Recent treatment patterns and real-world survival following first-line anti-PD-L1 treatment for extensive-stage small cell lung cancer.

BACKGROUND: The landscape of small cell lung cancer (SCLC) has changed since the 2019 and 2020 approvals of anti-PD-L1 atezolizumab and durvalumab for first-line (1L) treatment in combination with chemotherapy. We studied treatment patterns and real-world overall survival (rwOS) following 1L-3L therapy. PATIENTS AND METHODS: A nationwide electronic health record (EHR)-derived de-identified database was used to describe treatment patterns, characteristics, and survival of patients with extensive-stage (ES)-SCLC by 1L anti-PD-L1 treatment. Patients with ES-SCLC who initiated ≥1 line of systemic therapy from 2013 to 2021, with potential follow-up through 2022, were included. RESULTS: Among 9952 patients with SCLC, there were 4308 patients with ES-SCLC treated during the study period who met eligibility criteria. Etoposide + platinum (EP) chemotherapy was most common in the 1L, with addition of anti-PD-L1 therapy to most regimens by 2019. Second-line regimens varied by platinum sensitivity status and shifted from topotecan to lurbinectedin over time. Median rwOS following 1L therapy was 8.3 months (95% CI, 7.9-8.8) in those treated with 1L anti-PD-L1 and 8.0 months (95% CI, 7.8-8.2) in those who were not. Following 2L and 3L, median rwOS was 5.6 (95% CI, 4.9-6.3) and 4.9 months (95% CI, 3.4-6.0), respectively, among 1L anti-PD-L1-treated, and 4.5 (95% CI, 4.2-4.9) and 4.0 months (95% CI, 3.7-4.5), respectively, among those who were not. CONCLUSION: Despite the introduction of frontline anti-PD-L1 therapy, survival remains dismal among patients with ES-SCLC treated in the real-world setting.

Outcomes of an Emergency Department Program to Identify and Link Patients at Increased Risk for Acquiring HIV Infection to Outpatient HIV Prevention Services: The HIV PreventED Program.

BACKGROUND: Emergency departments (EDs) provide care to patients at increased risk for acquiring HIV, and for many of them, the ED serves as their sole point of entry into the healthcare system. We implemented the HIV PreventED Program to increase access to HIV prevention services for ED patients. SETTING: ED in Oakland, CA with an annual census of 57,000 visits. METHODS: This cross-sectional study evaluated the first 9 months of the HIV PreventED Program. In this program, a navigator surveyed adult ED patients who tested HIV negative to determine their risk for acquiring HIV infection, incorporating HIV prevention counseling into their assessments. Patients at higher risk for acquiring HIV were referred to outpatient prevention services, if interested. The primary outcome measure was the number and proportion of ED patients at higher risk for acquiring HIV who followed up for outpatient prevention services. RESULTS: In this study, 1233 patients who tested HIV negative were assessed by the navigator and received ED-based HIV prevention counseling. Of these, 193 (15.7%) were identified at higher risk and offered an outpatient referral for prevention services, of which 104 accepted (53.9%), 23 (11.9%) attended the referral, and 13 (6.7%) were prescribed preexposure prophylaxis (PrEP). The median time to linkage was 28 days (interquartile range 15-41 days). CONCLUSION: A navigator focused on providing ED-based HIV prevention counseling and linkage to outpatient services is feasible. Strategies to more efficiently identify ED patients at higher risk for HIV acquisition, such as automated identification of risk data from the electronic health record, and policies to improve follow-up and the receipt of PrEP, such as same-day PrEP initiation, should be prospectively evaluated.

The Intersection of Substance Use Disorders and Infectious Diseases in the Emergency Department.

Substance use disorders (SUDs) intersect clinically with many infectious diseases, leading to significant morbidity and mortality if either condition is inadequately treated. In this article, we will describe commonly seen SUDs in the emergency department (ED) as well as their associated infectious diseases, discuss social drivers of patient outcomes, and introduce novel ED-based interventions for co-occurring conditions. Clinicians should come away from this article with prescriptions for both antimicrobial medications and pharmacotherapy for SUDs, as well as an appreciation for social barriers, to care for these patients.

