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Disease-State Understanding and Experience of Patients Receiving Continuous Intravenous Inotropic Support as Palliative Therapy: A Multicenter Survey

J Palliat Med. 2024 Apr 1. doi: 10.1089/jpm.2023.0670. Online ahead of print.

ABSTRACT

Background: The use of continuous intravenous inotropic support (CIIS) as palliative therapy in patients with advanced heart failure (HF) has increased over the past decade. CIIS improves New York Heart Association (NYHA) functional class but does not impact survival. Objective: The objective of this study was to examine patients’ understanding of the therapeutic intent of CIIS, prognostic awareness, and quality of life with CIIS. Design: We conducted a prospective, cross-sectional, multicenter study of patients with advanced HF receiving CIIS as palliative therapy between 2020 and 2022. Settings/Subjects: An investigator-developed survey instrument was administered to outpatients on CIIS in the United States via telephone. Measurements: Survey data were analyzed using descriptive and inferential statistics. Results: Forty-eight patients, 63% male, 81% African American/Black, with a mean age of 68.9 (standard deviation 12.3) years, participated in this study. The majority of patients responded that they expected CIIS to make them feel better (79%) and increase longevity (75%), but few expected that CIIS would cure their HF (19%). Patients described their overall quality of life on CIIS as not better/worse (19%), somewhat better (46%), and significantly better (35%) and reported high treatment satisfaction (87% were at least somewhat satisfied). Conclusions: In this study, patients report improved quality of life with CIIS as palliative therapy. Patients on CIIS as palliative therapy expected increased survival on CIIS, which is incongruent with current evidence. Further studies on how we can improve care processes so that patients have accurate prognostic and disease-state awareness, and receive goal concordant care, are warranted.

PMID:38564223 | DOI:10.1089/jpm.2023.0670

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Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders

JAMA Netw Open. 2024 Apr 1;7(4):e244525. doi: 10.1001/jamanetworkopen.2024.4525.

ABSTRACT

IMPORTANCE: Biomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent.

OBJECTIVE: To examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023.

EXPOSURES: Lipid, apolipoprotein, and carbohydrate biomarkers measured in blood.

MAIN OUTCOMES AND MEASURES: The associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls.

RESULTS: A total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants.

CONCLUSIONS AND RELEVANCE: In this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

PMID:38564219 | DOI:10.1001/jamanetworkopen.2024.4525

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Quality of Large Language Model Responses to Radiation Oncology Patient Care Questions

JAMA Netw Open. 2024 Apr 1;7(4):e244630. doi: 10.1001/jamanetworkopen.2024.4630.

ABSTRACT

IMPORTANCE: Artificial intelligence (AI) large language models (LLMs) demonstrate potential in simulating human-like dialogue. Their efficacy in accurate patient-clinician communication within radiation oncology has yet to be explored.

OBJECTIVE: To determine an LLM’s quality of responses to radiation oncology patient care questions using both domain-specific expertise and domain-agnostic metrics.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study retrieved questions and answers from websites (accessed February 1 to March 20, 2023) affiliated with the National Cancer Institute and the Radiological Society of North America. These questions were used as queries for an AI LLM, ChatGPT version 3.5 (accessed February 20 to April 20, 2023), to prompt LLM-generated responses. Three radiation oncologists and 3 radiation physicists ranked the LLM-generated responses for relative factual correctness, relative completeness, and relative conciseness compared with online expert answers. Statistical analysis was performed from July to October 2023.

MAIN OUTCOMES AND MEASURES: The LLM’s responses were ranked by experts using domain-specific metrics such as relative correctness, conciseness, completeness, and potential harm compared with online expert answers on a 5-point Likert scale. Domain-agnostic metrics encompassing cosine similarity scores, readability scores, word count, lexicon, and syllable counts were computed as independent quality checks for LLM-generated responses.

