Visibility graph-based covariance functions for scalable spatial analysis in non-convex partially Euclidean domains.

We present a new method for constructing valid covariance functions of Gaussian processes for spatial analysis in irregular, non-convex domains such as bodies of water. Standard covariance functions based on geodesic distances are not guaranteed to be positive definite on such domains, while existing non-Euclidean approaches fail to respect the partially Euclidean nature of these domains where the geodesic distance agrees with the Euclidean distances for some pairs of points. Using a visibility graph on the domain, we propose a class of covariance functions that preserve Euclidean-based covariances between points that are connected in the domain while incorporating the non-convex geometry of the domain via conditional independence relationships. We show that the proposed method preserves the partially Euclidean nature of the intrinsic geometry on the domain while maintaining validity (positive definiteness) and marginal stationarity of the covariance function over the entire parameter space, properties which are not always fulfilled by existing approaches to construct covariance functions on non-convex domains. We provide useful approximations to improve computational efficiency, resulting in a scalable algorithm. We compare the performance of our method with those of competing state-of-the-art methods using simulation studies on synthetic non-convex domains. The method is applied to data regarding acidity levels in the Chesapeake Bay, showing its potential for ecological monitoring in real-world spatial applications on irregular domains.

The evolution of evidence-based medicine.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

EDucated: The emergency medicine pharmacotherapy literature of 2023.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2023. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the collective group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 6 guidelines, and 5 meta-analyses covering topics including guideline releases and updates on rapid sequence intubation in the critically ill, managing cardiac arrest or life-threatening toxicity due to poisoning, and management of major bleeding following trauma. Also discussed are ongoing controversies surrounding fluid resuscitation, time and treatment modalities for ischemic stroke, steroid use in community-acquired pneumonia, targeted blood product administration, and much more.

Pilot Study on the Impact of Early Subcutaneous Basal Insulin Administration in Diabetic Ketoacidosis.

Purpose/Background: Recent studies have shown improved outcomes with the initiation of earlier subcutaneous (SQ) basal insulin. The purpose of this study was to examine the effects of early SQ basal insulin administration on hospital length of stay in patients with mild to moderate diabetic ketoacidosis (DKA). Methods: This was a retrospective, single-center study from a large community teaching hospital that included patients 18 years or older with mild to moderate DKA, identified using ICD-10 codes, who received intravenous (IV) insulin. Patients who received SQ basal insulin prior to a documented anion gap ≤12 mmol/L were considered to have received early SQ basal insulin and were compared to patients who received SQ basal insulin after closure of their anion gap (AG). The primary outcome was hospital length of stay. Secondary outcomes included intensive care unit length of stay, duration of IV insulin, time to anion gap closure, and incidences of rebound hyperglycemia. Safety outcomes included incidences of hypoglycemia, and hypokalemia. Results: Of 301 patients screened, 108 patients were included in the final analysis. Forty patients received early SQ basal insulin and 68 did not. Median hospital length of stay in the nonearly group was 71 h, compared to 62 h in the early group (P = .57). Secondary and safety outcomes were similar between groups. Conclusions: In this study, there was no statistically significant difference in length of stay in patients that received early SQ basal insulin. Larger trials are needed to determine the significance of earlier SQ basal insulin in DKA.

Prothrombin complex concentrate administration timing in warfarin-associated intracranial hemorrhage.

INTRODUCTION: Guidelines recommend "rapid" and "urgent" reversal of anticoagulation for warfarin-associated intracranial hemorrhage (ICH) treatment; however, they do not specify goals for time-to-administration. There are limited studies evaluating time to reversal, or international normalized ratio (INR) correction, on hematoma expansion and outcomes in intervals of <4 h. The purpose of this study was to evaluate the association of 4-factor prothrombin concentrate (4F-PCC) time-to-administration on rates of achieving effective hemostasis, determined by hematoma expansion, for treatment of warfarin-associated ICH. METHODS: This was a retrospective, observational, single center study performed at a large community teaching hospital. Patients were stratified into three groups based on time of CT diagnosis of ICH to administration of 4F-PCC: <45 min, 45-90 min, and >90 min. The primary outcome was rates of achieving effective hemostasis in each group defined as a ≤20% increase in hematoma volume as estimated by a radiologist. RESULTS: A total of 227 patients were screened for inclusion with ultimately 39 being included. Baseline characteristics were similar between groups. The primary outcome was not significantly different among groups stratified by time to 4F-PCC administration of <45 min, 45-90 min, and >90 min (85.7% vs 73.3% vs 90%, p value 0.514). There was no difference among secondary outcomes between groups including in-hospital mortality, hospital length of stay (LOS), and intensive care unit LOS. CONCLUSION: There was no association with time-to-administration of 4F-PCC on rates of hemostasis achievement, defined as hematoma expansion of ≤20%, identified in this study.

