Dopamine-driven Increase in IL-1ß in Myeloid Cells is Mediated by Differential Dopamine Receptor Expression and Exacerbated by HIV.

The catecholamine neurotransmitter dopamine is classically known for regulation of central nervous system (CNS) functions such as reward, movement, and cognition. Increasing evidence also indicates that dopamine regulates critical functions in peripheral organs and is an important immunoregulatory factor. We have previously shown that dopamine increases NF-κB activity, inflammasome activation, and the production of inflammatory cytokines such as IL-1ß in human macrophages. As myeloid lineage cells are central to the initiation and resolution of acute inflammatory responses, dopamine-mediated dysregulation of these functions could both impair the innate immune response and exacerbate chronic inflammation. However, the exact pathways by which dopamine drives myeloid inflammation are not well defined, and studies in both rodent and human systems indicate that dopamine can impact the production of inflammatory mediators through both D1-like dopamine receptors (DRD1, DRD5) and D2-like dopamine receptors (DRD2, DRD3, and DRD4). Therefore, we hypothesized that dopamine-mediated production of IL-1ß in myeloid cells is regulated by the ratio of different dopamine receptors that are activated. Our data in primary human monocyte-derived macrophages (hMDM) indicate that DRD1 expression is necessary for dopamine-mediated increases in IL-1ß, and that changes in the expression of DRD2 and other dopamine receptors can alter the magnitude of the dopamine-mediated increase in IL-1ß. Mature hMDM have a high D1-like to D2-like receptor ratio, which is different relative to monocytes and peripheral blood mononuclear cells (PBMCs). We further confirm in human microglia cell lines that a high ratio of D1-like to D2-like receptors promotes dopamine-induced increases in IL-1ß gene and protein expression using pharmacological inhibition or overexpression of dopamine receptors. RNA-sequencing of dopamine-treated microglia shows that genes encoding functions in IL-1ß signaling pathways, microglia activation, and neurotransmission increased with dopamine treatment. Finally, using HIV as an example of a chronic inflammatory disease that is substantively worsened by comorbid substance use disorders (SUDs) that impact dopaminergic signaling, we show increased effects of dopamine on inflammasome activation and IL-1ß in the presence of HIV in both human macrophages and microglia. These data suggest that use of addictive substances and dopamine-modulating therapeutics could dysregulate the innate inflammatory response and exacerbate chronic neuroimmunological conditions like HIV. Thus, a detailed understanding of dopamine-mediated changes in inflammation, in particular pathways regulating IL-1ß, will be critical to effectively tailor medication regimens.

Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer.

This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).

Developing an educational "hub": impact of a distance-learning curriculum in a multinational cohort.

PURPOSE: To address a gap in radiation oncology education in low- and middle-income countries (LMICs), we sought to evaluate the effectiveness and generalizability of a refined curriculum on intensity modulated radiotherapy (IMRT) offered to existing radiation therapy (RT) clinics across Africa and Latin America (LATAM) at no cost. METHODS: A curriculum was created based on prior needs assessments and adapted for participating medical physicists, radiation oncologists, radiation therapists, and trainees in LMICs. English-speaking and Spanish-speaking teams of volunteer educators delivered 27 hour-long sessions 1-2 times weekly for 4 months using video conferencing to African and LATAM cohorts, respectively. Pre- and post-course multiple-choice examinations were administered to LATAM participants, and pre- and post-course self-confidence (1-5 Likert-scale) and open-ended feedback were collected from all participants. RESULTS: Twenty-five centers across Africa (13) and LATAM (12) participated, yielding a total of 332 enrolled participants (128 African, 204 LATAM). Sessions were delivered with a mean of 44 (22.5) and 85 (25.4) participants in the African and LATAM programs, respectively. Paired pre and post-course data demonstrated significant (p < 0.001) improvement in knowledge from 47.9 to 89.6% and self-confidence across four domains including foundations (+ 1.1), commissioning (+ 1.3), contouring (+ 1.7), and treatment planning (+ 1.0). Attendance was a significant predictor of change in self-confidence in "high attendance" participants only, suggesting a threshold effect. Qualitative data demonstrates that participants look forward to applying their knowledge in the clinical setting. CONCLUSION: A specialized radiation oncology curriculum adapted for LMIC audiences was effective for both African and LATAM participants. Participant feedback suggests that the refined IMRT course empowered clinics with knowledge and confidence to help train others. This feasible "Hub and Spokes" approach in which a distance-learning course establishes a hub to be leveraged by spokes (learners) may be generalizable to others aiming to reduce global health care disparities through training efforts.