RESULTS: Of the 115 radiation oncology questions retrieved from 4 professional society websites, the LLM performed the same or better in 108 responses (94%) for relative correctness, 89 responses (77%) for completeness, and 105 responses (91%) for conciseness compared with expert answers. Only 2 LLM responses were ranked as having potential harm. The mean (SD) readability consensus score for expert answers was 10.63 (3.17) vs 13.64 (2.22) for LLM answers (P < .001), indicating 10th grade and college reading levels, respectively. The mean (SD) number of syllables was 327.35 (277.15) for expert vs 376.21 (107.89) for LLM answers (P = .07), the mean (SD) word count was 226.33 (191.92) for expert vs 246.26 (69.36) for LLM answers (P = .27), and the mean (SD) lexicon score was 200.15 (171.28) for expert vs 219.10 (61.59) for LLM answers (P = .24).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the LLM generated accurate, comprehensive, and concise responses with minimal risk of harm, using language similar to human experts but at a higher reading level. These findings suggest the LLM’s potential, with some retraining, as a valuable resource for patient queries in radiation oncology and other medical fields.

PMID:38564215 | DOI:10.1001/jamanetworkopen.2024.4630

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Code-Free Machine Learning Approach for EVO-ICL Vault Prediction: A Retrospective Two-Center Study

Transl Vis Sci Technol. 2024 Apr 2;13(4):4. doi: 10.1167/tvst.13.4.4.

ABSTRACT

PURPOSE: Establishing a development environment for machine learning is difficult for medical researchers because learning to code is a major barrier. This study aimed to improve the accuracy of a postoperative vault value prediction model for implantable collamer lens (ICL) sizing using machine learning without coding experience.

METHODS: We used Orange data mining, a recently developed open-source, code-free machine learning tool. This study included eye-pair data from 294 patients from the B&VIIT Eye Center and 26 patients from Kim’s Eye Hospital. The model was developed using OCULUS Pentacam data from the B&VIIT Eye Center and was internally evaluated through 10-fold cross-validation. External validation was performed using data from Kim’s Eye Hospital.

RESULTS: The machine learning model was successfully trained using the data collected without coding. The random forest showed mean absolute errors of 124.8 µm and 152.4 µm for the internal 10-fold cross-validation and the external validation, respectively. For high vault prediction (>750 µm), the random forest showed areas under the curve of 0.725 and 0.760 for the internal and external validation datasets, respectively. The developed model performed better than the classic statistical regression models and the Google no-code platform.

CONCLUSIONS: Applying a no-code machine learning tool to our ICL implantation datasets showed a more accurate prediction of the postoperative vault than the classic regression and Google no-code models.

TRANSLATIONAL RELEVANCE: Because of significant bias in measurements and surgery between clinics, the no-code development of a customized machine learning nomogram will improve the accuracy of ICL implantation.

PMID:38564200 | DOI:10.1167/tvst.13.4.4

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Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma

Cell Oncol (Dordr). 2024 Apr 2. doi: 10.1007/s13402-024-00940-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options.

METHODS: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy.

RESULTS: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy.

CONCLUSION: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

PMID:38564164 | DOI:10.1007/s13402-024-00940-y

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The causal impact of gut microbiota on circulating adipokine concentrations: a two-sample Mendelian randomization study

Hormones (Athens). 2024 Apr 2. doi: 10.1007/s42000-024-00553-y. Online ahead of print.

ABSTRACT

PURPOSE: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue.

METHODS: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results.

RESULTS: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: β = 0.063, P = 0.034), the genus Butyrivibrio (IVW: β = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: β=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: β=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: β=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: β = 0.235, P = 0.03) and the order Clostridiales (IVW: β = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: β = 0.953, P = 0.022) and the order Lactobacillales (IVW: β=-0.806, P = 0.042) were suggestive of an association with PAI-1.

CONCLUSION: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

PMID:38564143 | DOI:10.1007/s42000-024-00553-y

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Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials

Curr Atheroscler Rep. 2024 Apr 2. doi: 10.1007/s11883-024-01197-4. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.

