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Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial
No full textIMPORTANCE: Type 2 diabetes (T2D) is a risk factor for cognitive impairment. Whether the choice of the second-line glucose-lowering treatment added to metformin or glycemic control affects cognitive performance in T2D of relatively short duration (\u3c10 years) is not known. OBJECTIVE: To compare the relative effect of 4 classes of glucose-lowering medications that were randomly added to metformin on cognitive performance and to examine the association of longitudinal glycemic levels with cognitive performance. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial (the GRADE study) was conducted at 36 clinical centers in the US and included 3721 participants with T2D with baseline and follow-up cognitive performance data. GRADE was implemented 2013 to 2021, and data for this study were analyzed from February 2024 to February 2025. INTERVENTIONS: For the primary objective, the exposure was randomization of metformin-treated participants to receive long-acting insulin (insulin glargine U-100), sulfonylurea (glimepiride), glucagon-like peptide-1 receptor agonist (liraglutide), or dipeptidyl peptidase-4 inhibitor (sitagliptin). The secondary objective assessed time-weighted hemoglobin A1c levels over the follow-up period. MAIN OUTCOMES AND MEASURES: The primary cognitive outcome was the Digit Symbol Substitution Test score; the secondary cognitive outcomes were the immediate and delayed recall in the Spanish English Verbal Learning Test and letter and category fluency test scores. RESULTS: At baseline, the mean (SD) duration of T2D was 4.3 (2.7) years, and the mean (SD) age was 57.1 (9.8) years. Most participants were male (2320 [62.3%]; 1401 female individuals [37.7%]) and non-Hispanic (3015 [81.6%]; 681 Hispanic individuals [18.4%]); 712 (19.1%) were Black and 2452 (65.9%) were White; 777 (20.9%) were recruited from Veterans Affairs medical centers. There were no statistically significant differences between treatment groups in the cognitive outcomes at follow-up. However, a 1-unit increase in time-weighted hemoglobin A1c levels was associated with modestly lower Digit Symbol Substitution Test scores (-0.94 points; 95% CI, -1.30 to -0.57), Spanish English Verbal Learning Test scores (immediate recall, -0.27 points; 95% CI, -0.49 to -0.06), and category fluency test scores (animal fluency, -0.28 points; 95% CI, -0.47 to -0.09) over the mean (SD) of 4.1 (0.1) years of follow-up. Severe hypoglycemia requiring assistance was uncommon in all 4 groups (34 participants [0.9%]). CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial suggest that choice of second-line glucose-lowering medication class added to metformin is not associated with change in cognitive performance in persons with early T2D. Worse glycemic control is associated with modestly worse cognitive performance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01794143
\u27How are we going to harm the next trauma patient?\u27 Trauma care providers\u27 perspective on potential harm to trauma patients
No full textBACKGROUND: The question, How will the next patient be harmed? is a component of strategies used to identify latent safety risks in healthcare. We sought to survey a broad audience attending the 2023 annual conference of the American College of Surgeons-Trauma Quality Improvement Program to record their perception of the risks that might lead to patient harm at their own trauma centers. METHODS: Attendees were surveyed with a single free-text question How are we going to harm the next patient? using a quick response code. All responses were categorized into clustered themes. To report the results using a standardized reporting taxonomy, the responses were also classified according to the Joint Commission (JC) patient safety event taxonomy for near misses and adverse events. Results were reported as counts and as proportions of responders. RESULTS: During the 3-day duration of the conference, 64 participants provided 80 responses. Provider-related risk (n=16, 25.0%) was the most commonly reported category, followed closely by practice management guideline related (n=14, 21.9%) and communication gaps or failures (n=12, 18.8%). Clinical performance was the most commonly reported subclassification in the main category type of the JC patient safety event taxonomy (n=34, 53.1%), followed by patient management (n=30, 46.9%). Human error was the most common subclassification in the main category cause (n=48, 75.0%). CONCLUSIONS: Human failures, rather than systems issues, were perceived to be responsible for the majority of potential harm in trauma patients by a broad audience of trauma care providers. These results require amplified focus on strategies that decrease the impact of the human element while enhancing process standardization and addressing barriers to the implementation of processes and guidelines. It might also suggest an opportunity to bring forward alternative conceptual frameworks to advance safety in trauma care