The Effects of COVID-19 on General Surgery Residency Programs in the United States.

Introduction: The COVID-19 pandemic impacted multiple aspects of surgical education. This survey delineates steps taken by general surgery residency programs to meet changing patient-care needs while continuing to provide adequate education. Methods: A survey was administered to program directors and coordinators of all United States general surgery residency programs to assess the early effects of the pandemic on residents from March 1 through May 31, 2020. Results: Of 303 programs contacted, 132 (43.6%) completed the survey. Residents were asked to work in areas outside of their specialty at 27.3% of programs. Residency curriculum was changed in 35.6% of programs, and 76.5% of programs changed their academic conferences. Resident schedules were altered at a majority of programs to limit resident-patient exposure, increase ICU coverage, or improve resident utilization. Surgical caseloads decreased at 93.8% of programs; 31.8% of those programs reported concerns regarding residents' achieving the minimum case numbers required to graduate. Conclusions: These results provided insight into the restructuring of general surgery residency programs during a pandemic and may be used to establish future pandemic response plans.

Approaches to Precision-based Anticoagulation management in the critically Ill.

Anticoagulant therapy is commonly associated with a high incidence of avoidable adverse events, especially in the acute care setting. This has led to several initiatives by key national health care stakeholders, including specific attention to The Joint Commission's National Patient Safety Goals, to improve anticoagulation management. The subject of special populations has long been identified as challenging by clinicians with the use of anticoagulants. This is driven in part by numerous variables that can contribute to hard outcomes such as bleeding, thrombosis, length of stay, hospital re-admission, morbidity, and mortality. Despite the notable effort to improve the use of anticoagulants with numerous clinical trials, guidelines, guidance statements, and other sources of published evidence, notable difficulties continue to challenge practitioners in managing this class of medications. This is especially the case with very diverse critically ill populations where countless variables exist, many of which were never explored in trials or have historically been frequently excluded. Trials evaluating anticoagulation therapy often can only account for small portions of variables that may affect thrombosis and hemostasis, and study methods often do not reflect the constantly changing dynamic conditions seen in unique critically ill patients. Clinicians providing care to the numerous critically ill populations are faced with conditions that lead to relatively small therapeutic windows, which makes designing safe optimal anticoagulation management plans difficult when dealing with complex patients and mechanical support devices. The approach to crafting a successful management plan for anticoagulant therapy must incorporate the numerous variables that are continuously assessed and revised during the patient's time in the intensive care unit. We explore considerations and approaches when developing, assessing, and implementing an individualized or precision-based management plan that involves the use of anticoagulants in the critically ill. The skills and thought process provided will assist clinicians in managing this unique, variable, and challenging population.

In-vivo and human evidence for potential efficacy of therapeutic polyclonal RSV neutralizing antibodies for palivizumab-resistant RSV infections.

BACKGROUND: Monoclonal antibody (palivizumab), intravenous immune globulin (IGIV), or respiratory syncytial virus (RSV)-polyclonal-hyperimmune-globulin (RSV-IG as Respigam®, RI-001, RI-002) are used with ribavirin in RSV-infected immunocompromised patients, with debated efficacy. Palivizumab-resistance (PR) can arise during treatment of persistent infections in this population. RSV-IG may confer benefit in PR-RSV infection. METHODS: RSV-IG [RI-001] was provided for an immunocompromised infant with RSV-pneumonitis refractory to ribavirin and palivizumab. RSV-neutralizing antibody, respiratory RSV load (qPCR), and F-gene-sequence-detection of PR was determined. Prophylactic RSV-IG [RI-002] or palivizumab was administered in a cotton-rat model infected with wild-type and PR-RSV. Lung RSV load and neutralizing antibody were measured. RESULTS: As protective RI-001-neutralizing antibody titers waned in the infant, a subpopulation of PR-escape mutants were detected with a fatal RSV-burden in the lungs. In PR-RSV-infected cotton rats, prophylactic RI-002 reduced RSV-load in the lungs (2.45 vs 0.28 log10 PFU/g lung-tissue reduction, respectively, p < 0.05) and provided protective RSV-neutralizing antibody. CONCLUSIONS: RSV-IG and ribavirin use in immunocompromised patients requires further study.

What are we waiting for? A review of early basal insulin therapy in diabetic ketoacidosis management.

