Bring It Up: An Adapted Collaborative Care Model for Depression in a Safety-Net Primary Care Clinic.

Objective: Over 90 clinical trials demonstrate the efficacy of the collaborative care model (CoCM) to treat depression in primary care but there is significant variability in real-world CoCM implementation and scalability. This study aimed to determine the feasibility and effectiveness of an adapted CoCM in a safety-net primary care setting. Methods: Bring It Up! (BIU) is a pilot trial comparing an adapted CoCM (intervention group) to usual care (historical controls) for primary care safety-net clinic patients with depression. Inclusion criteria: (1) age ≥18; (2) Patient Health Questionnaire-9 (PHQ-9) score ≥10; and (3) major depressive disorder diagnosis. Patients who completed ≥6 months of treatment upon rolling enrollment (April 1, 2018-October 31, 2019) were included. Historical controls completed ≥6 months of usual care in 2017. BIU included all aspects of CoCM except accountable care and leveraged existing staff rather than a dedicated care manager. The primary outcome was depression remission (PHQ-9 <5) within 6 months. Secondary outcomes included depression response, adherence to treatment guidelines and care coordination process. Data were extracted from the electronic health record. Results: Thirty-six patients received the intervention; 41 controls received usual care. Depression remission was achieved in 33.3% of intervention patients and 0% of controls (p = 0.001). Of intervention patients, 44.4% achieved ≥50% reduction in PHQ-9 compared to 4.9% of controls (p = 0.003). Further, 66.7% of intervention patients had guideline-recommended antidepressant medication titration compared to 26.9% of controls (p = 0.003); 94.4% of intervention patients had PHQ-9 repeated compared to 53.7% of controls (p < 0.001). Conclusions: An adapted CoCM was feasible and improved depression care in a safety-net clinic.

First-generation college graduates have similar depressive symptoms in midlife as multi-generational college graduates.

Purpose: Higher education may protect an individual against depressive symptoms, yet, disadvantaged socioeconomic status (SES) during childhood, often measured by lower parental education, may put them at higher risk for depressive symptoms later in life. This study evaluates if midlife depression is similar for first-generation and multi-generation college graduates. Methods: For US Health and Retirement Study (HRS) participants ages 55-63 (N = 16,752), we defined a 4-category exposure from parents' (highest of mother or father's) and participant's own years of education, with 16 years indicating college completion: multi-gen (both ≥ 16 years: reference); first-gen (parents <16; own ≥ 16); only parent(s) (parents ≥ 16; own <16); and neither (both <16) college graduates across three birth cohorts. We used linear regressions to evaluate relationships between college completion and depressive symptoms measured by an 8-item Center for Epidemiologic Studies - Depression (CES-D) scale. Models pooled over time evaluated differences by sex, race/ethnicity, and birthplace. Results: First-gen and multi-gen college graduates averaged similar depressive symptoms in midlife (ß: 0.01; 95% CI: 0.15, 0.13). Results were similar by sex and race/ethnicity. Conclusion: Consistent with resource substitution theory, college completion may offset the deleterious effects of lower parental education on midlife depressive symptoms for first-generation graduates.

Telemedicine and Depression Screening After the Start of the COVID-19 Pandemic.

This cohort study investigates the probability of depression screening by visit type and by patient demographic characteristics in a large health system during the early COVID-19 pandemic.

Language Access Systems Improvement initiative: impact on professional interpreter utilisation, a natural experiment.