Screening for Syphilis Infection During Pregnancy: US Preventive Services Task Force Reaffirmation Recommendation Statement
No full textIMPORTANCE: Untreated syphilis infection during pregnancy can be passed to the fetus, causing congenital syphilis. Congenital syphilis is associated with premature birth, low birth weight, stillbirth, neonatal death, and significant abnormalities in the infant such as deformed bones, anemia, enlarged liver and spleen, jaundice, brain and nerve problems (eg, permanent vision or hearing loss), and meningitis. In 2023, there were 3882 cases of congenital syphilis in the US, including 279 congenital syphilis-related stillbirths and neonatal/infant deaths, the highest number reported in more than 30 years. OBJECTIVE: The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focused on the benefits and harms of screening for syphilis infection in pregnancy. POPULATION: Adolescents and adults who are pregnant. EVIDENCE ASSESSMENT: The USPSTF concludes with high certainty that screening for syphilis infection in pregnancy has a substantial net benefit. RECOMMENDATION: The USPSTF recommends early, universal screening for syphilis infection during pregnancy; if an individual is not screened early in pregnancy, the USPSTF recommends screening at the first available opportunity. (A recommendation)
Prolonged Hospitalization and Adverse Events in Veterans Awaiting Guardianship: A Retrospective Cohort Analysis
No full textBACKGROUND: Hospitalized adults who are deemed to lack both capacity for medical decision-making and an appropriate surrogate often have prolonged hospital stays while awaiting a guardian. OBJECTIVE: To characterize the inpatient management, adverse hospital events, and outcomes of patients hospitalized while pending guardianship in the Veterans Affairs (VA) system. DESIGN: Retrospective cohort analysis completed via chart review and standardized data abstraction. PARTICIPANTS: Veterans admitted to an inpatient medicine service with a guardianship application pending at any point during hospitalization and discharged between Jan 2020 and Dec 2021 at 14 VA hospitals across the USA. MAIN MEASURES: We analyzed patient demographics, length of stay, capacity assessment, inpatient medication management, adverse events, guardianship attainment, disposition, readmission, and mortality rates of medicine patients hospitalized while pending guardianship. KEY RESULTS: One hundred seventy Veterans hospitalized while awaiting guardianship were included. The median length of stay was 38.5 days and 60% (n = 102) of patients were admitted for placement or a mix of placement plus medical/surgical reasons. Forty-five percent (n = 77) of patients experienced at least one of the following: involuntary hold, behavioral code, elopement attempt, or use of restraints; and 28% (n = 47) of patients experienced at least one hospital acquired infection or fall. Three percent (n = 5) of patients died, one related to an adverse hospital event. At the endpoint of the study, 72% (122/170) of patients obtained guardianship. CONCLUSIONS: At VA hospitals, medicine patients awaiting guardianship have prolonged length of stay and a significant number are admitted for placement reasons. Patients experienced high rates of hospital-acquired adverse events as well as anti-wandering and behavioral interventions such as restraints or medical holds. Most patients ultimately achieved guardianship. These findings have implications for policy makers and health care systems to address guardianship processes and mitigate effects of prolonged and sometimes unnecessary hospitalizations in this vulnerable population
DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features
No full textThe genetic subtypes of Burkitt Lymphoma (BL) have been defined, whereas the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents, for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by EBV status or mutation status, leading to two epitypes, described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression and mutational differences between the epitypes support a model in which each arises from a distinct cell-of-origin. These results, pending validation in external cohorts, point to a refined risk assessment for BL patients who may experience inferior outcomes
Biological sex and age influence GS-9620 activity ex vivo
