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1.
Int J Circumpolar Health ; 83(1): 2367273, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38875453

ABSTRACT

It has previously been shown that EpiPen® autoinjectors are likely to activate normally following up to five excursions to -25°C but data about the post-freezing performance of other brands of adrenaline autoinjectors has not previously been published. Additionally, conditions experienced by polar medics may be substantially colder than this and the performance of adrenaline autoinjectors following more extreme freeze-thaw cycles remains uncharacterised. Investigators in Antarctica and the United Kingdom performed laboratory testing on two brands of adrenaline autoinjector, EpiPen® and Jext® (12 devices of each type). A single freeze-thaw cycle involved freezing the device to -80°C then allowing it to come to room temperature. Devices were exposed to 0, 1, 5 or 15 freeze-thaw cycles. The mass of liquid ejected from each device, when activated, was then measured. No significant differences in the mass of the liquid ejected was found between the test groups. Multiple freeze-thaw cycles to -80°C are unlikely to significantly impact the amount of adrenaline solution expelled from EpiPen® and EpiPen® autoinjectors. This preliminary finding encourages further work investigating the safety and effectiveness of adrenaline autoinjectors after exposure to very low temperatures. This information would be valuable for future polar medics planning and delivering medical provision in extreme environments.


Subject(s)
Cold Temperature , Epinephrine , Freezing , Epinephrine/administration & dosage , Humans , Injections, Intramuscular/instrumentation
2.
Hepatology ; 80(2): 488-499, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38557474

ABSTRACT

Patients with cirrhosis have abnormal coagulation indices such as a high international normalized ratio and low platelet count, but these do not correlate well with periprocedural bleeding risk. We sought to develop a consensus among the multiple stakeholders in cirrhosis care to inform process measures that can help improve the quality of the periprocedural management of coagulopathy in cirrhosis. We identified candidate process measures for periprocedural coagulopathy management in multiple contexts relating to the performance of paracentesis and upper endoscopy. An 11-member panel with content expertise was convened. It included nominees from professional societies for interventional radiology, transfusion medicine, and anesthesia as well as representatives from hematology, emergency medicine, transplant surgery, and community practice. Each measure was evaluated for agreement using a modified Delphi approach (3 rounds of rating) to define the final set of measures. Out of 286 possible measures, 33 measures made the final set. International normalized ratio testing was not required for diagnostic or therapeutic paracentesis as well as diagnostic endoscopy. Plasma transfusion should be avoided for all paracenteses and diagnostic endoscopy. No consensus was achieved for these items in therapeutic intent or emergent endoscopy. The risks of prophylactic platelet transfusions exceed their benefits for outpatient diagnostic paracentesis and diagnostic endosopies. For the other procedures examined, the risks outweigh benefits when platelet count is >20,000/mm 3 . It is uncertain whether risks outweigh benefits below 20,000/mm 3 in other contexts. No consensus was achieved on whether it was permissible to continue or stop systemic anticoagulation. Continuous aspirin was permissible for each procedure. Clopidogrel was permissible for diagnostic and therapeutic paracentesis and diagnostic endoscopy. We found many areas of consensus that may serve as a foundation for a common set of practice metrics for the periprocedural management of coagulopathy in cirrhosis.


Subject(s)
Blood Coagulation Disorders , Delphi Technique , Liver Cirrhosis , Paracentesis , Humans , Paracentesis/methods , Liver Cirrhosis/complications , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/diagnosis , Consensus , International Normalized Ratio
4.
Anesth Analg ; 138(4): 728-737, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38335136

