, 71.6%; other race or ethnicity, 3.0%) with OUD seen at O-HQIP-attesting or non-O-HQIP-attesting hospital EDs. The rate of prescription fills for buprenorphine within 30 days of an OUD ED discharge in the O-HQIP attestation hospitals before the O-HQIP intervention was 5%. The O-HQIP attestation was associated with a statistically significant increase (2.6 percentage points) in prescription fills for buprenorphine within 30 days of an OUD ED discharge (β, 0.026; 95% CI, 0.005-0.047)., Conclusions and Relevance: In this cohort study, the O-HQIP was associated with an increased initiation of buprenorphine in patients with OUD presenting to the ED. These findings suggest that statewide incentive programs may effectively improve outcomes for patients with OUD.

Objective: To identify locations with higher need for acute pediatric mental health (MH) interventions or services and describe these communities' socio-demographic characteristics., Methods: This single-center retrospective study included patients 5 to 18 years old with an emergency department (ED) or hospital admission between 2017 and 2019 for a primary known MH diagnosis or symptoms. We extracted visit data from the electronic medical record, mapped patients to their home census tract, calculated normalized visit rates by census tract, and performed spatial analysis to identify nonrandom geographic clusters and outliers of high utilization. Census tract utilization rates were stratified into quartiles, and socioeconomic and demographic characteristics obtained from the US Census Bureau were compared using analysis of variance, chi-square tests, and multivariable analysis., Results: There were 10,866 qualifying visits across 617 census tracts. ED and hospital admission rates ranged from 2.7 to 428.6 per 1000 children. High utilization clusters localized to neighborhoods with lower socioeconomic status (p < .05). Southern regions with high utilizers were more likely to have fewer children per neighborhood, higher rates of teen births, and lower socioeconomic status. Multivariate analysis showed regions with high utilizers had fewer children per neighborhood, lower median household income, and more families that lacked computer access., Conclusion: ED and hospital utilization for pediatric MH concerns varied significantly by neighborhood and demographics. Divergent social factors map onto these locations and are related to MH utilization. Leveraging geography can be a powerful tool in the development of targeted, culturally tailored interventions to decrease acute pediatric MH utilization and advance child MH equity., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: In response to increased prenatal drug use since the 2000s, states have adopted treatment-oriented laws giving pregnant and postpartum people priority access to public drug treatment programs as well as multiple punitive policy responses. No prior studies have systematically characterized these state statutes or examined implementation of state priority access laws in the context of co-existing punitive laws., Methods: We conducted legal mapping to examine state priority access laws and their overlap with state laws deeming prenatal drug use to be child maltreatment, mandating reporting of prenatal drug use to child protective services, or criminalizing prenatal drug use. We also conducted interviews with 51 state leaders with expertise on their states' prenatal drug use laws to understand how priority access laws were implemented., Results: Thirty-three states and the District of Columbia have a priority access law, and more than 80% of these jurisdictions also have one of the punitive prenatal drug use laws described. Leaders reported major barriers to implementing state priority access laws, including the lack of drug treatment programs, stigma, and conflicts with punitive prenatal drug use laws., Conclusions: Our results suggest that state laws granting pregnant and postpartum people priority access to drug treatment programs are likely insufficient to significantly increase access to evidence-based drug treatment. Punitive state prenatal drug use laws may counteract priority access laws by impeding treatment seeking. Findings highlight the need to allocate additional resources to drug treatment for pregnant and postpartum people., (Copyright © 2022 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Introduction: Clinically, detection of disease-causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD-related plasma biomarkers to determine their relationships with human post mortem neuropathology., Method: Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age., Results: Included cases (N = 90) showed increased tau/amyloid beta (Aβ)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF-A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aβ42/Aβ40 ratio was inversely associated. Higher PlGF, VEGF-A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aβ42/Aβ40 ratio was positively associated., Discussion: Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology., (© 2022 the Alzheimer's Association.)