Prolonging the lives of African-Americans with metastatic breast cancer by adding palbociclib to an aromatase inhibitor in routine clinical practice: a plain language summary of a real-world database study.

WHAT IS THIS SUMMARY ABOUT?: This summary is about a study that was published in the medical journal The Oncologist in July 2023. The combination of palbociclib with an aromatase inhibitor (AI) was approved by the FDA in 2015 as a treatment for people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, the effectiveness of palbociclib in African-Americans with MBC is not well studied. The goal of this study was to find out whether adding palbociclib to an AI helped African-Americans with HR+/HER2- MBC live longer. WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study.This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone. Also, the study showed that African-Americans treated with palbociclib plus an AI lived longer without their cancer getting worse than those treated with an AI alone. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: These results support the use of palbociclib with an AI as a first treatment for African-Americans with HR+/HER2- MBC.Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effectiveness of palbociclib plus an aromatase inhibitor in African Americans with metastatic breast cancer in routine clinical practice: a plain language summary.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.

Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database.

There are limited real-world comparative effectiveness data for palbociclib plus an aromatase inhibitor (AI) as a first-line (1L) treatment examining endpoints that require long term follow-up and post 1L progression. The Flatiron Health Analytic Database was used to characterize treatment and dosing patterns in patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) receiving palbociclib plus an AI vs an AI alone in routine US clinical practice. In addition, time to chemotherapy (TTC) and real-world progression-free survival (rwPFS) when combining 1L and second-line of therapy (rwPFS2) were assessed. Of 1324 patients who received palbociclib plus an AI between February 3, 2015 and March 31, 2020, 1110 (83.8%) started palbociclib at the recommended 125 mg/day dose. After stabilized inverse probability treatment-weighting (sIPTW), median TTC in patients treated with palbociclib plus an AI and AI alone was 37.4 months (95% confidence interval [CI], 33.7-40.7) and 29.2 months (95% CI, 26.8-33.5), respectively (hazard ratio [HR] = 0.77 [95% CI, 0.69-0.86], P < .0001); median rwPFS2 was 32.6 months (95% CI, 29.4-35.2) and 20.7 months (95% CI, 18.9-22.6), respectively (HR = 0.62 [95% CI, 0.54-0.70], P < .0001). Sensitivity analyses with propensity score matching showed similar results to sIPTW analyses. Results from this large real-world study examining additional effectiveness outcomes beyond 1L rwPFS and overall survival support the use of palbociclib plus an AI as a 1L treatment for patients with HR+/HER2- mBC.

Palbociclib Combined with an Aromatase Inhibitor in Patients with Breast Cancer with Lung or Liver Metastases in US Clinical Practice.

A cyclin-dependent kinase 4/6 inhibitor combined with endocrine therapy is the standard of care for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC), but real-world effectiveness data for patients with lung or liver metastases are limited. This retrospective study included data from the US Flatiron Health database of patients with HR+/HER2- mBC and lung or liver metastases treated with first-line palbociclib (PAL) plus an aromatase inhibitor (AI) or an AI alone in routine clinical practice. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed. A total of 891 patients were included (622 with lung metastasis, 376 with liver metastasis, and 107 with both lung and liver metastasis). After stabilized inverse probability of treatment weighting to balance patient characteristics, PAL + AI versus AI alone was associated with significantly prolonged OS (HR = 0.62; p < 0.001) and rwPFS (HR = 0.55; p < 0.001) in patients with lung metastases and numerically longer OS (HR = 0.73; p = 0.056) and significantly longer rwPFS (HR = 0.57, p < 0.001) for those with liver metastases. Overall, PAL + AI versus AI alone was associated with prolonged OS and rwPFS in routine clinical practice, supporting the use of first-line PAL + AI for patients with HR+/HER2- mBC with lung and/or liver metastases.

Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older.