ABSTRACT

BACKGROUND: Preoperative anemia is associated with adverse outcomes in cardiac surgery, yet it remains unclear what proportion of this association is mediated through red blood cell (RBC) transfusions. METHODS: This is a historical observational cohort study of adults undergoing coronary artery bypass grafting or valve surgery on cardiopulmonary bypass at an academic medical center between May 1, 2008, and May 1, 2018. A mediation analysis framework was used to evaluate the associations between preoperative anemia and postoperative outcomes, including a primary outcome of acute kidney injury (AKI). Intraoperative RBC transfusions were evaluated as mediators of preoperative anemia and outcome relationships. The estimated total effect, average direct effect of preoperative anemia, and percent of the total effect mediated through transfusions are presented with 95% confidence intervals and P -values. RESULTS: A total of 4117 patients were included, including 1234 (30%) with preoperative anemia. Overall, 437 of 4117 (11%) patients went on to develop AKI, with a greater proportion of patients having preoperative anemia (219 of 1234 [18%] vs 218 of 2883 [8%]). In multivariable analyses, the presence of preoperative anemia was associated with increased postoperative AKI (6.4% [4.2%-8.7%] absolute difference in percent with AKI, P < .001), with incremental decreases in preoperative hemoglobin concentrations displaying greater AKI risk (eg, 11.9% [6.9%-17.5%] absolute increase in probability of AKI for preoperative hemoglobin of 9 g/dL compared to a reference of 14 g/dL, P < .001). The association between preoperative anemia and postoperative AKI was primarily due to direct effects of preoperative anemia (5.9% [3.6%-8.3%] absolute difference, P < .001) rather than mediated through intraoperative RBC transfusions (7.5% [-4.3% to 21.1%] of the total effect mediated by transfusions, P = .220). Preoperative anemia was also associated with longer hospital durations (1.07 [1.05-1.10] ratio of geometric mean length of stay, P < .001). Of this total effect, 38% (22%, 62%; P < .001) was estimated to be mediated through subsequent intraoperative RBC transfusion. Preoperative anemia was not associated with reoperation or vascular complications. CONCLUSIONS: Preoperative anemia was associated with higher odds of AKI and longer hospitalizations in cardiac surgery. The attributable effects of anemia and transfusion on postoperative complications are likely to differ across outcomes. Future studies are necessary to further evaluate mechanisms of anemia-associated postoperative organ injury and treatment strategies.


Subject(s)
Acute Kidney Injury , Anemia , Cardiac Surgical Procedures , Adult , Humans , Mediation Analysis , Risk Factors , Anemia/complications , Anemia/diagnosis , Anemia/epidemiology , Cardiac Surgical Procedures/adverse effects , Hemoglobins/analysis , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Retrospective Studies
5.
J Clin Anesth ; 94: 111405, 2024 06.
Article in English | MEDLINE | ID: mdl-38309132

ABSTRACT

STUDY OBJECTIVE: To evaluate the association between pretransfusion and posttransfusion hemoglobin concentrations and the outcomes of children undergoing noncardiac surgery. DESIGN: Retrospective review of patient records. We focused on initial postoperative hemoglobin concentrations, which may provide a more useful representation of transfusion adequacy than pretransfusion hemoglobin triggers (the latter often cannot be obtained during acute surgical hemorrhage). SETTING: Single-center, observational cohort study. PATIENTS: We evaluated all pediatric patients undergoing noncardiac surgery who received intraoperative red blood cell transfusions from January 1, 2008, through December 31, 2018. INTERVENTIONS: None. MEASUREMENTS: Associations between pre- and posttransfusion hemoglobin concentrations (g/dL), hospital-free days, intensive care unit admission, postoperative mechanical ventilation, and infectious complications were evaluated with multivariable regression modeling. MAIN RESULTS: In total, 113,713 unique noncardiac surgical procedures in pediatric patients were evaluated, and 741 procedures met inclusion criteria (median [range] age, 7 [1-14] years). Four hundred ninety-eight patients (68%) with a known preoperative hemoglobin level had anemia; of these, 14% had a preexisting diagnosis of anemia in their health record. Median (IQR) pretransfusion hemoglobin concentration was 8.1 (7.4-9.2) g/dL and median (IQR) initial postoperative hemoglobin concentration was 10.4 (9.3-11.6) g/dL. Each decrease of 1 g/dL in the initial postoperative hemoglobin concentration was associated with increased odds of transfusion within the first 24 postoperative hours (odds ratio [95% CI], 1.62 [1.37-1.93]; P < .001). No significant relationships were observed between postoperative hemoglobin concentrations and hospital-free days (P = .56), intensive care unit admission (P = .71), postoperative mechanical ventilation (P = .63), or infectious complications (P = .74). CONCLUSIONS: In transfused patients, there was no association between postoperative hemoglobin values and clinical outcomes, except the need for subsequent transfusion. Most transfused patients presented to the operating room with anemia, which suggests a potential opportunity for perioperative optimization of health before surgery.


