Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation.

BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted key secondary outcomes were ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other key secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Preoperative Prediction of Postoperative Infections Using Machine Learning and Electronic Health Record Data.

OBJECTIVE: To estimate preoperative risk of postoperative infections using structured electronic health record (EHR) data. BACKGROUND: Surveillance and reporting of postoperative infections is primarily done through costly, labor-intensive manual chart reviews on a small sample of patients. Automated methods using statistical models applied to postoperative EHR data have shown promise to augment manual review as they can cover all operations in a timely manner. However, there are no specific models for risk-adjusting infectious complication rates using EHR data. METHODS: Preoperative EHR data from 30,639 patients (2013-2019) were linked to the American College of Surgeons National Surgical Quality Improvement Program preoperative data and postoperative infection outcomes data from 5 hospitals in the University of Colorado Health System. EHR data included diagnoses, procedures, operative variables, patient characteristics, and medications. Lasso and the knockoff filter were used to perform controlled variable selection. Outcomes included surgical site infection, urinary tract infection, sepsis/septic shock, and pneumonia up to 30 days postoperatively. RESULTS: Among >15,000 candidate predictors, 7 were chosen for the surgical site infection model and 6 for each of the urinary tract infection, sepsis, and pneumonia models. Important variables included preoperative presence of the specific outcome, wound classification, comorbidities, and American Society of Anesthesiologists physical status classification. The area under the receiver operating characteristic curve for each model ranged from 0.73 to 0.89. CONCLUSIONS: Parsimonious preoperative models for predicting postoperative infection risk using EHR data were developed and showed comparable performance to existing American College of Surgeons National Surgical Quality Improvement Program risk models that use manual chart review. These models can be used to estimate risk-adjusted postoperative infection rates applied to large volumes of EHR data in a timely manner.

The deimplementation of laboratory testing in low-risk patients as recommended by the American society of anesthesiologists: An ACS-NSQIP longitudinal analysis.

BACKGROUND: In 2012, the American Society of Anesthesiologists (ASA) published guidelines recommending against routine preoperative laboratory testing for low-risk patients to reduce unnecessary medical expenditures. The aim of this study was to assess the change in routine preoperative laboratory testing in low-risk versus higher-risk patients before and after release of these guidelines. METHODS: The ACS-NSQIP database, 2005-2018, was separated into low-risk versus higher-risk patients based upon a previously published stratification. The guideline implementation date was defined as January 2013. Changes in preoperative laboratory testing over time were compared between low- and higher-risk patients. A difference-in-differences model was applied. The primary outcome included any laboratory test obtained ≤90 days prior to surgery. RESULTS: Of 7,507,991 patients, 972,431 (13.0%) were defined as low-risk and 6,535,560 (87.0%) higher-risk. Use of any preoperative laboratory test declined in low-risk patients from 66.5% before to 59.6% after guidelines, a 6.9 percentage point reduction, versus 93.0%-91.9% in higher-risk patients, a 1.1 percentage point reduction (p < 0.0001, comparing percentage point reductions). After risk-adjustment, the adjusted odds ratio for having any preoperative laboratory test after versus before the guidelines was 0.77 (95% CI 0.76-0.78) in low-risk versus 0.93 (0.92-0.94) in higher-risk patients. In low-risk patients, lack of any preoperative testing was not associated with worse outcomes. CONCLUSIONS: While a majority of low-risk patients continue to receive preoperative laboratory testing not recommended by the ASA, there has been a decline after implementation of guidelines. Continued effort should be directed at the deimplementation of routine preoperative laboratory testing for low-risk patients.

Preoperative Prediction of Unplanned Reoperation in a Broad Surgical Population.

