A clinically applicable approach to continuous prediction of future acute kidney injury.

The early prediction of deterioration could have an important role in supporting healthcare professionals, as an estimated 11% of deaths in hospital follow a failure to promptly recognize and treat deteriorating patients1. To achieve this goal requires predictions of patient risk that are continuously updated and accurate, and delivered at an individual level with sufficient context and enough time to act. Here we develop a deep learning approach for the continuous risk prediction of future deterioration in patients, building on recent work that models adverse events from electronic health records2-17 and using acute kidney injury-a common and potentially life-threatening condition18-as an exemplar. Our model was developed on a large, longitudinal dataset of electronic health records that cover diverse clinical environments, comprising 703,782 adult patients across 172 inpatient and 1,062 outpatient sites. Our model predicts 55.8% of all inpatient episodes of acute kidney injury, and 90.2% of all acute kidney injuries that required subsequent administration of dialysis, with a lead time of up to 48 h and a ratio of 2 false alerts for every true alert. In addition to predicting future acute kidney injury, our model provides confidence assessments and a list of the clinical features that are most salient to each prediction, alongside predicted future trajectories for clinically relevant blood tests9. Although the recognition and prompt treatment of acute kidney injury is known to be challenging, our approach may offer opportunities for identifying patients at risk within a time window that enables early treatment.

Tympanomastoidectomy versus parenteral antibiotic therapy for pediatric otorrhea.

OBJECTIVE: To evaluate the efficacy of tympanomastoidectomy versus parenteral antibiotic therapy for otorrhea as a result of chronic suppurative otitis media (CSOM) without cholesteatoma in the pediatric population. METHODS: A retrospective review of 221 patients treated for otorrhea at a tertiary academic pediatric hospital was performed to evaluate the impact of tympanomastoidectomy versus parenteral antibiotic therapy on resolution of otorrhea. Inclusion criteria were age 0-18 years, prior treatment with otic and/or oral antibiotic, prior history of tympanostomy tube placement for recurrent otitis media, history of otorrhea, treatment with tympanomastoidectomy or parenteral antibiotic therapy, and follow-up of at least 1 month after intervention. Time to resolution was compared between the two modalities adjusting for age, bilateral ear disease status, and comorbidities using a Cox proportional hazard model. RESULTS: Eighty-three ears from 58 children met the inclusion criteria. Ears that initially underwent tympanomastoidectomy had a significantly shorter time to resolution of symptoms (median time to resolution) 9 months (95 % confidence interval CI: 6.2-14.8) vs. 48.5 months (95 % lower CI 9.4, p = 0.006). On multivariate analysis, however, only bilateral ear disease status was independently associated with time to resolution of symptoms (hazard ratio 0.4, 95 % CI 0.2-0.9, p = 0.03). There was no statistically significant difference in the rate of treatment-related complications when comparing tympanomastoidectomy to parenteral antibiotic therapy (p = 0.37). CONCLUSION: When adjusting for age, bilateral ear disease status, and comorbidities, there does not appear to be a significant difference in time to resolution of symptoms when comparing parenteral antibiotic therapy to tympanomastoidectomy. An informed discussion regarding risks and benefits of each approach should be employed when deciding on the next step in management for patients with CSOM who have failed more conservative therapies.

Probing the Chemical Bond between Lanthanides and Carbon: CeC, PrC, NdC, LuC, and TmC2.

Resonant two-photon ionization experiments have been conducted to probe the bond dissociation energy (BDE) of the lanthanide-carbon bond, allowing the BDEs of CeC, PrC, NdC, LuC, and Tm-C2 to be measured to high precision. Values of D0(CeC) = 4.893(3) eV, D0(PrC) = 4.052(3) eV, D0(NdC) = 3.596(3) eV, D0(LuC) = 3.685(4) eV, and D0(Tm-C2) = 4.797(6) eV are obtained. Additionally, the adiabatic ionization energy of LuC was measured, giving IE(LuC) = 7.05(3) eV. The electronic structure of these species, along with the previously measured LaC, has been further investigated using quantum chemical calculations. Despite LaC, CeC, PrC, and NdC having ground electronic configurations that differ only in the number of 4f electrons present and have virtually identical bond orders, bond lengths, fundamental stretching frequencies, and metallic oxidation states, a peculiar 1.30 eV range in bond dissociation energies exists for these molecules. A natural bond orbital analysis shows that the metal atoms in these molecules have a natural charge of +1 with a 5d2 4fn 6s0 configuration while the carbon atom has a natural charge of -1 and a 2p3 configuration. The diabatic bond dissociation energies, calculated with respect to the lowest energy level of this separated ion configuration, show a greatly reduced energy range of 0.32 eV, with the diabatic BDE decreasing as the amount of 4f character in the σ-bond increases. Thus, the wide range of measured BDEs for these molecules is a consequence of the variation in atomic promotion energies at the separated ion limit. TmC2 has a smaller BDE than the other LnC2 molecules, due to the tiny amount of 5d participation in the valence molecular orbitals.