Subject(s)
Anemia , Humans , Child , Infant , Child, Preschool , Adolescent , Anemia/epidemiology , Anemia/therapy , Blood Transfusion , Hemoglobins/analysis , Cohort Studies , Erythrocyte Transfusion/adverse effects , Retrospective Studies
6.
Chem Commun (Camb) ; 60(9): 1188-1191, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38193881

ABSTRACT

A versatile, robust, and stable tetrabutylammonium difluorotriphenylsilicate (TBAT) catalyst has been deployed for efficient depolymerization of silicones. This catalyst is soluble in a variety of organic solvents and is stable up to 170 °C, enabling a wide range of reaction conditions under which F--catalysed siloxane bond cleavage can be initiated. This effort offers significant advancement overcoming the traditional limitations of silicone depolymerization, such as high catalyst loading, storage and handling, and few viable reaction media.

7.
Ann Thorac Surg ; 117(5): 1053-1060, 2024 May.
Article in English | MEDLINE | ID: mdl-38286201

ABSTRACT

BACKGROUND: This study characterized the association of preoperative anemia and intraoperative red blood cell (RBC) transfusion on outcomes of elective coronary artery bypass grafting (CABG). METHODS: Data from 53,856 patients who underwent CABG included in The Society of Thoracic Surgeons (STS) Adult Cardiac Database in 2019 were used. The primary outcome was operative mortality. Secondary outcomes were postoperative complications. The association of anemia with outcomes was analyzed with multivariable regression models. The influence of intraoperative RBC transfusion on the effect of preoperative anemia on outcomes was studied using mediation analysis. RESULTS: Anemia was present in 25% of patients. Anemic patients had a higher STS Predicted Risk of Operative Mortality (1.2% vs 0.7%; P < .001). Anemia was associated with operative mortality (odds ratio [OR], 1.27; 99.5% CI, 1.00-1.61; P = .047), postoperative RBC transfusion (OR, 2.28; 99.5% CI, 2.12-2.44; P < .001), dialysis (OR, 1.58; 99.5% CI, 1.19-2.11; P < .001), and prolonged intensive care unit and hospital length of stay. Intraoperative RBC transfusion largely mediated the effects of anemia on mortality (76%), intensive care unit stay (99%), and hospital stay, but it only partially mediated the association with dialysis (34.9%). CONCLUSIONS: Preoperative anemia is common in patients who undergo CABG and is associated with increased postoperative risks of mortality, complications, and RBC transfusion. However, most of the effect of anemia on mortality is mediated through intraoperative RBC transfusion.


Subject(s)
Anemia , Coronary Artery Bypass , Databases, Factual , Erythrocyte Transfusion , Postoperative Complications , Societies, Medical , Humans , Male , Female , Anemia/epidemiology , Anemia/complications , Coronary Artery Bypass/adverse effects , Aged , Middle Aged , Erythrocyte Transfusion/statistics & numerical data , Postoperative Complications/epidemiology , United States/epidemiology , Retrospective Studies , Thoracic Surgery , Treatment Outcome , Coronary Artery Disease/surgery , Coronary Artery Disease/mortality , Coronary Artery Disease/complications
8.
JAMA ; 330(19): 1837-1838, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37824133

ABSTRACT

This Viewpoint discusses how patient blood management can help curb the demand for blood products and reduce harm by determining who would most benefit from a blood transfusion.


