Influence of screw configuration on reduction and stabilization of simulated complete lateral condylar fracture in equine limbs.

OBJECTIVE: To determine the influence of screw configuration on the reduction and stabilization of simulated complete lateral condylar fracture. STUDY DESIGN: Randomized experimental crossover study. METHODS: A lateral condylar fracture was simulated in 18 cadaver limbs from nine horses. Each limb underwent repair with 4.5 mm diameter cortex screws, tightened to 4 Nm, in a linear and triangular configuration. Computed tomography (CT) of each repair was performed with the limbs in unloaded and loaded conditions. Fracture gaps were measured at the dorsal, palmar, and middle locations of the third metacarpal condyle. Fracture gap measurements were graded 0-4, based on voxels. Following descriptive analysis, a Bayesian network (BN) model was fitted to the data. RESULTS: The median fracture grade was 0 (range: 0-4) for unloaded linear repairs and 2 (0-4) for loaded linear repairs. The median fracture grade was 0 (0-3) for unloaded triangular repairs and 1 (0-3) for loaded triangular repairs. Bayesian network sensitivity analysis showed that the construct configuration reduced the uncertainty in the measured fracture outcome by 0.8%. CONCLUSION: Triangular screw configuration resulted in better fracture reduction and stability in comparison with linear screw configuration. However, the BN sensitivity analysis results showed that the effect of construct configuration on fracture outcome was weak. CLINICAL SIGNIFICANCE: These findings indicate a low probability that triangular repair of lateral condylar fracture will result in improved outcomes, when compared with linear repair.

Elevated atmospheric CO2 drives decreases in stable soil organic carbon in arid ecosystems: Evidence from a physical fractionation and organic compound analysis.

The increasing concentration of CO2 in the atmosphere is perturbing the global carbon (C) cycle, altering stocks of organic C, including soil organic matter (SOM). The effect of this disturbance on soils in arid ecosystems may differ from other ecosystems due to water limitation. In this study, we conducted a density fractionation on soils previously harvested from the Nevada Desert FACE Facility (NDFF) to understand how elevated atmospheric CO2 (eCO2 ) affects SOM stability. Soils from beneath the perennial shrub, Larrea tridentata, and from unvegetated interspace were subjected to a sodium polytungstate density fractionation to separate light, particulate organic matter (POM, <1.85 g/cm3 ) from heavier, mineral associated organic matter (MAOM, >1.85 g/cm3 ). These fractions were analyzed for organic C, total N, δ13 C and δ15 N, to understand the mechanisms behind changes. The heavy fraction was further analyzed by pyrolysis GC/MS to assess changes in organic compound composition. Elevated CO2 decreased POM-C and MAOM-C in soils beneath L. tridentata while interspace soils exhibited only a small increase in MAOM-N. Analysis of δ13 C revealed incorporation of new C into both POM and MAOM pools indicating eCO2 stimulated rapid turnover of both POM and MAOM. The largest losses of POM-C and MAOM-C observed under eCO2 occurred in soils 20-40 cm in depth, highlighting that belowground C inputs may be a significant driver of SOM decomposition in this ecosystem. Pyrolysis GC/MS analysis revealed a decrease in organic compound diversity in the MAOM fraction of L. tridentata soils, becoming more similar to interspace soils under eCO2 . These results provide further evidence that MAOM stability may be compromised under disturbance and that SOC stocks in arid ecosystems are vulnerable under continued climate change.

Evaluation of Multisite Programmatic Bundle to Reduce Unnecessary Antibiotic Prescribing for Respiratory Infections: A Retrospective Cohort Study.