RECENT FINDINGS: The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: – 0.258; 95% CI: – 0.398, – 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.

PMID:38564140 | DOI:10.1007/s11883-024-01197-4

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Material flow analysis and statistical entropy evaluation of plastic packaging for express delivery in China

Environ Sci Pollut Res Int. 2024 Apr 2. doi: 10.1007/s11356-024-33120-4. Online ahead of print.

ABSTRACT

Encouraging the recycling of plastic packaging materials in express delivery is a necessary step toward environmentally friendly industrial development. In this study, we present a framework for analyzing the flow of materials in express plastic packaging, from production and manufacturing to consumption and recycling. In examining the use of recycled materials in post-consumer express plastic packaging and the destination of consumer packaging waste in 2020 and 2021, we found that 44.4% (1613.6 Gg) of the studied express plastic packaging was incinerated. Additionally, approximately 1296.6 Gg of express plastic packaging flowed into rural areas. Our calculations showed that the ΔRSE in 2020 was 15.1%, and on the condition that 25% separated collection with 80% recycling, ΔRSE would be – 0.5%. Results verified that separated collection is an important step in the recycling strategy for packaging materials. Survey data from universities in Beijing indicate that currently, 26% of college students are participating in the separate collection of packaging.

PMID:38564128 | DOI:10.1007/s11356-024-33120-4

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Laparoscopic Versus Open Gastrectomy for Advanced Gastric Cancer: A Meta-Analysis of Randomized Controlled Trials

J Gastrointest Cancer. 2024 Apr 2. doi: 10.1007/s12029-024-01048-0. Online ahead of print.

ABSTRACT

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a well-established surgical technique in treating patients with early gastric cancer. However, the efficacy and safety of LAG versus open gastrectomy (OG) in patients with advanced gastric cancer (AGC) remains unclear.

METHODS: We systematically searched PubMed, Embase, and Cochrane Library in June 2023 for RCTs comparing LAG versus OG in patients with AGC. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous endpoints, respectively. We performed all statistical analyses using R software version 4.3.1 and a random-effects model.

RESULTS: Nine RCTs comprising 3827 patients were included. There were no differences in terms of intraoperative complications (RR 1.14; 95% CI 0.72 to 1.82), number of retrieved lymph nodes (MD -0.54 lymph nodes; 95% CI -1.18 to 0.09), or mortality (RR 0.91; 95% CI 0.30 to 2.83). LAG was associated with a longer operative time (MD 49.28 minutes; 95% CI 30.88 to 67.69), lower intraoperative blood loss (MD -51.24 milliliters; 95% CI -81.41 to -21.06), shorter length of stay (MD -0.83 days; 95% CI -1.60 to -0.06), and higher incidence of pancreatic fistula (RR 2.44; 95% CI 1.08 to 5.50). Postoperatively, LAG was also superior to OG in reducing bleeding rates (RR 0.44; 95% CI 0.22 to 0.86) and time to first flatus (MD -0.27 days; 95% CI -0.47 to -0.07), with comparable results in anastomotic leakage, wound healing issues, major complications, time to ambulation, or time to first liquid intake. In the long-term analyses at 3 and 5 years, there were no significant differences between LAG and OG in terms of overall survival (RR 0.99; 95% CI 0.96 to 1.03) or relapse-free survival (RR 0.99; 95% CI 0.94 to 1.04).

CONCLUSION: This meta-analysis of RCTs suggests that LAG may be an effective and safe alternative to OG for treating AGC; albeit, it may be associated with an increased risk for pancreatic fistula.

PMID:38564116 | DOI:10.1007/s12029-024-01048-0

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Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial

Int J Clin Oncol. 2024 Apr 2. doi: 10.1007/s10147-024-02489-0. Online ahead of print.

ABSTRACT

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients.

METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation.

RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed.

CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients.

TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

PMID:38564107 | DOI:10.1007/s10147-024-02489-0