Subject(s)
Blood Transfusion , Patient Care Management , Humans , Patient Care Management/organization & administration
9.
Anesth Analg ; 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37801575

ABSTRACT

BACKGROUND: Kidney transplant is the most common transplant operation performed in the United States. Although various approaches to pain management have been described, the optimal analgesic strategy remains undefined. Specifically, the role of intrathecal opioids in this patient population has not been comprehensively evaluated. METHODS: Using a retrospective cohort design, data from kidney transplant operations at a single tertiary care medical center between August 1, 2017, and July 31, 2022, were extracted. Inverse probability of treatment weighting (IPTW) was used to assess differences in clinical outcomes based on the presence or absence of intrathecal opioid administration before surgical incision. The primary outcome was total opioid exposure expressed in milligram morphine equivalents (MME) in the first 72 hours postoperatively, with secondary outcomes including total MME (intraoperative plus postoperative MME, postoperative pain scores, and the presence of postoperative nausea/vomiting [PONV], pruritus, or adverse events). RESULTS: A total of 1014 kidney transplants in 1012 unique patients were included, with 411 (41%) receiving intrathecal opioids preoperatively. Hydromorphone was the intrathecal opioid used in all cases with median dose of 100 µg (interquartile range [IQR], 100, 100; range 50-200). Subjects receiving intrathecal opioids had significantly lower postoperative opioid requirements at 72 hours (30 [0-68] vs 64 [22, 120] MME), with ratio of geometric means in the IPTW analysis (ratio of geometric means 0.34, 95% confidence interval [CI], 0.26-0.43; P < .001). Similar findings were observed for total opioids (45 [30-75] vs 75 [60-90] MME; ratio of geometric means 0.58, 95% CI, 0.54-0.63; P < .001). Maximum reported pain scores in the intrathecal group were lower at 24 hours (4 [2-7] vs 7 [5, 8]; OR, 0.28; 95% CI, 0.21-0.37 for experiencing a higher pain score with intrathecal opioids, P < .001) and 72 hours (6 [4-7] vs 7 [5-8]; OR, 0.41; 95% CI, 0.31-0.54; P < .001). Patients receiving intrathecal opioids were more likely to experience PONV (225 of 411 [55%] vs 232 of 603 [38%]; OR, 2.16; 95% CI, 1.63-2.86; P < .001). CONCLUSIONS: Intrathecal opioid administration was associated with improved pain outcomes in patients undergoing kidney transplantation, including lower opioid requirements and pain scores through 72 hours. However, this was accompanied by an increased risk of PONV.

11.
Int J Circumpolar Health ; 82(1): 2230633, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37389990

ABSTRACT

Injury in Antarctica can have a significant impact when considering transfer timelines of several weeks. Medical support to the British Antarctic Territory (BAT) is provided by deployed healthcare professionals and the utilisation of "reach-back" with telemedicine. This is paired with robust training and familiarisation with a system of modularised deployed equipment.This paper examines the current telemedicine strategy, infrastructure modularisation, and influence from military practice by the British Antarctic Survey Medical Unit (BASMU) for medical care at extreme reach. Current telemedicine practices and utilisation, as well as modular equipment capabilities across the BAT were reviewed to provide an outline of care delivery.Requests varied from expert advice to remote supervision of clinical procedures. Integration of commercially available solutions enabled real-time display of patient physiology. The deployment of modular resources has improved equipment availability and greater standardisation between sites. The sending of case notes and digital x-rays has been generally sufficient but, when greater supervision was required, limited data transfer bandwidth was a challenge.An ongoing review of deployed equipment capabilities may also enhance the ease with which remote support can be offered but an uplift in telemedicine capability will likely require infrastructure upgrades to maintain data transfer from 8000 miles away.


Subject(s)
Delivery of Health Care , Military Personnel , Telemedicine , Humans , Antarctic Regions , Health Personnel
12.
Phys Chem Chem Phys ; 25(17): 12522-12531, 2023 May 03.
Article in English | MEDLINE | ID: mdl-37133822

