GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV.

BACKGROUND: Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. METHODS: A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. RESULTS: A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss. CONCLUSIONS: Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.

Characterization of patients with brain metastases referred to palliative care.

PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.

Direct to Patient Synchronous Teledermatology During COVID-19 Pandemic.

Background: During the COVID-19 pandemic, teledermatology became a popular mode of health care delivery. Thus, deciphering which diagnoses are best suited for synchronous video visits is important to guide providers on appropriate patient care. Methods: We conducted a retrospective study of 1,647 submitted synchronous video visits from September 1, 2020 to March 31, 2021 at a single, large academic institution. Results: Video visits' follow-up rate was significantly associated with diagnosis subtype (p < 0.001). Compared with patients with skin lesions and nonskin dermatologic conditions, patients with a rash had higher odds of being recommended to have their follow-up visit as a video visit (odds ratio [OR] = 0.222, p < 0.001; OR = 0.296, p < 0.001). Patients with a rash had lower odds of being recommended to have their follow-up visit as an in-person office visit when compared with skin lesions (OR = 9.679, p < 0.001), nonskin dermatologic conditions (OR = 4.055, p < 0.001), and other skin dermatologic conditions (OR = 2.23, p < 0.01). Demographically, employed, middle-aged patients with private insurance made up the majority of video visit usage. African American patients were less likely to utilize a video visit compared with Asian patients (OR = 2.06, p < 0.038). Conclusions: Certain dermatologic diagnoses, most notably rashes, are more conducive to video visit management. Rashes made up 86% of new patient video visits, were more likely to have video visit follow-up if needed and were more likely to not require further follow-up indicating that the management of rashes from initial diagnosis to completion in care is suitable for video visit management.

Frequency of vaccine hesitancy among patients with advanced cancer.

BACKGROUND: Vaccine hesitancy has become prevalent in society. Vulnerable populations, such as those with cancer, are susceptible to increased morbidity and mortality from diseases that may have been prevented through vaccination. OBJECTIVES: Our objective was to determine patient perception of vaccine efficacy and safety and sources of information that influence decisions. METHODS: This study was a prospective cross-sectional survey trial conducted from March 10, 2022, to November 1, 2022, at a Supportive Care Clinic. Patients completed the survey with a research assistant or from a survey link. Vaccine hesitancy was defined as a response of 2 or more on the Parent Attitudes About Childhood Vaccines (PACV-4). Perception on vaccine safety and efficacy along with the importance of sources of information were determined by a questionnaire. RESULTS: Of the 72 patients who completed the PACV-4, 30 were considered vaccine-hesitant (42%). Of those who completed the survey alone (35), 23 (66%) were vaccine-hesitant; and of those who completed the survey with the help of a study coordinator (37), 7 (19%) were vaccine-hesitant. The most important source for decision-making was their doctor (82%, 95% CI 73-89), followed by family (42%, 95% CI 32-52), news/media (31%, 95% CI 22-41), and social media (9%, 95% CI 4-16). Clinical and demographic factors including age, gender, race/ethnicity, education level, and location of residence were not associated with vaccine hesitancy. SIGNIFICANCE OF RESULTS: Vaccine hesitancy is present among patients with advanced cancer. The high value given to the doctor's recommendation suggests that universal precautions regarding vaccine recommendation may be an effective intervention.

Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis.