Background: The aim of this study was to evaluate the frequency of unnecessary antibiotic prescribing for Tier 3 upper respiratory infection (URI) syndromes across the Mayo Clinic Enterprise before and after a multifaceted antimicrobial stewardship intervention, and to determine ongoing factors associated with antibiotic prescribing and repeat respiratory healthcare contact in the postintervention period. Methods: This was a quasi-experimental, pre/post, retrospective cohort study from 1 January 2019 through 31 December 2022, with 12-month washout during implementation from 1 July 2020 through 30 June 2021. All outpatient encounters, adult and pediatric, from primary care, urgent care, and emergency medicine specialties with a Tier 3 URI diagnosis were included. The intervention was a multifaceted outpatient antibiotic stewardship bundle. The primary outcome was the rate of antibiotic prescribing in Tier 3 encounters. Secondary outcomes included 14-day repeat healthcare contact for respiratory indications and factors associated with persistent unnecessary prescribing. Results: A total of 165 658 Tier 3 encounters, 96 125 in the preintervention and 69 533 in the postintervention period, were included. Following intervention, the prescribing rate for Tier 3 encounters decreased from 21.7% to 11.2% (P < .001). Repeat 14-day respiratory healthcare contact in the no antibiotic group was lower postintervention (9.9.% vs 9.4%; P = .004). Multivariable models indicated that increasing patient age, Charlson comorbidity index, and primary diagnosis selected were the most important factors associated with persistent unnecessary antibiotic prescribing. Conclusions: Outpatient antibiotic stewardship initiatives can reduce unnecessary antibiotic prescribing for Tier 3 URIs without increasing repeat respiratory healthcare contact. Advancing age and number of comorbidities remain risk factors for persistent unnecessary antibiotic prescribing.

A review of evidence, antimicrobial stability, and feasibility considerations for OPAT continuous infusion.

Outpatient parenteral antimicrobial therapy (OPAT) has been widely used in clinical practice for many decades because of its associated cost savings, reductions in inpatient hospital days, and decreases in hospital-associated infections. Despite this long history, evolving practice patterns and new drug delivery devices continue to present challenges as well as opportunities for clinicians when designing appropriate outpatient antimicrobial regimens. One such change is the increasing use of extended and continuous infusion (CI) of antimicrobials to optimize the achievement of pharmacokinetic and pharmacodynamic targets. Elastomeric devices are also becoming increasingly popular in OPAT, including for the delivery of CI. In this article, we review the clinical evidence for CI in OPAT, as well as practical considerations of patient preferences, cost, and antimicrobial stability.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered.

Drug level monitoring is commonly used to evaluate appropriate dosing and effectiveness of posaconazole, a medication used to treat fungal infections. Patients with high levels commonly had side effects. Posaconazole monitoring should be completed, and doses reduced when levels are high.

Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care.

Background: Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin-tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. Results: AKI occurred in 14.4% of patients in the VPT group (n = 15/104) compared to 5.5% in the other BL group (n = 40/722) (p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7-12.0) days in the VPT group and 10.9 (5-22.7) days in the other BL group (p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33-4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group (n = 15/104) and 5.3% in the other BL group (n = 11/208) (p = 0.006). Receipt of VPT [HR: 2.55 (1.36-4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19-4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Conclusion: Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

Identification of priority targets for intervention in outpatient antimicrobial stewardship.

A multimodal antimicrobial stewardship intervention was associated with a decrease in antibiotic prescribing for targeted non-coronavirus disease 2019 (COVID-19) upper respiratory infections from 27.6% in 2019 to 7.6% in 2021. We describe our approach to prioritizing departments for 3 levels of interventions in the setting of limited stewardship personnel.

Multiple Simultaneous Infections With Nontuberculous Mycobacteria in the Setting of GATA2 Mutation and Myelodysplastic Syndrome.

GATA2 mutation can result in profoundly reduced monocytes, dendritic cells, natural killer cells, and B cells, and is associated with a predisposition for recurrent and disseminated nontuberculous mycobacterial (NTM) infections and myelodysplasias. Herein, we describe a unique case of 3 simultaneous disseminated NTM infections in a patient with GATA2 mutations.

Impacts of Phantom Off-Center Positioning on CT Numbers and Dose Index CTDIv: An Evaluation of Two CT Scanners from GE.