OBJECTIVES: This study aims to evaluate the Language Access Systems Improvement (LASI) initiative's impact on professional interpreter utilisation in primary care and to explore patient and clinician perspectives on professional interpreter use. DESIGN: Multi methods: Quantitative natural experiment pre-LASI and post-LASI, qualitative semistructured interviews with clinicians and focus groups with patients post-LASI. SETTING: Large, academic primary care practice. PARTICIPANTS: Cantonese, Mandarin, Spanish, English-speaking adult patients and their clinicians. INTERVENTION: LASI initiative: Implementation of a clinician language proficiency test and simultaneous provision of on-demand access to professional interpreters via video medical interpretation. MAIN OUTCOME MEASURES: Quantitative: Proportion of language discordant primary care visits which were professionally interpreted. Qualitative: Salient themes related to professional interpreter use and non-use. RESULTS: The researchers categorised language concordance for 1475 visits with 152 unique clinicians; 698 were not fully language concordant (202 pre-LASI and 496 post-LASI). Professional interpreter utilisation increased (pre-LASI 57% vs post-LASI 66%; p=0.01); the visits with the lowest percentage of profssional interpreter use post-LASI were those in which clinicians and patients had partial language concordance. In inverse probability weighted analysis, restricting to 499 visits with strict estimated propensity score overlap (100% common support), post-LASI visits had higher odds of using a professional interpreter compared with pre-LASI visits (OR 2.39; 95% CI 1.04 to 5.48). Qualitative results demonstrate video interpretation was convenient and well liked by both clinicians and patients. Some partially bilingual clinicians reported frustration with patient refusal of interpreter services; others reported using the video interpreters as a backup during visits. Views of the care-partner role differed for clinicians and patients. Clinicians reported sometimes having family interpret out of convenience or habit, whereas patients reported wanting family members present for support and advocacy, not interpretation. CONCLUSIONS: LASI increased utilisation of professional interpreters; however, this was least prominent for partially language concordant visits. Health systems wishing to implement LASI or similar interventions will need to support clinicians and patients with partial bilingual skills in their efforts to use professional interpreters. TRIAL REGISTRATION NUMBER: HSRP20153367.

Barriers and facilitators to depression care among Latino men in a primary care setting: a qualitative study.

BACKGROUND: In the United States, Latinos face a wide array of cultural and structural barriers to accessing and utilizing mental health care. Latino men specifically are at high risk of receiving inadequate mental health care, possibly due to additional obstacles they experience that are related to masculinity. Among men more generally, greater adherence to emotional control and self-reliance is associated with higher depression severity and less depression help-seeking. Men experience more stigma toward depression and help-seeking and are less likely to be diagnosed with depression than women. However, Latino men's barriers and facilitators to depression care remain largely unexplored. The objective of this study was to examine barriers and facilitators to depression care that are related to masculinity among English- and Spanish-speaking Latino men in a primary care setting. METHODS: We used convenience and purposive sampling to recruit primary care patients who self-identified as Latino men, spoke English or Spanish, and screened positive for depressive symptoms on the Patient Health Questionnaire-2 or had a history of depression. Semi-structured interviews were conducted between December 2020 and August 2021. The interview guide examined views and experiences of depression, masculinity, and barriers and facilitators to engaging in depression care. Utilizing consensual qualitative research and thematic analysis informed by modified grounded theory, barriers and facilitators to depression care were identified. RESULTS: We interviewed thirteen participants who varied in English proficiency, education, income, and country of origin. Barriers and facilitators were placed into three domains-Self-Recognition of Depression, Seeking Help for Depression, and Depression Diagnosis and Treatment. Participants described aspects of masculinity as barriers (emotional control and pressure to provide), facilitators (honesty, courage, collaboration, practicality, and responsibility), or both (self-reliance and autonomy). CONCLUSIONS: Masculinity influences barriers and facilitators for depression care among Latino men at the levels of self-recognition, seeking help, and diagnosis and treatment. Clinicians may promote Latino men's engagement in depression care by understanding patients' values and framing depression care as affirming masculinity. Providing education to primary care physicians and other healthcare professionals on gender and depression and addressing structural barriers are essential to providing access to all who need depression care.

Ataxia-telangiectasia mutated ( Atm ) disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse midline gliomas to radiation therapy.

Diffuse midline gliomas (DMGs) are lethal brain tumors characterized by p53-inactivating mutations and oncohistone H3.3K27M mutations that rewire the cellular response to genotoxic stress, which presents therapeutic opportunities. We used RCAS/tv-a retroviruses and Cre recombinase to inactivate p53 and induce K27M in the native H3f3a allele in a lineage- and spatially-directed manner, yielding primary mouse DMGs. Genetic or pharmacologic disruption of the DNA damage response kinase Ataxia-telangiectasia mutated (ATM) enhanced the efficacy of focal brain irradiation, extending mouse survival. This finding suggests that targeting ATM will enhance the efficacy of radiation therapy for p53-mutant DMG but not p53-wildtype DMG. We used spatial in situ transcriptomics and an allelic series of primary murine DMG models with different p53 mutations to identify transactivation-independent p53 activity as a key mediator of such radiosensitivity. These studies deeply profile a genetically faithful and versatile model of a lethal brain tumor to identify resistance mechanisms for a therapeutic strategy currently in clinical trials.