INTRODUCTION: Recent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer the opportunity to address current challenges in AS diagnosis and management. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS. This study reports the first proteomic and miRNA profiling of plasma-derived exosomes in AS using comprehensive computational biology analysis. METHODS: Plasma samples from patients with AS and healthy controls (HC) were isolated via ultracentrifugation and subjected to extracellular vesicle flow cytometry analysis to characterise exosome surface markers by a multiplex immunocapture assay. Cytokine profiling of plasma-derived exosomes and cell culture supernatants was performed. Next-generation sequencing was used to identify miRNA populations in exosomes enriched from plasma fractions. CD4+ T cells were sorted, and the frequency and proliferation of CD4+ T-cell subsets were analysed after treatment with AS-exosomes using flow cytometry. RESULTS: The expression of exosome marker proteins CD63 and CD81 was elevated in the patients with AS compared with HC (q<0.05). Cytokine profiling in plasma-derived AS-exosomes demonstrated downregulation of interleukin (IL)-8 and IL-10 (q<0.05). AS-exosomes cocultured with HC CD4+ T cells induced significant upregulation of IFNα2 and IL-33 (q<0.05). Exosomes from patients with AS inhibited the proliferation of regulatory T cells (Treg), suggesting a mechanism for chronically activated T cells in this disease. Culture of CD4+ T cells from healthy individuals in the presence of AS-exosomes reduced the proliferation of FOXP3+ Treg cells and decreased the frequency of FOXP3+IRF4+ Treg cells. miRNA sequencing identified 24 differentially expressed miRNAs found in circulating exosomes of patients with AS compared with HC; 22 of which were upregulated and 2 were downregulated. CONCLUSIONS: Individuals with AS have different immunological and genetic profiles, as determined by evaluating the exosomes of these patients. The inhibitory effect of exosomes on Treg in AS suggests a mechanism contributing to chronically activated T cells in this disease.

MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma.

PURPOSE: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound. METHODS: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline. RESULTS: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10-3mm2/s increase 12 months after treatment (p = 0.15). CONCLUSION: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

Nonmedical opioid use at the end of life: A tale of addiction and a last wish.

BACKGROUND: Nonmedical opioid use (NMOU) has been associated with opioid overdose deaths. This pattern of misuse can be seen in those using opioids for cancer-associated pain. We present a case that highlights the complexities associated with NMOU and a patient's care at the end of life. CASES DESCRIPTION: A patient with a metastatic solid tumor malignancy along with co-occurring history of polysubstance abuse was admitted to an acute palliative and supportive care unit (APSCU). The patient demonstrated behaviors concerning for NMOU during her hospital stay but had increased symptom expression concerning for worsening dyspnea while in the APSCU. Unfortunately, she used home opioids, which was unknown to the team at the time along with requesting for higher doses of opioids that were being prescribed. This caused a worsening respiratory status and affected her care. Using an interdisciplinary approach, the providers managed her symptoms and discharged her safely to see her child. CONCLUSION: This highlights the complexities of the alleviation of suffering in those with NMOU. It is important to continue to manage NMOU at the end of life due to its effects on quality of life. A multimodal approach is recommended to identify and care for these patients.

Distress, demoralization, and fulfillment among palliative care providers during the COVID-19 pandemic.

OBJECTIVES: Prolonged distress is a risk factor for burnout among health-care providers (HCP) and may contribute to demoralization. We examined sources of distress during the COVID-19 pandemic and associations with demoralization. METHODS: This prospective cross-sectional survey of HCP was conducted among palliative care providers of an academic medical center. Participants completed a survey evaluating sources of distress and the Demoralization Scale-II (DS-II) to measure the intensity of demoralization. RESULTS: Of 106 eligible participants, 74 (70%) completed the survey. DS-II median (range) score was 2 (0-19). There were no statistically significant associations with demographic characteristics. Participants reported high rates of distress for multiple reasons and high rates of sense of fulfillment (90%) and satisfaction (89%) with their profession. SIGNIFICANCE OF RESULTS: Our study identified high levels of distress but low demoralization rates. Further study to evaluate fulfillment and satisfaction as protective factors against demoralization and burnout is indicated.

Catalytic Performance and Near-Surface X-ray Characterization of Titanium Hydride Electrodes for the Electrochemical Nitrate Reduction Reaction.

The electrochemical nitrate reduction reaction (NO3RR) on titanium introduces significant surface reconstruction and forms titanium hydride (TiHx, 0 < x ≤ 2). With ex situ grazing-incidence X-ray diffraction (GIXRD) and X-ray absorption spectroscopy (XAS), we demonstrated near-surface TiH2 enrichment with increasing NO3RR applied potential and duration. This quantitative relationship facilitated electrochemical treatment of Ti to form TiH2/Ti electrodes for use in NO3RR, thereby decoupling hydride formation from NO3RR performance. A wide range of NO3RR activity and selectivity on TiH2/Ti electrodes between -0.4 and -1.0 VRHE was observed and analyzed with density functional theory (DFT) calculations on TiH2(111). This work underscores the importance of relating NO3RR performance with near-surface electrode structure to advance catalyst design and operation.