Early Transition Metals Strengthen the B2 Bond in MB2 Complexes.

The bond dissociation energies of early transition metal diborides (M-B2, M = Sc, Ti, V, Y, Mo) have been measured by observation of the sharp onset of predissociation in a highly congested spectrum. Density functional and CCSD(T) ab initio calculations, extrapolated to the complete basis set limit, have been used to examine the electronic structure of these species. The computations demonstrate the formation of bonding orbitals between the metal d orbitals and the 1πu bonding orbitals of B2, leading to the transfer of metallic electron density into the bonding 1πu orbitals, strengthening both the M-B and B-B bonds in the molecule. This runs counter to most metal-ligand π interactions, where electron density is generally transferred into π antibonding orbitals of the ligand.

Chemical Bonding and Electronic Structure of the Early Transition Metal Borides: ScB, TiB, VB, YB, ZrB, NbB, LaB, HfB, TaB, and WB.

The predissociation thresholds of the early transition metal boride diatomics (MB, M = Sc, Ti, V, Y, Zr, Nb, La, Hf, Ta, W) have been measured using resonant two-photon ionization (R2PI) spectroscopy, allowing for a precise assignment of the bond dissociation energy (BDE). No previous experimental measurements of the BDE exist in the literature for these species. Owing to the high density of electronic states arising from the ground and low-lying separated atom limits in these open d-subshell species, a congested spectrum of vibronic transitions is observed as the energy of the ground separated atom limit is approached. Nonadiabatic and spin-orbit interactions among these states, however, provide a pathway for rapid predissociation as soon as the ground separated atom limit is reached, leading to a sharp decrease in signal to background levels when this limit is reached. Accordingly, the BDEs of the early transition metal borides have been assigned as D0(ScB) 1.72(6) eV, D0(TiB) 1.956(16) eV, D0(VB) 2.150(16) eV, D0(YB) 2.057(3) eV, D0(ZrB) 2.573(5) eV, D0(NbB) 2.989(12) eV, D0(LaB) 2.086(18) eV, D0(HfB) 2.593(3) eV, D0(TaB) 2.700(3) eV, and D0(WB) 2.730(4) eV. Additional insight into the chemical bonding and electronic structures of these species has been achieved by quantum chemical calculations.

The bond dissociation energy of VO measured by resonant three-photon ionization spectroscopy.

The predissociation threshold of VO has been measured using resonant three-photon ionization (R3PI) spectroscopy. Given the high density of electronic states in the molecule, it is argued that the molecule dissociates rapidly as soon as the thermochemical bond dissociation energy (BDE) is exceeded, allowing the measured predissociation threshold to be assigned as the BDE. This is the first time a BDE has been measured using the R3PI method. The first photon is provided by an optical parametric oscillator (OPO) laser that promotes VO into a high-energy, discrete vibronic state. A tunable dye laser then excites the molecule further to a resonant state close to the dissociation limit where there is a quasi-continuum of states. A second photon from the same dye laser pulse ionizes the molecule, generating VO+ ions. The dye laser is then scanned to higher energies, and when the energy of one OPO photon plus one dye photon exceeds the BDE, the molecule dissociates before another dye photon can be absorbed to induce ionization. The combined photon energy at the sharp drop in the ion signal is assigned as the BDE. The experiment has been repeated using four different intermediate states, all yielding the same BDE, D0(VO) = 6.545(2) eV. Using thermochemical cycles, a revised value for the BDE of cationic VO is obtained, D0(V+-O) = 6.053(2) eV. The 0 K enthalpy of formation for VO(g) is also derived as ΔfH0K 0VO(g) = 128.6(1.0) kJ mol-1. Previous spectroscopic and thermochemical studies of VO are reviewed.

