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BMC Nephrology May 2024Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD.... (Comparative Study)
Comparative Study
BACKGROUND
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
METHODS
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
RESULTS
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
CONCLUSIONS
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
Topics: Humans; Female; Citrulline; Male; Protein Carbamylation; Biomarkers; Middle Aged; Renal Insufficiency, Chronic; Aged; Prospective Studies; Risk Assessment; Kidney Failure, Chronic; Prognosis; Proportional Hazards Models; Serum Albumin
PubMed: 38816682
DOI: 10.1186/s12882-024-03619-6 -
Journal For Immunotherapy of Cancer May 2024Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed....
BACKGROUND
Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined.
METHODS
We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared.
RESULTS
Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p<0.01) and completeness (3.83 vs 3.46, p<0.01). Scores of 1-2 (completely or mostly inaccurate or incomplete) were particularly rare for ChatGPT (6/800 answer-ratings, 0.75%). Of the 50 questions, all eight physician raters gave ChatGPT a rating of 4 (fully accurate or complete) for 22 questions (for accuracy) and 16 questions (for completeness). In the 20 patient scenarios, the average accuracy score was 3.725 (median 4) and the average completeness was 3.61 (median 4).
CONCLUSIONS
AI chatbots provided largely accurate and complete information regarding irAEs, and wildly inaccurate information ("hallucinations") was uncommon. However, until accuracy and completeness increases further, appropriate guidelines remain the gold standard to follow.
Topics: Humans; Artificial Intelligence; Immunotherapy; Neoplasms; Drug-Related Side Effects and Adverse Reactions
PubMed: 38816231
DOI: 10.1136/jitc-2023-008599 -
The Journal of Pharmacology and... May 2024Haloperidol decanoate (HD) was implicated in cognitive impairment. Agomelatine (AGO) was claimed to improve cognition. We aimed at investigating the effects of HD + low-...
High- Dose Agomelatine Combined to Haloperidol Decanoate Improves Cognition, Downregulating , Against Upregulating , Maintaining , Though Alters Cardiac Electrophysiology.
Haloperidol decanoate (HD) was implicated in cognitive impairment. Agomelatine (AGO) was claimed to improve cognition. We aimed at investigating the effects of HD + low- or high- dose AGO on cognition, verifying the melatonergic/dopaminergic-to-the cholinergic hypothesis of cognition and exploring relevant cardiovascular issues in adult male albino rats. HD + high- dose AGO prolonged the step through latency increased the time spent in bright light , reduced the time spent in dim light , and increased the percent of alternations despite the reductions in brain acetylcholine level by -10.67%, Neurodegeneration was minimal, while the mean power frequency of source wave was reduced by -23.39% Concurrently, the relative expression of brain melatonin type-2 receptors was reduced by , against increased expressions of dopamine type- 5 receptors ) and angiopoietin-like 4 ( ). Meanwhile, ECG demonstrated inverted P wave and reduced P wave duration by and PR interval , prolonged RR interval by , increased R wave amplitude by , a depressed ST segment and inverted T wave. In rats administered AGO, HD, or HD+ low- dose AGO, Alzheimer's disease-like neuropathologic features were more evident, accompanied by extensive ECG and neurochemical alterations. HD + high- dose AGO enhances cognition but alters cardiac electrophysiology. Given the issue of cognitive impairment associated with haloperidol decanoate (HD) and the claimed cognitive enhancing activity of agomelatine (AGO), combined high- dose AGO to HD improved cognition of adult male rats, and exhibited minimal neurodegenerative changes. HD+ high- dose AGO was relatively safe regarding triggering epileptogenesis, while altered cardiac electrophysiology. In presence of low ACh, the melatonergic/dopaminergic hypothesis, added to ANGPTL4 and KLF9, could have some clue, thus, offering novel targets for pharmacologic manipulation of cognition.
PubMed: 38816228
DOI: 10.1124/jpet.123.002087 -
BMJ Open Diabetes Research & Care May 2024We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus...
INTRODUCTION
We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.
RESEARCH DESIGN AND METHODS
Using the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.
RESULTS
At baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was -0.80 mL/min/1.73 m/year (95% CI -1.05 to -0.54) among SGLT2 inhibitors group and -1.78 mL/min/1.73 m/year (95% CI -2.08 to -1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.