Diabetic ketoacidosis (DKA) remains a significant challenge for healthcare systems due to prolonged lengths of stay and rising costs. The current American Diabetes Association (ADA) guidelines recommend starting basal insulin after resolution of DKA. However, these guidelines have not been updated since 2009, which can potentially limit optimal care. Meanwhile, the Joint British Society guidelines on DKA management, which were more recently updated in March 2023, do advocate for early administration of basal insulin in their treatment algorithm. This article assesses the rationale and literature associated with the recommendation for early basal insulin administration in the management of DKA. Benefits of early basal insulin in this cohort appears to be associated with less rebound hyperglycemia, reduction in time to DKA resolution, reduced intravenous insulin requirements, and reduced length of stay without associated increases in hypoglycemic or hypokalemic events.

Correlation between heparin anti-Xa activity and thromboelastography in adult critically ill COVID-19 patients.

STUDY OBJECTIVE: Severe coronavirus disease 2019 (COVID-19) increases the risk of thrombotic complications with unfractionated heparin (UFH) as a commonly used agent in managing venous thromboembolism (VTE). The optimal anticoagulation intensity and monitoring parameters in intensive care unit (ICU) COVID-19 patients remains controversial. The primary study aim was to evaluate the relationship between anti-Xa and thromboelastography (TEG) reaction (R) time in patients with severe COVID-19 receiving therapeutic UFH infusions. DESIGN: Single-center, retrospective study conducted over a 15-month period (2020-2021). SETTING: Academic medical center (Banner University Medical Center Phoenix). PATIENTS: Adult patients with severe COVID-19 administered therapeutic UFH infusions with one or more corresponding TEG, and anti-Xa assessments drawn within ≤2 hours of each other were included. The primary end point was the correlation between anti-Xa and TEG R time. Secondary aims were to describe the correlation between activated partial thromboplastin time (aPTT) and TEG R time, as well as clinical outcomes. Pearson's coefficient was used to evaluate the correlation using a kappa measure of agreement.

A Review of Thromboelastography for Nurses.

BACKGROUND: Thromboelastography is a viscoelastic test with multiple potential advantages over conventional coagulation tests in various disease states. Thromboelastography rapidly provides qualitative and quantitative information related to a patient's coagulation status. OBJECTIVE: To describe recent studies of the use of thromboelastography in various clinical states and how thromboelastography is used in coagulation management. METHODS: A literature review using the MEDLINE and PubMed databases was conducted. The updated methodology for integrated reviews by Whittemore and Knafl was followed. Coauthors evaluated separate areas that were independently reviewed by other coauthors to ensure appropriateness for inclusion. RESULTS: The use of thromboelastography for various clinical conditions with challenging hemostatic profiles has increased. This integrative review covers the use of thromboelastography in patients with trauma, medication-induced coagulopathy, acute and chronic liver failure, and cardiothoracic surgery. Potential future directions are also discussed. DISCUSSION: Thromboelastography has numerous potential benefits over conventional coagulation tests for assessing coagulation status in patients in various clinical states. Nurses can support clinical decisions to use the most appropriate test for their patients. CONCLUSIONS: Each team member should be involved in assessing the usefulness of thromboelastography. Critical care nurses and the multidisciplinary team must identify patients in whom its use is warranted, interpret the results, and provide appropriate interventions in response to the results and clinical status of the patient.

UpdatED: The emergency medicine pharmacotherapy literature of 2022.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2022. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors, with disagreements adjudicated by a third author. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 4 guidelines, and 3 meta-analyses covering topics including anticoagulant reversal, tenecteplase in acute ischemic stroke, guideline updates for heart failure and aortic aneurysm, magnesium in atrial fibrillation, sedation in mechanically ventilated patients and pain management strategies in the Emergency Department (ED), and tranexamic acid use in epistaxis and GI bleed.

Multi-Cause Calibration of Verbal Autopsy-Based Cause-Specific Mortality Estimates of Children and Neonates in Mozambique.

The Countrywide Mortality Surveillance for Action platform is collecting verbal autopsy (VA) records from a nationally representative sample in Mozambique. These records are used to estimate the national and subnational cause-specific mortality fractions (CSMFs) for children (1-59 months) and neonates (1-28 days). Cross-tabulation of VA-based cause-of-death (COD) determination against that from the minimally invasive tissue sampling (MITS) from the Child Health and Mortality Prevention project revealed important misclassification errors for all the VA algorithms, which if not accounted for will lead to bias in the estimates of CSMF from VA. A recently proposed Bayesian VA-calibration method is used that accounts for this misclassification bias and produces calibrated estimates of CSMF. Both the VA-COD and the MITS-COD can be multi-cause (i.e., suggest more than one probable COD for some of the records). To fully use this probabilistic COD data, we use the multi-cause VA calibration. Two different computer-coded VA algorithms are considered-InSilicoVA and EAVA-and the final CSMF estimates are obtained using an ensemble calibration that uses data from both the algorithms. The calibrated estimates consistently offer a better fit to the data and reveal important changes in the CSMF for both children and neonates in Mozambique after accounting for VA misclassification bias.