ABSTRACT

In this study, we investigate the molecular mechanisms of a microwave-driven selective heating process by performing molecular dynamics simulations for three different systems including pure water, pure polyethylene oxide (PEO), and water-PEO mixed systems in the presence of a microwave with two different intensities of electric field such as 0.001 V Å-1 and 0.01 V Å-1 at a frequency of 100 GHz. First, from performing molecular dynamics simulations of CO and CO2 in the presence of the microwave, it is confirmed that the molecular dipole moment is responsible for the rotational motion induced by the oscillating electric field. Second, by analyzing the MD simulations of the pure water system, we discover that the dipole moment of water exhibits a time lag with respect to the microwave. During the heating process, however, the temperature, kinetic, and potential energies increase synchronously with the oscillating electric field of the microwave, showing that the heating of the water system is caused by the molecular reaction of water to the microwave. Comparing the water-PEO mixed system to the pure water and pure PEO systems, the water-PEO mixed system has a higher heating rate than the pure PEO system but a lower heating rate than the pure water system. Therefore, we conclude that heating the water-PEO mixed system is driven by water molecules selectively activated by microwave irradiation. We also calculate the diffusion coefficients of water molecules and PEO chains by describing their mean square displacements, demonstrating that the diffusion coefficients are increased in the presence of microwaves for both water and PEO in pure and mixed systems. Lastly, during the microwave heating process, the structures of the water-PEO mixed system are altered as a function of the intensity of electric field, which is mainly driven by the response of water molecules.

13.
Anesthesiology ; 139(2): 153-163, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37155364

ABSTRACT

BACKGROUND: Delayed cold storage of room temperature platelets may extend shelf life from 5 to 14 days. The study hypothesized that the use of delayed cold-stored platelets in cardiac surgery would be associated with decreased postoperative platelet count increments but similar transfusion and clinical outcomes compared to room temperature-stored platelets. METHODS: This is an observational cohort study of adults transfused with platelets intraoperatively during elective cardiac surgery between April 2020 and May 2021. Intraoperative platelets were either room temperature-stored or delayed cold-stored based on blood bank availability rather than clinical features or provider preference. Differences in transfusion and clinical outcomes, including a primary outcome of allogenic transfusion exposure in the first 24 h postoperatively, were compared between groups. RESULTS: A total of 713 patient encounters were included: 529 (74%) room temperature-stored platelets and 184 (26%) delayed cold-stored platelets. Median (interquartile range) intraoperative platelet volumes were 1 (1 to 2) units in both groups. Patients receiving delayed cold-stored platelets had higher odds of allogeneic transfusion in the first 24 h postoperatively (81 of 184 [44%] vs. 169 of 529 [32%]; adjusted odds ratio, 1.65; 95% CI, 1.13 to 2.39; P = 0.009), including both erythrocytes (65 of 184 [35%] vs. 135 of 529 [26%]; adjusted odds ratio, 1.54; 95% CI, 1.03 to 2.29; P = 0.035) and platelets (48 of 184 [26%] vs. 79 of 529 [15%]; adjusted odds ratio, 1.91; 95% CI, 1.22 to 2.99; P = 0.005). There was no difference in the number of units administered postoperatively among those transfused. Platelet counts were modestly lower in the delayed cold-stored platelet group (-9 × 109/l; 95% CI, -16 to -3]) through the first 3 days postoperatively. There were no significant differences in reoperation for bleeding, postoperative chest tube output, or clinical outcomes. CONCLUSIONS: In adults undergoing cardiac surgery, delayed cold-stored platelets were associated with higher postoperative transfusion utilization and lower platelet counts compared to room temperature-stored platelets without differences in clinical outcomes. The use of delayed cold-stored platelets in this setting may offer a viable alternative when facing critical platelet inventories but is not recommended as a primary transfusion approach.


Subject(s)
Blood Platelets , Cardiac Surgical Procedures , Adult , Humans , Platelet Transfusion , Temperature , Retrospective Studies , Blood Preservation
14.
Int J Circumpolar Health ; 82(1): 2210340, 2023 12.
Article in English | MEDLINE | ID: mdl-37154780

ABSTRACT

INTRODUCTION: Cold Weather Injury (CWI) represents a spectrum of pathology, the two main divisions being Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI). Both are disabling conditions associated with microvascular and nerve injury often treated hours after initial insult when presenting to a healthcarestablishment. Given that iloprost is used for the treatment of FCI, could it be used in a forward operating environment to mitigate treatment delay? Is there a role for its use in the forward treatment of NFCI? This review sought to evaluate the strength of evidence for the potential use of iloprost in a forward operating environment. METHODS: Literature searches were undertaken using the following question for both FCI and NFCI: in [patients with FCI/NFCI] does [the use of iloprost] compared to [standard care] reduce the incidence of [long-term complications]. Medline, CINAHL and EMBASE databases were searched using the above question and relevant alternative terminology. Abstracts were reviewed before full articles were requested. RESULTS: The FCI search yielded 17 articles that were found to refer to the use of iloprost and FCI. Of the 17, one referred to pre-hospital treatment of frostbite at K2 base camp; however, this was utilising tPA. No articles referred to pre-hospital use in either FCI or NFCI. DISCUSSION: Although evidence exists to support the use of iloprost in the treatment of FCI, its use to date has been in hospital. A common theme is delayed treatment due to the challenges of evacuating casualties from a remote location. There may be a role for iloprost in the treatment of FCI; however, further study is required to better understand the risk of its use.