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.

BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer. METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events. CONCLUSIONS: Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.).

"ContraceptED": A Multidisciplinary Framework for Emergency Department-Initiated Contraception.

Emergency departments (EDs) are common access points for patients who are at high risk for unintended pregnancy. Low-barrier access to effective contraception represents a crucial and low-cost intervention to address this public health need. Same-day initiation of contraception during an ED visit is a unique opportunity to provide reproductive health care for high-risk patients with otherwise limited health care access. We collaborated with our obstetrics and gynecology (OB/GYN) department, pharmacists, and a team of community health advocates to support emergency clinicians (namely, emergency physicians and advanced practice providers) in assessing pregnancy and contraceptive readiness, increasing proficiency in contraception counseling, prescribing hormonal contraception, counseling on barrier and emergency contraception, and inserting (and removing) the Nexplanon implant, a form of long-acting reversible contraception. With this novel approach, we found that emergency clinicians voluntarily participated in trainings on contraception, including low-threshold long-acting reversible contraception initiation; and, after completing these trainings, clinicians integrated these skills into their workflow in the ED. We report our results after screening 38 patients during our current Pilot Phase of implementing this program.

The Emerging Value of Circular Noncoding RNA Research in Cancer Diagnosis and Treatment.

Circular RNAs (circRNA) are a recently described class of RNA molecules that have attracted substantial attention as new components of disease mechanisms and as potential biomarkers in multiple diseases, including cancer. CircRNAs are often highly conserved and exhibit developmental stage- and disease-specific expression. Several studies have reported circRNA expression patterns that are associated with specific cancer types and with patient prognosis. Here, we overview the active registered clinical trials that investigate the value of circRNAs as cancer biomarkers and discuss the potential of circRNAs in clinical cancer care. Taken together, circRNAs are actively being investigated as diagnostic, predictive, and prognostic biomarkers, and their potential to serve as therapeutic intervention points motivates ongoing translational and clinical research.

Effectiveness of Substance Use Navigation for Emergency Department Patients With Substance Use Disorders: An Implementation Study.

STUDY OBJECTIVE: We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders. METHODS: This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects. RESULTS: There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5). CONCLUSION: A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge.

Primary palliative care education in emergency medicine residency: A mixed-methods analysis of a yearlong, multimodal intervention.

Background: Emergency medicine (EM) physicians frequently care for seriously ill patients at the end of life. Palliative care initiated in the emergency department (ED) can improve symptom management and quality of life, align treatments with patient preferences, and reduce length of hospitalization. We evaluated an educational intervention with digital tools for palliative care discussions in an urban EM residency using the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. Methods: Our intervention, conducted from July 2020 to August 2021, included education on palliative care techniques, digital tools, and incentives for participation. We tracked goals of care conversations and palliative care consults using electronic medical record data, conducted pre- and posttraining surveys, and used semistructured interviews to assess resident perspectives on palliative care conversations in the ED. Outcomes included number of goals of care conversations recorded by EM residents, consults to palliative care from the ED, and resident perspectives on palliative care in EM. Results: The results were as follows: reach-45 residents participated in the intervention; effectiveness-89 goals of care conversations were documented by 23 ED residents, and palliative care consults increased from approximately four to 10 monthly; adoption-over half the residents who participated in the intervention documented goals of care discussions using an electronic dotphrase; implementation-by the completion of the intervention, residents reported increased comfort with goals of care conversations, saw palliative care as part of their responsibility as EM physicians, and effectively documented goals of care discussions; and maintenance-at 2-month follow up, palliative care consults from the ED remained at approximately 10 monthly, and digital tools to prompt and track palliative care discussions remained in use. Conclusions: An integrated palliative care training for EM residents with technological assists was successful in facilitating goals of care discussions and increasing palliative care consults from the ED.

Association of Social Needs and Housing Status Among Urban Emergency Department Patients.