CONCLUSIONS
The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Female; Male; Aged; Japan; Glomerular Filtration Rate; Diabetic Nephropathies; Databases, Factual; Renal Insufficiency, Chronic; Aged, 80 and over; Diabetes Mellitus, Type 2; Follow-Up Studies; Disease Progression; Hypoglycemic Agents; Prognosis; Treatment Outcome
PubMed: 38816204
DOI: 10.1136/bmjdrc-2024-004115 -
BMJ Open May 2024To evaluate co-prescribing of sedatives hypnotics and opioids.
OBJECTIVE
To evaluate co-prescribing of sedatives hypnotics and opioids.
DESIGN
Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing.
SETTING AND PARTICIPANTS
Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA.
OUTCOME MEASURES
Coprescription of sedative-hypnotics and opioids.
RESULTS
A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date.
CONCLUSIONS
Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.
Topics: Humans; Hypnotics and Sedatives; Female; Male; Analgesics, Opioid; Retrospective Studies; Adult; Middle Aged; United States; Practice Patterns, Physicians'; Drug Prescriptions; Comorbidity; Benzodiazepines; Logistic Models
PubMed: 38816043
DOI: 10.1136/bmjopen-2023-082339 -
Developmental Cognitive Neuroscience May 2024As adolescents acquire agency and become contributing members of society, it is necessary to understand how they help their community. Yet, it is unknown how prosocial...
As adolescents acquire agency and become contributing members of society, it is necessary to understand how they help their community. Yet, it is unknown how prosocial behavior develops in the context of community-based prosocial behaviors that are relevant to adolescents, such as donating time to charities. In this longitudinal functional magnetic resonance imaging study, adolescents (N=172; mean age at wave 1=12.8) completed a prosocial task annually for three years (N=422 and 375 total behavioral and neural data points, respectively), and 14 days of daily diaries reporting on their prosocial behaviors two years later. During the task, adolescents decided how many minutes they would donate to a variety of local charities. We found that adolescents donated less time to charities from early to mid adolescence. Longitudinal whole-brain analyses revealed declines in ventrolateral prefrontal cortex (vlPFC) activation, as well as inverted U-shaped changes in precuneus activation when adolescents donated their time from early to mid adolescence. A less steep decrease in vlPFC activation predicted greater real-life prosocial behaviors in youth's daily lives two years later. Our study elucidates the neurodevelopmental mechanisms of prosocial behavior from early to mid adolescence that have enduring effects on daily prosocial behaviors in late adolescence.
PubMed: 38815469
DOI: 10.1016/j.dcn.2024.101394 -
JMIR Human Factors May 2024Studies evaluating the usability of mobile-phone assessments in older adults are limited.
BACKGROUND
Studies evaluating the usability of mobile-phone assessments in older adults are limited.
OBJECTIVE
This study aims to identify design-based barriers and facilitators to mobile app survey completion among 2 samples of older adults; those in the Framingham Heart Study and a more diverse sample from a hospital-based setting.
METHODS
We used mixed methods to identify challenging and beneficial features of the mobile app in participants from the electronic Framingham Heart Study (n=15; mean age of 72 years; 6/15, 40% women; 15/15, 100% non-Hispanic and White) and among participants recruited from a hospital-based setting (n=15; mean age of 71 years; 7/15, 47% women; 3/15, 20% Hispanic; and 8/15, 53% non-White). A variety of app-based measures with different response formats were tested, including self-reported surveys, pictorial assessments (to indicate body pain sites), and cognitive testing tasks (eg, Trail Making Test and Stroop). Participants completed each measure using a think-aloud protocol, while being audio- and video-recorded with a qualitative interview conducted at the end of the session. Recordings were coded for participant usability errors by 2 pairs of coders. Participants completed the Mobile App Rating Scale to assess the app (response range 1=inadequate to 5=excellent).
RESULTS
In electronic Framingham Heart Study participants, the average total Mobile App Rating Scale score was 7.6 (SD 1.1), with no significant differences in the hospital-based sample. In general, participants were pleased with the app and found it easy to use. A large minority had at least 1 navigational issue, most committed only once. Most older adults did not have difficulty completing the self-reported multiple-choice measures unless it included lengthy instructions but participants had usability issues with the Stroop and Trail Making Test.
CONCLUSIONS
Our methods and results help guide app development and app-based survey construction for older adults, while also giving consideration to sociodemographic differences.