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking., Methods: A subset of research volunteers from the University of Kentucky Alzheimer's Disease Research Center longitudinal cohort came to autopsy and had ante mortem plasma homocysteine levels available. Brain tissue and blood plasma drawn closest to death were used to measure homocysteine and related metabolites in the current pilot study. Genetic expression profiles of inflammatory markers were evaluated using the Human Neuroinflammation NanoString panel. Further analyses included an evaluation of plasma homocysteine effects on amyloid beta, tau, ionized calcium-binding adaptor molecule 1, and glial fibrillary acidic protein immunohistochemistry in the frontal and occipital cortices. Analytes and other study outcomes were evaluated in relation to ante mortem HHcy status: We identified 13 persons with normal ante mortem plasma homocysteine levels (<14 µmol/L) and 18 who had high plasma homocysteine levels (≥14 µmol/L)., Results: Participants with HHcy demonstrated increased levels of several plasma homocysteine cycle metabolites such as total cysteine, S-adenosyl-homocysteine, cystathionine, and choline. Inflammatory gene expression profiles showed a general downregulation in the setting of elevated plasma homocysteine. HHcy was associated with more and longer microglial processes, but smaller and fewer astrocytes, especially in participants of older age at death. HHcy in older participants was also associated with occipital cortex microhemorrhages and increased severity of atherosclerosis throughout the cerebral vasculature., Conclusions: Increased plasma homocysteine and older age were associated with the downregulation of inflammatory gene expression markers in association with significant glial and vascular pathology changes. Impaired immune function is a plausible mechanism by which HHcy increases cerebrovascular damage leading to impaired cognitive function., Competing Interests: The authors declare they have no conflicts of interest. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Paracetamol (acetaminophen) use during pregnancy and early childhood was accepted as safe in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on the false assumption that drug interactions in babies and adults are the same, and on a complete absence of knowledge regarding the impact of the drug on brain development. At least fourteen epidemiological studies now indicate that prenatal exposure to paracetamol is associated with neurodevelopmental problems. Based on these studies, it can be concluded that prenatal exposure to paracetamol causes statistically significant risks of developmental delays, attention deficit hyperactivity disorder, and a subtype of autism spectrum disorder (ASD) associated with hyperkinetic behavior. In contrast, data regarding postnatal exposure to paracetamol are limited, and several factors impede a classic multivariate analysis of epidemiologic data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and a lack of alternative suspects that fit the evidence-derived profile. Based on this evidence, it can be concluded without any reasonable doubt that oxidative stress puts some babies and children at risk of paracetamol-induced neurodevelopmental injury, and that postnatal exposure to paracetamol in those susceptible babies and children is responsible for many if not most cases of ASD.

Policy Points Over the past several decades, states have adopted policies intended to address prenatal drug use. Many of these policies have utilized existing child welfare mechanisms despite potential adverse effects. Recent federal policy changes were intended to facilitate care for substance-exposed infants and their families, but state uptake has been incomplete. Using legal mapping and qualitative interviews, we examine the development of state child welfare laws related to substance use in pregnancy from 1974 to 2019, with a particular focus on laws adopted between 2009 and 2019. Our findings reveal policies that may disincentivize treatment-seeking and widespread implementation challenges, suggesting a need for new treatment-oriented policies and refined state and federal guidance., Context: Amid increasing drug use among pregnant individuals, legislators have pursued policies intended to reduce substance use during pregnancy. Many states have utilized child welfare mechanisms despite evidence that these policies might disincentivize treatment-seeking. Recent federal changes were intended to facilitate care for substance-exposed infants and their families, but implementation of these changes at the state level has been slowed and complicated by existing state policies. We seek to provide a timeline of state child welfare laws related to prenatal drug use and describe stakeholder perceptions of implementation., Methods: We catalogued child welfare laws related to prenatal drug use, including laws that defined child abuse and neglect and established child welfare reporting standards, for all 50 states and the District of Columbia (DC), from 1974 to 2019. In the 19 states that changed relevant laws between 2009 and 2019, qualitative interviews were conducted with stakeholders to capture state-level perspectives on policy implementation., Findings: Twenty-four states and DC have passed laws classifying prenatal drug use as child abuse or neglect. Thirty-seven states and DC mandate reporting of suspected prenatal drug use to the state. Qualitative findings suggested variation in implementation within and across states between 2009 and 2019 and revealed that implementation of changes to federal law during that decade, intended to encourage states to provide comprehensive social services and linkages to evidence-based care to drug-exposed infants and their families, has been complicated by existing policies and a lack of guidance for practitioners., Conclusions: Many states have enacted laws that may disincentivize treatment-seeking among pregnant people who use drugs and lead to family separation. To craft effective state laws and support their implementation, state policymakers and practitioners could benefit from a treatment-oriented approach to prenatal substance use and additional state and federal guidance., (© 2022 Milbank Memorial Fund.)

Importance: Over time, the American Thyroid Association (ATA) guidelines have increasingly promoted more limited treatments for well-differentiated thyroid cancers., Objective: To determine whether the 2009 and 2015 ATA guidelines were associated with changes in the management of low-risk papillary thyroid carcinomas on a national scale., Design, Setting, and Participants: This historical cohort study used the National Cancer Database. All papillary thyroid carcinomas diagnosed from 2004 to 2019 in the National Cancer Database were selected. Patients with tumors of greater than 4 cm, metastases, or clinical evidence of nodal disease were excluded. Data were analyzed from August 1, 2021, to September 1, 2022., Main Outcomes and Measures: The primary aim was to tabulate changes in the rates of thyroid lobectomy (TL), total thyroidectomy (TT), and TT plus radioactive iodine (RAI) therapy after the 2009 and 2015 ATA guidelines. The secondary aim was to determine in which settings (eg, academic vs community) the practice patterns changed the most., Results: A total of 194 254 patients (155 796 [80.2%] female patients; median [range] age at diagnosis, 51 [18-90] years) who underwent treatment during the study period were identified. Among patients who underwent surgery, rates of TL decreased from 15.1% to 13.7% after the 2009 guidelines but subsequently increased to 22.9% after the 2015 changes. Among patients undergoing TT, rates of adjuvant RAI decreased from 48.7% to 37.1% after 2009 and to 19.3% after the 2015 guidelines. Trends were similar for subgroups based on sex and race and ethnicity. However, academic institutions saw larger increases in TL rates (14.9% to 25.7%) than community hospitals (16.3% to 19.5%). Additionally, greater increases in TL rates were observed for tumors 1 to 2 cm (6.8% to 18.9%) and 2 to 4 cm (6.6% to 16.0%) than tumors less than 1 cm (22.8% to 29.2%)., Conclusions and Relevance: In this cohort study among patients with papillary thyroid carcinomas up to 4 cm, ATA guideline changes corresponded with increased TL and reduced adjuvant RAI. These changes were primarily seen in academic institutions, suggesting an opportunity to expand guideline-based care in the community setting.