INTRODUCTION: People experiencing homelessness have high rates of social needs when presenting for emergency department (ED) services, but less is known about patients with housing instability who do not meet the established definitions of homelessness. METHODS: We surveyed patients in an urban, safety-net ED from June-August 2018. Patients completed two social needs screening tools and responded to additional questions on housing. Housing status was determined using validated questions about housing stability. RESULTS: Of the 1,263 eligible patients, 758 (60.0%) completed the survey. Among respondents, 40% identified as Latinx, 39% Black, 15% White, 5% Asian, and 8% other race/ethnicities. The median age was 42 years (interquartile range [IQR]: 29-57). and 54% were male. Of the 758 patients who completed the survey, 281 (37.1%) were housed, 213 (28.1%) were unstably housed, and 264 (34.8%) were homeless. A disproportionate number of patients experiencing homelessness were male (63.3%) and Black (54.2%), P <0.001, and a disproportionate number of unstably housed patients were Latinx (56.8%) or were primarily Spanish speaking (49.3%), P <0.001. Social needs increased across the spectrum of housing from housed to unstably housed and homeless, even when controlling for demographic characteristics. CONCLUSION: Over one in three ED patients experience homelessness, and nearly one in three are unstably housed. Notable disparities exist by housing status, and there is a clear increase of social needs across the housing spectrum. Emergency departments should consider integrating social screening tools for patients with unstable housing.

A Unique Spectrum of Spontaneous Tumors in Dino Knockout Mice Identifies Tissue-Specific Requirements for Tumor Suppression.

Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino-/- mice develop significantly more malignant tumors than Dino+/+ littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence of lymphomas and sarcomas in Dino-/- mice is similar to that of mice with p53 loss, important distinctions emerged. p53-null mice predominantly develop T cell lymphomas; however, no spontaneous T cell lymphoma was observed in Dino-/- mice. Rather than being a phenocopy of the p53-null tumor spectrum, spontaneous tumors in Dino-/- mice resemble the spectrum of human cancers in which DINO is recurrently silenced by methylation in a manner that is mutually exclusive with TP53 alterations, suggesting that similar tissues in human and mouse require DINO for tumor suppression. Consistent with a tissue-specific role for Dino in tumor suppression, loss of Dino had no impact on the development of radiation-induced T cell lymphoma and oncogene-driven medulloblastoma, tumors that are accelerated by the loss of p53. Taken together, these data indicate that Dino serves as a potent tumor suppressor molecule specific to a select subset of tissues in mice and humans.

Facemasks: Perceptions and use in an ED population during COVID-19.

STUDY OBJECTIVE: Facemask use is associated with reduced transmission of SARS-CoV-2. Most surveys assessing perceptions and practices of mask use miss the most vulnerable racial, ethnic, and socio-economic populations. These same populations have suffered disproportionate impacts from the pandemic. The purpose of this study was to assess beliefs, access, and practices of mask wearing across 15 urban emergency department (ED) populations. METHODS: This was a secondary analysis of a cross-sectional study of ED patients from December 2020 to March 2021 at 15 geographically diverse, safety net EDs across the US. The primary outcome was frequency of mask use outside the home and around others. Other outcome measures included having enough masks and difficulty obtaining them. RESULTS: Of 2,575 patients approached, 2,301 (89%) agreed to participate; nine had missing data pertaining to the primary outcome, leaving 2,292 included in the final analysis. A total of 79% of respondents reported wearing masks "all of the time" and 96% reported wearing masks over half the time. Subjects with PCPs were more likely to report wearing masks over half the time compared to those without PCPs (97% vs 92%). Individuals experiencing homelessness were less likely to wear a mask over half the time compared to those who were housed (81% vs 96%). CONCLUSIONS: Study participants reported high rates of facemask use. Respondents who did not have PCPs and those who were homeless were less likely to report wearing a mask over half the time and more likely to report barriers in obtaining masks. The ED may serve a critical role in education regarding, and provision of, masks for vulnerable populations.

Clinical Utility of the Signal-to-Cutoff Ratio of Reactive HIV Antigen/Antibody Screening Tests in Guiding Emergency Physician Management.