INTRODUCTION: Unplanned reoperation is an undesirable outcome with considerable risks and an increasingly assessed quality of care metric. There are no preoperative prediction models for reoperation after an index surgery in a broad surgical population in the literature. The Surgical Risk Preoperative Assessment System (SURPAS) preoperatively predicts 12 postoperative adverse events using 8 preoperative variables, but its ability to predict unplanned reoperation has not been assessed. This study's objective was to determine whether the SURPAS model could accurately predict unplanned reoperation. METHODS: This was a retrospective analysis of the American College of Surgeons' National Surgical Quality Improvement Program adult database, 2012-2018. An unplanned reoperation was defined as any unintended operation within 30 d of an initial scheduled operation. The 8-variable SURPAS model and a 29-variable "full" model, incorporating all available American College of Surgeons' National Surgical Quality Improvement Program nonlaboratory preoperative variables, were developed using multiple logistic regression and compared using discrimination and calibration metrics: C-indices (C), Hosmer-Lemeshow observed-to-expected plots, and Brier scores (BSs). The internal chronological validation of the SURPAS model was conducted using "training" (2012-2017) and "test" (2018) datasets. RESULTS: Of 5,777,108 patients, 162,387 (2.81%) underwent an unplanned reoperation. The SURPAS model's C-index of 0.748 was 99.20% of that for the full model (C = 0.754). Hosmer-Lemeshow plots showed good calibration for both models and BSs were similar (BS = 0.0264, full; BS = 0.0265, SURPAS). Internal chronological validation results were similar for the training (C = 0.749, BS = 0.0268) and test (C = 0.748, BS = 0.0250) datasets. CONCLUSIONS: The SURPAS model accurately predicted unplanned reoperation and was internally validated. Unplanned reoperation can be integrated into the SURPAS tool to provide preoperative risk assessment of this outcome, which could aid patient risk education.

Does Work Relative Value Unit Measure Surgical Complexity for Risk Adjustment of Surgical Outcomes?

INTRODUCTION: The purpose of this study was to determine whether the work relative value unit (workRVU) of a patient's operation can be useful as a measure of surgical complexity for the risk adjustment of surgical outcomes. METHODS: We retrospectively analyzed the American College of Surgeon's National Surgical Quality Improvement Program database (2005-2018). We examined the associations of workRVU of the patient's primary operation with preoperative patient characteristics and associations with postoperative complications. We performed forward selection multiple logistic regression analysis to determine the predictive importance of workRVU. We then generated prediction models using patient characteristics with and without workRVU and compared c-indexes to assess workRVU's additive predictive value. RESULTS: 7,507,991 operations were included. Patients who were underweight, functionally dependent, transferred from an acute care hospital, had higher American Society of Anesthesiologists class or who had medical comorbidities had operations with higher workRVU (all P < 0.0001). The subspecialties with the highest workRVU were neurosurgery (mean = 22.2), thoracic surgery (mean = 21.1), and vascular surgery (mean = 18.8) (P < 0.0001). For all postoperative complications, mean workRVU was higher for patients with the complication than those without (all P < 0.0001). For eight of 12 postoperative complications, workRVU entered the logistic regression models as a predictor variable in the 1st to 4th steps. Addition of workRVU as a preoperative predictive variable improved the c-index of the prediction models. CONCLUSIONS: WorkRVU was associated with sicker patients and patients experiencing postoperative complications and was an important predictor of postoperative complications. When added to a prediction model including patient characteristics, it only marginally improved prediction. This is possibly because workRVU is associated with patient characteristics.

Inpatient Versus Outpatient Surgery: A Comparison of Postoperative Mortality and Morbidity in Elective Operations.

BACKGROUND: Operations performed outpatient offer several benefits. The prevalence of outpatient operations is growing. Consequently, the proportion of patients with multiple comorbidities undergoing outpatient surgery is increasing. We compared 30-day mortality and overall morbidity between outpatient and inpatient elective operations. METHODS: Using the 2005-2018 ACS-NSQIP database, we evaluated trends in percent of hospital outpatient operations performed over time, and the percent of operations done outpatient versus inpatient by CPT code. Patient characteristics were compared for outpatient versus inpatient operations. We compared unadjusted and risk-adjusted 30-day mortality and morbidity for inpatient and outpatient operations. RESULTS: A total of 6,494,298 patients were included. The proportion of outpatient operations increased over time, from 37.8% in 2005 to 48.2% in 2018. We analyzed the 50 most frequent operations performed outpatient versus inpatient 25-75% of the time (n = 1,743,097). Patients having outpatient operations were younger (51.6 vs 54.6 years), female (70.3% vs 67.3%), had fewer comorbidities, and lower ASA class (I-II, 69.3% vs. 59.9%). On both unadjusted and risk-adjusted analysis, 30-day mortality and overall morbidity were less likely in outpatient versus inpatient operations. CONCLUSION: In this large multi-specialty analysis, we found that patients undergoing outpatient surgery had lower risk of 30-day morbidity and mortality than those undergoing the same inpatient operation. Patients having outpatient surgery were generally healthier, suggesting careful patient selection occurred even with increasing outpatient operation frequency. Patients and providers can feel reassured that outpatient operations are a safe, reasonable option for selected patients.

Steroid phobia on social media platforms.

Topical corticosteroids (TCS) are the most commonly prescribed treatment for children with atopic dermatitis and are supported by the American Academy of Dermatology (AAD) atopic dermatitis treatment guidelines with level I strength A evidence; however, fear regarding their use, coined "steroid phobia," is widespread. In this study, we analyzed steroid phobia-related content on popular social media platforms. We found much of this content consists of patients describing negative personal experiences with TCS and subsequently discouraging viewer use. We conclude that social media may contribute to steroid phobia, and we hope that our study motivates dermatologists with social media platforms to combat common misconceptions surrounding TCS use.

Using the Surgical Risk Preoperative Assessment System to Define the "High Risk" Surgical Patient.

BACKGROUND: Defining a "high risk" surgical population remains challenging. Using the Surgical Risk Preoperative Assessment System (SURPAS), we sought to define "high risk" groups for adverse postoperative outcomes. MATERIALS AND METHODS: We retrospectively analyzed the 2009-2018 American College of Surgeons National Surgical Quality Improvement Program database. SURPAS calculated probabilities of 12 postoperative adverse events. The Hosmer Lemeshow graphs of deciles of risk and maximum Youden index were compared to define "high risk." RESULTS: Hosmer-Lemeshow plots suggested the "high risk" patient could be defined by the 10th decile of risk. Maximum Youden index found lower cutoff points for defining "high risk" patients and included more patients with events. This resulted in more patients classified as "high risk" and higher number needed to treat to prevent one complication. Some specialties (thoracic, vascular, general) had more "high risk" patients, while others (otolaryngology, plastic) had lower proportions. CONCLUSIONS: SURPAS can define the "high risk" surgical population that may benefit from risk-mitigating interventions.

Environmental Fate of Cl-PFPECAs: Predicting the Formation of PFAS Transformation Products in New Jersey Soils.

Although next-generation per- and polyfluorinated substances (PFAS) were designed and implemented as safer and environmentally degradable alternatives to "forever" legacy PFAS, there is little evidence to support the actual transformation of these compounds and less evidence of the safety of transformed products in the environment. Multiple congeners of one such PFAS alternative, the chloro-perfluoropolyether carboxylates (Cl-PFPECAs), have been found in New Jersey soils surrounding a manufacturing facility. These compounds are ideal candidates for investigating environmental transformation due to the existence of potential reaction centers including a chlorinated carbon and ether linkages. Transformation products of the chemical structures of this class of compounds were predicted based on analogous PFAS transformation pathways documented in peer-reviewed literature. Potential reaction products were used as the basis for high-resolution mass-spectrometric suspect screening of the soils. Suspected transformation products of multiple congeners, the Cl-PFPECAs, including H-PFPECAs, epox-PFPECAs, and diOH-PFPECAs, were tentatively observed in these screenings. Although ether linkages have been hypothesized as potential reaction centers under environmental conditions, to date, no documentation of ether scission has been identified. Despite exhaustive scrutiny of the high-resolution data for our Cl-PFPECA-laden soils, we found no evidence of ether scission.

Associations Between Preoperative Risk, Postoperative Complications, and 30-Day Mortality.

BACKGROUND: Comorbidities and postoperative complications increase mortality, making early recognition and management critical. It is useful to understand how they are associated with one another. This study assesses associations between comorbidities, complications, and mortality. METHODS: We calculated associations between comorbidities, complications, and 30-day mortality using the 2012-2018 ACS-NSQIP database. We examined the association between mortality and number of complications which complications were most associated with mortality. RESULTS: 5,777,108 patients were included. 30-day mortality was 0.95%. For most comorbidities or postoperative complications, patients with these had higher mortality than patients without. Having ≥ 1 complication increased mortality risk by 32.5-fold (6.5% vs. 0.2%). Mortality rate significantly increased with increasing number of complications, particularly after two or more complications. Bleeding and sepsis were associated with the most deaths. CONCLUSION: The 30-day mortality rate was < 1% but was 32-fold higher in patients with complications and increased rapidly for patients with ≥ 2 complications. Bleeding and sepsis were the most prominent complications associated with mortality.

Postoperative pulmonary complications with adjuvant regional anesthesia versus general anesthesia alone: a sub-analysis of the Perioperative Research Network study.

BACKGROUND: Adjuvant regional anesthesia is often selected for patients or procedures with high risk of pulmonary complications after general anesthesia. The benefit of adjuvant regional anesthesia to reduce postoperative pulmonary complications remains uncertain. In a prospective observational multicenter study, patients scheduled for non-cardiothoracic surgery with at least one postoperative pulmonary complication surprisingly received adjuvant regional anesthesia more frequently than those with no complications. We hypothesized that, after adjusting for surgical and patient complexity variables, the incidence of postoperative pulmonary complications would not be associated with adjuvant regional anesthesia. METHODS: We performed a secondary analysis of a prospective observational multicenter study including 1202 American Society of Anesthesiologists physical status 3 patients undergoing non-cardiothoracic surgery. Patients were classified as receiving either adjuvant regional anesthesia or general anesthesia alone. Predefined pulmonary complications within the first seven postoperative days were prospectively identified. Groups were compared using bivariable and multivariable hierarchical logistic regression analyses for the outcome of at least one postoperative pulmonary complication. RESULTS: Adjuvant regional anesthesia was performed in 266 (22.1%) patients and not performed in 936 (77.9%). The incidence of postoperative pulmonary complications was greater in patients receiving adjuvant regional anesthesia (42.1%) than in patients without it (30.9%) (site adjusted p = 0.007), but this association was not confirmed after adjusting for covariates (adjusted OR 1.37; 95% CI, 0.83-2.25; p = 0.165). CONCLUSION: After adjusting for surgical and patient complexity, adjuvant regional anesthesia versus general anesthesia alone was not associated with a greater incidence of postoperative pulmonary complications in this multicenter cohort of non-cardiothoracic surgery patients.

Health economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): a cost-effectiveness analysis.

PURPOSE: We sought to compare the cost-effectiveness of probiotics and usual care with usual care without probiotics in mechanically ventilated, intensive care unit patients alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT). METHODS: We conducted a health economic evaluation alongside the PROSPECT randomized control trial (October 2013-March 2019). We adopted a public healthcare payer's perspective. Forty-four intensive care units in three countries (Canada/USA/Saudi Arabia) with adult critically ill, mechanically ventilated patients (N = 2,650) were included. Interventions were probiotics (Lactobacillus rhamnosus GG) vs placebo administered enterally twice daily. We collected healthcare resource use and estimated unit costs in 2019 United States dollars (USD) over a time horizon from randomization to hospital discharge/death. We calculated incremental cost-effectiveness ratios (ICERs) comparing probiotics vs usual care. The primary outcome was incremental cost per ventilator-associated pneumonia (VAP) event averted; secondary outcomes were costs per Clostridioides difficile-associated diarrhea (CDAD), antibiotic-associated diarrhea (AAD), and mortality averted. Uncertainty was investigated using nonparametric bootstrapping and sensitivity analyses. RESULTS: Mean (standard deviation [SD]) cost per patient was USD 66,914 (91,098) for patients randomized to probiotics, with a median [interquartile range (IQR)] of USD 42,947 [22,239 to 76,205]. By comparison, for those not receiving probiotics, mean (SD) cost per patient was USD 62,701 (78,676) (median [IQR], USD 41,102 [23,170 to 75,140]; incremental cost, USD 4,213; 95% confidence interval [CI], -2,269 to 10,708). Incremental cost-effectiveness ratios for VAP or AAD events averted, probiotics were dominated by usual care (more expensive, with similar effectiveness). The ICERs were USD 1,473,400 per CDAD event averted (95% CI, undefined) and USD 396,764 per death averted (95% CI, undefined). Cost-effectiveness acceptability curves reveal that probiotics were not cost-effective across wide ranges of plausible willingness-to-pay thresholds. Sensitivity analyses did not change the conclusions. CONCLUSIONS: Probiotics for VAP prevention among critically ill patients were not cost-effective. Study registration data www. CLINICALTRIALS: gov (NCT01782755); registered 4 February 2013.

RéSUMé: OBJECTIF: Nous avons cherché à comparer le rapport coût-efficacité d'un traitement avec probiotiques ajoutés aux soins habituels avec des soins habituels prodigués sans probiotiques chez les patients des soins intensifs sous ventilation mécanique dans le cadre de l'étude PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial). MéTHODE: Nous avons réalisé une évaluation de l'économie de la santé parallèlement à l'étude randomisée contrôlée PROSPECT (octobre 2013-mars 2019). Nous avons adopté le point de vue d'un payeur public de services de santé. Quarante-quatre unités de soins intensifs dans trois pays (Canada/États-Unis/Arabie saoudite) prenant soin de patients adultes gravement malades sous ventilation mécanique (n = 2650) ont été inclus. Les interventions ont été les suivantes : probiotiques (Lactobacillus rhamnosus GG) vs placebo administrés par voie entérale deux fois par jour. Nous avons recueilli les données concernant l'utilisation des ressources en soins de santé et estimé les coûts unitaires en dollars américains (USD) de 2019 sur un horizon temporel allant de la randomisation au congé de l'hôpital / décès. Nous avons calculé des rapports coût-efficacité différentiels (RCED) en comparant les probiotiques vs les soins habituels. Le critère d'évaluation principal était le coût différentiel par événement évité de pneumonie associée au ventilateur (PAV); les critères d'évaluation secondaires étaient les coûts par diarrhée associée au Clostridioides difficile (DACD), diarrhée associée aux antibiotiques (DAA) et mortalité évitées. L'incertitude a été étudiée à l'aide d'analyses d'amorçage et de sensibilité non paramétriques. RéSULTATS: Le coût moyen (écart type [ÉT]) par patient était de 66 914 (91 098) USD pour les patients randomisés au groupe probiotiques, avec une médiane [écart interquartile (ÉIQ)] de 42 947 USD [22 239 à 76 205]. En comparaison, pour ceux ne recevant pas de probiotiques, le coût moyen (ÉT) par patient était de 62 701 USD (78 676) (médiane [ÉIQ], 41 102 USD [23 170 à 75 140]; coût différentiel, 4213 USD; intervalle de confiance [IC] à 95%, -2269 à 10 708). En matière de rapports coût-efficacité différentiels pour les événements de PAV ou DAA évités, les probiotiques étaient dominés par les soins habituels (plus coûteux, avec une efficacité similaire). Les RCED étaient de 1 473 400 USD par événement de DACD évitée (IC 95 %, non défini) et de 396 764 USD par décès évité (IC 95 %, non défini). Les courbes d'acceptabilité coût-efficacité révèlent que les probiotiques n'étaient pas rentables dans de larges gammes de seuils plausibles de volonté de payer. Les analyses de sensibilité n'ont pas modifié les conclusions. CONCLUSION: Les probiotiques utilisés pour prévenir la PAV chez les patients gravement malades n'étaient pas rentables. Enregistrement de l'étude : www.clinicaltrials.gov (NCT01782755); enregistrée le 4 février 2013.

A Pilot Study of Patient-Reported Outcome Measures Across a Broad Sample of Surgical Patients.