Bond dissociation energies of diatomic transition metal sulfides: ScS, YS, TiS, ZrS, HfS, NbS, and TaS.

The early transition metal diatomic sulfides, MS, M = Sc, Y, Ti, Zr, Hf, Nb, and Ta, have been investigated using resonant two-photon ionization spectroscopy in the vicinity of their bond dissociation energies (BDEs). Due to the high density of vibronic states in this energy range, the molecular spectra appear quasicontinuous, and when the excitation energy exceeds the ground separated atom limit, excited state decay by dissociation becomes possible. The dissociation process typically occurs so rapidly that the molecule falls apart before a second photon can be absorbed to ionize the species, leading to a sharp drop in ion signal, which is identified as the 0 K BDE. The observed predissociation thresholds yield BDEs of 4.852(10) eV (ScS), 5.391(3) eV (YS), 4.690(4) eV (TiS), 5.660(4) eV (ZrS), 5.780(20) eV (HfS), 5.572(3) eV (NbS), and 5.542(3) eV (TaS). Utilizing thermochemical cycles, the enthalpies of formation, ΔfH0K o(g), of 182.7(4.3) kJ mol-1 (ScS), 178.3(4.2) kJ mol-1 (YS), 293.1(16.7) kJ mol-1 (TiS), 337.3(8.4) kJ mol-1 (ZrS), 335.0(6.6) kJ mol-1 (HfS), 467.0(8.0) kJ mol-1 (NbS), and 521.5(2.1) kJ mol-1 (TaS) are obtained. Another thermochemical cycle has been used to combine the previously measured M+-S BDEs with the M-S BDEs and atomic ionization energies to obtain the MS ionization energies of 6.44(5) eV (ScS), 6.12(8) eV (YS), 6.78(7) eV (TiS), 6.60(10) eV (ZrS), and 6.88(9) eV (NbS). Using this same cycle, we obtain D0(Hf+-S) = 4.926(20) eV. The bonding trends of the early transition metal sulfides, along with the corresponding selenides, are discussed.

Bond dissociation energies of transition metal oxides: CrO, MoO, RuO, and RhO.

Through the use of resonant two-photon ionization spectroscopy, sharp predissociation thresholds have been identified in the spectra of CrO, MoO, RuO, and RhO. Similar thresholds have previously been used to measure the bond dissociation energies (BDEs) of many molecules that have a high density of vibronic states at the ground separated atom limit. A high density of states allows precise measurement of the BDE by facilitating prompt dissociation to ground state atoms when the BDE is exceeded. However, the number of states required for prompt predissociation at the thermochemical threshold is not well defined and undoubtedly varies from molecule to molecule. The ground separated atom limit generates 315 states for RuO, 252 states for RhO, and 63 states for CrO and MoO. Although comparatively few states derive from this limit for CrO and MoO, the observation of sharp predissociation thresholds for all four molecules nevertheless allows BDEs to be assigned as 4.863(3) eV (RuO), 4.121(3) eV (RhO), 4.649(5) eV (CrO), and 5.414(19) eV (MoO). Thermochemical cycles are used to derive the enthalpies of formation of the gaseous metal oxides and to obtain IE(RuO) = 8.41(5) eV, IE(RhO) = 8.56(6) eV, D0(Ru-O-) = 4.24(2) eV, D0(Cr-O-) = 4.409(8) eV, and D0(Mo-O-) = 5.243(20) eV. The mechanisms leading to prompt predissociation at threshold in the cases of CrO and MoO are discussed. Also presented is a discussion of the bonding trends for the transition metal oxides, which are compared to the previously measured transition metal sulfides.

Predictive Modeling and Concentration of the Risk of Suicide: Implications for Preventive Interventions in the US Department of Veterans Affairs.

OBJECTIVES: The Veterans Health Administration (VHA) evaluated the use of predictive modeling to identify patients at risk for suicide and to supplement ongoing care with risk-stratified interventions. METHODS: Suicide data came from the National Death Index. Predictors were measures from VHA clinical records incorporating patient-months from October 1, 2008, to September 30, 2011, for all suicide decedents and 1% of living patients, divided randomly into development and validation samples. We used data on all patients alive on September 30, 2010, to evaluate predictions of suicide risk over 1 year. RESULTS: Modeling demonstrated that suicide rates were 82 and 60 times greater than the rate in the overall sample in the highest 0.01% stratum for calculated risk for the development and validation samples, respectively; 39 and 30 times greater in the highest 0.10%; 14 and 12 times greater in the highest 1.00%; and 6.3 and 5.7 times greater in the highest 5.00%. CONCLUSIONS: Predictive modeling can identify high-risk patients who were not identified on clinical grounds. VHA is developing modeling to enhance clinical care and to guide the delivery of preventive interventions.