BACKGROUND: The signal-to-cutoff (S/CO) ratio of the HIV antigen/antibody test may help immediately to differentiate true-positive results from false-positive results, which may be particularly useful in time-sensitive circumstances, such as when providing emergency department (ED) care. SETTING: Seven US EDs with HIV screening programs using HIV antigen/antibody assays. METHODS: This cross-sectional study of existing data correlated S/CO ratios with confirmed HIV status. Test characteristics at predetermined S/CO ratios and the S/CO ratio with the best performance by receiver operator characteristic (ROC) curve were calculated. RESULTS: Of 1035 patients with a reactive HIV antigen/antibody test, 232 (22.4%) were confirmed HIV-negative and 803 (77.6%) were confirmed HIV-positive. Of the 803 patients, 713 (88.8%) experienced chronic infections and 90 (11.2%) experienced acute infections. S/CO ratios were greater for HIV-positive (median 539.2) than for HIV-negative patients (median 1.93) (P < 0.001) and lower for acute infection (median 22.8) than for chronic infection (median 605.7) (P < 0.001). All patients with an S/CO ratio < 1.58 (n = 93) were HIV-negative (NPV 100%), and nearly all with an S/CO ≥ 20.7 (n = 760) (optimal level by ROC analysis) were HIV-positive (PPV 98.6%). Of patients with S/CO values between 1.58 and 20.7 (n = 182), 29.7% were HIV-positive. CONCLUSIONS: The S/CO ratio may be used in real time to classify most ED patients as almost certain to be either HIV-positive or HIV-negative long before nucleic acid confirmatory testing is available. When combined with clinical judgment, this could guide preliminary result disclosure and management.

The Social Context of Unhealthy Alcohol Use Among Emergency Department Patients: A Cross Sectional Study.

BACKGROUND: Housing status and additional social determinants of health are important data for clinicians and policy makers to design and implement effective interventions for emergency department (ED) patients with unhealthy alcohol use (UAU). METHODS: We surveyed patients in an urban, safety-net ED from June to August 2018. UAU was assessed by a validated single-item screening question endorsed by the National Institute on Alcohol Abuse and Alcoholism. Housing status was assessed using items validated for housing stability. RESULTS: Seven hundred fifty-eight patients completed the survey (60% response rate), and 296 (39%; 95% confidence interval: 36%-43%) reported UAU. Patients with and without UAU had the same rates of ED visits (median 2, interquartile range: 1-4; P = 0.69) and hospitalizations (median 0, interquartile range: 0-0; P = 0.31) in the 12 months before index visit. Patients with UAU were more likely to lack stable housing compared to patients without UAU (69% vs 59%; P = 0.006). Illicit drug use and prescription drug misuse was more common in patients with UAU compared to those without UAU (29% vs 14%, P < 0.001; and 18% vs 10%; P < 0.001, respectively). Only 60 (20.3%) of the 296 patients with UAU had a documented diagnosis of UAU in the medical record. CONCLUSIONS: UAU is common in the general ED patient population and usually not clinically recognized. Patients with UAU have high rates of homelessness and co-occurring substance use. Future studies should consider strategies to incorporate social determinants of health and harm reduction treatments into ED-based interventions for UAU.

Synergistic Effect of Ketamine and Buprenorphine Observed in the Treatment of Buprenorphine Precipitated Opioid Withdrawal in a Patient With Fentanyl Use.

BACKGROUND: Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (µORs). Buprenorphine's partial agonism (low intrinsic efficacy) at µORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N -methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct µOR binding, synergistically potentiates the effectiveness of buprenorphine µOR signaling, reverses (resensitizes) fentanyl induced µOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described. CASE DESCRIPTION: We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use. CONCLUSIONS: This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.

Implementation of Oral and Extended-Release Naltrexone for the Treatment of Emergency Department Patients With Moderate to Severe Alcohol Use Disorder: Feasibility and Initial Outcomes.