Introduction: dHACM is a source of factors including cytokines that allow anti-inflammatory and proliferative elements to be utilized for wound and ulcer management. We present our experience of using dHACM in a cohort of patients undergoing nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RALP). Our objective is to investigate the functional and oncological outcomes of NS after placing amniotic or dehydrated human amnion/chorion membrane (dHACM) on preserved neurovascular bundles (NVBs). From 2013 to 2019, our institution performed transperitoneal multi-port da Vinci robotic prostatectomy. The NVBs are spared by releasing their fascial planes posteriorly, followed by an anterior release of the plane at a similar level. Once the retrograde release of the NVB is performed then 599 patients underwent placement of dHACM graft (AmnioFix by MiMedx, Marietta, GA, USA). The graft was cut into two 4 × 1 cm pieces and laid over the NVB as a wrap. In order to inform the urological community of oncological and functional outcomes, we excluded patients with less than 12 months follow up (n = 64), benign prostatic hyperplasia (n = 5), and unilateral NS (n = 1). 529 (88%) patients were included in this study who underwent a partial or full bilateral NS with dHACM. 529 patients were followed-up for a median (IQR) of 42 months (25-89). Demographics include median (IQR) age 57 years (52-62), median preoperative SHIM score of 24 (21-15), and AUASS of 5 (2-11). Full NS was performed in 74% (391/529). Pathological staging was pT2 = 399 (75%), pT3a = 107 (20%), pT3b = 19 (4%) and pT4 = 4 (1%) with N1 = 3 (0.6%). The number of patients with PSM was 86 (16%), and the overall BCR in the entire cohort was 10%. Postoperatively, 434 (82%) were sexually active. Median time to potency was 119 (37-420) days and time to continence was 42 (23-91) days. Regarding full vs partial NS: median post op SHIM score 18 (13-20) vs 15 (6-20), median time to potency 92 (35-365) days vs 184 (42-560) days, and median time to continence 42 (23-91) days vs 44 (30-92) days. Age > 55 vs ≤ 55 years: median post op SHIM score 18 (12-20) vs 15 (10-20), median time to potency 167 days (42-549) vs 80 (35-288) days, and median time to continence 42 (25-116) days vs 42 (29-76) days. In our series the application of amniotic membrane/dHACM has led to acceptable post RALP outcomes. The BCR rate of 10% in addition to the recovery of potency at a median time of 3 months and continence at 6 weeks is an encouraging result of dHACM. Our findings indicate that dHACM allowed for an even faster period for continence recovery which was independent of grade of NS. Future comparative studies may further assess the impact of new amniotic membrane types on the functional and oncological outcomes after RALP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives/hypothesis: Non-squamous cell carcinoma (SCC) malignancies are rare, but well described laryngeal pathologies. However, the epidemiology and clinical behavior of these tumors is not well studied., Study Design: Retrospective cohort study., Methods: Patients diagnosed with non-squamous cell larynx cancer from 2004 to 2017 in the National Cancer Database were selected. Demographic, clinicopathologic factors, treatments, and survival were analyzed. Univariable and multivariable cox regression were performed. Survival was compared with a propensity score-matched (PSM) population of laryngeal SCC patients., Results: A total of 136,235 cases of larynx cancer were identified. After excluding SCC variants, 2,172 (1.6%) patients met inclusion criteria. The most common histology was chondrosarcoma (374, 17.2%), followed by small cell (345, 15.9%), and spindle cell carcinoma (268, 12.3%). The most common treatment was surgery (683, 31.4%) followed by chemoradiation (409, 18.8%) and surgery and adjuvant radiation (288, 13.3%). Overall, 3- and 5-year survival was 67.9% and 59.4%, respectively. In multivariate analysis controlling for age, stage, comorbidity, histology, and treatment modality; chondrosarcoma had the best survival (hazard ratio [HR] 0.11, confidence interval [CI] 0.07-0.19, P < .001). In a PSM population, matched for age, stage, comorbidity, and treatments; non-SCC patients had significantly lower survival (51.5% vs. 59.9%, P < .001)., Conclusion: A diverse range of non-squamous cell malignancies occur in the larynx. In general, these tumors have poor survival, with few exceptions such as chondrosarcoma. While the majority of these histologies undergo surgical-based treatments in other sites, only 53% of patients underwent surgical-based treatment in the larynx. These data could guide clinicians in determining the outcome of treatment in these patients., Level of Evidence: 4 Laryngoscope, 132:1771-1777, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The population aged 65 and over is growing rapidly and with it are increased demands for integrative care and management of cognitive health issues. Such care models often do not include neuropsychologists or other psychology specialties., Methods: In this study, 72 medical charts of VA patients diagnosed with neurocognitive disorders were reviewed using best practice guidelines for diagnosing and managing neurocognitive disorders, adapted from Downs et al. (2006)., Results: Results indicated that physicians typically used clinical judgment through review of medications, blood work within the past year, and a history of symptoms to make diagnostic conclusions. Cognitive assessment and consideration of other reversible causes of cognitive decline (e.g., depression) were less commonly considered., Conclusions: The results are discussed in terms of potential implications for neuropsychologists and the integration of neuropsychology and primary care.