Subject(s)
Cold Injury , Frostbite , Military Personnel , Humans , Iloprost/therapeutic use , Cold Injury/drug therapy , Cold Injury/epidemiology , Cold Temperature , Frostbite/drug therapy
15.
J Cardiothorac Vasc Anesth ; 37(6): 933-941, 2023 06.
Article in English | MEDLINE | ID: mdl-36863984

ABSTRACT

OBJECTIVE: No recent prospective studies have analyzed the accuracy of standard coagulation tests and thromboelastography (TEG) to identify patients with excessive microvascular bleeding following cardiopulmonary bypass (CPB). The aim of this study was to assess the value of coagulation profile tests, as well as TEG, for the classification of microvascular bleeding after CPB. DESIGN: A prospective observational study. SETTING: At a single-center academic hospital. PARTICIPANTS: Patients ≥18 years of age undergoing elective cardiac surgery. INTERVENTIONS: Qualitative assessment of microvascular bleeding post-CPB (surgeon and anesthesiologist consensus) and the association with coagulation profile tests and TEG values. MEASUREMENTS AND MAIN RESULTS: A total of 816 patients were included in the study-358 (44%) bleeders and 458 (56%) nonbleeders. Accuracy, sensitivity, and specificity for the coagulation profile tests and TEG values ranged from 45% to 72%. The predictive utility was similar across tests, with prothrombin time (PT) (62% accuracy, 51% sensitivity, 70% specificity), international normalized ratio (INR) (62% accuracy, 48% sensitivity, 72% specificity), and platelet count (62% accuracy, 62% sensitivity, 61% specificity) displaying the highest performance. Secondary outcomes were worse in bleeders versus nonbleeders, including higher chest tube drainage, total blood loss, transfusion of red blood cells, reoperation rates (p < 0.001, respectively), readmission within 30 days (p = 0.007), and hospital mortality (p = 0.021). CONCLUSIONS: Standard coagulation tests and individual components of TEG in isolation agree poorly with the visual classification of microvascular bleeding after CPB. The PT-INR and platelet count performed best but had low accuracy. Further work is warranted to identify better testing strategies to guide perioperative transfusion decisions in cardiac surgical patients.


Subject(s)
Cardiopulmonary Bypass , Hemorrhage , Humans , Prospective Studies , Cardiopulmonary Bypass/adverse effects , Blood Coagulation Tests , Prothrombin Time , Thrombelastography
16.
Anesthesiol Clin ; 41(1): 161-174, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36871997

ABSTRACT

Patient blood management (PBM) is a systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood and minimizing allogenic transfusion need and risk. According to the PBM approach, the goals of perioperative anemia management include early diagnosis, targeted treatment, blood conservation, restrictive transfusion except in cases of acute and massive hemorrhage, and ongoing quality assurance and research efforts to advance overall blood health.


Subject(s)
Anemia , Specialties, Surgical , Humans , Blood Transfusion
17.
Microbiol Spectr ; : e0526122, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36862002