Relationships between the importation, transmission, and nosocomial infections of methicillin-resistant Staphylococcus aureus: an observational study of 112 Veterans Affairs Medical Centers.

BACKGROUND: The study of hospital methicillin-resistant Staphylococcus aureus (MRSA) epidemiology is complicated by its transmissibility. Our objective was to understand how MRSA importation and transmission influence MRSA nosocomial infections in Veterans Affairs Medical Centers (VAMCs). METHODS: We performed hospital-level analyses of acute-care MRSA admission prevalence, acquisition rates, and incident nosocomial clinical culture (INCC) rates, each a surrogate measure of importation, transmission, and nosocomial infection, respectively. We studied 112 VAMCs from October 2007 through September 2010, after the start of a bundled intervention including active surveillance for MRSA. We analyzed data using generalized linear mixed models. RESULTS: A total of 2.9 million surveillance tests were collected from 1.4 million patient admissions. Overall MRSA admission prevalence was 11.4%, acquisition was 5.2 per 1000 patient-days at risk, and INCC was 1.8 per 1000 patient-days at risk. A 10% increase in a hospital's average admission prevalence was associated with a 9.7% increase in its weekly acquisition rates (P < .001) and a 9.8% increase in its weekly INCC rates (P < .001). Significant decreases were observed in all 3 measures during the study period (P < .001). When INCC rates were stratified by nasal MRSA carriage at admission, a significant downward trend was observed only among those initially negative. CONCLUSIONS: Measured associations between MRSA admission prevalence, acquisition rate, and INCC rate were consistent with the hypothesis that decreased acquisition led to decreased importation, which in turn further abated acquisition. The downward trend in INCC rate specifically among individuals with negative admission surveillance tests suggests that decreasing transmission contributed to lower rates of nosocomial MRSA infection.

Does universal active MRSA surveillance influence anti-MRSA antibiotic use? A retrospective analysis of the treatment of patients admitted with suspicion of infection at Veterans Affairs Medical Centers between 2005 and 2010.

OBJECTIVES: After the implementation of an active surveillance programme for MRSA in US Veterans Affairs (VA) Medical Centers, there was an increase in vancomycin use. We investigated whether positive MRSA admission surveillance tests were associated with MRSA-positive clinical admission cultures and whether the availability of surveillance tests influenced prescribers' ability to match initial anti-MRSA antibiotic use with anticipated MRSA results from clinical admission cultures. METHODS: Analyses were based on barcode medication administration data, microbiology data and laboratory data from 129 hospitals between January 2005 and September 2010. Hospitalized patient admissions were included if clinical cultures were obtained and antibiotics started within 2 days of admission. Mixed-effects logistic regression was used to examine associations between positive MRSA admission cultures and (i) admission MRSA surveillance test results and (ii) initial anti-MRSA therapy. RESULTS: Among 569,815 included admissions, positive MRSA surveillance tests were strong predictors of MRSA-positive admission cultures (OR 8.5; 95% CI 8.2-8.8). The negative predictive value of MRSA surveillance tests was 97.6% (95% CI 97.5%-97.6%). The diagnostic OR between initial anti-MRSA antibiotics and MRSA-positive admission cultures was 3.2 (95% CI 3.1-3.4) for patients without surveillance tests and was not significantly different for admissions with surveillance tests. CONCLUSIONS: The availability of nasal MRSA surveillance tests in VA hospitals did not seem to improve the ability of prescribers to predict the necessity of initial anti-MRSA treatment despite the high negative predictive value of MRSA surveillance tests. Prospective trials are needed to establish the safety and effectiveness of using MRSA surveillance tests to guide antibiotic therapy.

Hearing Following Prolonged and Delayed Ganciclovir Treatment in a Murine Cytomegalovirus Model.