Novice users of telesurgery could be limited by their experience and technical ability. The impact of the COVID-19 pandemic on health care systems is unprecedented, and telehealth allowed care providers and patients a safety margin. An indirect impact of redeployment of hospital staff during COVID-19 management has been on the reduced educational opportunities for residents. Proximie can be considered as a virtual teaching platform or classroom for any user. Twenty-one students voluntarily participated in utilizing a da Vinci ® skills simulator (dVSS) to carry out surgical training simulation tasks. Our study focuses on digital native's adaptation to utilizing Proximie's augmented reality platform to direct task performance, to gauge its feasibility by this unique cohort., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Soluble epoxide hydrolase (sEH) is upregulated in microvascular endothelium of human brain with vascular cognitive impairment (VCI). Transgenic endothelial expression of human sEH in mice (Tie2hsEH) induces endothelial dysfunction (ED), a pathogenetic mechanism of VCI. We sought to determine if endothelial upregulation of sEH is sufficient to cause cognitive impairment, and if cognitive impairment due to chronic hypoperfusion induced by unilateral common carotid artery occlusion (CCAO) is exacerbated in Tie2hsEH mice. Behavioral performance was assessed by the open field, rotarod, novel object, Morris water maze and fear conditioning tests. Cerebral blood flow and brain morphology were evaluated by MRI, and inflammatory changes investigated using immunohistochemistry and flow cytometry. We demonstrate that transgenic endothelial expression of sEH is sufficient to induce cognitive impairment, associated with leukocyte infiltration, brain atrophy and accelerated, age-dependent ventriculomegaly, identifying ED and sEH upregulation as potential underlying mechanisms and therapeutic targets for VCI., (© 2022. The Author(s).)

Maternal mortality is a worldwide epidemic, with rates in the United States far surpassing those in similar high-income countries, and years of implicit bias and systemic racism have impacted outcomes for individuals belonging to racial and ethnic minorities. Structural racism must be dismantled to ensure better care for all., Competing Interests: Declaration of interests S.R. reports serving as a consultant for Roche Diagnostics, Thermo Fisher, Beckman Coulter, and Siemens and has received research funding from Roche Diagnostics and Siemens for work related to angiogenic biomarkers that is completely unrelated to this work. The other authors did not report any potential conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Spontaneous adrenal haemorrhage (SAH) is a rare condition. The incidence of adrenal haemorrhage in pregnancy is currently not known; however, an association with pregnancy has been reported.An acute presentation with severe back or flank pain should raise suspicion of this condition. Diagnosis is based on imaging. An ultrasound scan is a basic and readily available investigation in pregnancy to rule out renal and suprarenal pathology while CT or MRI scan can help to confirm the diagnosis. A multidisciplinary team (MDT) approach, involving the obstetric, anaesthetic, medical and endocrine team, is essential in management of this condition.We present a case of an SAH; managed conservatively, in an otherwise healthy and low-risk pregnant woman and describe the literature review on this rare condition, including pathophysiology and management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Emergency departments (ED) are a critical touchpoint for patients with opioid use disorder (OUD). In 2019, Pennsylvania had the fifth highest drug overdose mortality rate in the United States. State efforts have focused on implementing evidence-based ED care protocols, including induction of buprenorphine and warm handoffs to community treatment., Objective: We examined hospital staff's perspectives on the processes, challenges, and facilitators to buprenorphine initiation and warm handoff protocols in the ED., Methods: We used a qualitative case study design to focus on six Pennsylvania hospitals. The study selected hospitals using purposive sampling to capture varying hospital size, rurality, teaching status, and phase of protocol implementation. The study staff interviewed hospital staff with key roles in OUD care delivery in the ED, which included administrators, physicians, nurses, recovery support professionals, care coordinators, a social worker, and a pharmacist. Guided by the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured virtual interviews with 21 key informants from June to November 2020. Interviews were transcribed, deductively coded, and analyzed using CFIR domains and constructs to summarize factors influencing implementation of OUD ED care protocols and warm handoff to care protocols, as well as suggestions that emerged between and across cases., Results: Despite variation in the local context between hospitals, we identified common themes that influenced buprenorphine and warm handoffs across sites. Attention to hospital OUD care through state-level initiatives like the Hospital Quality Improvement Program generated hospital leadership buy-in toward implementing best OUD care practices. Factors at the hospital-level that influenced implementation success included supporting interdisciplinary OUD care champions, addressing knowledge gaps and biases around patients with OUD, having data systems that capture OUD care and integrate clinical protocols, incorporating patient comorbidities and non-medical needs into care, and fostering community provider linkages and capacity for warm handoffs. Although themes were largely consistent among hospital and staff types, protocol implementation was tailored by each hospital's size, patient volume, and hospital and community resources., Conclusions: By understanding frontline staff's perspectives around factors that impact OUD care practices in the ED, stakeholders may better optimize implementation efforts., (Copyright © 2021. Published by Elsevier Inc.)