Topics: Humans; Mobile Applications; Aged; Female; Male; Smartphone; Surveys and Questionnaires; Aged, 80 and over
PubMed: 38815261
DOI: 10.2196/56653 -
The Oncologist May 2024In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and...
BACKGROUND
In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported.
MATERIALS AND METHODS
Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ-Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated.
RESULTS
The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, -5.54; 95% CI, -10.93 to -0.16) and pain (LSM difference, -2.94; 95% CI, -5.86 to -0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95).
CONCLUSION
The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer.
CLINICALTRIALS.GOV ID
NCT03189719.
PubMed: 38815152
DOI: 10.1093/oncolo/oyae087 -
PloS One 2024The aim of this study was to investigate the mediating effects of health literacy on the relationship between frailty and health-related quality of life (HRQOL) among...
PURPOSE
The aim of this study was to investigate the mediating effects of health literacy on the relationship between frailty and health-related quality of life (HRQOL) among community-dwelling older adults.
METHODS
This study used the Korean Frailty and Aging Cohort Database (KFACD) for secondary data analysis. We selected data from 1,631 people without missing main variable values for analysis. Frailty was determined based on the modified Fried's phenotype [MFP], and HRQOL was measured using the Korean version of the 5-level EuroQol questionnaire (EQ-5D-5L). Health literacy was assessed using the questions on the Behavioral Risk Factor Surveillance System (BRFSS) used by the U.S. Center for Disease Control and Prevention. To examine the mediating role of health literacy in the relationship between frailty and HRQOL, Baron & Kenny's three-step mediating effect verification method was utilized.
RESULTS
The participants had a mean frailty score of 1.37±1.02, health literacy score of 8.56±2.59, and HRQOL score of 0.84±0.10. Frailty was negatively correlated with health literacy (r = -0.27, p < .001) and HRQOL (r = -0.32, p < .001), while health literacy was positively correlated with HRQOL (r = 0.34, p < .001). We observed that health literacy played a partial mediating role in the relationship between frailty and HRQOL.
CONCLUSION
To increase older adults' HRQOL, measures that directly prevent and manage frailty as well as interventions that target the enhancement of health literacy are needed.
Topics: Humans; Quality of Life; Aged; Male; Female; Health Literacy; Independent Living; Frailty; Aged, 80 and over; Republic of Korea; Frail Elderly; Surveys and Questionnaires
PubMed: 38814978
DOI: 10.1371/journal.pone.0303164 -
PloS One 2024Clinicians commonly use manual therapy to treat low back pain by palpating the spine to identify the spinous processes. This study aims to evaluate the ability of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Clinicians commonly use manual therapy to treat low back pain by palpating the spine to identify the spinous processes. This study aims to evaluate the ability of experienced clinicians to consistently locate the spinous processes from S1 to T12 through palpation. The results will be compared to topographical data representing the lumbar lordosis at baseline and four follow-up time points.
MATERIALS AND METHODS
In a prior prospective randomized trial, experienced clinicians used palpation to locate the lumbar spinous processes (S1-T12) and then digitized these locations in three-dimensional space. The same digitizing equipment was then used to continuously collect three-dimensional position data of a wheel that rolled along the back's surface through a trajectory that connected the previously digitized locations of the spinous processes. This process was repeated at 4 days, 1, 4, and 12 weeks. The resulting lordosis trajectories were plotted and aligned using the most anterior point in the lordosis to compare the locations of the spinous processes identified in different trials. This way, spinous palpation points could be compared to surface topography over time. Intra- and interrater reliability and agreement were estimated using intraclass correlations of agreement and Bland-Altman limits of agreement.
RESULTS
Five clinicians palpated a total of 119 participants. The results showed a large degree of variation in precision estimates, with a mean total value of 13 mm (95%CI = 11;15). This precision error was consistent across all time points. The smallest precision error was found at L5, followed by S1 File, after which the error increased superiorly. Intra- and interrater reliability was poor to moderate.
CONCLUSIONS
Comparison of palpation results to a topographic standard representing the lumbar lordosis is a new approach for evaluating palpation. Our results confirm the results of prior studies that find palpation of lumbar spinous processes imprecise, even for experienced clinicians.
Topics: Humans; Palpation; Lumbar Vertebrae; Female; Male; Lordosis; Adult; Low Back Pain; Prospective Studies; Middle Aged
PubMed: 38814967
DOI: 10.1371/journal.pone.0304571