OBJECTIVE: Compare hearing outcomes utilizing standard, prolonged and delayed ganciclovir (GCV) therapy in a murine model of cytomegalovirus (CMV). METHODS: BALB/c mice were inoculated with mouse cytomegalovirus (mCMV) or saline via intracerebral injection on postnatal day 3 (p3). Intraperitoneal GCV or saline was administered at 12 h intervals for the duration of the standard (p3-p17), delayed (p30-p44), or prolonged treatment windows (p3-p31). Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Blood and tissue samples were harvested from mice on p17 and p37 one hour after GCV administration, and their concentrations were assessed via liquid chromatography-mass spectrometry. RESULTS: A delayed course of GCV improved ABR but not DPOAE thresholds in mCMV-infected mice. A prolonged course of GCV did not provide better hearing thresholds than those administered standard treatment. The average GCV concentration in all 17-day-old mice tissue was significantly higher than those in older 37-day-old mice. CONCLUSION: Delayed GCV treatment provided a hearing benefit on ABR over untreated mCMV infected mice. Prolonged CGV administration showed no benefit compared to a shorter duration GCV treatment. GCV drug concentrations both systemically and in the cochlea are much lower in older mice. These results have potential implications for the clinical management of cCMV infected children. LEVEL OF EVIDENCE: NA Laryngoscope, 134:433-438, 2024.

Can Ganciclovir and Quercetin-P188 Ameliorate Cytomegalovirus Induced Hearing Loss?

OBJECTIVE: Determine whether combination therapy with ganciclovir (GCV) and a Quercetin-P188 solution improves hearing outcomes in a murine cytomegalovirus (CMV) model. METHODS: BALB/c mice were infected with murine CMV on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either GCV, QP188, GCV and QP188, or P188 delivery vehicle BID at 12-hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen, saline or P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV-infected groups were harvested at p10, and viral load was determined by quantitative polymerase chain reaction. RESULTS: CMV-infected mice receiving combination therapy GCV+QP188 demonstrated statistically significant lower ABR (p < 0.001) and DPOAE thresholds (p < 0.001) compared with mice treated with GCV monotherapy, QP188 monotherapy, and P188 delivery vehicle at 4, 6, and 8 weeks of age. GCV+QP188 combination therapy, GCV monotherapy, and QP188 monotherapy resulted in a nonsignificant reduction in mean viral titers compared to P188 monotherapy (p = 0.08). CONCLUSION: Combining GCV with the excipients quercetin and P188 effectively ameliorated CMV-induced sensorineural hearing loss in a murine model. This result may be partially explained by a reduction in viral titers in mouse temporal bones that correlate with in vitro studies demonstrating additive antiviral effect in cell culture. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1457-1463, 2024.

Predicting risk of hospitalization or death among patients receiving primary care in the Veterans Health Administration.

BACKGROUND: Statistical models that identify patients at elevated risk of death or hospitalization have focused on population subsets, such as those with a specific clinical condition or hospitalized patients. Most models have limitations for clinical use. Our objective was to develop models that identified high-risk primary care patients. METHODS: Using the Primary Care Management Module in the Veterans Health Administration (VHA)'s Corporate Data Warehouse, we identified all patients who were enrolled and assigned to a VHA primary care provider on October 1, 2010. The outcome variable was the occurrence of hospitalization or death during the subsequent 90 days and 1 year. We extracted predictors from 6 categories: sociodemographics, medical conditions, vital signs, prior year use of health services, medications, and laboratory tests and then constructed multinomial logistic regression models to predict outcomes for over 4.6 million patients. RESULTS: In the predicted 95th risk percentiles, observed 90-day event rates were 19.6%, 6.2%, and 22.6%, respectively, for hospitalization, death, and either hospitalization or death, compared with population averages of 2.7%, 0.7%, and 3.4%, respectively; 1-year event rates were 42.3%, 19.4%, and 51.3%, respectively, compared with population averages of 8.2%, 2.6%, and 10.8%, respectively. The C-statistics for 90-day outcomes were 0.83, 0.86, and 0.81, respectively, for hospitalization, death, and either hospitalization or death and were 0.81, 0.85, and 0.79, respectively, for 1-year outcomes. CONCLUSIONS: Prediction models using electronic clinical data accurately identified patients with elevated risk for hospitalization or death. This information can enhance the coordination of care for patients with complex clinical conditions.

Comparing Aerosol Generation in Human and Animal Tissues During Common Otolaryngology Procedures.

