UC Irvine Department of Medicine

Introduction: Children and adolescents are not impervious to the unprecedented epidemic of opioid misuse in the United States. In 2016 more than 88,000 adolescents between the ages of 12–17 reported misusing opioid medication, and evidence suggests that there has been a rise in opioid-related mortality for pediatric patients. A major source of prescribed opioids for the treatment of pain is the emergency department (ED). The current study sought to assess the complex relationship between opioid administration, pain severity, and parent satisfaction with children’s care in a pediatric ED.

Methods: We examined data from a tertiary pediatric care facility. A health survey questionnaire was administered after ED discharge to capture the outcome of parental likelihood of providing a positive facility rating. We abstracted patient demographic, clinical, and top diagnostic information using electronic health records. Data were merged and multivariable models were constructed. 

Results: We collected data from 15,895 pediatric patients between the ages of 0–17 years (mean = 6.69; standard deviation = 5.19) and their parents. Approximately 786 (4.94%) patients were administered an opioid; 8212 (51.70%) were administered a non-opioid analgesic; and 3966 (24.95%) expressed clinically significant pain (pain score >/= 4). Results of a multivariable regression analysis from these pediatric patients revealed a three-way interaction of age, pain severity, and opioid administration (odds ratio 1.022, 95% confidence interval, 1.006, 1.038, P = 0.007). Our findings suggest that opioid administration negatively impacted parent satisfaction of older adolescent patients in milder pain who were administered an opioid analgesic, but positively influenced the satisfaction scores of parents of younger children who were administered opioids. When pain levels were severe, the relationship between age and patient experience was not statistically significant.

Conclusion: This investigation highlights the complexity of the relationship between opioid administration, pain severity, and satisfaction, and suggests that the impact of opioid administration on parent satisfaction is a function of the age of the child.

Groundbreaking strategies for preventive cardiology were showcased at the 2024 American Society for Preventive Cardiology (ASPC) Congress on Cardiovascular Disease (CVD) Prevention held in Salt Lake City, Utah, from August 2nd to 4th, 2024. The event featured 69 moderators and 13 scientific sessions comprised of 98 topics, 36 satellite events, 133 poster presentations, and 27 lifestyle classes. The conference highlighted innovative strategies focused on integrating cardiovascular, kidney, and metabolic health, presenting a cohesive approach for managing complex, interrelated conditions. Pivotal studies have addressed the role of lipid-lowering therapies, the benefits of early statin initiation, and the importance of precision medicine in preventing CVD. The ASPCs emphasis on translating this research into practical clinical tools has the potential to revolutionize preventive care strategies, making strides toward reducing the burden of CVD globally and improving long-term patient outcomes through personalized and early intervention approaches.

PURPOSE: A significant number of cancer survivors experience cancer-related cognitive impairment (CRCI), which can impact their ability to think, reason, make decisions, and perform daily actions. In recent years, non-pharmacological interventions for CRCI have gained significant attention. These interventions include exercise, cognitive behavioural therapy, cognitive training/remediation, dietary, mind-body, and multi-modal/complex interventions. This umbrella review provides a critical overview to inform guidelines and current practice, identify the most promising interventions, and uncover gaps in the research literature. METHODS: This umbrella review of systematic reviews was pre-registered on Open Science Framework and PROSPERO. Six databases were searched. Systematic reviews (SR) assessing any non-pharmacological interventions to improve cognition in cancer (any type) were included. The overview followed gold-standard guidelines and recommendations. The results were narratively synthesised, and descriptive statistics and effect size ranges were calculated. RESULTS: Sixty-four (n = 64) SRs were included. Results were synthesised into four non-pharmacological domains. Cognitive training/rehabilitation had the strongest evidence for efficacy. Physical activity/exercise showed promising efficacy; however, the variability of findings was considerable. Mind-body and psychological/behavioural therapy interventions were limited, but there was evidence for short-term effectiveness. Multi-modal/complex interventions showed potential for improving cognition in cancer but were poorly defined. CONCLUSIONS: Overall, non-pharmacological interventions demonstrated efficacy for improving cognition in cancer. There were limited intervention characteristics within domains which were consistently related to efficacy. Three key recommendations are provided for future research: (1) adopt harmonisation and reporting guidelines; (2) develop definitional guidelines of cognitive domains for CRCI research; and (3) assess intervention and participant characteristics associated with positive versus null/negative findings.