Background: Elderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data are needed to inform clinical management of elderly patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This subanalysis of the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness of palbociclib plus an aromatase inhibitor (AI) versus an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years treated in routine clinical practice in the United States. Methods: This retrospective observational cohort study used electronic health records from the Flatiron Health Analytic Database. Palbociclib treatment patterns, overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Three methods were used for comparative analyses: (1) an unadjusted analysis, (2) stabilized inverse probability treatment weighting (sIPTW; primary analysis), and (3) propensity score matching (PSM; sensitivity analysis). Results: A total of 961 patients aged ≥ 75 years with HR+/HER2- mBC were identified who started palbociclib plus an AI (n = 313) or an AI alone (n = 648) as first-line (1L) therapy between February 2015 and March 2020 (data cut-off: September 30, 2020). Among patients in the palbociclib plus an AI group with a documented palbociclib starting dose (n = 306), approximately 75% started palbociclib at 125 mg/day, and approximately 40% experienced dose adjustment. After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51-0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59-0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55-0.87]; P = 0.0014). These significant improvements in OS, rwPFS, and TTC remained consistent in the unadjusted analysis and after PSM. Conclusion: This real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years. These findings support palbociclib plus an AI as a standard-of-care 1L treatment for elderly patients with HR+/HER2- mBC.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

Feasibility and Clinical Acceptability of Automation-Assisted 3D Conformal Radiotherapy Planning for Patients With Cervical Cancer in a Resource-Constrained Setting.

PURPOSE: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system. MATERIALS AND METHODS: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety metrics, and clinical acceptability by two ORCI physician investigators. Dice similarity coefficient (DSC) agreement analysis was conducted between original and new contour sets. RESULTS: The average time to manually develop treatment plans was 7 days. Applying RPA, automated same-day contours and plans were developed for 29 of 30 patients (97%). Of the 29 evaluable contours, all were approved with <2 minutes of edit time. Agreement between clinical and RPA contours was highest for the rectum (median DSC, 0.72) and bladder (DSC, 0.90). Agreement was lower with the primary tumor clinical target volume (CTVp; DSC, 0.69) and elective nodal clinical target volume (CTVn; DSC, 0.63). All RPA plans were approved with <4 minutes of edit time. RPA target coverage was excellent, covering the CTVp with median V45 Gy 100% and CTVn with median V45 Gy 99.9%. CONCLUSION: Automation-assisted 3DCRT contouring yielded high levels of agreement for normal structures. The RPA met all planning safety metrics and sustained high levels of clinical acceptability with minimal edit times. This tool offers the potential to significantly decrease RT planning timelines while maintaining high-quality RT delivery in resource-constrained settings.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. PATIENTS AND METHODS: This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. RESULTS: Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). CONCLUSION: This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. TRIAL NUMBER: NCT05361655.

Real-World Tumor Response of Palbociclib in Combination With an Aromatase Inhibitor as First-Line Therapy in Pre/Perimenopausal Women With Metastatic Breast Cancer.

BACKGROUND: Limited real-world data exist regarding the efficacy of palbociclib in combination with endocrine therapy in pre/perimenopausal women with metastatic breast cancer. OBJECTIVE: We aimed to compare real-world tumor responses among pre/perimenopausal women who initiated palbociclib plus an aromatase inhibitor (AI) or AI monotherapy as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. METHODS: This retrospective observational cohort study (NCT05012644) used electronic health record data from The US Oncology Network. Tumor responses were determined based on treating clinicians' assessments of radiologic evidence for changes in disease burden. Normalized inverse probability treatment weighting was used to balance baseline characteristics between treatment cohorts. RESULTS: Of 196 pre/perimenopausal women, 116 and 80 were in the palbociclib plus AI cohort and AI cohort, respectively. Real-world response rates (complete or partial response) were 52.1% and 46.2%, respectively (odds ratio, 1.27 [95% confidence interval 0.72‒2.24]). Among patients with one or more tumor assessments on treatment, real-world response rates were 60.0% in the palbociclib plus AI cohort (n = 103) and 49.9% in the AI cohort (n = 71; odds ratio, 1.51 [95% confidence interval 0.82‒2.77]). CONCLUSIONS: This real-world analysis suggests that pre/perimenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer appear more likely to respond to palbociclib plus AI versus AI alone as first-line therapy, which may support the combination as a standard-of-care treatment for this patient population.