No full textToll-like receptors (TLRs) are being explored to enhance immunity in HIV cure strategies. The TLR7 agonist GS-9620 promotes immune activation, reactivates latent HIV, and delays viral rebound in some people with HIV. Previous work has shown that biological sex influences TLR7 signaling. This study examined the interplay between biological sex, age, and the sex hormones 17β-estradiol, progesterone, and testosterone on GS-9620\u27s ability to promote cytokine secretion and activate CD4, CD8, and NK cells ex vivo. Interestingly, sex hormones had no effect on GS-9620-mediated immune activation or cytokine induction. However, we found that GS-9620 activity was influenced by age only in female donors. Further, we found that GS-9620-mediated CD4 T cell activation was positively correlated with the induction of IFN-γ and IL-12, while CD4 T cell activation and IL-12 production were negatively correlated with age. Additionally, CD8 T cell activation was positively correlated with IFN-γ production. Mechanistically, IFN-γ was sufficient to promote higher immune activation of both CD4 and CD8 T cells in female versus male donors. In conclusion, biological sex and age, but not sex hormones, influence GS-9620-mediated immune activation. Understanding these factors will help design and evaluate future clinical trials using GS-9620 for an HIV cure
ACR Appropriateness Criteria® Suspected and Known Heart Failure: 2024 Update
No full textHeart failure (HF) is a prevalent and complex clinical syndrome with no single reference standard diagnostic test. Imaging has a supportive role in patients with suspected and known HF, including initial imaging assessment of an adult with suspected HF, but without history of HF, including evaluation of pulmonary edema and detection of left ventricular dysfunction (Variant 1). In adults with established diagnosis of HF but unknown etiology, imaging also has an important role in the assessment of the underlying disease process, including ischemic and nonischemic etiologies (Variant 2). In the course of continuing care for adult patients with an established diagnosis of HF without new symptoms, follow-up imaging is performed to assess for longitudinal changes in ventricular function, response to therapy and prognostication (Variant 3). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation
ACR Appropriateness Criteria® Cervical Pain or Cervical Radiculopathy: 2024 Update
No full textCervical spine pain is one of the most common reasons for seeking medical care as it ranks in the top 5 causes of global years lost to disability. The economic burden of cervical pain is also significant. Imaging is at the center of diagnosis of cervical pain and its causes. However, different symptoms and potential causes of cervical pain require different initial imaging to maximize the benefit of diagnostic usefulness of imaging. In this document we address different cervical pain variants with detailed assessment of the strengths and weaknesses of different modalities for addressing each specific variant. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation
Local versus general anesthesia in initial open inguinal hernia repair with prolonged operative time: A propensity-score matched study from the ACS-NSQIP database
No full textSeizures May Worsen Outcomes of Neonatal Hypoxic-Ischemic Encephalopathy: A Longitudinal Serum Biomarkers Study
No full textBACKGROUND: Understanding if neonatal seizures (Sz) worsen brain injury and outcomes would optimize treatment decisions. We hypothesized that serum central nervous system-specific biomarkers would discriminate neonates with Sz and relate to outcomes. METHODS: This is a retrospective cohort study (April 2009 to November 2019), including neonates in three groups: (1) only Sz without HIE (Sz-no HIE), (2) HIE with Sz (Sz-HIE), and (3) HIE without Sz (no Sz-HIE). Levels of glial fibrillary acidic protein (GFAP, astrocytic reactivity), Tau (neuronal injury), and neurofilament light chain (NF-L, axonal degeneration) were studied at admission/\u3c6 h, \u3c72 h, and 72-144 h of life against time to achieve full oral feeds and NICHD-NRN MRI score. RESULTS: In 145 neonates included (61% male; 33% black), admission GFAP levels were higher in Sz-HIE than in no Sz-HIE. During the first 72 hours of life, GFAP, Tau, and NF-L levels were similar between Sz-no HIE and Sz-HIE but higher than in no Sz-HIE. After 72 hours, NF-L and Tau remained higher in both Sz groups (versus no Sz-HIE). In adjusted regression models, higher Tau and NF-L percentiles related to longer time to reach full oral feeding and higher odds of more than minimal brain injury in MRI in Sz-HIE. CONCLUSIONS: Tau and NF-L levels are higher in those neonates developing Sz. Although relationships with worse brain injury may be driven by the HIE severity itself, modeling shows Sz as the most important feature, providing support to the notion that Sz may worsen brain injury in neonates with HIE even after TH