OBJECTIVE: To determine whether hamster and human tissues generate similar amounts of aerosolized particles using common otolaryngology surgical techniques. STUDY DESIGN: Quantitative experimental research. STUDY SETTING: University research laboratory. METHODS: Drilling, electrocautery, and coblation were performed on human and hamster tissues. Particle size and concentration were measured during the surgical procedures using a scanning mobility particle sizer and an aerosol particle sizer (SMPS-APS) and GRIMM aerosol particle spectrometer. RESULTS: SMPS-APS and GRIMM measurements detected at least 2-fold increases in aerosol concentrations compared to baseline during all procedures. Procedures performed on human and hamster tissues produced similar trends and order of magnitude of aerosol concentrations. Generally, hamster tissues produced higher aerosol concentrations compared to human tissues, and some of these differences were statistically significant. Mean particle sizes for all procedures were small (<200 nm), although statistically significant differences in particle size were identified between human and hamster tissues during coblation and drilling. CONCLUSION: Aerosol-generating procedures performed on human and hamster tissue produce similar trends in aerosol particle concentrations and sizes, although we observed some differences between the 2 tissue types. Further studies should be performed to understand the clinical significance of these differences.

Analysis of an Expanded Targeted Early Cytomegalovirus Testing Program.

OBJECTIVE: Determine the detection rate from an expanded targeted early cytomegalovirus (CMV) testing program implemented from a large healthcare system (Intermountain Healthcare, IHC). STUDY DESIGN: Retrospective review. SETTING: Tertiary medical center. METHODS: An electronic system was modified to include indications for testing whenever a provider placed an order for CMV testing. A retrospective analysis of this database was performed. RESULTS: From March 1, 2021 to August 31, 2022, there were 3450 (8.8%) patients who underwent CMV testing out of 39,245 total live births within the IHC system. Since the formal implementation of this program in 2019, annual CMV testing has increased almost 10-fold: 2668 CMV tests were performed in 2021 compared to 289 CMV tests in 2015. The most frequent indication for congenital CMV (cCMV) testing was small for gestational age (SGA) (68.2%), followed by macrocephaly (13.5%), an abnormal hearing test (5.0%), and microcephaly (4.4%). Fourteen cCMV-infected infants were diagnosed all of them meeting the criteria for symptomatic cCMV. The most common indication resulting in a positive diagnosis was those who presented with SGA (n = 10 patients). The positivity rate would result in a prevalence of 35.7 symptomatic cCMV cases diagnosed per 100,000 live births, numbers comparable to those expected for universal cCMV screening. CONCLUSION: An expanded targeted early cCMV testing program may improve detection rates of symptomatic cCMV cases and should be considered as a feasible alternative approach to universal or hearing-targeted early CMV testing.

Double trouble: how big a problem is redundant anaerobic antibiotic coverage in Veterans Affairs medical centres?

OBJECTIVES: To assess the prevalence of, and the variation in, avoidable use of metronidazole in the Veterans Affairs (VA) healthcare system METHODS: Barcode Medication Administration (BCMA) data were retrospectively assessed for all patients hospitalized between January 2006 and December 2010 in acute-care wards of all VA medical centres (VAMCs) with complete BCMA data and at least 10 acute-care non-intensive care unit (ICU) beds. Potentially avoidable metronidazole days of therapy (DOT) were defined as the administration of metronidazole with another anti-anaerobic antibiotic on the same day for at least two consecutive days during the same hospitalization. Metronidazole was not considered redundant in combination with another anti-anaerobic agent within 28 days after a positive test for Clostridium difficile and during hospitalizations associated with discharge diagnosis codes for cholecystitis or cholangitis. RESULTS: A total of 128 VAMCs satisfied the inclusion criteria. Over the study period there were a total of 782,821 DOT of metronidazole (57.4 DOT per 1000 patient-days), of which 183,267 (23.4%) fulfilled the criteria for avoidable metronidazole DOT. The percentage of avoidable metronidazole DOT remained stable over the study period (22.8% in 2006 and 22.9% in 2010) despite a decrease in overall metronidazole use. There was wide variation in the percentage of avoidable metronidazole DOT among facilities (2010: median 20.3%, IQR 15.3%-29.4%). Piperacillin/tazobactam was the most commonly administered drug on avoidable metronidazole DOT (56.8%). CONCLUSIONS: Potentially avoidable use of metronidazole affected about a quarter of all days when metronidazole was given. The combination of metronidazole with piperacillin/tazobactam was particularly common and represents a possible target for antibiotic stewardship interventions.

Identification of methicillin-resistant Staphylococcus aureus within the nation's Veterans Affairs medical centers using natural language processing.