Correcting for Verbal Autopsy Misclassification Bias in Cause-Specific Mortality Estimates.

Verbal autopsies (VAs) are extensively used to determine cause of death (COD) in many low- and middle-income countries. However, COD determination from VA can be inaccurate. Computer coded verbal autopsy (CCVA) algorithms used for this task are imperfect and misclassify COD for a large proportion of deaths. If not accounted for, this misclassification leads to biased estimates of cause-specific mortality fractions (CSMFs), a critical piece in health-policy making. Recent work has demonstrated that the knowledge of the CCVA misclassification rates can be used to calibrate raw VA-based CSMF estimates to account for the misclassification bias. In this manuscript, we review the current practices and issues with raw COD predictions from CCVA algorithms and provide a complete primer on how to use the VA calibration approach with the calibratedVA software to correct for verbal autopsy misclassification bias in cause-specific mortality estimates. We use calibratedVA to obtain CSMFs for child (1-59 months) and neonatal deaths using VA data from the Countrywide Mortality Surveillance for Action project in Mozambique.

Countrywide Mortality Surveillance for Action in Mozambique: Results from a National Sample-Based Vital Statistics System for Mortality and Cause of Death.

Sub-Saharan Africa lacks timely, reliable, and accurate national data on mortality and causes of death (CODs). In 2018 Mozambique launched a sample registration system (Countrywide Mortality Surveillance for Action [COMSA]-Mozambique), which collects continuous birth, death, and COD data from 700 randomly selected clusters, a nationally representative population of 828,663 persons. Verbal and social autopsy interviews are conducted for COD determination. We analyzed data collected in 2019-2020 to report mortality rates and cause-specific fractions. Cause-specific results were generated using computer-coded verbal autopsy (CCVA) algorithms for deaths among those age 5 years and older. For under-five deaths, the accuracy of CCVA results was increased through calibration with data from minimally invasive tissue sampling. Neonatal and under-five mortality rates were, respectively, 23 (95% CI: 18-28) and 80 (95% CI: 69-91) deaths per 1,000 live births. Mortality rates per 1,000 were 18 (95% CI: 14-21) among age 5-14 years, 26 (95% CI: 20-31) among age 15-24 years, 258 (95% CI: 230-287) among age 25-59 years, and 531 (95% CI: 490-572) among age 60+ years. Urban areas had lower mortality rates than rural areas among children under 15 but not among adults. Deaths due to infections were substantial across all ages. Other predominant causes by age group were prematurity and intrapartum-related events among neonates; diarrhea, malaria, and lower respiratory infections among children 1-59 months; injury, malaria, and diarrhea among children 5-14 years; HIV, injury, and cancer among those age 15-59 years; and cancer and cardiovascular disease at age 60+ years. The COMSA-Mozambique platform offers a rich and unique system for mortality and COD determination and monitoring and an opportunity to build a comprehensive surveillance system.

Countrywide Mortality Surveillance for Action in Mozambique: Results from a National Sample-Based Vital Statistics System for Mortality and Cause of Death

Sub-Saharan Africa lacks timely, reliable, and accurate national data on mortality and causes of death (CODs). In 2018 Mozambique launched a sample registration system (Countrywide Mortality Surveillance for Action [COMSA]-Mozambique), which collects continuous birth, death, and COD data from 700 randomly selected clusters, a nationally representative population of 828,663 persons. Verbal and social autopsy interviews are conducted for COD determination. We analyzed data collected in 2019-2020 to report mortality rates and cause-specific fractions. Cause-specific results were generated using computer-coded verbal autopsy (CCVA) algorithms for deaths among those age 5 years and older. For under-five deaths, the accuracy of CCVA results was increased through calibration with data from minimally invasive tissue sampling. Neonatal and under-five mortality rates were, respectively, 23 (95% CI: 18-28) and 80 (95% CI: 69-91) deaths per 1,000 live births. Mortality rates per 1,000 were 18 (95% CI: 14-21) among age 5-14 years, 26 (95% CI: 20-31) among age 15-24 years, 258 (95% CI: 230-287) among age 25-59 years, and 531 (95% CI: 490-572) among age 60+ years. Urban areas had lower mortality rates than rural areas among children under 15 but not among adults. Deaths due to infections were substantial across all ages. Other predominant causes by age group were prematurity and intrapartum-related events among neonates; diarrhea, malaria, and lower respiratory infections among children 1-59 months; injury, malaria, and diarrhea among children 5-14 years; HIV, injury, and cancer among those age 15-59 years; and cancer and cardiovascular disease at age 60+ years. The COMSA-Mozambique platform offers a rich and unique system for mortality and COD determination and monitoring and an opportunity to build a comprehensive surveillance system.