STUDY OBJECTIVE: Despite evidence supporting naltrexone as an effective treatment for alcohol use disorder, its use in emergency department (ED) patients has not been described. We implemented a protocol that combined substance use navigation with either oral naltrexone or extended-release intramuscular naltrexone for patients with alcohol use disorder as a strategy to improve follow-up in addiction treatment after ED discharge. METHODS: In this descriptive study, we analyzed the results from adult patients discharged from the ED with moderate to severe alcohol use disorder who received either oral naltrexone or extended-release intramuscular naltrexone between May 1, 2020, and October 31, 2020, and assessed their engagement in formal addiction treatment within 30 days after discharge from the ED. RESULTS: Among 59 patients with moderate to severe alcohol use disorder who accepted naltrexone treatment, 41 received oral naltrexone and 18 received extended-release intramuscular naltrexone. The mean (SD) age of the patients was 45.2 (13.4) years; 22 patients (37.3%) were Latinx, 18 (30.5%) were Black, and 16 (27.1%) were White. Among all patients, 9 (15.3%) attended follow-up formal addiction treatment within 30 days after discharge; 5 patients (27.8%) who received extended-release intramuscular naltrexone and 4 patients (9.8%) who received oral naltrexone attended follow-up treatment within 30 days. CONCLUSION: We implemented a clinical protocol for ED patients with moderate to severe alcohol use disorder using oral naltrexone and extended-release intramuscular naltrexone together with substance use navigation. Identification of alcohol use disorder, a brief intervention, and initiation of naltrexone resulted in a 15% follow-up rate in formal addiction treatment. Future work should prospectively examine the effectiveness of naltrexone as well as the effect of substance use navigation for ED patients with alcohol use disorder.

High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder.

Importance: Emergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care. Objective: To examine the safety and tolerability of high-dose (>12 mg) buprenorphine induction for patients with OUD presenting to an ED. Design, Setting, and Participants: In this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021. Interventions: ED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented. Main Outcomes and Measures: Vital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to >28 mg). Results: Among a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (>12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours. Conclusions and Relevance: These findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.

p53-intact cancers escape tumor suppression through loss of long noncoding RNA Dino.

Many long noncoding RNA (lncRNA) genes exist near cancer-associated loci, yet evidence connecting lncRNA functions to recurrent genetic alterations in cancer are lacking. Here, we report that DINO, the lncRNA transcribed from the cancer-associated DINO/CDKN1A locus, suppresses tumor formation independent of p21, the protein encoded at the locus. Loss of one or two alleles of Dino impairs p53 signaling and apoptosis, resulting in a haplo-insufficient tumor suppressor phenotype in genetically defined mouse models of tumorigenesis. A discrete region of the DINO/CDKN1A locus is recurrently hypermethylated in human cancers, silencing DINO but not CDKN1A, the gene encoding p21. Hypermethylation silences DINO, impairs p53 signaling pathway in trans, and is mutually exclusive with TP53 alterations, indicating that DINO and TP53 comprise a common tumor suppressor module. Therefore, DINO encodes a lncRNA essential for tumor suppression that is recurrently silenced in human cancers as a mechanism to escape p53-dependent tumor suppression.

HIV testing among people with and without substance use disorder in emergency departments: A nationwide cohort study.

OBJECTIVE: To determine HIV testing trends during emergency department (ED) visits among those with and without substance use disorder (SUD) and examine factors associated with test receipt. METHODS: We identified individuals age ≥ 15 with an ED visit between 2014 and 2018 in the National Hospital Ambulatory Medical Care Survey (NHAMCS), a representative sample of United States ED visits. We examined HIV testing trends by SUD status and used multivariable logistic regression accounting for NHAMCS's complex survey design to identify factors associated with HIV testing. RESULTS: We identified 6399 SUD and 75,498 non-SUD ED visits. Of SUD visits, 1.4% [95% Confidence Interval (95%CI 0.9-1.9)] resulted in HIV testing compared to 0.6% (95%CI 0.4-0.7) of non-SUD visits. During the second half of the study (Q3, 2016 - Q4, 2018), HIV testing increased from 1.1% (95%CI 0.6-1.6) to 1.7% (95%CI 1.0-2.5) among those with SUD and from 0.5% (95%CI 0.3-0.6) to 0.6% (95%CI 0.5-0.8) among those without SUD. In adjusted models, SUD status was associated with increased odds of HIV testing [Adjusted Odds Ratio (AOR) 1.6 (95%CI 1.1-2.2)]. Those receiving toxicology testing (AOR 2.2, 95%CI 1.6-3.2), Black (AOR 3.6, 95%CI 2.6-4.9) and Hispanic people (AOR 2.7, 95%CI 1.9-3.7), insured by Medicaid (AOR 1.6, 95%CI 1.2-2.2) or self-pay (AOR 1.7, 95%CI 1.1-2.8), and with venipuncture (AOR 3.0, 95%CI 2.2-4.1) also had greater odds of HIV testing. CONCLUSION: HIV testing in the ED was rare, but slightly more common in individuals with SUD. Efforts to increase ED HIV testing among people with SUD are needed.

High Rates of COVID-19 Infection Among Indigenous Maya at a US Safety-Net Health System in California.

Coronavirus disease 2019 (COVID-19) has disproportionately and negatively affected communities of color in the United States, especially Black, Latinx, and Indigenous populations. We report a cluster of COVID-19 cases among the Maya in Alameda County, California, most of whom were misclassified in public health data as nonindigenous Spanish-speaking people. We conducted a retrospective cohort study of all COVID-19 tests performed from April 1 through May 31, 2020, at Alameda Health System. A total of 1561 tests from 1533 patients were performed, with an overall test positivity rate of 17.0% (N = 265). We used the language field from the electronic health record to identify 29 patients as speaking an indigenous Mayan language; by medical record review, we identified 52 additional Maya patients. Maya patients had a test positivity rate of 72.8% as compared with 27.1% (P < .001) for nonindigenous Latinx patients and 8.2% (P < .001) for all other patients. In our sample, 39.6% of patients who had a positive test result for COVID-19 were hospitalized, 11.3% required admission to the intensive care unit (ICU), and 4.9% died of COVID-19. Maya patients had lower rates of hospitalization, ICU admission, and 30-day in-hospital mortality than non-Maya patients. We shared our data with the county health department to inform responses for education, testing, and isolation for Maya patients in Alameda County. Ongoing COVID-19 public health efforts should assess the community prevalence of COVID-19 in the Maya community and other indigenous communities and implement interventions that are linguistically and culturally appropriate.

Racial/ethnic disparities in COVID-19 disease burden & mortality among emergency department patients in a safety net health system.

BACKGROUND: We sought to examine racial and ethnic disparities in test positivity rate and mortality among emergency department (ED) patients tested for COVID-19 within an integrated public health system in Northern California. METHODS: In this retrospective study we analyzed data from patients seen at three EDs and tested for COVID-19 between April 6 through May 4, 2020. The primary outcome was the test positivity rate by race and ethnicity, and the secondary outcome was 30 day in-hospital mortality. We used multivariable logistic regression to examine associations with COVID-19 test positivity. RESULTS: There were 526 patients tested for COVID-19, of whom 95 (18.1%) tested positive. The mean age of patients tested was 54.2 years, 54.7% were male, and 76.1% had at least one medical comorbidity. Black patients accounted for 40.7% of those tested but 16.8% of the positive tests, and Latinx patients accounted for 26.4% of those tested but 58.9% of the positive tests. The test positivity rate among Latinx patients was 40.3% (56/139) compared with 10.1% (39/387) among non-Latinx patients (p < 0.001). Latinx ethnicity was associated with COVID-19 test positivity (adjusted odds ratio 9.6, 95% confidence interval: 3.5-26.0). Mortality among Black patients was higher than non-Black patients (18.7% vs 1.3%, p < 0.001). CONCLUSION: We report a significant disparity in COVID-19 adjusted test positivity rate and crude mortality rate among Latinx and Black patients, respectively. Results from ED-based testing can identify racial and ethnic disparities in COVID-19 testing, test positivity rates, and mortality associated with COVID-19 infection and can be used by health departments to inform policy.