ABSTRACT

Exebacase (CF-301) belongs to a novel class of protein-based antibacterial agents, called lysins (peptidoglycan hydrolases). Exebacase exhibits potent antistaphylococcal activity and is the first lysin to initiate clinical trials in the United States. To support clinical development, the potential for resistance development to exebacase was assessed over 28 days of serial daily subculture in the presence of increasing concentrations of the lysin performed in its reference broth medium. Exebacase MICs remained unchanged over serial subculture for three replicates each of methicillin-susceptible Staphylococcus aureus (MSSA) strain ATCC 29213 and methicillin-resistant S. aureus (MRSA) strain MW2. For comparator antibiotics also tested, oxacillin MICs increased by 32-fold with ATCC 29213 and daptomycin and vancomycin MICs increased by 16- and 8-fold, respectively, with MW2. Serial passage was also used to examine the capacity of exebacase to suppress selection for increased oxacillin, daptomycin, and vancomycin MICs when used together in combination, wherein daily exposures to increasing concentrations of antibiotic were performed over 28 days with the added presence of fixed sub-MIC amounts of exebacase. Exebacase suppressed increases in antibiotic MICs over this period. These findings are consistent with a low propensity for resistance to exebacase and an added benefit of reducing the potential for development of antibiotic resistance. IMPORTANCE To guide development of an investigational new antibacterial drug, microbiological data are required to understand the potential for development of resistance to the drug in the target organism(s). Exebacase is a lysin (peptidoglycan hydrolase) that represents a novel antimicrobial modality based on degradation of the cell wall of Staphylococcus aureus. Exebacase resistance was examined here using an in vitro serial passage method that assesses the impact of daily exposures to increasing concentrations of exebacase over 28 days in medium approved for use in exebacase antimicrobial susceptibility testing (AST) by the Clinical and Laboratory Standards Institute (CLSI). No changes in susceptibility to exebacase were observed over the 28-day period for multiple replicates of two S. aureus strains, indicating a low propensity for resistance development. Interestingly, while high-level resistance to commonly used antistaphylococcal antibiotics was readily obtained using the same method, the added presence of exebacase acted to suppress antibiotic resistance development.

18.
Anesth Analg ; 137(2): 375-382, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36791019

ABSTRACT

BACKGROUND: Increased burnout and decreased professional fulfillment among intensive care physicians is partly due to intensive care unit (ICU) workload. Although the SARS-CoV-2 (COVID-19) pandemic increased ICU workload, it also may have increased feelings of personal fulfillment due to positive public perceptions of physicians caring for COVID patients. We surveyed critical care anesthesiologists to identify the effect of provider demographics, ICU workload, and COVID-19-related workload, on professional fulfillment and burnout. METHODS: We performed an exploratory survey of 606 members of the Society of Critical Care Anesthesiologists (SOCCA) in January and February 2022. We used the Stanford Professional Fulfillment Index (PFI) to grade levels of professional fulfillment and markers of burnout (ie, work exhaustion and disengagement). Univariable and multivariable models were used to identify associations between provider demographics and practice characteristics and professional fulfillment and work exhaustion. RESULTS: One hundred and seventy-five intensivists (29%) responded. A total of 65% were male and 49% were between 36 and 45 years old. The overall median PFI score-0 (none) to 24 (most professional fulfillment)-was 17 (IQR, 1-24), with a wide distribution of responses. In multivariable analysis, factors associated with higher professional fulfillment included age >45 years ( P =.004), ≤15 weeks full-time ICU coverage in 2020 ( P =.02), role as medical director ( P =.01), and nighttime home call with supervision of in-house ICU fellows ( P =.01). CONCLUSIONS: Professional fulfillment and work exhaustion in this cross-sectional survey were associated with several demographic and practice characteristics but not COVID-19-related workload, suggesting that COVID-19 workload may not have either positive or negative perceptions on professional fulfillment.


Subject(s)
Burnout, Professional , COVID-19 , Humans , Male , Middle Aged , Adult , Female , Anesthesiologists , Cross-Sectional Studies , SARS-CoV-2 , Critical Care , Burnout, Professional/diagnosis , Burnout, Professional/epidemiology , Surveys and Questionnaires
19.
Transfusion ; 63(2): 315-322, 2023 02.
Article in English | MEDLINE | ID: mdl-36605019

ABSTRACT

BACKGROUND: Preoperative anemia is common and associated with adverse postoperative outcomes. Assessment of hemoglobin concentrations may facilitate optimization prior to surgery. However, phlebotomy-based hemoglobin measurement may contribute to patient discomfort and iatrogenic blood loss, which makes non-invasive hemoglobin estimation attractive in this setting. STUDY DESIGN AND METHODS: This is a prospective study of adult patients presenting for preoperative evaluation before elective surgery at a tertiary care medical center. The Masimo Pronto Pulse CO-Oximeter was utilized to estimate blood hemoglobin concentrations (SpHb), which were then compared with hemoglobin concentrations obtained via complete blood count. Receiver operating curves were used to identify SpHb values maximizing specificity for anemia detection while meeting a minimum sensitivity of 80%. RESULTS: A total of 122 patients were recruited with a median (interquartile range) age of 66 (58, 72) years. SpHb measurements were obtained in 112 patients (92%). SpHb generally overestimated hemoglobin with a mean (± 1.96 × standard deviation) difference of 0.8 (-2.2, 3.9) g/dL. Preoperative anemia, defined by hemoglobin <12.0 g/dL in accordance with institutional protocol, was present in 22 patients (20%). The optimal SpHb cut-point to identify anemia was 13.5 g/dL: sensitivity 86%, specificity 81%, negative predictive value 96%, and positive predictive value 53%. Utilizing this cut-point, 60% (73/122) of patients could have avoided phlebotomy-based hemoglobin assessment, while an anemia diagnosis would have been missed in <3% (3/122). CONCLUSION: The use of SpHb devices for anemia screening in surgical patients is feasible with the potential to reliably rule-out anemia despite limited accuracy.


Subject(s)
Anemia , Hemoglobins , Adult , Humans , Anemia/diagnosis , Hematologic Tests , Hemoglobins/analysis , Oximetry/methods , Prospective Studies , Preoperative Care
20.
Anesth Analg ; 136(2): 295-307, 2023 02 01.
Article in English | MEDLINE | ID: mdl-35950751

ABSTRACT

BACKGROUND: Despite the growing contributions of critical care anesthesiologists to clinical practice, research, and administrative leadership of intensive care units (ICUs), relatively little is known about the subspecialty-specific clinical practice environment. An understanding of contemporary clinical practice is essential to recognize the opportunities and challenges facing critical care anesthesia, optimize staffing patterns, assess sustainability and satisfaction, and strategically plan for future activity, scope, and training. This study surveyed intensivists who are members of the Society of Critical Care Anesthesiologists (SOCCA) to evaluate practice patterns of critical care anesthesiologists, including compensation, types of ICUs covered, models of overnight ICU coverage, and relationships between these factors. We hypothesized that variability in compensation and practice patterns would be observed between individuals. METHODS: Board-certified critical care anesthesiologists practicing in the United States were identified using the SOCCA membership distribution list and invited to take a voluntary online survey between May and June 2021. Multiple-choice questions with both single- and multiple-select options were used for answers with categorical data, and adaptive questioning was used to clarify stem-based responses. Respondents were asked to describe practice patterns at their respective institutions and provide information about their demographics, salaries, effort in ICUs, as well as other activities. RESULTS: A total of 490 participants were invited to take this survey, and 157 (response rate 32%) surveys were completed and analyzed. The majority of respondents were White (73%), male (69%), and younger than 50 years of age (82%). The cardiothoracic/cardiovascular ICU was the most common practice setting, with 69.5% of respondents reporting time working in this unit. Significant variability was observed in ICU practice patterns. Respondents reported spending an equal proportion of their time in clinical practice in the operating rooms and ICUs (median, 40%; interquartile range [IQR], 20%-50%), whereas a smaller proportion-primarily those who completed their training before 2009-reported administrative or research activities. Female respondents reported salaries that were $36,739 less than male respondents; however, this difference was not statistically different, and after adjusting for age and practice type, these differences were less pronounced (-$27,479.79; 95% confidence interval [CI], -$57,232.61 to $2273.03; P = .07). CONCLUSIONS: These survey data provide a current snapshot of anesthesiology critical care clinical practice patterns in the United States. Our findings may inform decision-making around the initiation and expansion of critical care services and optimal staffing patterns, as well as provide a basis for further work that focuses on intensivist satisfaction and burnout.


Subject(s)
Anesthesiology , Physicians , Humans , Male , Female , United States , Anesthesiologists , Practice Patterns, Physicians' , Critical Care , Surveys and Questionnaires
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