Multi-Cause Calibration of Verbal Autopsy-Based Cause-Specific Mortality Estimates of Children and Neonates in Mozambique

The Countrywide Mortality Surveillance for Action platform is collecting verbal autopsy (VA) records from a nationally representative sample in Mozambique. These records are used to estimate the national and subnational cause-specific mortality fractions (CSMFs) for children (1-59 months) and neonates (1-28 days). Cross-tabulation of VA-based cause-of-death (COD) determination against that from the minimally invasive tissue sampling (MITS) from the Child Health and Mortality Prevention project revealed important misclassification errors for all the VA algorithms, which if not accounted for will lead to bias in the estimates of CSMF from VA. A recently proposed Bayesian VA-calibration method is used that accounts for this misclassification bias and produces calibrated estimates of CSMF. Both the VA-COD and the MITS-COD can be multi-cause (i.e., suggest more than one probable COD for some of the records). To fully use this probabilistic COD data, we use the multi-cause VA calibration. Two different computer-coded VA algorithms are considered-InSilicoVA and EAVA-and the final CSMF estimates are obtained using an ensemble calibration that uses data from both the algorithms. The calibrated estimates consistently offer a better fit to the data and reveal important changes in the CSMF for both children and neonates in Mozambique after accounting for VA misclassification bias.

Correcting for Verbal Autopsy Misclassification Bias in Cause-Specific Mortality Estimates

Verbal autopsies (VAs) are extensively used to determine cause of death (COD) in many low- and middle-income countries. However, COD determination from VA can be inaccurate. Computer coded verbal autopsy (CCVA) algorithms used for this task are imperfect and misclassify COD for a large proportion of deaths. If not accounted for, this misclassification leads to biased estimates of cause-specific mortality fractions (CSMFs), a critical piece in health-policy making. Recent work has demonstrated that the knowledge of the CCVA misclassification rates can be used to calibrate raw VA-based CSMF estimates to account for the misclassification bias. In this manuscript, we review the current practices and issues with raw COD predictions from CCVA algorithms and provide a complete primer on how to use the VA calibration approach with the calibratedVA software to correct for verbal autopsy misclassification bias in cause-specific mortality estimates. We use calibratedVA to obtain CSMFs for child (1-59 months) and neonatal deaths using VA data from the Countrywide Mortality Surveillance for Action project in Mozambique.

Correlation between partial thromboplastin time and thromboelastography in adult critically ill patients requiring bivalirudin for extracorporeal membrane oxygenation.

STUDY OBJECTIVE: Thromboelastography (TEG) offers a more dynamic assessment of hemostasis over activated partial thromboplastin time (aPTT). However, the clinical utility of TEG in monitoring bivalirudin during extracorporeal membrane oxygenation (ECMO) remains unknown. The purpose of this study was to evaluate the correlation between aPTT and TEG in adult ECMO patients anticoagulated with bivalirudin. DESIGN: Multicenter, retrospective, cohort study conducted over a 2-year period. SETTING: Two academic university medical centers (Banner University Medical Center) in Phoenix and Tucson, AZ. PATIENTS: Adult patients requiring ECMO and bivalirudin therapy with ≥1 corresponding standard TEG and aPTT plasma samples drawn ≤4 h of each other were included. The primary endpoint was to determine the correlation coefficient between the standard TEG reaction (R) time and bivalirudin aPTT serum concentrations. MEASUREMENTS AND MAIN RESULTS: A total of 104 patients consisting of 848 concurrent laboratory assessments of R time and aPTT were included. A moderate correlation between TEG R time and aPTT was demonstrated in the study population (r = 0.41; p < 0.001). Overall, 502 (59.2%) concurrent assessments of TEG R time and aPTT values showed agreement on whether they were sub-, supra-, or therapeutic according to the institution's classification for bivalirudin. The 42.2% (n = 271/642) discordant TEG R times among "therapeutic" aPTT were almost equally distributed between subtherapeutic and supratherapeutic categories. CONCLUSIONS: Moderate correlation was found between TEG R time and aPTT associated with bivalirudin during ECMO in critically ill adults. Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients.