Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis.

BACKGROUND: Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. METHODS: We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. DISCUSSION: This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023402365.

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T.

AIMS: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. METHODS AND RESULTS: Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88). CONCLUSION: Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Consistent time allocation fraction to vegetation green-up versus senescence across northern ecosystems despite recent climate change.

Extended growing season lengths under climatic warming suggest increased time for plant growth. However, research has focused on climatic impacts to the timing or duration of distinct phenological events. Comparatively little is known about impacts to the relative time allocation to distinct phenological events, for example, the proportion of time dedicated to leaf growth versus senescence. We use multiple satellite and ground-based observations to show that, despite recent climate change during 2001 to 2020, the ratio of time allocated to vegetation green-up over senescence has remained stable [1.27 (± 0.92)] across more than 83% of northern ecosystems. This stability is independent of changes in growing season lengths and is caused by widespread positive relationships among vegetation phenological events; longer vegetation green-up results in longer vegetation senescence. These empirical observations were also partly reproduced by 13 dynamic global vegetation models. Our work demonstrates an intrinsic biotic control to vegetation phenology that could explain the timing of vegetation senescence under climate change.

Patient characteristics associated with acute kidney injury following coronary angiography.

Objective: The objective of this study was to identify patient characteristics associated with acute kidney injury (AKI) post-coronary angiography with or without percutaneous coronary intervention. Methods: This retrospective, single-center study analyzed 350 patients from October 1, 2017 to September 30, 2018. The primary endpoint was AKI, defined as a rise in creatinine >0.3 mg/dL within 48 hours of coronary angiography. Results: AKI occurred in 41 of 350 patients (8.8%). Patients experiencing AKI had a higher incidence of hypertension (100%; P = 0.005), hyperlipidemia (98%; P = 0.001), diabetes mellitus (68%; P = 0.0005), and heart failure (37%; P = 0.0057). AKI occurred in 30 of 185 (16%) and 11 of 165 (6.7%) patients undergoing femoral and radial access, respectively. AKI incidence was not significantly affected by contrast dose (99 ± 9 vs 93 ± 3 mL; P = 0.52), fluoroscopy time (10.3 min [IQR 6.3, 17.7] vs 8.5 min [IQR 4.5, 13.9]; P = 0.2), or preprocedural computed tomography with contrast (P = 0.66). Multivariable regression showed significantly higher AKI among patients with peripheral artery disease (odds ratio [OR] = 12.4; 95% confidence interval [CI] 3.4-33.6; P = 0.0001), multivessel coronary artery disease (OR = 11.9; 95% CI 2.3-61.1; P = 0.003), and initial creatinine >1.5 mg/dL (OR = 4.4; 95% CI 1.4-13.6; P = 0.01). Conclusion: Peripheral artery disease, multivessel disease, and creatinine >1.5 mg/dL were associated with a higher risk of AKI in patients undergoing coronary angiography in this single-center retrospective cohort.

High Baseline High-Sensitivity Cardiac Troponin T Concentrations and Risk of Index Acute Myocardial Infarction.

OBJECTIVE: To evaluate the diagnostic performance of the previously recommended baseline high-sensitivity cardiac troponin T (hs-cTnT) thresholds of 52 and 100 ng/L in identifying patients at high risk of acute myocardial infarction (AMI). PATIENTS AND METHODS: This study compared the positive predictive value (PPV) for index AMI of these high-risk hs-cTnT thresholds in adult patients in the emergency department undergoing hs-cTnT measurement. RESULTS: The adjudicated MAyo Southwest Wisconsin 5th Gen Troponin T ImplementatiON cohort included 2053 patients, with 157 (7.6%) who received a diagnosis of AMI. The hs-cTnT concentrations of greater than 52 and greater than 100 ng/L resulted in PPVs of 41% (95% CI, 35%-48%) and 57% (95% CI, 48%-66%). In patients with chest discomfort, hs-cTnT concentrations greater than 52 ng/L resulted in a PPV of 66% (95% CI, 56%-76%) and hs-cTnT concentrations greater than 100 ng/L resulted in a PPV of 77% (95% CI, 65%-87%). The CV Data Mart Biomarker cohort included 143,709 patients, and 3003 (2.1%) received a diagnosis of AMI. Baseline hs-cTnT concentrations greater than 52 and greater than 100 ng/L resulted in PPVs of 12% (95% CI, 11%-12%) and 17% (95% CI, 17%-19%), respectively. In patients with chest pain and hs-cTnT concentrations greater than 52 ng/L, the PPV for MI was 17% (95% CI, 15%-18%) and in those with concentrations greater than 100 ng/L, only 22% (95% CI, 19%-25%). CONCLUSION: In unselected patients undergoing hs-cTnT measurement, the hs-cTnT thresholds of greater than 52 and greater than 100 ng/L provide suboptimal performance for identifying high-risk patients. In patients with chest discomfort, an hs-cTnT concentration of greater than 100 ng/L, but not the European Society of Cardiology-recommended threshold of greater than 52 ng/L, provides an acceptable performance but should be used only with other clinical features.

Limited impact of weathered residues from the Deepwater Horizon oil spill on the gut-microbiome and foraging behavior of sheepshead minnows (Cyprinodon variegatus).

The Deepwater Horizon disaster of April 2010 was the largest oil spill in U.S. history and exerted catastrophic effects on several ecologically important fish species in the Gulf of Mexico (GoM). Within fish, the microbiome plays a key symbiotic role in maintaining host health and aids in acquiring nutrients, supporting immune function, and modulating behavior. The aim of this study was to examine if exposure to weathered oil might produce significant shifts in fish gut-associated microbial communities as determined from taxa and genes known for hydrocarbon degradation, and whether foraging behavior was affected. The gut microbiome (16S rRNA and shotgun metagenomics) of sheepshead minnow (Cyprinodon variegatus) was characterized after fish were exposed to oil in High Energy Water Accommodated Fractions (HEWAF; tPAH = 81.1 ± 12.4 µg/L) for 7 days. A foraging behavioral assay was used to determine feeding efficiency before and after oil exposure. The fish gut microbiome was not significantly altered in alpha or beta diversity. None of the most abundant taxa produced any significant shifts as a result of oil exposure, with only rare taxa showing significant shifts in abundance between treatments. However, several bioindicator taxa known for hydrocarbon degradation were detected in the oil treatment, primarily Sphingomonas and Acinetobacter. Notably, the genus Stenotrophomonas was detected in high abundance in 16S data, which previously was not described as a core member of fish gut microbiomes. Data also demonstrated that behavior was not significantly affected by oil exposure. Potential low bioavailability of the oil may have been a factor in our observation of minor shifts in taxa and no behavioral effects. This study lays a foundation for understanding the microbiome of captive sheepshead minnows and indicates the need for further research to elucidate the responses of the fish gut-microbiome under oil spill conditions.

Prophylactic Intravenous Aminophylline for Preventing Bradyarrhythmias During Coronary Atherectomy: A 10-Year Single-Center Experience.

Background: Aminophylline, an adenosine antagonist, can be used to prevent adenosine-mediated bradyarrhythmias. Methods: Retrospective, observational, descriptive analysis of patients undergoing rotational atherectomy with intravenous (IV) aminophylline pretreatment during a 10-year period (2010-2020). The primary composite outcome was the occurrence of a documented bradyarrhythmia requiring pharmacologic intervention and/or temporary pacemaker (TPM) implantation. Results: A total of 296 patients received IV aminophylline pretreatment. The primary composite outcome occurred in 1.7% (n = 5) of patients. None of the patients required rescue TPM. Bradyarrhythmias were documented in 2.4% (n = 7) of patients. Pharmacologic interventions, typically with IV atropine, were used in 15% (n = 43) of patients. Per-vessel analyses demonstrated that patients undergoing atherectomy to the circumflex and right coronary arteries were more likely than those undergoing atherectomy to other vessels to have bradyarrhythmias requiring pharmacologic intervention (3.4% vs 0%, P = .01). Conclusions: In this 10-year single-center experience using IV aminophylline pretreatment to prevent major bradyarrhythmias in patients undergoing coronary atherectomy, none of the patients required rescue TPM implantation. These data demonstrate that coronary atherectomy can be performed safely without prophylactic TPM, with aminophylline pretreatment and selective use of atropine representing an effective noninvasive approach.