Purpose of the Review: Racial disparities are prevalent in many aspects of obstetric care in the USA. Non-Hispanic black women have a higher prevalence of the diagnosis of hypertensive disorders of pregnancy in addition to associated morbidity and mortality. The purpose of this review is to review current data regarding racial disparities in the diagnosis and management of hypertensive disorders of pregnancy., Recent Findings: Diagnosis of hypertensive disorders of pregnancy is more common among non-Hispanic black women even after adjustment for comorbidities. Furthermore, prevalence of severe morbidity among those with hypertensive disorders of pregnancy is increased in non-Hispanic black women, including cardiovascular events related. Proposed management solutions include quality improvement initiatives, telehealth, and strategies to reduce both structural racism and implicit bias. Racial disparities exist in both diagnosis and management of hypertensive disorders of pregnancy; further innovative work is needed to reduce these disparities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Two multicentre adaptive radiotherapy trials utilising Plan of the Day (PoD) with a library of plans were introduced in 35 centres. The common issues that arose from all centres when introducing PoD were collated retrospectively, through reviewing the data pertaining to the pre-trial and on-trial quality assurance programme. It was found that 1,295 issues arose when introducing PoD in outlining, planning, treatment delivery i.e., PoD selection, and in the overall process of delivering PoD. There was no difference in the number of issues that arose from pre-trial to on-trial. Thus, it is recommended that the implementation of PoD is supported by guidance, reviews, and continuous monitoring., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shaista Hafeez: SH acknowledges support from the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. SH reports non-financial support from Elekta (Elekta AB, Stockholm, Sweden), non- financial support from Merck Sharp & Dohme (MSD), personal fees and non-financial support from Roche outside the submitted work. Emma Hall: EH declares grant funding to Institution from Cancer Research UK; grant funding to Institution from Accuray Inc. and Varian Medical Systems Inc. outside the submitted work. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Surveillance colonoscopy is rcommended for patients with colon cancer who obtain a hemicolectomy for tumor resection. Guidelines from many organizations require this colonoscopy to be performed within one year after resection. The objective of this study was to evaluate the difference in surveillance colonoscopy rates between white people and African Americans who had their colon tumors resected. The second objective was to determine whether the COVID-19 pandemic affected these colonoscopy rates. The study goal was to shed light on the issue of low colonoscopy rates among African Americans with colon cancer after tumor removal by hemicolectomy and on how the pandemic exacerbated this issue., Methods: A total of 800 patient charts from Brooklyn Methodist Hospital were reviewed. The selected patients had a history of colon cancer and received hemicolectomy in the past. The patients were divided according to race and their expected surveillance colonoscopy dates. One group included patients with an expected one-year follow-up date for colonoscopy after hemicolectomy before the start of the pandemic. Another group included patients with colonoscopies due to be performed during the pandemic. A two-sample proportions test was used to compare the colonoscopy rates before and during the pandemic for African Americans. The two-sample equal variance t-test was used to compare the average distance from the patients' home to hospital between African Americans and whites., Results: The surveillance colonoscopy rates among African Americans were 54% before and 45% during the pandemic. This difference was significant (p < 0.001). The colonoscopy rates between whites and African Americans differed. The surveillance colonoscopy rates among whites were 97% before and 84% during the pandemic. The distance between the patients' homes and the hospital where the procedure was performed also significantly differed. The average travel distance for whites was 1.33 miles and that for African Americans was 3.98 miles (p < 0.001). A total of 215 of the 416 African American patients included had tumors in the cecum and ascending colon., Conclusion: A significant difference was observed in the colonoscopy rates for African Americans before and during the pandemic. A substantial difference was found in the colonoscopy rates between whites and African Americans, which increased during the pandemic. The distance from the patients' home to the hospital performing the colonoscopy was twice as far for African Americans than whites in the borough of Brooklyn. These data support the hypothesis that a significant difference in colonoscopy rates exists between African Americans and whites, probably because of a healthcare disparity in access to this procedure. The study objective was to highlight the long-standing issue of low colonoscopy rates in African Americans and how the pandemic further decreased these low rates., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Singh et al.)

Background: The US Census confirms a rise in Spanish-speakers, many of whom have limited English proficiency (LEP) and require interpreters. Parent perceptions of interpreter services throughout hospitalization are unknown., Objective: To explore Spanish-speaking LEP parents' views regarding roles of interpreters and providers (attending, resident, or nurse) during a hospital encounter, optimal modalities of interpretation, and barriers to services., Methods: Spanish-speaking LEP parents of children discharged from the hospital medicine service participated in focus groups. Sessions were audio-recorded and transcribed in Spanish, translated into English, and verified for translation accuracy. Qualitative methods were used for thematic analysis., Results: Four sessions (n = 23 participants representing 15 families) were held. Parents felt the interpreter's primary role was to act as a conduit for word-for-word interpretation. They desired kind and trustworthy interpreters with medical knowledge. They saw providers as leaders of the encounter who should allot enough time for interpretation, not use Spanish unless they were fluent, and give frequent medical updates. In-person interpreters were preferred over telephone and video for their ability to convey body language and build relationships. Barriers to requesting interpreters included embarrassment and inability to directly request services, which resulted in using family members as interpreters. On family-centered rounds, parents preferred professional interpreters over bilingual providers., Conclusions: Modifications are required to improve interpreter services to meet the needs of LEP families. Parents emphasized in-person interpreters' social skills, frequent provider updates, and additional navigation support as essential components of effective care. Next steps include implementing guidelines and interventions to optimize interpreter services., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Alzheimer disease (AD) is a neurodegenerative disease characterized by a cognitive decline leading to dementia. The most impactful genetic risk factor is apolipoprotein E (APOE). APOE-ε4 significantly increases AD risk, APOE-ε3 is the most common gene variant, and APOE-ε2 protects against AD. However, the underlying mechanisms of APOE-ε4 on AD risk remains unclear, with APOE-ε4 impacting many pathways. We investigated how the APOE isoforms associated with the neuroinflammatory state of the brain with and without AD pathology. Frozen brain tissue from the superior and middle temporal gyrus was analyzed from APOE-ε3/3 (n = 9) or APOE-ε4/4 (n = 10) participants with AD pathology and APOE-ε3/3 (n = 9) participants without AD pathology. We determined transcript levels of 757 inflammatory related genes using the NanoString Human Neuroinflammation Panel. We found significant pathways impaired in APOE-ε4/4-AD individuals compared to APOE-ε3/3-AD. Of interest, expression of genes related to microglial activation (SALL1), motility (FSCN1), epigenetics (DNMT1), and others showed altered expression. Additionally, we performed immunohistochemistry of P2RY12 to confirm reduced microglial activation. Our results suggest APOE-ε3 responds to AD pathology while potentially having a harmful long-term inflammatory response, while APOE-ε4 shows a weakened response to pathology. Overall, APOE isoforms appear to modulate the brain immune response to AD-type pathology., (© 2021 American Association of Neuropathologists, Inc. All rights reserved.)

Although currently available data indicate that Africa has the lowest usage of antimicrobials in animals in the world (adjusted by animal biomass), data show a high prevalence of antimicrobial resistance in foodborne pathogens isolated from animals and animal products. Apart from the lack of solid data on antimicrobial use in many countries in Africa, different hypotheses could explain this situation. Qualitative interviews of farmers show a lack of knowledge and uninformed use of antimicrobials. Considering the development of animal farming to meet an increasing demand for proteins, this deficiency represents a serious public health issue. We advocate for policies that consider the specific challenges faced by family farmers in Africa, to simultaneously improve access to veterinary drugs while strengthening the regulation of their use. We propose a global approach targeting the agri-food system, offering innovative social and technical interventions on antimicrobial usage, adapted to family farmers.

Background: Due to differential training, nurse practitioners (NPs) and physicians may provide different quantities of services to patients., Purpose: To assess differences in the number of laboratory, imagining, and procedural services provided by primary care NPs and physicians., Methods: Secondary analysis of 2012-2016 National Ambulatory Medical Care Survey (NAMCS), containing 308 NP-only and 73,099 physician-only patient visits, using multivariable regression and propensity score techniques., Findings: On average, primary care visits with NPs versus physicians were associated with 0.521 fewer laboratory (95% CI -0.849, -0.192), and 0.078 fewer imaging services (95% CI -0.103,-0.052). Visits for routine and preventive care with NPs versus physicians were associated with 1.345 fewer laboratory (95% CI -2.037,-0.654), and 0.086 fewer imaging services (95% CI -0.118,-0.054) on average. Primary care visits for new problems with NPs versus physicians were associated with 0.051 fewer imaging services (95% CI -0.094,-0.007) on average., Discussion: NPs provide fewer laboratory and imaging services than physicians during primary care visits., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The American College of Obstetricians and Gynecologists recommends universal screening for tobacco, alcohol, and drug use as a part of routine prenatal care. However, little is known about the prevalence of prenatal substance use screening or factors that may contribute to differential rates of screening during prenatal care., Objective: This study aimed to describe the prevalence of prenatal substance use screening by substance, year, state, and state-level prenatal substance use policies and to examine individual-level factors associated with receipt of screening., Study Design: We analyzed 2016 to 2018 data from 103,608 women participating in the Pregnancy Risk Assessment Monitoring System, a population-based survey among women with recent live births. The Pregnancy Risk Assessment Monitoring System survey sampling weights were applied to all analyses. We described the percentage of individuals asked by a healthcare worker about substance use during a prenatal care appointment by substance, year, and state. Using chi-squared tests, we examined differences in the prevalence of screening by state-level prenatal substance use policies, including policies regarding classification of prenatal substance use as child abuse or neglect, mandatory testing or reporting of prenatal substance use, and targeted treatment funding and access for pregnant individuals with substance use disorders. Finally, we estimated the association between individual-level characteristics and receipt of prenatal substance use screening using logistic regression, controlling for year and state fixed effects and accounting for missingness using multiple imputation., Results: In 2018, approximately 95% individuals reported being asked about cigarette or alcohol use during a prenatal care appointment, whereas only 80% reported being asked about drug use. The percentage of individuals who were asked about substance use during a prenatal care appointment increased overall between 2016 and 2018, with variability across states. For all substances, states with laws designating prenatal drug use as child abuse or neglect had lower prevalence of screening, whereas states with laws mandating providers to test for substance use in pregnancy had higher prevalence of screening. Several individual-level characteristics were associated with increased odds of reported prenatal substance use screening for one or more substances, including being younger, less educated, unmarried, Black (vs White), non-Hispanic, or publicly insured (vs privately insured), receiving adequate prenatal care, and having a history of prepregnancy cigarette use., Conclusion: Our study finds that despite recommendations for universal prenatal substance use screening, there are differences in who is actually asked about substance use during prenatal care appointments. This may be influenced by state-level prenatal substance use policies and selective screening approaches in which certain individuals are more likely to be asked about substance use during their prenatal care appointment. A better understanding of the repercussions of selective screening approaches on outcomes and the roles that policies, systems, and provider biases play in perpetuating these approaches is needed to advance guideline implementation efforts in prenatal care settings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose/objective: Self-assessment is a fundamental skill for dentists and other health care providers. It enables these professionals' ability to critically evaluate the quality of their clinical work and improve through self-directed learning. Researchers have investigated how gender affects self-assessment skills and have shown that male students tend to overestimate their performance while female students tend to underestimate theirs as compared to peer or faculty assessment. The goal of this study was to evaluate how the self-assessment skills of dental students differ by gender in operative preclinical dentistry., Methods: Third-year dental students (N = 208, Class of 2016-2021) self-assessed their work using the same rubrics as faculty on four operative dentistry competency examination procedures: Class II amalgam preparation and restoration and Class III resin-composite preparation and restoration. Two calibrated full-time faculty graded all procedures independently. The Student self-assessment-Faculty grade (S-F) gap scores were calculated and statistically analyzed., Results: Overall, both genders overestimated their self-assessment for all four procedures as compared to actual scores given by faculty. Males overestimated more significantly than females for Class II Amalgam preparation, but not for the other three procedures. However, when the S-F gap for all procedures was combined and analyzed together, male students significantly overestimated their self-assessments compared to female students. When female and male students grading scores were stratified into quartiles, there were significantly larger differences between males and females in the lower quartiles, which suggest that difference in self-assessment abilities was more prominent among the lower performing students., Conclusion: The results of this study demonstrate that gender may affect the accuracy of self-assessment in operative preclinical dentistry., (© 2021 American Dental Education Association.)

Purpose: Hypofractionated radiation therapy can be used to treat patients with muscle-invasive bladder cancer unable to have radical therapy. Toxicity is a key concern, but adaptive plan-of the day (POD) image-guided radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy., Methods: HYBRID is a Phase II randomized trial that was conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle-invasive bladder cancer unsuitable for radical therapy received 36 Gy in 6 weekly fractions, randomized (1:1) to standard planning (SP) or adaptive planning (AP) using a minimization algorithm. For AP, a pretreatment cone beam computed tomography (CT) was used to select the POD from 3 plans (small, medium, and large). Follow-up included standard cystoscopic, radiologic, and clinical assessments. The primary endpoint was nongenitourinary Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (≥G3) toxicity within 3 months of radiation therapy. A noncomparative single stage design aimed to exclude ≥30% toxicity rate in each planning group in patients who received ≥1 fraction of radiation therapy. Local control at 3-months (both groups combined) was a key secondary endpoint., Results: Between April 15, 2014, and August 10, 2016, 65 patients were enrolled (SP, n = 32; AP, n = 33). The median follow-up time was 38.8 months (interquartile range [IQR], 36.8-51.3). The median age was 85 years (IQR, 81-89); 68% of participants (44 of 65) were male; and 98% of participants had grade 3 urothelial cancer. In 63 evaluable participants, CTCAE ≥G3 nongenitourinary toxicity rates were 6% (2 of 33; 95% confidence interval [CI], 0.7%-20.2%) for the AP group and 13% (4 of 30; 95% CI, 3.8%-30.7%) for the SP group. Disease was present in 9/48 participants assessed at 3 months, giving a local control rate of 81.3% (95% CI, 67.4%-91.1%)., Conclusions: POD adaptive radiation therapy was successfully implemented across multiple centers. Weekly ultrahypofractionated 36 Gy/6 fraction radiation therapy is safe and provides good local control rates in this older patient population., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3-4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline., Objective: The goal of this study was to assess the effects of chronic SHS exposure (10 months' exposure to ∼ 30   mg / m 3 ) on behavioral and cognitive function, metabolism, and neuropathology in mice., Methods: Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression., Results: Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: a ) lower body weights in WT, but not htau, mice; b ) less spontaneous alternation in WT, but not htau, mice in the Y maze; c ) faster swim speeds of WT, but not htau, mice in the water maze; d ) lower activity levels of WT and htau mice in the open field; e ) lower expression of brain PHF1, TTCM1, IGF 1 β , and HSP90 protein levels in WT male, but not female, mice; and f ) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice., Discussion: The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428.