BACKGROUND: Patient-reported outcomes (PROs) have the potential to aid in surgical decision-making, predict surgical outcomes, assess recovery, and evaluate long-term success. We performed a pilot study testing the ability to use PROs in a broad surgical population in preparation for wide spread use. MATERIAL AND METHODS: Surgical patients completed five Patient-Reported Outcome Measurement Information System (PROMIS) measures during their preoperative encounter in the preanesthesia clinic and again postoperatively via emailed link. Preoperative to postoperative changes in PROMIS scores, factors related to completion of postoperative measures, intercorrelations between PROMIS measures, and numbers of patients with normal function, and mild, moderate, and severe deficits in PROMIS scores were analyzed. RESULTS: A total of 393 patients undergoing surgery in 8 specialties completed preoperative PROMIS measures; 239 (60.8%) completed them postoperatively. Physical function (P < 0.0001), pain (P < 0.0001), and cognitive function (P = 0.03) PROMIS scores significantly worsened after surgery but not mental PROMIS scores (P = 0.48). Hispanic and sicker patients had lower completion rates of postoperative measures. Intercorrelations were very high (>0.80) among the physical function and self-efficacy for activities of daily living PROMIS measures. Physical function and pain PROMIS measures had the largest number of patients in the "severe" range after surgery. CONCLUSIONS: Patients across a broad surgical population completed PROMIS measures successfully, both preoperatively and postoperatively, although the postoperative completion rate was lower than other studies reported in the literature. PROMIS scores were reflective of the effects of surgery. Some of the PROMIS measures were highly correlated suggesting that some measures could be eliminated or replaced with measures assessing other important effects of surgery. Consideration could be made to alert health care providers about patients having PROs in the "severe" range for potential intervention.

Perioperative myocardial injury risk after elective knee and hip arthroplasty in patients with a high risk of obstructive sleep apnea.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) occurs in approximately 8-13% of patients and has significant 30-day mortality. Patients with obstructive sleep apnea (OSA) suffer recurrent hypoxemia during sleep and surgical patients with OSA are known to have increased risk of cardiorespiratory complications. We hypothesized that patients at high risk for OSA may have an increased risk of MINS. As a secondary analysis, we assessed rates of postoperative cardiopulmonary complications. METHODS: Adult patients undergoing elective knee or hip arthroplasty with STOPBANG score ≥ 5 were recruited. MINS was determined by measuring troponin-I on postoperative days 1 and 2. RESULTS: A total of 82 patients were studied. Only one patient had a positive troponin (MINS rate of 1.2%). The rate of cardiopulmonary complications was low (4.9%) and the 30-day mortality rate for these patients was 0. CONCLUSION: The incidence of MINS and postoperative cardiopulmonary complications in patients with elective arthroplasty and a high risk of OSA were low.

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial.

Importance: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. Objective: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). Design, Setting, and Participants: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). Interventions: Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. Main Outcomes and Measures: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. Results: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001). Conclusions and Relevance: Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02462590.

Ab Initio Molecular Dynamics Investigation of Beryllium Complexes.

Structures of aqueous [Be(H2O)4]2+, its outer-sphere and inner-sphere complexes with F-, Cl-, and SO42-, and dinuclear complexes with a [Be2(κ-OH)(κ-SO4)]+ core have been studied through Car-Parrinello molecular dynamics (CPMD) simulations with the BLYP functional. According to constrained CPMD/BLYP simulations and pointwise thermodynamic integration, the free energy of deprotonation of [Be(H2O)4]2+ and its binding free energy with F- are 9.6 and -6.2 kcal/mol, respectively, in good accord with available experimental data. The computed activation barriers for replacing a water ligand in [Be(H2O)4]2+ with F- and SO42-, 10.9 and 13.6 kcal/mol, respectively, are also in good qualitative agreement with available experimental data. These ligand-substitution reactions are indicated to follow associative interchange mechanisms with backside (SN2-like) attack of the anion relative to the aquo ligand it is displacing. Outperforming static density functional theory computations of the salient kinetic and thermodynamic quantities involving simple polarizable continuum solvent models, CPMD simulations are validated as a promising tool for studying the structures and speciation of beryllium complexes in aqueous solution.

Preventative Root-Collar Excavation Reduces Peach Tree Mortality Caused By Armillaria Root Rot On Replant Sites.

In the southeastern United States, Armillaria root rot (ARR) is caused by Desarmillaria tabescens and has become the primary cause of premature mortality in peach orchards. Most rootstocks used in commercial orchards are susceptible and management options are limited. A postinfection practice known as root-collar excavation (RCE), which involves permanent removal of the soil from the base of the trunk, has been shown to improve yields and prolong the productive life of symptomatic trees. However, symptomatic trees already have an advanced infection at the base of the trunk. This study evaluated the efficacy of preventative RCE on the progression of tree mortality in two orchards that were planted in infested replant sites. To provide convincing data for growers, the study was carried out in a commercial orchard and an experimental orchard for 8 years. Furthermore, representative enterprise budgets and net present value (NPV) analysis were utilized to compare the profitability of the two approaches. Trees were planted shallow on berms (45 by 90 cm) to facilitate RCE with hoes and AirSpade 2 years later. Tree mortality in the RCE treatment of the experimental orchard was first observed in year 6 and increased 8% on average per year thereafter. In contrast, tree mortality in the "Grower Standard" treatment was first observed in year 4 and increased 12.7% on average per year thereafter. At the commercial orchard, tree mortality in the RCE treatment was first observed in year 7 and increased 1.9% on average thereafter, while tree mortality in the Grower Standard treatment first appeared in year 5 and increased 4.3% on average thereafter. The delayed onset of ARR-associated tree mortality and the lower annual tree mortality rate in the RCE treatment led to higher NPVs in both locations. There were no negative effects on yield or fruit quality. However, the new planting system can create horticultural challenges, including the formation of a proper berm, uneven ground around the tree interfering with tree care and harvest, increased erosion due to channeling of rainwater, and increased rootstock suckering. The RCE is a valid option for southeastern growers needing to manage high ARR disease pressure on replant sites or on sites only recently cleared from ARR-infected forest land.

Electrospray Ionization Mass Spectrometric Study of the Gas-Phase Coordination Chemistry of Be2+ Ions with 1,2- and 1,3-Diketone Ligands.

Electrospray ionization mass spectrometry (ESI MS) is a powerful technique for the study of coordination complexes because of its ability to analyze solution systems involving very low concentrations of metal complexes. In this work, the coordination chemistry of Be ions with a selection of well-known 1,3-diketone and related 1,2-diketone ligands has been investigated using ESI MS. With acetylacetone (Hacac), a range of acac-containing ions is observed, including [Be(acac)2H]+, [Be(acac)(MeOH) n]+ ( n = 1, 2), and polynuclear species such as the dinuclear [Be2(acac)3]+ and trinuclear [Be3O(acac)3]+. Density functional theory calculations indicate that the latter species has a central Be3(µ3-O) core, with each Be chelated (as opposed to being bridged) by an acac ligand. The effect of changing the substituents on 1,3-diketone was explored by an investigation of mixtures of Be2+ with other 1,3-diketones such as dibenzoylmethane (Hdbm), where the [Be(dbm)2H]+ ion showed a lesser tendency to undergo fragmentation and aggregation processes. Comparisons with the corresponding aluminum acetylacetone system were also made. In contrast, mixtures of Be2+ and the 1,2-diketones diacetyl and phenanthrenequinone showed poor metal-ligand interactions. Be2+ interacted with the 1,2-diketone benzil [PhC(O)C(O)Ph], forming the [Be(benzil) n]2+ ( n = 2-4) ions. The synthesis (from BeCl2) and X-ray structures of the dibenzoylmethanato (dbm) complex Be(dbm)2 and the benzil complex [BeCl2(benzil)] are also reported.

Tuning receptors for the encapsulation of beryllium2.

Two series of tetradentate tripodal di-pyridine-based receptors designed to bind Be2+ cations have been studied in the aqueous phase at the B3LYP/6-311++G(d,p) computational level. The first series comprise simple tetrahedral receptors; the second series incorporates additional scaffolding groups capable of second sphere hydrogen-bonding in order to more finely tune the binding strength towards the Be2+ cation. Out of the five ligand candidates, one containing a tri-pyridyl N-donor along with a phenolato O-donor (L1) exhibited a significant improvement in binding energy stabilisation (47.8 kJ mol-1) towards the Be2+ cation in the presence of second-sphere H-bonding interactions.

First Report of the Root-Knot Nematode, Meloidogyne floridensis Infecting Guardian® Peach Rootstock in South Carolina, USA.

In 2018 to 2019, soil and root samples from some declining peach orchards were collected in Edgefield County, South Carolina, USA. Excavated roots of Guardian® peach (Prunus persica) rootstock showed strong gall symptoms. Extracted root-knot nematodes (RKN) were identified by both morphological and molecular methods as M. floridensis. This is the first detection of the peach RKN in South Carolina and the third state in the USA after Florida and California.