Incidence of acute kidney injury (AKI) and its impact on patient outcomes among adult hospitalized patients with carbapenem-resistant Gram-negative infections who received targeted treatment with a newer ß-lactam or ß-lactam/ß-lactamase inhibitor-, polymyxin- or aminoglycoside-containing regimen.

BACKGROUND: Limited comparative data exist on acute kidney injury (AKI) risk and AKI-associated outcomes in hospitalized patients with carbapenem-resistant Gram-negative infections (CR-GNIs) treated with a newer ß-lactam/ß-lactam-ß-lactamase inhibitor (BL/BL-BLI)-, polymyxin (PB)- or aminoglycoside (AG)-containing regimen. This study quantified the risk of AKI and AKI-related outcomes among patients with CR-GNIs treated with a newer BL/BL-BLI-, PB- or AG-containing regimen. METHODS: A multicentre, retrospective, observational study was performed (2016-20). The study included adult hospitalized patients with (i) baseline estimated glomerular filtration rates ≥30 mL/min/1.73 m2; (ii) CR-GN pneumonia, complicated urinary tract infection or bloodstream infection; and (iii) receipt of newer BL/BL-BLI, PG or AG within 7 days of index CR-GN culture for ≥3 days. Outcomes included AKI, in-hospital mortality and hospital costs. RESULTS: The study included 750 patients and most (48%) received a newer BL/BL-BLI. The median (IQR) treatment duration was 8 (5-11), 5 (4-8) and 7 (4-8) days in the newer BL/BL-BLI group, AG group and PB group, respectively. The PB group had the highest adjusted AKI incidence (95% CI) (PB: 25.1% (15.6%-34.6%) versus AG: 8.9% (5.7%-12.2%) versus newer BL/BL-BLI: 11.9% (8.1%-15.7%); P = 0.001). Patients with AKI had significantly higher in-hospital mortality (AKI: 18.5% versus 'No AKI': 5.6%; P = 0.001) and mean hospital costs (AKI: $49 192 versus 'No AKI': $38,763; P = 0.043). CONCLUSIONS: The AKI incidence was highest among PB patients and patients with AKI had worse outcomes. Healthcare systems should consider minimizing the use of antibiotics that augment AKI risk as a measure to improve outcomes in patients with CR-GNIs.

Comparative evaluation of early treatment with ceftolozane/tazobactam versus ceftazidime/avibactam for non-COVID-19 patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR-Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam. METHODS: The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016-22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission. RESULTS: The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%-66.8%)]. CONCLUSIONS: Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA.

The Public Health and Economic Impact of Drug Overdose Out-of-Hospital Cardiac Arrest in the United States.

OBJECTIVE: To calculate disability-adjusted life years (DALY) and labor productivity loss due to drug overdose out-of-hospital cardiac arrest (DO-OHCA) and compare its contribution to the burden of disease and economic impact of all-cause nontraumatic out-of-hospital cardiac arrest (OHCA) in the US. METHODS: We performed a retrospective observational cohort analysis of all adult (age ≥18 years) nontraumatic emergency medical services-treated OHCA events, including those due to DO-OHCA, from the national Cardiac Arrest Registry to Enhance Survival (CARES) database from January 1, 2017 and December 31, 2020. The main outcome measures of interest were disability-adjusted life years, annual, and lifetime labor productivity loss over the 4-year study period. The findings for the study population were extrapolated to a national level using the CARES population catchment and U.S. population estimates by year. RESULTS: A total of 378,088 adult OHCA events, including 23,252 DO-OHCA (6.2%) met study inclusion criteria. The DO-OHCA DALY increased from 156,707 in 2017 to 265,692 in 2020. Per year, DO-OHCA contributed to 11.4%, 12.0%, 10.5%, and 11.4% of all OHCA DALY lost from 2017-2020, respectively. The mean annual and lifetime productivity losses for all OHCA were stable over time (annual: $47K in 2017 to $50K in 2020; lifetime: $647K in 2017 to $692K in 2020). The CARES population catchment increased by 39.8% over the study period (102.6 M in 2017 to 143.4 M in 2020). For DO-OHCA, the mean annual productivity loss was approximately 30% higher than non-DO-OHCA ($64K vs. $49K in 2020, respectively). The mean lifetime productivity loss for DO-OHCA was 2.5 times higher than non-DO-OHCA ($1.6 M vs. $630K in 2020, respectively). CONCLUSIONS: The DALY due to DO-OHCA has increased over time with expansion of the CARES dataset, but its relative contribution to total OHCA DALY (all non-traumatic etiologies) remained fairly stable. The DO-OHCAs represent approximately 6% of all adult non-traumatic EMS-treated OHCA events but has a disproportionately greater economic impact. Continued efforts to reduce DO-OHCA through public health initiatives are warranted to lessen the societal impact of OHCA in the U.S.