BACKGROUND: Semaglutide 2.4 mg benefits weight loss and reduction of cardiovascular disease (CVD) risk factors in adults with obesity. We estimated the US population eligibility for semaglutide 2.4 mg (based on the weight management indication) and the impact on obesity and CVD events. METHODS: We applied STEP 1 trial eligibility criteria to US adults aged ≥ 18 years in the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 to estimate the US eligible population. Semaglutide weight changes in STEP 1 were applied to estimate the population impact on weight changes and obesity prevalence. We also estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. The difference in estimated risks with and without semaglutide treatment multiplied by the eligible NHANES weighted population represented the estimated preventable CVD events. RESULTS: We identified 3999 US adults weighted to an estimated population size of 93.0 million [M] (38% of US adults) who fit STEP 1 eligibility criteria. Applying STEP 1 treatment effects on weight loss resulted in an estimated 69.1% (64.3 M) and 50.5% (47.0 M) showing ≥ 10% and ≥ 15% weight reductions, respectively, translating to a 46.1% (43.0 M) reduction in obesity (BMI ≥ 30 kg/m2) prevalence. Among those without CVD, estimated 10-year CVD risks were 10.15% before and 8.34% after semaglutide treatment reflecting a 1.81% absolute (and 17.8% relative) risk reduction translating to 1.50 million preventable CVD events over 10 years. CONCLUSION: Semaglutide treatment in eligible US adults may substantially reduce obesity prevalence and CVD events, which may dramatically impact associated healthcare costs.

BACKGROUND: Because cirrhosis is often unrecognized, we aimed to develop a stepwise screening algorithm for cirrhosis in the Veterans Health Administration (VHA) and assess this approachs feasibility and acceptability. METHODS: VHA hepatology clinicians (champions) were invited to participate in a pilot program from June 2020 to October 2022. The VHA Corporate Data Warehouse was queried to identify Veterans with possible undiagnosed cirrhosis using Fibrosis-4 (FIB-4) ≥ 3.25 and at least one risk factor for liver disease (e.g., obesity), and generate an age-stratified sample. Champions at four sites reviewed charts to confirm eligibility and contacted Veterans to offer further evaluation with elastography. Feasibility was defined as protocol implementation with completion of at least one elastography test and acceptability was defined based on Veteran- and clinician-reported surveys. Participation in the program, patient outcomes, adaptations to the protocol, and implementation barriers were also assessed. RESULTS: Four sites were able to implement the screening protocol. Adaptations included type of outreach (primary care vs. hepatology, phone vs. mail) and type of elastography used. One site chose to refer patients with clear evidence of cirrhosis directly to hepatology (n = 12) rather than to elastography. Key implementation barriers included staffing, primary care provider (PCP) comfort with interpreting and communicating results, and appointment availability during the COVID-19 pandemic. Of 488 patients whose charts were reviewed, 230 were excluded from outreach based on predefined criteria (e.g., advanced cancer, prior or current referral to hepatology). Champions and PCPs attempted to contact 165 of 246 Veterans who were deemed eligible for evaluation with elastography. Among 53 Veterans who completed elastography, 22 (42%) had findings consistent with significant fibrosis and were referred to hepatology. Clinicians and Veterans reported high acceptability of the program on surveys (80% of Veterans who completed survey). CONCLUSIONS: This pilot demonstrated the feasibility, acceptability, and challenges of a multisite approach to cirrhosis screening.

PURPOSE: Cancer-related cognitive impairment (CRCI) can have a profound impact on the lives of cancer survivors. A multitude of subjective and objective assessment tools exist to assess the presence and severity of CRCI. However, no purpose-built tool exists to assess the unmet needs of cancer survivors directly relating to CRCI. This paper details the development and initial validation of the Multinational Association of Supportive Care in Cancer - Unmet Needs Assessment of Cancer-Related Cognitive Impairment Impact (the MASCC COG-IMPACT). METHODS: A multistep mixed-methods measurement development and validation approach was taken with a strong emphasis on co-design. Qualitative interviews were conducted with cancer survivors (n = 32) and oncology health professionals (n = 19), followed by a modified Delphi survey with oncology health professionals (n = 29). Cognitive interviews with cancer survivors (n = 22) over two rounds were then conducted to finalise the penultimate version of the unmet needs assessment tool for CRCI. Four-hundred and ninety-one (n = 491) cancer survivors then completed the MASCC COG-IMPACT and other established measures to inform structural, reliability, validity, acceptability, appropriateness, and feasibility analyses. RESULTS: The final MASCC COG-IMPACT is a 55-item and eight subscale tool including two indices: difficulties and unmet needs. The MASCC COG-IMPACT was found to have strong structural validity, convergent validity, discriminant validity, internal consistency, and test-retest reliability. The MASCC COG-IMPACT was also found to be highly acceptable, appropriate, and feasible. CONCLUSION: The MASCC COG-IMPACT may facilitate optimal care and referral in line with a cancer survivors CRCI-related difficulties and unmet needs. The MASCC COG-IMPACT may also be used to explore factors and contributors to CRCI-related difficulties and unmet needs. Overall, the MASCC COG-IMPACT is a highly reliable and valid tool for the assessment of CRCI-related difficulties and unmet needs in both clinical and research settings. The MASCC COG-IMPACT and supporting materials can be accessed on the MASCC webpage or via the MASCC COG-IMPACT Open Science Framework webpage ( https://osf.io/5zc3a/ ).

NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that NKp46 is indispensable for expressing IL-2 receptor-α (IL-2Rα) by non-NK liver-resident type-1 innate lymphoid cells (ILC1s). Deletion of NKp46 reduces IL-2Rα on ILC1s by downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity in vitro and in vivo. The binding of anti-NKp46 antibody to NKp46 triggers the activation of NF-κB, the expression of IL-2Rα, interferon-γ (IFN-γ), tumor necrosis factor (TNF), proliferation, and cytotoxicity. Functionally, NKp46 expressed on mouse ILC1s interacts with tumor cells through cell-cell contact, increasing ILC1 production of IFN-γ and TNF, and enhancing cytotoxicity. In a mouse model of acute myeloid leukemia, deletion of NKp46 impairs the ability of ILC1s to control tumor growth and reduces survival. This can be reversed by injecting NKp46+ ILC1s into NKp46 knock-out mice. Human NKp46+ ILC1s exhibit stronger cytokine production and cytotoxicity than their NKp46- counterparts, suggesting that NKp46 plays a similar role in humans. These findings identify an NKp46-NF-κB-IL-2Rα axis and suggest that activating NKp46 with an anti-NKp46 antibody may provide a potential strategy for anti-tumor innate immunity.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality around the world. Despite advances in surgery, chemotherapy, and targeted therapies, the prognosis for patients with metastatic or advanced CRC remains poor. Immunotherapies comprising immune checkpoint inhibitors showed disappointing responses in metastatic CRC (mCRC). However, cellular immunotherapy, specifically using classical dendritic cells (cDCs), may hold unique promise in immune recognition for CRC antigens. cDCs are substantial players in immune recognition and are instrumental in orchestrating innate and adaptive immune responses by processing and presenting tumor antigens to effector cells. Natural killer T (NKT) cells are insufficiently studied but unique effector cells because of their ability to bridge innate and adaptive immune reactions and the crosstalk with dendritic cells in cancer. This review explores the therapeutic potential of using both cDCs and NKT cells as a synergistic therapy in CRC, focusing on their biological roles, strategies for harnessing their capabilities, clinical applications, and the challenges within the tumor microenvironment. Both cDCs and NKT cells can be used as a new effective approach for cell-based therapies in cancers to provide a new hope for CRC patients that are challenging to treat.

Background: Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the Advanced Biliary Cancer (ABC)-02 study, remains to be assessed. We performed a retrospective observational cohort study to assess real-world treatment patterns and overall survival (OS) in patients with de novo or recurrent aBTCs treated with first-line gemcitabine-based chemotherapy in the United States. Methods: This retrospective observational cohort study used Optums de-identified Market Clarity Data (Market Clarity). Adults diagnosed with de novo or recurrent aBTCs in the United States who began first-line gemcitabine-based chemotherapy from January 2016-March 2022 were identified and followed from index until death, the end of continuous enrolment, or the end of study period. Treatment patterns and OS were assessed. Results: Overall, 559 patients were included (de novo, n = 462; recurrent, n = 97). GemCis was the most common first-line therapy received (de novo: 73.8%; recurrent: 57.7%). Most patients received approximately five cycles of GemCis; median (95% CI) time to discontinuation was 4.6 (4.3-5.1) months. Most patients died over the follow-up period (de novo: 70.3%; recurrent: 62.9%). Median OS (95% CI) was 14.2 (12.1-16.1) months (de novo) and 18.5 (15.6-26.9) months (recurrent). Conclusions: GemCis was the most common first-line therapy received during the study period; most patients were unable to receive eight cycles of GemCis. Survival was limited over the follow-up period, highlighting the need for new treatments for aBTCs. Future studies are warranted to understand the real-world impact of first-line immunotherapy plus GemCis for patients with aBTCs.

BACKGROUND/OBJECTIVES: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation. METHODS: The intervention program includes 16 weeks of intensive hands-on culinary and lifestyle education classes followed by eight monthly virtual classes. Psychometric assessments and biometric data will be collected at baseline, 4, 12, and 18 months. Semi-structured interviews and open-ended surveys will be conducted during the 12-month follow-up assessment. RESULTS: Feasibility will be assessed through recruitment, attendance, and fidelity data. Secondary outcomes will analyze changes in health behaviors, biometric data, and anthropometric measures using mixed-effects regression models. Qualitative data will undergo thematic analysis. CONCLUSIONS: As envisioned and described in detail in this manuscript, this study will inform the development and implementation of reproducible, scalable teaching kitchen interventions. The protocol described here is intended to set the stage for future investigations to evaluate evidence for the impact of teaching kitchen interventions on dietary habits, physical activity, and overall health and well-being.