Palbociclib (Ibrance^®) is a medicine for patients with metastatic breast cancer (MBC). Metastatic means that the cancer has spread to other places in the body. Patients take palbociclib with hormone therapy, such as an aromatase inhibitor (AI). Palbociclib plus an AI is a treatment for a type of MBC called HR+/HER2‒ MBC. HR+/HER2‒ stands for hormone receptor positive, human epidermal growth factor receptor 2 negative. Researchers wanted to observe responses to treatment in routine clinical practice among women with HR+/HER2­ MBC who had not reached menopause. A response is if a tumor shrinks or disappears after treatment. This study used healthcare information reported in electronic medical records of patients seen by doctors in The US Oncology Network. This study included 196 women with HR+/HER2­ MBC who had not reached menopause and had not received prior treatment for MBC. A total of 116 women received palbociclib plus an AI, and 80 women received an AI alone. Researchers used standard statistical approaches to balance baseline characteristics between the two treatment groups. These adjustments made the groups more similar so that researchers could compare treatment responses. Sixty percent of patients who took palbociclib plus an AI responded, compared with 50% of patients who took an AI alone. These results suggest that palbociclib plus an AI may benefit women with HR+/HER2‒ MBC who have not reached menopause.

Nonfatal Injuries Sustained in Mass Shootings in the US, 2012-2019: Injury Diagnosis Matrix, Incident Context, and Public Health Considerations.

INTRODUCTION: The epidemic of gun violence in the United States (US) is exacerbated by frequent mass shootings. In 2021, there were 698 mass shootings in the US, resulting in 705 deaths and 2,830 injuries. This is a companion paper to a publication in JAMA Network Open, in which the nonfatal outcomes of victims of mass shootings have been only partially described. METHODS: We gathered clinical and logistic information from 31 hospitals in the US about 403 survivors of 13 mass shootings, each event involving greater than 10 injuries, from 2012-19. Local champions in emergency medicine and trauma surgery provided clinical data from electronic health records within 24 hours of a mass shooting. We organized descriptive statistics of individual-level diagnoses recorded in medical records using International Classification of Diseases codes, according to the Barell Injury Diagnosis Matrix (BIDM), a standardized tool that classifies 12 types of injuries within 36 body regions. RESULTS: Of the 403 patients who were evaluated at a hospital, 364 sustained physical injuries-252 by gunshot wound (GSW) and 112 by non-ballistic trauma-and 39 were uninjured. Fifty patients had 75 psychiatric diagnoses. Nearly 10% of victims came to the hospital for symptoms triggered by, but not directly related to, the shooting, or for exacerbations of underlying conditions. There were 362 gunshot wounds recorded in the Barell Matrix (1.44 per patient). The Emergency Severity Index (ESI) distribution was skewed toward higher acuity than typical for an emergency department (ED), with 15.1% ESI 1 and 17.6% ESI 2 patients. Semi-automatic firearms were used in 100% of these civilian public mass shootings, with 50 total weapons for 13 shootings (Route 91 Harvest Festival, Las Vegas. 24). Assailant motivations were reported to be associated with hate crimes in 23.1%. CONCLUSION: Survivors of mass shootings have substantial morbidity and characteristic injury distribution, but 37% of victims had no GSW. Law enforcement, emergency medical systems, and hospital and ED disaster planners can use this information for injury mitigation and public policy planning. The BIDM is useful to organize data regarding gun violence injuries. We call for additional research funding to prevent and mitigate interpersonal firearm injuries, and for the National Violent Death Reporting System to expand tracking of injuries, their sequelae, complications, and societal costs.

Exploring the effects of habituation and scent in first-person 360-degree videos on consumption behavior.

Although immersive virtual environments can influence food-related thoughts, emotions and behavior, the influence of repeated exposure to food cues in such environments has rarely been explored. This study seeks to understand if habituation, a decrease in one's physiological and behavioral response that results from repeated simulation, can take place while repeatedly watching 360-degrees of food being consumed. The influence of scent as an olfactory cue is further explored, based on past research on embodied cognition. In Study One (n = 42), participants who viewed 30 repetitions of someone eating an M&M ate significantly fewer M&Ms than those who viewed three repetitions. Study Two (n = 114) used a 2 (behavior: eating M&M/inserting a coin) × 2 (repetitions: 3/30) between-subjects experiment to confirm that results from Study One were due to habituation of the consumption video, finding that there were only significant differences between repetitions in the M&M condition. Finally, Study Three (n = 161) comprised a 2 (repetition: 3/30) × 2 (scent: present/absent) between-subjects experiment. Participants in the 30-repetition condition and those in the scent-present condition ate significantly fewer M&Ms respectively, but no interaction effects were found. The theoretical and practical implications of these findings are discussed.