BACKGROUND: Accurate information is needed to direct healthcare systems' efforts to control methicillin-resistant Staphylococcus aureus (MRSA). Assembling complete and correct microbiology data is vital to understanding and addressing the multiple drug-resistant organisms in our hospitals. METHODS: Herein, we describe a system that securely gathers microbiology data from the Department of Veterans Affairs (VA) network of databases. Using natural language processing methods, we applied an information extraction process to extract organisms and susceptibilities from the free-text data. We then validated the extraction against independently derived electronic data and expert annotation. RESULTS: We estimate that the collected microbiology data are 98.5% complete and that methicillin-resistant Staphylococcus aureus was extracted accurately 99.7% of the time. CONCLUSIONS: Applying natural language processing methods to microbiology records appears to be a promising way to extract accurate and useful nosocomial pathogen surveillance data. Both scientific inquiry and the data's reliability will be dependent on the surveillance system's capability to compare from multiple sources and circumvent systematic error. The dataset constructed and methods used for this investigation could contribute to a comprehensive infectious disease surveillance system or other pressing needs.

Surgical outcomes inchildren with perioperative SARS-CoV-2 diagnosis.

OBJECTIVE: To understand whether perioperative SARS-CoV-2 infection increases risk of pulmonary complications in children. METHODS: A retrospective cohort study of children who underwent surgery with perioperative SARS-CoV-2 infection at a children's hospital from March 1, 2020, to June 30, 2021. Uninfected, age-matched control patients who underwent the same procedure as infected patients over the past ten years were included in the study in a 3:1 ratio to infected patients. Primary outcomes were 7- and 30-day mortality. Secondary outcomes were development of pulmonary complications, readmission, length of hospital or ICU stay, and oxygen administration in post-anesthesia care unit (PACU). RESULTS: Our study included 73 patients who underwent surgery with perioperative diagnosis of SARS-CoV-2, and 218 control patient undergoing similar procedures. One total mortality event was observed within 7 days in an uninfected control patient, and none occurred in infected patients. Perioperative SARS-CoV-2 infection was associated with increased risk for pulmonary complications in univariate analysis. Infection was not associated with any of our other secondary outcomes. Symptomatic SARS-CoV-2 infection and timing of diagnosis was not associated with development of pulmonary complications among infected patients. CONCLUSIONS: Children with perioperative SARS-CoV-2 infection may be at increased risk for development of pulmonary complications. Larger studies should be performed to confirm our results.

Hearing loss caused by CMV infection is correlated with reduced endocochlear potentials caused by strial damage in murine models.

Congenital cytomegalovirus (CMV) infection is a significant cause of neonatal hearing loss. However, at the cochlear level, the anatomical lesions and pathophysiological mechanisms that underlie hearing loss are still not clearly understood. In murine models of CMV infection, we have observed early damage to the capillary networks in stria vascularis, as well as hearing loss manifested in ABR threshold elevations. Our experimental hypothesis is that strial damage causes a reduced endocochlear potential (EP) resulting in impaired haircell activation and consequent hearing loss. We have studied strial damage, EP, and ABR threshold elevations in two mouse models (BALB/c and C57BL6 strains) infected with murine CMV. Neonatal (P3) pups were inoculated with murine CMV (2µl of 200pfu) by intra cerebral injection. Control mice were saline injected. At 6 weeks, ABR thresholds to tonal stimuli at 8, 16 and 32 kHz were determined for each ear. At 8 weeks a sub-group of treated and control animals was prepared for study of cochlear capillary networks using scanning electron microscopy of corrosion cast specimens. In a second group, at 8 weeks, EP measurements from both cochleas were made. We report that in both mouse strains, CMV infection caused capillary loss in the stria vascularis, initially at the cochlear apex, and extending to lower cochlear turns in some subjects. After CMV infection, in both BALB/c and C57BL6 mice, reduced EPs and ABR threshold elevations were observed, and there was a within-animal correlation between loss of EP and ABR threshold elevations across the sound frequencies tested. These results suggest that CMV induced damage to stria vascularis results in EP reduction that is correlated with ABR threshold elevations. Extrapolating to the human condition, we suggest that strial damage and its physiological consequences may contribute to the initial hearing loss in congenital CMV infection. The early involvement of cochlear capillary damage may encourage a focus on therapeutic interventions that can prevent vascular damage, or subsequently promote vascular healing or angiogenesis.