The purpose of this work is to evaluate the impacts of body off-center positioning on CT numbers and dose index CTDIv of two scanners from GE. HD750 and APEX scanners were used to acquire a PBU60 phantom of Kagaku and a 062M phantom of CIRS respectively. CT images were acquired at various off-center positions under automatic tube current modulation using various peak voltages. CTDIv were recorded for each of the acquisitions. An abdomen section of the PBU60 phantom was used for CT number analysis and tissue inserts of the 062M phantom were filled with water balloons to mimic the human abdomen. CT numbers of central regions of interests were averaged using the Fiji software. As phantoms were lifted above the iso-center, both CTDIv and CT numbers were increased for the HD750 scanner whilst they were approximately constant for the APEX scanner. The measured sizes of anterior-posterior projection images were also increased for both scanners whilst the sizes of lateral projection images were increased for the HD750 scanner but decreased for the APEX scanner. Off-center correction algorithms were implemented in the APEX scanner. Matching the X-ray projection center with the system's iso-center could improve the accuracy of CT imaging.

A retrospective antibiotic prescribing assessment and examination of potential antibiotic stewardship targets in patients with COVID-19.

OBJECTIVES: Despite low rates of bacterial coinfection in patients admitted with COVID-19, antimicrobials are frequently prescribed. Our primary objective was to evaluate antimicrobial prescribing over time in patients admitted with COVID-19. The secondary objectives were to evaluate the role of ID providers in antimicrobial utilization, describe the rate of confirmed bacterial infection and determine factors associated with empirical antimicrobial prescribing in COVID-19. MATERIALS AND METHODS: Retrospective review was performed for adult patients admitted to a tertiary care centre with COVID-19 between 1 March 2020 and 30 November 2020. Patient demographics, disease severity, risk factors for severe disease, clinical outcomes, antimicrobial prescribing and respiratory microbiological testing were collected and analysed. Prescribing trends were evaluated by month, and factors contributing to prescribing were established using univariate and multivariable analysis. RESULTS: Antibiotics were prescribed during admission in 37.9% of the study cohort, with 85.1% of patients who received antibiotics having therapy initiated within 48 h of admission. Antibiotic prescribing incidence increased with disease. Over the study period, antimicrobial prescribing rates decreased by 8.7% per month. Multivariable analysis found ICU admission, obtainment of procalcitonin values, intubation, heart failure, haemodialysis and nursing home residence were associated with empirical antimicrobial prescribing. CONCLUSIONS: Unnecessary antimicrobial prescribing in patients with viral syndromes like COVID-19 continues to represent an area of concern. Antimicrobial stewardship efforts during COVID-19 should consider patient-specific factors associated with antibiotic prescribing. Recognition of such factors, in combination with application of well-established antimicrobial stewardship tactics, may serve to impact antimicrobial prescribing trends, even as patient volumes rise.

Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care.

In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

Initial and subsequent 3-year cost after hospitalization for first acute ischemic stroke and intracerebral hemorrhage.

AIMS: To examine 1) the major drivers of index hospitalization and 3-year post-acute follow-up care, 2) cost for rehabilitation and homecare, and 3) indirect cost from lost productivity after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Retrospective study of adults hospitalized with AIS (n = 811) and ICH (N = 145) between 2003 and 2014. Direct costs standardized to Medicare reimbursement rates were captured for hospitalization and 3-year follow-up or death. Adjusted cost estimates were assessed using generalized linear modeling with gamma distribution. Costs for rehabilitation, home healthcare, and lost productivity were assessed using sets of cost captured through literature review. RESULTS: Calculated as mean cost per person: hospitalization $18,154 for AIS and $24,077 for ICH; monthly 3-year aggregate $5138 for AIS and $8172 for ICH; 3-year inpatient rehabilitation $4185 for AIS and $4196 for ICH; homecare $19,728 for AIS and $14,487 for ICH; indirect cost from lost productivity $77,078 for AIS and $56,601 for ICH. Age < 55 years, being non-white, and stroke severity were strongly associated with greater hospitalization cost for AIS and ICH. Hyperlipidemia incurred lower while cancer, coronary artery disease, asthma/chronic obstructive pulmonary disease, heart failure, and anemia incurred higher 3-year aggregate cost for AIS. Cancer and diabetes mellitus incurred higher 3-year aggregate cost for ICH. CONCLUSIONS: We provide estimates of direct and indirect costs incurred for acute and continuing post-acute care through a 3-year follow-up period after first-ever AIS and ICH with important comparisons for predictors between index hospitalization and 3-year post-stroke costs.