Interdisciplinary intervention for the management of nonmedical opioid use among patients with cancer pain.

BACKGROUND: Few studies have assessed interventions aimed at managing nonmedical opioid use (NMOU) behavior among patients with cancer. The authors developed the Compassionate High-Alert Team (CHAT) intervention to manage patients receiving opioids for cancer pain who demonstrate NMOU behavior. The objective of this study was to determine the change in frequency of NMOU behaviors, pain intensity, and opioid requirements among those who received the intervention. METHODS: A total of 130 patients receiving opioids for cancer pain that had documented evidence of NMOU and received the CHAT intervention were reviewed. Demographic and clinical information such as NMOU behaviors, pain scores, and morphine equivalent daily dose at baseline, 3, and 6 months post-intervention was obtained. RESULTS: NMOU behaviors significantly decreased from a median (interquartile range) of 2 (1-3) at baseline to 0 (0-1) at both 3 and 6 months post-intervention (p < .001). A total of 45 of 75 (60%) and 31 of 50 (62%) of CHAT recipients achieved complete response to the intervention at 3 and 6 months, respectively. Higher baseline number of NMOU behaviors was independently associated with patient response to the intervention (odds ratio [OR], 1.97; 95% confidence interval [CI],1.09-4.28, p = .049 at 3 months; OR, 2.5; 95% CI, 1.20-6.47, p = .03 at 6 months). The median pain score decreased from 7 at baseline to 6 at both 3 and 6 months (p = .01). Morphine equivalent daily dose did not significantly change during that same period (143 mg/day vs. 139 mg/day, p = .13). CONCLUSIONS: Most patients who received the CHAT intervention improved in their NMOU behaviors and pain intensity scores 3 and 6 months post-intervention. These preliminary findings support the efficacy of CHAT in managing patients receiving opioids for cancer pain who demonstrate NMOU behavior.

People with HIV have a higher risk of COVID-19 diagnosis but similar outcomes to the general population.

BACKGROUND: We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and comorbidity burden. METHODS: This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability-weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV-IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis. RESULTS: Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV-IPW [95% confidence interval (CI): 1.6-2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1-1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31-3.80) or of in-hospital death (aIRR = 0.92, 95% CI: 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. CONCLUSIONS: People living with HIV have a higher risk of COVID-19 diagnosis than those without HIV but the outcomes are similar in both groups.

A Comparison of 3 T and 7 T MRI for the Clinical Evaluation of Uveal Melanoma.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis and treatment planning of uveal melanoma (UM), the most common primary intraocular tumor. Initially, 7 T MRI was primarily used, but more recently these techniques have been translated to 3 T, as it is more commonly available. PURPOSE: Compare the diagnostic performance of 3 T and 7 T MRI of UM. STUDY TYPE: Prospective. POPULATION: Twenty-seven UM patients (19% female). FIELD STRENGTH/SEQUENCE: 3 T: T1- and T2-weighted three-dimensional (3D) spin echo (SE) and multi-slice (MS) SE, 7 T: T1-weighted 3D gradient echo (GE), T2-weighted 3D SE and MS SE, 3 T and 7 T GE dynamic contrast-enhanced. T1 weighted images: acquired before and after Gadolinium (Gd) administration. ASSESSMENT: For all sequences, scan and diagnostic quality was quantified using a 5-point Likert scale. Signal intensities on T1 and T2 relative to choroid and eye muscle respectively were assessed as well as the tumor prominence. Finally, the perfusion time-intensity curves (TICs) were classified as plateau, progressive, or wash-out. STATISTICAL TESTS: Image quality scores were compared between both field strengths using Wilcoxon signed-rank and McNemar tests. Paired t-tests and Bland-Altman were used for comparing tumor prominences. P < 0.05 was considered statistically significant. RESULTS: Image quality was comparable between 3 T and 7 T, for 3DT1, 3DT2, 3DT1Gd (P = 0.86; P = 0.34; P = 0.78, respectively) and measuring tumor dimensions (P = 0.40). 2DT1 and 2DT2 image quality were rated better on 3 T compared to 7 T. Most UM had the same relative signal intensities at 3 T and 7 T on T1 (17/21) and T2 (13/17), and 16/18 diagnostic TICs received the same classification. Tumor prominence measurements were similar between field strengths (95% confidence interval: -0.37 mm to 0.03 mm, P = 0.097). DATA CONCLUSION: Diagnostic performance of the evaluated 3 T protocol proved to be as capable as 7 T, with the addition of 3 T being superior in assessing tumor growth into nearby anatomical structures compared to 7 T. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Social isolation at the end of life: A case report of one person's journey navigating the medical landscape during the COVID-19 pandemic.

BACKGROUND: In addition to physical symptom burden, psychological suffering at end of life (EOL) is quite pervasive. As such, the interdisciplinary team in our Palliative and Supportive Care Unit strives to provide quality care sensitive to the physical and psychosocial needs of patients. Involving and allowing for the presence of family members is one way in which we afford our patients some additional comfort. Unfortunately, the current pandemic has placed limitations on this rather fundamental need for both patients and their family members. Here, we present a case illustrating the effects of visitor restrictions/isolation due to COVID-19 on the suffering of a patient at the EOL. CASE DESCRIPTION: A male in his 20s with a refractory hematologic malignancy decided to pursue a comfort-based approach to care after a rapid clinical deterioration. Due to visitor restrictions, he had to face this decision with limited support at the bedside, which caused significant distress. He was forced to choose among several immediate family members who would be at his side through his hospitalization, to be his advocate, at times his voice, his confidant, and the person to relay all information to those on the outside. He expressed a wish to be married before he died, which occurred in our palliative care unit. This life goal was one we would normally encourage those he loved to gather around him, but this was not possible. He passed peacefully two days after he was married. CONCLUSION: Although social limitations are necessary to help provide safety to the patients and staff in a hospital, they can have a direct impact on the suffering of patients and families at the EOL. Helping to maintain dignity, reflect on their life, and resolve any conflicts in the presence of family members is a benchmark for providing quality palliative care. Being barred from visitation due to isolation, threatens this care and lays the foundation for complicated grief among family members. Further research is needed to help balance the needs of those at the EOL with public safety. One such measure to help ease distress is to allow for more virtual visitation through electronic measures.

COVID-19 Telemedicine and Vaccination at an Urban Safety Net HIV Medicine Clinic.

In response to the emerging coronavirus disease 2019 (COVID-19) pandemic in March 2020, the Owen Clinic at UC San Diego Health scaled up telemedicine to ensure the continuity of human immunodeficiency virus primary care. A group of nurse practitioners, physicians, and a physician assistant developed a dedicated COVID-19 telemedicine clinic to provide virtual health care services to patients with or at risk for severe acute respiratory syndrome coronavirus 2 infection. This effort contributed to successful health outcomes for the clinic's 476 patients diagnosed with COVID-19. The Owen Clinic was also the first ambulatory clinic within UC San Diego Health to implement on-site COVID-19 vaccines. Nurse practitioners and a physician assistant spearheaded these 2 clinical initiatives.

Random urine drug testing among patients receiving opioid therapy for cancer pain.

BACKGROUND: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics. METHODS: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU. RESULTS: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01). CONCLUSIONS: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.

Association among rescue neuroleptic use, agitation, and perceived comfort: secondary analysis of a randomized clinical trial on agitated delirium.

BACKGROUND: Few studies have examined how the use of rescue medications could be used to inform on the efficacy of interventions in delirium clinical trials. The objective of this study was to determine the association among rescue medication use, Richmond Agitation-Sedation Scale (RASS), and perceived comfort by the nurses and caregivers. METHODS: This was a pre-planned secondary analysis of a double-blind, randomized clinical trial comparing the use of a single dose of lorazepam plus haloperidol versus placebo plus haloperidol in patients with agitated delirium. Rescue medications were considered the gold standard for this analysis. The optimal cutoff for RASS analysis was calculated by using general linear regression models and determining the area of the curve and using the top left approach. We used 2 × 2 tables to examine the association between rescue medication use and perceived comfort. RESULTS: Fifty-eight patients received the study medications and 52 (89%) completed the 8-h observation period. There were 26 (50%) patients in each arm. The lorazepam/haloperidol arm required fewer rescue doses (4/26 (15%)) vs. 16/26 (62%), p = 0.004). Patients with a greater initial RASS reduction required fewer rescue doses. The cutoff value for RASS improvement was 4 points, area under the curve (AUC) 0.64 (95% CI 0.49-0.79) for those who required no rescue doses, and 3 points, AUC 0.74 (95% CI 0.52-0.96) for those who required more than one rescue dose. CONCLUSIONS: Rescue medication use was responsive to change and associated with both RASS scores and perceived patient comfort by the nurse and caregiver.