Validity of the Spanish-Language Patient Health Questionnaires 2 and 9: A Systematic Review and Meta-Analysis.

Importance: Reliable screening for major depressive disorder (MDD) relies on valid and accurate screening tools. Objective: To examine the validity, accuracy, and reliability of the Spanish-language Patient Health Questionnaires 2 and 9 (PHQ-2 and PHQ-9) to screen for MDD. Data Sources: PubMed, Web of Science, Embase, and PsycINFO from data initiation through February 27, 2023. Study Selection: English- and Spanish-language studies evaluating the validity of the Spanish-language PHQ-2 or PHQ-9 in screening adults for MDD compared with a standardized clinical interview (gold standard). Search terms included PHQ-2, PHQ-9, depression, and Spanish. Data Extraction and Synthesis: Two reviewers performed abstract and full-text reviews, data extraction, and quality assessment. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Random-effects meta-analyses of sensitivity, specificity, and area under the curve (AUC) were performed. Internal consistency was evaluated using Cronbach α and McDonald ψ. Main Outcomes and Measures: Test accuracy and internal consistency. The PHQ-2 is composed of the first 2 questions of the PHQ-9 (targeting core depression symptoms of depressed mood and anhedonia; a score of 3 or higher (score range, 0-6) is generally considered a positive depression screen. If a patient screens positive with the PHQ-2, a follow-up assessment with the PHQ-9 and a clinical diagnostic evaluation are recommended. Once depression is diagnosed, a PHQ-9 score of 10 or higher (score range, 0-27) is often considered an acceptable threshold for treating depression. Results: Ten cross-sectional studies involving 5164 Spanish-speaking adults (mean age range, 34.1-71.8 years) were included; most studies (n = 8) were in primary care settings. One study evaluated the PHQ-2, 7 evaluated the PHQ-9, and 2 evaluated both the PHQ-2 and PHQ-9. For the PHQ-2, optimal cutoff scores ranged from greater than or equal to 1 to greater than or equal to 2, with an overall pooled sensitivity of 0.89 (95% CI, 0.81-0.95), overall pooled specificity of 0.89 (95% CI, 0.81-0.95), and overall pooled AUC of 0.87 (95% CI, 0.83-0.90); Cronbach α was 0.71 to 0.75, and McDonald ψ was 0.71. For the PHQ-9, optimal cutoff scores ranged from greater than or equal to 5 to greater than or equal to 12, with an overall pooled sensitivity of 0.86 (95% CI, 0.82-0.90), overall pooled specificity of 0.80 (95% CI, 0.75-0.85), and overall pooled AUC of 0.88 (95% CI, 0.87-0.90); Cronbach α was 0.78 to 0.90, and McDonald ψ was 0.79 to 0.90. Four studies were considered to have low risk of bias; 6 studies had indeterminate risk of bias due to a lack of blinding information. Conclusions and Relevance: In this systematic review and meta-analysis, limited available evidence supported the use of the Spanish-language PHQ-2 and PHQ-9 in screening for MDD, but optimal cutoff scores varied greatly across studies, and few studies reported on blinding schemes. These results suggest that MDD should be considered in Spanish-speaking individuals with lower test scores. Given the widespread clinical use of the tools and the heterogeneity of existing evidence, further investigation is needed.

Community-Based Workshops to Involve Rural Communities in Wildlife Management Case Study: Bighorn Sheep in Baja California, Mexico.

The description of natural history, and information on the factors threatening conservation, the distribution area, and the status of species population are necessary for proper wildlife management. The objective of this research was to generate such information in two rural communities and to engage residents in bighorn sheep management through a program of three workshops. The first one covered training regarding natural history and management of the species. The second one consisted in the description of the habitat of the species through a dynamic of participatory mapping. The third, include a design of a one strategy to monitor the bighorn sheep population. The workshops were attended by 37 people from the two rural communities. The results suggest the economic element was the main interest of the inhabitants regarding the bighorn sheep. Eleven risk factors were identified to the bighorn sheep in the study sites, a participatory map with relevant information for the management of the species on each community was developed, and a monitoring strategy of the bighorn sheep population was prepared. The workshop program proposed in this research is a tool that can be applied in rural communities to lay the groundwork for a long-term management project of wildlife species.

Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

"How's your mood": Recorded physician mental health conversations with Chinese and Latino patients in routine primary care visits.