Psychosocial Wellbeing among Patients with Breast Cancer during COVID-19.

The impact of coronavirus disease 2019 (COVID-19) on the wellbeing of breast cancer (BC) patients is not well understood. This study described psychosocial problems among these patients in the United States (US) during the COVID-19 pandemic. Data were collected from BC patients via an online self-report survey between 30 March-6 July 2021 to assess the prevalence of COVID-19 diagnosis history and potential depression, health-related quality of life, COVID-related stress, and financial toxicity. Patients with early-stage (eBC) and metastatic (mBC) disease were compared. Of 669 patients included in the analysis, the prevalence of COVID-19 diagnosis history (10.9% versus 7.7%) and potential depression (33.7% versus 28.3%) were higher in mBC than eBC patients. Patients with eBC (versus mBC) had higher scores on nearly all Functional Assessment of Cancer Therapy-Breast scales (all, p < 0.001). For the Psychological Impact of Cancer subscales measuring negative coping strategies, the emotional distress score was the highest (9.1 ± 1.8) in the overall sample. Comprehensive Score for Financial Toxicity scores were higher in eBC than in mBC patients (24.2 ± 11.3 vs. 21.3 ± 10.2, p < 0.001). Overall, the COVID-19-related stress score was highest for danger/contamination fears (8.2 ± 5.6). In conclusion, impairments to psychosocial wellbeing among patients during the pandemic were observed, particularly financial toxicity and poor mental health and emotional functioning, with greater problems among mBC patients.

Social media use for coping with stress and psychological adjustment: A transactional model of stress and coping perspective.

Introduction: The psychological well-being of individuals has become an essential issue during the global pandemic. As a pervasive activity for individuals to pull through COVID-19, social media use may play a role in psychological well-being. Drawing on the transactional model of stress and coping, the current study investigated the relationships between COVID-19-related stressors and the use of social media to facilitate specific coping strategies. We further investigated how social media coping strategies impact users' psychological adjustment. Methods: We collected the data from 641 quarantined residents through a two-wave survey that was conducted in two cities in China during government-mandated lockdowns. Results: The results showed that perceived COVID-19 stress was related to the intensity of social media use for problem-focused coping, socioemotional coping, and mental disengagement. In addition, individuals' psychological adjustment was positively associated with social media use for socioemotional coping and mental disengagement while negatively related to problem-focused coping. Age was also found to be a moderator of the relationship between socioemotional coping and psychological adjustment. Discussion: To relieve pandemic-related stress, individuals can actively utilize social media to implement various coping strategies. However, coping activities with social media may not always induce psychological benefits. By revealing the different levels of psychological adjustment among social media users with specific coping strategies, the current research enriched the literature on the effects of social media use on mental health. Findings from this study suggest the need for the prudent use of social media to cope with public health crises.

Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer.

BACKGROUND: Palbociclib, the first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study compared real-world effectiveness of palbociclib plus letrozole versus letrozole in older patients with MBC in US clinical practice. METHODS: This retrospective analysis included patients from the Flatiron Health longitudinal database. Overall, 796 women with HR+/HER2- MBC aged ≥65 years starting palbociclib plus letrozole or letrozole as first-line therapy between February 2015 and September 2018 were included. Patients were evaluated from treatment start until December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS), overall survival (OS), and real-world best tumor responses (rwBTR) were endpoints. Stabilized inverse probability treatment weighting (sIPTW) balanced patient characteristics. RESULTS: After sIPTW, 450 patients treated with palbociclib plus letrozole and 335 treated with letrozole were included; median age was 74.0 years. Median rwPFS was 22.2 (95% CI, 20.0-30.4) months for palbociclib plus letrozole versus 15.8 (12.9-18.9) months for letrozole (hazard ratio, 0.59 [0.47-0.74]; P<0.001). Median OS was not reached for palbociclib plus letrozole versus 43.4 months (30.0-not estimable) with letrozole (hazard ratio, 0.55 [0.42-0.72]; P<0.001). No interactions between age groups (65-74 and ≥75 years) and treatment groups were observed for rwPFS or OS. Rate of rwBTR was significantly higher for palbociclib plus letrozole (52.4%) versus letrozole (22.1%; odds ratio, 2.0 [1.4-2.7]; P<0.001). CONCLUSION: This analysis demonstrates the effectiveness of palbociclib combination therapy as standard-of-care for older patients with HR+/HER2- MBC in the first-line setting.