Outcomes and Clinical Characteristics of Intracranial Hemorrhage in Patients with Hematologic Malignancies: A Systematic Literature Review.

BACKGROUND: Many clinical and demographic factors can influence survival of patients with hematologic malignancies who have intracranial hemorrhages (ICHs). Understanding the influence of these factors on patient survival can guide treatment decisions and may inform prognostic discussions. We conducted a systematic literature review to determine survival of patients with intracranial hemorrhages and concomitant hematologic malignancy. METHODS: A systematic literature review was conducted and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed/MEDLINE, Web of Science, Ovid, SCOPUS, and Embase databases were queried with the following terms: ("intracranial hemorrhages" OR "brain hemorrhage" OR "cerebral hemorrhage" OR "subdural hematoma" OR "epidural hematoma" OR "intraparenchymal hemorrhage") AND ("Hematologic Neoplasms" OR "Myeloproliferative Disorders" OR "Myelofibrosis" OR "Essential thrombocythemia" OR "Leukemia"). Abstracts and articles were screened according to inclusion and exclusion criteria that were determined a priori. RESULTS: Literature review yielded 975 abstracts from which a total of 68 full-text articles were reviewed. Twelve articles capturing 634 unique patients were included in the final qualitative analysis. Median overall survival for all patients ranged from 20 days to 1.5 months while median overall survival for the subset of patients having ICH within 10 days of diagnosis of hematologic malignancy was 5 days. Intraparenchymal hemorrhages, multiple foci of hemorrhage, transfusion-resistant low platelet counts, leukocytosis, low Glasgow Coma Scale scores at presentation, and ICH early in treatment course were associated with worse outcomes. CONCLUSIONS: Survival for patients with hematologic malignancies and concomitant ICHs remains poor. Early detection, recognition of poor prognostic factors, and correction of hematologic abnormalities essential to prevention and treatment of ICHs in this patient population.

Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis.

Objectives: The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods: Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results: In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58-0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions: In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

Association between hyperlipidemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score matched cohort study and a meta-analysis.

OBJECTIVE: To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature. DESIGN: Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis. SETTING: Large academic centre, 1996-2015. PARTICIPANTS: Hospitalised patients with AMI or ADHF. MAIN OUTCOMES AND MEASURES: All-cause mortality and meta-analysis of relative risks (RR). RESULTS: Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81). CONCLUSIONS: Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis.

Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax.

IMPACT STATEMENT: Bax induces mitochondria-dependent programed cell death. While cytotoxic drugs activating Bax have been developed for cancer treatment, clinically effective therapeutics suppressing Bax-induced cell death rescuing essential cells have not been developed. This mini-review will summarize previously reported Bax inhibitors including peptides, small compounds, and antibodies. We will discuss potential applications and the future direction of these Bax inhibitors.

Slow saccades in cerebellar disease.

Eye movements are frequently considered diagnostic markers indicating involvement of the cerebellum. Impaired amplitude of saccades (saccade dysmetria), impaired gaze holding function (horizontal or downbeat nystagmus), and interrupted (choppy) pursuit are typically considered hallmarks of cerebellar disorders. While saccade dysmetria is a frequently considered abnormality, the velocity of saccades are rarely considered part of the constellation of cerebellar involvement. Reduced saccade velocity, frequently called "slow saccades" are typically seen in a classic disorder of the midbrain called progressive supranuclear palsy. It is also traditionally diagnostic of spinocerebellar ataxia type 2. In addition to its common causes, the slowness of vertical saccades is not rare in cerebellar disorders. Frequently this phenomenology is seen in multisystem involvement that substantially involves the cerebellum. In this review we will first discuss the physiological basis and the biological need for high saccade velocities. In subsequent sections we will discuss disorders of cerebellum that are known to cause slowing of saccades. We will then discuss possible pathology and novel therapeutic strategies.