OBJECTIVE: Patient-physician communication patterns may influence discussions around depressive symptoms and contribute to engagement in depression care among racial/ethnic minority adults. We examined patient-physician communication about depressive symptoms during routine primary care visits with Chinese and Latino patients with and without language barriers. METHODS: We examined 17 audio-recorded conversations between primary care physicians and Chinese (N = 7) and Latino (N = 10) patients who discussed mental health during their visit and reported depressive symptoms on a post-visit survey. Conversations (in English, Cantonese, Mandarin, Hoisan-wa, Spanish) were transcribed and translated by bilingual/bicultural research assistants and analyzed using inductive and deductive thematic and discourse analysis. RESULTS: Patients initiated mental health discussion in eleven visits. Physicians demonstrated care in word choice and sometimes avoided openly mentioning depression; this could contribute to miscommunication around symptoms and treatment goals. Interpreters had difficulty finding single words to convey terms used by either patients or physicians. CONCLUSION: Patients and doctors appeared willing to discuss mental health; however, variability in terminology presented challenges in mental health discussions in this culturally and linguistically diverse sample. PRACTICE IMPLICATIONS: Further understanding patient preferred terminology about mental health symptoms and interpreter training in these terms could improve patient-physician communication about depressive symptoms and treatment preferences.

"Long Overdue": Nurse and Resident Physician Perspectives on Implementation of Dual-Handset Interpreter Phones in the Inpatient Setting.

Background: Patients with language barriers suffer significant health disparities, including adverse events and poor health outcomes. While remote language services can help improve language access, these modalities remain persistently underused. The objective of this study was to understand clinician experiences and challenges using dual-handset interpreter telephones and to inform recommendations for future language access interventions. Methods: We conducted four focus groups with nurses (N=14) and resident physicians (N=20) to understand attitudes toward dual-handset interpreter telephones in the hospital, including general impressions, effects on communication, situations in which they did and did not use them, and impact on clinical care. Three researchers independently coded all transcripts using a constant comparative approach, meeting repeatedly to discuss coding and to reconcile differences to reach consensus. Results: We identified five salient themes, including increased language access (improved convenience, flexibility, and versatility of phones over in-person or ad hoc interpreters); effects on interpersonal processes of care (improved ability to communicate directly with patients); effects on clinical processes of care (improvements in critical patient care functions, including pain and medication management); impact on time (needing extra time for interpreted encounters and perceived delays impacting future use); and patients for whom, and circumstances in which, the dual-handset interpreter telephone is inadequate (e.g., complex discussions, hands-on instruction, or multiple speakers are present). Conclusions: Our findings indicate that clinicians value dual-handset interpretation in bridging communication barriers and highlight recommendations to guide future implementation interventions to increase the uptake of remote language services in hospital settings.

Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expressed in the neuroectoderm (neural precursor cells) during embryogenesis. New insights are needed to refine tumor classification and to identify therapeutic approaches. We evaluated five gangliogliomas with single nucleus RNA-seq, cellular indexing of transcriptomes and epitopes by sequencing, and/or spatially-resolved RNA-seq. We uncovered a population of CD34+ neoplastic cells with mixed neuroectodermal, immature astrocyte, and neuronal markers. Gene regulatory network interrogation in these neuroectoderm-like cells revealed control of transcriptional programming by TCF7L2/MEIS1-PAX6 and SOX2, similar to that found during neuroectodermal/neural development. Developmental trajectory analyses place neuroectoderm-like tumor cells as precursor cells that give rise to neuron-like and macroglia-like neoplastic cells. Spatially-resolved transcriptomics revealed a neuroectoderm-like tumor cell niche with relative lack of vascular and immune cells. We used these high resolution results to deconvolute clinically-annotated transcriptomic data, confirming that CD34+ cell-associated gene programs associate with gangliogliomas compared to other glial brain tumors. Together, these deep transcriptomic approaches characterized a ganglioglioma cellular hierarchy-confirming CD34+ neuroectoderm-like tumor precursor cells, controlling transcription programs, cell signaling, and associated immune cell states. These findings may guide tumor classification, diagnosis, prognostication, and therapeutic investigations.

Validity of the Chinese Language Patient Health Questionnaire 2 and 9: A Systematic Review.