Neovascularization Detection and Localization in Fundus Images Using Deep Learning.

Proliferative Diabetic Retinopathy (PDR) is a severe retinal disease that threatens diabetic patients. It is characterized by neovascularization in the retina and the optic disk. PDR clinical features contain highly intense retinal neovascularization and fibrous spreads, leading to visual distortion if not controlled. Different image processing techniques have been proposed to detect and diagnose neovascularization from fundus images. Recently, deep learning methods are getting popular in neovascularization detection due to artificial intelligence advancement in biomedical image processing. This paper presents a semantic segmentation convolutional neural network architecture for neovascularization detection. First, image pre-processing steps were applied to enhance the fundus images. Then, the images were divided into small patches, forming a training set, a validation set, and a testing set. A semantic segmentation convolutional neural network was designed and trained to detect the neovascularization regions on the images. Finally, the network was tested using the testing set for performance evaluation. The proposed model is entirely automated in detecting and localizing neovascularization lesions, which is not possible with previously published methods. Evaluation results showed that the model could achieve accuracy, sensitivity, specificity, precision, Jaccard similarity, and Dice similarity of 0.9948, 0.8772, 0.9976, 0.8696, 0.7643, and 0.8466, respectively. We demonstrated that this model could outperform other convolutional neural network models in neovascularization detection.

How to Measure Pain.

PURPOSE OF REVIEW: Pain is a multi-faceted symptom. Effective pain assessment involves properly defining the pain syndrome, utilizing various assessment tools, and recognizing different conditions which may affect the expression and the management of pain. RECENT FINDINGS: Pain results from multiple physical and psychosocial etiological interplay. It has traditionally been categorized as acute or chronic with chronic pain having been categorized further into 6 categories in ICD 11. At the same time, the opioid epidemic and the recent surge in cannabis popularity further complicates pain assessment and effective pain management. Adequate management of pain begins with proper assessment including conducting extensive medical and psychosocial history and physical examination, and utilizing various pain and substance risk assessment tools. An interdisciplinary team approach may be more effective in managing complex pain behaviors compared to a solo approach.

Tumor Dendritic Cells (DCs) Derived from Precursors of Conventional DCs Are Dispensable for Intratumor CTL Responses.

The success of adoptive CTL therapy for cancer depends on interactions between tumor-infiltrating CTLs and cancer cells as well as other cells and molecules in the tumor microenvironment. Tumor dendritic cells (DCs) comprise several subsets: CD103+CD11b- DC1 and CD11b+CD64- DC2, which originate from circulating precursors of conventional DCs, and CD11b+CD64+ DC3, which arise from monocytes. It remains controversial which of these subset(s) promotes intratumor CTL proliferation, expansion, and function. To address this issue, we used the Zbtb46-DTR-transgenic mouse model to selectively deplete DC1 and DC2 from tumors and lymphoid tissues. Wild-type and Zbtb46-DTR bone marrow chimeras were inoculated with B16 melanoma cells that express OVA and were treated with OT-1 CTLs. We found that depletion of DCs derived from precursors of conventional DCs in Zbtb46-DTR bone marrow chimeras abolished CTL proliferation and expansion in tumor-draining lymph nodes. By contrast, intratumor CTL accumulation, proliferation, and IFN-γ expression were unaffected by their absence. We found that adoptive cell therapy increases the frequency of monocyte-derived tumor DC3, which possess the capacity to cross-present tumor Ags and induce CTL proliferation. Our findings support the specialized roles of different DC subsets in the regulation of antitumor CTL responses.