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: American Indians and Alaska Natives (AI/ANs) are disproportionately affected by the opioid overdose crisis. Treatment with medications for opioid use disorder (MOUD) can significantly reduce overdose risk, but no national studies to date have reported on the extent to which AI/ANs access these treatments overall and in relation to other groups., Methods: The current study used two national databases - the 2018 National Survey on Substance Abuse Treatment Services and the 2017 Treatment Episode Dataset - to estimate the extent to which MOUD is available and used among AI/ANs across the U.S., Results: We found that facilities serving AI/ANs (N = 1,532) offered some MOUD at similar rates as other facilities (N = 13,277) (39.6 vs. 40.6 %, p = 0.435) but were less likely to offer the standard of care with buprenorphine or methadone maintenance (22.4 % vs. 27.6 %, p < 0.001). AI/AN clients in specialty treatment (N = 8,136) exhibited slightly higher MOUD use (40.0 % vs. 38.6 %, p = 0.009) relative to other race groups (N = 673,938). AI/AN clients were also more likely to exhibit greater prescription opioid use and methamphetamine co-use relative to other groups. AI/AN clients in the South (aOR:0.23[95 %CI: 0.19-0.28] or referred by criminal justice sources (aOR:0.13[95 %CI: 0.11-0.16] were least likely to receive MOUD., Conclusions: We conclude that most AI/ANs in specialty treatment do not receive medications for opioid use disorder, and that rates of MOUD use are similar to those of other race groups. Efforts to expand MOUD among AI/ANs that are localized and cater to unique characteristics of this population are gravely needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Primate sleeping site selection is influenced by multiple ecological factors including predation avoidance, thermoregulation and food access. To test these hypotheses, we studied the sleeping trees used by a group of wild silky sifakas (Propithecus candidus) in Marojejy National Park, Madagascar. During this 10-month study, the group slept in 828 sleeping trees from approximately 35 genera. In support of thermoregulation, generalized linear models revealed that as temperature decreased, the number of individuals sleeping together significantly increased and they slept at further distances from the trunk. As rainfall increased, sleep site height significantly increased. Weinmannia was the most frequented tree genus, despite low abundance, accounting for 29% of all sleeping trees. In support of food access, 94.8% of sleeping trees were food trees. Weinmannia is among the most highly preferred food trees. The group slept at a mean height of 16.0 m near the top of tall trees which averaged 19.5 m. Sleep trees were significantly taller than trees in botanical plots within the sifaka's home range. They never slept in the same trees on consecutive nights, and sleeping heights were significantly higher than daytime heights which is consistent with predation avoidance. Social sleeping in groups of 2 or 3 individuals (62.9%) was more common than solitary sleeping (37.1%). At such heights, huddling may increase vigilance and lessen the risk of predation by fossa (Cryptoprocta ferox) while also reducing heat loss. These patterns suggest that silky sifaka sleep site choice is influenced by thermoregulation and food access in addition to predation avoidance. We suggest that understanding sleep site use can assist in conservation of species like silky sifakas by enabling researchers to find new groups, protect habitats with key tree species and inform reforestation efforts., (© 2021 S. Karger AG, Basel.)

The SARS-CoV-2 (COVID-19) pandemic has particularly serious consequences for cancer patients, as they are at high risk for severe complications and mortality due to the virus since cancer patients are immunocompromised. Preliminary evidence suggests that patients with hematological, and metastatic malignancies are particularly susceptible to developing severe COVID-19 illness, which leads to poor prognosis. Biomarkers including C-reactive protein and interleukin-6 may be predictors of outcome and, therefore, crucial in assessing COVID-19 illness severity in cancer patients. A patient-specific risk and benefit inventory should be completed, and expert guidelines consulted when deciding to continue or postpone therapeutic interventions. This review presents preliminary evidence of COVID-19 infection and its impact on cancer, as well as discussion of general guidelines for the treatment and management of cancer patients with COVID-19., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity., Methods and Analysis: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes., Ethics and Dissemination: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities., Trial Registration Number: NCT02447549; Pre-results., Competing Interests: Competing interests: SH reports non-financial support from Elekta (Elekta AB, Stockholm, Sweden), non-financial support from Merck Sharp & Dohme (MSD), personal fees and non-financial support from Roche outside the submitted work; AC reports grants from National Institute of Health Research Manchester Biomedical Research Centre, grants from Cancer Research, UK, grants from Medical Research Council, UK, grants from Prostate Cancer, UK, grants from Bayer, UK, personal fees from Janssen Pharmaceutical, non-financial support from ASCO, grants and non-financial support from Elekta AB, outside the submitted work; AH reports grants from CRUK, grants from MRC, grants from NIHR, outside the submitted work; TK reports reports grants from Cancer Australia, during the conduct of the study; and his group has a research collaborative agreement with Varian Medical System not related to this project; EH reports grants from Cancer Research UK during the conduct of the study; grants from Accuray Inc., grants from Varian Medical Systems Inc., outside the submitted work; RH reports non-financial support from Janssen, grants and personal fees from MSD, personal fees from Bristol Myers Squibb, grants from Cancer Research UK, other from Nektar Therapeutics, personal fees and non-financial support from Roche outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)