Introduction: Chinese Americans with limited English proficiency have higher mental health needs than English speakers but are more likely to be undiagnosed and undertreated for depression. Increasing anti-Asian hate crimes during the COVID-19 pandemic has increased the urgency to accurately detect depressive symptoms in this community. This systematic review examines the validity of the Patient Health Questionnaire (PHQ)-2/9 for depression screening in Chinese-speaking populations. Methods: We queried PubMed, Web of Science, Embase, and PsycINFO databases, examining studies through September 2021. Studies were included if they evaluated the Chinese language PHQ-2 or PHQ-9 and diagnosed depression using a clinical interview. Two investigators independently extracted study data and assessed quality using the QUADAS-2. Study sensitivities and specificities were combined in random effects meta-analyses. Results: Of 513 articles, 20 met inclusion criteria. All examined the PHQ-9; seven also examined the PHQ-2. Studies were conducted in Mainland China (17), Hong Kong (1), Taiwan (1), and the United States (1). Fourteen studies were published in English; six in Chinese. Studies were diverse in setting, participant age, and comorbidities. For the Chinese language PHQ-9, Cronbach's alpha ranged from 0.765 to 0.938 for included studies (optimal cutoff scores ranged from 6 to 11). For the PHQ-2, Cronbach's alpha ranged from 0.727 to 0.785 (optimal cutoff scores 1-3). Overall, the PHQ-9 pooled sensitivity was 0.88 (95% CI 0.86-0.90), and pooled specificity was 0.87 (95% CI 0.83-0.91). Similarly, the pooled PHQ-2 sensitivity was 0.84 (95% CI 0.80-0.87), and pooled specificity was 0.87 (95% CI 0.78-0.93). The overall risk of bias was low (12 studies) or indeterminate (8 studies). Discussion: While limited by missing study information, the Chinese language PHQ-9 appears to be a valid depression screening tool among Chinese-speaking populations across geographic and clinical settings. Further research should explore optimal cutoff scores for this population for routine depression screening and the validity of the tool to measure response to depression treatment.

The Effect of Atm Loss on Radiosensitivity of a Primary Mouse Model of Pten-Deleted Brainstem Glioma.

Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of the phosphoinositide-3-kinase (PI3K)-like kinase, ataxia-telangiectasia mutated (ATM), which orchestrates the cellular response to radiation-induced DNA damage, may enhance the efficacy of radiation therapy. Diffuse midline gliomas in the brainstem contain loss-of-function mutations in the tumor suppressor PTEN, or functionally similar alterations in the phosphoinositide-3-kinase (PI3K) pathway, at moderate frequency. Here, we sought to determine if ATM inactivation could radiosensitize a primary mouse model of brainstem glioma driven by Pten loss. Using Cre/loxP recombinase technology and the RCAS/TVA retroviral gene delivery system, we established a mouse model of brainstem glioma driven by Pten deletion. We find that Pten-null brainstem gliomas are relatively radiosensitive at baseline. In addition, we show that deletion of Atm in the tumor cells does not extend survival of mice bearing Pten-null brainstem gliomas after focal brain irradiation. These results characterize a novel primary mouse model of PTEN-mutated brainstem glioma and provide insights into the mechanism of radiosensitization by ATM deletion, which may guide the design of future clinical trials.

Equitability of Depression Screening After Implementation of General Adult Screening in Primary Care.

Importance: Depression is a debilitating and costly medical condition that is often undertreated. Men, racial and ethnic minority individuals, older adults, and those with language barriers are at increased risk for undertreatment of depression. Disparities in screening may contribute to undertreatment. Objective: To examine depression screening rates among populations at risk for undertreatment of depression during and after rollout of general screening. Design, Setting, and Participants: This cohort study from September 1, 2017, to December 31, 2019, of electronic health record data from 52 944 adult patients at 6 University of California, San Francisco, primary care facilities assessed depression screening rates after implementation of a general screening policy. Patients were excluded if they had a baseline diagnosis of depression, bipolar disorder, schizophrenia, schizoaffective disorder, or dementia. Exposures: Screening year, including rollout (September 1, 2017, to December 31, 2017) and each subsequent calendar year (January 1 to December 31, 2018, and January 1 to December 31, 2019). Main Outcomes and Measures: Rates of depression screening performed by medical assistants using the Patient Health Questionnaire-2. Data collected included age, sex, race and ethnicity, and language preference (English vs non-English); to compare English and non-English language preference groups and also assess depression screening by race and ethnicity within the English-speaking group, a single language-race-ethnicity variable with non-English language preference and English language preference categories was created. In multivariable analyses, the likelihood of being screened was evaluated using annual logistic regression models for 2018 and 2019, examining sex, age, language-race-ethnicity, and comorbidities, with adjustment for primary care site. Results: There were 52 944 unique, eligible patients with 1 or more visits in one of the 6 primary care practices during the entire study period (59% female; mean [SD] age, 48.9 [17.6] years; 178 [0.3%] American Indian/Alaska Native, 13 241 [25.0%] English-speaking Asian, 3588 [6.8%] English-speaking Black/African American, 4744 [9.0%] English-speaking Latino/Latina/Latinx, 760 [1.4%] Pacific Islander, 22 689 [42.9%] English-speaking White, 4857 [9.0%] English-speaking other [including individuals who indicated race and ethnicity as other and individuals for whom race and ethnicity data were missing or unknown], and 2887 [5.5%] with language barriers [non-English language preference]). Depression screening increased from 40.5% at rollout (2017) to 88.8% (2019). In 2018, the likelihood of being screened decreased with increasing age (adusted odds ratio [aOR], 0.89 [95% CI, 0.82-0.98] for ages 45-54 and aOR, 0.75 [95% CI, 0.65-0.85] for ages 75 and older compared with ages 18-30); and, except for Spanish-speaking patients, patients with limited English proficiency were less likely to be screened for depression than English-speaking White patients (Chinese language preference: aOR, 0.59 [95% CI, 0.51-0.67]; other non-English language preference: aOR, 0.55 [95% CI, 0.47-0.64]). By 2019, depression screening had increased dramatically for all at-risk groups, and for most, disparities had disappeared; the odds of screening were only still significantly lower for men compared with women (aOR, 0.87 [95% CI, 0.81 to 0.93]). Conclusions and Relevance: In this cohort study in a large academic health system, full implementation of depression screening was associated with a substantial increase in screening rates among groups at risk for undertreatment of depression. In addition, depression screening disparities narrowed over time for most groups, suggesting that routine depression screening in primary care may reduce screening disparities and improve recognition and appropriate treatment of depression for all patients.

Assessing Medical Student Readiness to Navigate Language Barriers in Telehealth: Cross-sectional Survey Study.

BACKGROUND: The COVID-19 pandemic has greatly increased telehealth usage in the United States. Patients with limited English proficiency (LEP) face barriers to health care, which may be mitigated when providers work with professional interpreters. However, telehealth may exacerbate disparities if clinicians are not trained to work with interpreters in that setting. Although medical students are now involved in telehealth on an unprecedented scale, no educational innovations have been published that focus on digital care across language barriers. OBJECTIVE: The aim of this study is to investigate advanced medical students' confidence in caring for patients with LEP during telehealth encounters. METHODS: We administered a written survey to medical students on clinical clerkships at one US institution in August and September 2020. We assessed students' overall confidence in working with interpreters; confidence in performing 8 clinical tasks during in-person versus telehealth encounters; and frequency of performing 5 different clinical tasks with patients with LEP compared to English-speaking patients during in-person versus telehealth encounters. Wilcoxon signed-rank tests and chi-square tests were used to compare confidence and task performance frequency, respectively, for patients with LEP versus English-speaking patients during telehealth encounters. Students were also asked to identify barriers to care for patients with LEP. The free-response questions were qualitatively analyzed using open coding to identify key themes. RESULTS: Of 300 medical students surveyed, 121 responded. Furthermore, 72 students answered >50% of questions and were included in the analyses. Compared to caring for patients with LEP during in-person encounters, respondents were less confident in working with interpreters (P<.001), developing trust (P<.001), identifying agenda (P=.005), eliciting preferences for diabetes management (P=.01), and empowering patients in lifestyle modifications (P=.04) during telehealth encounters. During both in-person and telehealth encounters, approximately half of students (40%-78%) reported engaging less frequently in every clinical task with patients with LEP and this was as low as 22% (13/59) for some tasks. Students identified these key barriers to care for patients with LEP: time pressure, interpretation quality and access, technical difficulties, cultural differences, and difficulty with rapport building. CONCLUSIONS: Advanced medical students were significantly less confident caring for patients with LEP via telehealth than in person. Broader implementation of training around navigating language barriers is necessary for telehealth care, which has rapidly expanded in the United States. Our study identified potential key areas for curricular focus, including creating patient-centered agendas and management plans within the constraints of virtual settings. These developments must take place simultaneously with systems-level improvements in interpreter infrastructure to ensure high-quality care for linguistically diverse patients.

Lymphocyte Subsets in Defense Against New Pathogens in Patients with Cancer.

INTRODUCTION: Immunity in cancer patients is modified both by the cancer itself and by oncospecific treatments. Whether a patient's adaptive immunity is impaired depends on their levels of naive lymphocytes and other cell populations. During the COVID-19 pandemic, cancer patients are at greater risk of progressing to severe forms of the disease and have higher mortality rates than individuals without cancer, particularly while they are receiving cancer-specific therapies. An individual's protection against infection, their response to vaccines, and even the tests that determine the humoral immune response to SARS-CoV-2, depend on lymphocyte populations, meriting their study. OBJECTIVE: Estimate blood concentrations of lymphocytes involved in the immune response to new pathogens in cancer patients. METHODS: We carried out an analytical study of 218 cancer patients; 124 women and 94 men, 26-93 years of age, who were treated at the National Oncology and Radiobiology Institute in Havana, Cuba, March-June, 2020. Patients were divided into five groups: (1) those with controlled disease who were not undergoing cancer-specific treatment; (2) those undergoing debulking surgery; (3) patients undergoing chemotherapy; (4) patients undergoing radiation therapy and (5) patients currently battling infection. We evaluated the following peripheral blood lymphocyte subpopulations via flow cytometry: B lymphocytes (total, naive, transitional, memory, plasmablasts and plasma cells); T lymphocytes (total, helper, cytotoxic and their respective naive, activated, central memory and effector memory subsets); and total, secretory and cytotoxic natural killer cells and T natural killer cells. We also estimated neutrophil/lymphocyte ratios. Lymphocyte concentrations were associated with controlled disease and standard cancer therapy. For variables that did not fall within a normal distribution, ranges were set by medians and 2.5-97.5 percentiles. The two-tailed Mann-Whitney U test was used to measure the effect of sex and to compare lymphocyte populations. We calculated odds ratios to estimate lymphopenia risk. RESULTS: All cancer patients had lower values of naive helper and cytotoxic T lymphocyte populations, naive B lymphocytes, and natural killer cells than normal reference medians. Naive helper T cells were the most affected subpopulation. Memory B cells, plasmablasts, plasma cells, activated T helper cells, and cytotoxic central memory T cells were increased. Patients undergoing treatment had lower levels of naive lymphocytes than untreated patients, particularly during radiation therapy. The risk of B lymphopenia was higher in patients in treatment. The odds ratio for B lymphopenia was 8.0 in patients who underwent surgery, 12.9 in those undergoing chemotherapy, and 13.9 in patients in radiotherapy. CONCLUSIONS: Cancer and conventional cancer therapies significantly affect peripheral blood B lymphocyte levels, particularly transitional T helper lymphocytes, reducing the immune system's ability to trigger primary immune responses against new antigens.

PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.

The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition.

Radiosensitizing the Vasculature of Primary Brainstem Gliomas Fails to Improve Tumor Response to Radiation Therapy.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) arise in the pons and are the leading cause of death from brain tumors in children. DIPGs are routinely treated with radiation therapy, which temporarily improves neurological symptoms but generally fails to achieve local control. Because numerous clinical trials have not improved survival from DIPG over standard radiation therapy alone, there is a pressing need to evaluate new therapeutic strategies for this devastating disease. Vascular damage caused by radiation therapy can increase the permeability of tumor blood vessels and promote tumor cell death. METHODS AND MATERIALS: To investigate the impact of endothelial cell death on tumor response to radiation therapy in DIPG, we used dual recombinase (Cre + FlpO) technology to generate primary brainstem gliomas which lack ataxia telangiectasia mutated (Atm) in the vasculature. RESULTS: Here, we show that Atm-deficient tumor endothelial cells are sensitized to radiation therapy. Furthermore, radiosensitization of the vasculature in primary gliomas triggered an increase in total tumor cell death. Despite the observed increase in cell killing, in mice with autochthonous DIPGs treated with radiation therapy, deletion of Atm specifically in tumor endothelial cells failed to improve survival. CONCLUSIONS: These results suggest that targeting the tumor cells, rather than endothelial cells, during radiation therapy will be necessary to improve survival among children with DIPG.