The temporal trend of placebo response in migraine prevention from 1990 to 2021: a systematic literature review and meta-analysis with regression.

BACKGROUND: Migraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression. METHODS: We conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥ 50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders. RESULTS: A total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho = 0.32, p = 0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho = 0.08, p = 0.596). Placebo response also varied by route of administration. CONCLUSION: Placebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.

Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019.

OBJECTIVES: Multiple randomized controlled trials exploring the outcomes of patients with ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia have noted that hospital-acquired bacterial pneumonia patients who require subsequent ventilated hospital-acquired bacterial pneumonia suffered higher mortality than either those who did not (nonventilated hospital-acquired bacterial pneumonia) or had ventilator-associated bacterial pneumonia. We examined the epidemiology and outcomes of all three conditions in a large U.S. database. DESIGN: Retrospective cohort. SETTING: Two hundred fifty-three acute-care hospitals, United States, contributing data (including microbiology) to Premier database, 2012-2019. PATIENTS: Patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia identified based on a slightly modified previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition-Clinical Modification algorithm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 17,819 patients who met enrollment criteria, 26.5% had nonventilated hospital-acquired bacterial pneumonia, 25.6% vHAPB, and 47.9% ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia predominated in the Northeastern United States and in large urban teaching hospitals. Patients with nonventilated hospital-acquired bacterial pneumonia were oldest (mean 66.7 ± 15.1 yr) and most likely White (76.9%), whereas those with ventilator-associated bacterial pneumonia were youngest (59.7 ± 16.6 yr) and least likely White (70.3%). Ventilated hospital-acquired bacterial pneumonia was associated with the highest comorbidity burden (mean Charlson score 4.1 ± 2.8) and ventilator-associated bacterial pneumonia with the lowest (3.2 ± 2.5). Similarly, hospital mortality was highest among patients with ventilated hospital-acquired bacterial pneumonia (29.2%) and lowest in nonventilated hospital-acquired bacterial pneumonia (11.7%), with ventilator-associated bacterial pneumonia in-between (21.3%). Among survivors, 24.5% of nonventilated hospital-acquired bacterial pneumonia required a rehospitalization within 30 days of discharge, compared with 22.5% among ventilated hospital-acquired bacterial pneumonia and 18.8% ventilator-associated bacterial pneumonia. Unadjusted hospital length of stay after infection onset was longest among ventilator-associated bacterial pneumonia and shortest among nonventilated hospital-acquired bacterial pneumonia patients. Median total hospital costs mirrored length of stay: ventilator-associated bacterial pneumonia $77,657, ventilated hospital-acquired bacterial pneumonia $62,464, and nonventilated hospital-acquired bacterial pneumonia $39,911. CONCLUSIONS: Both hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia remain associated with significant mortality and cost in the United States. Our analyses confirm that of all three conditions, ventilated hospital-acquired bacterial pneumonia carries the highest risk of death. In contrast, ventilator-associated bacterial pneumonia remains most costly. Nonventilated hospital-acquired bacterial pneumonia survivors were most likely to require a readmission within 30 days of discharge.

Factors affecting need for blood transfusion in paediatric patients undergoing open surgery for hip dysplasia.

BACKGROUND AND OBJECTIVES: The management of intraoperative blood loss in the surgical treatment of paediatric hip dysplasia is resource intensive. There are numerous clinical factors that impact the need for intraoperative transfusion. Identification of patient and surgical factors associated with increased blood loss may reduce the unnecessary use of resources. This study aimed to identify factors predictive of intraoperative transfusion in children undergoing hip dysplasia surgery. MATERIALS AND METHODS: This is a single-centre retrospective review of patients undergoing surgery for hip dysplasia from 1 January 2012 to 15 April 2021. Patient demographic factors, anaesthetic, surgical and transfusion histories were reviewed. Multivariable logistic regression analysis was performed to identify factors predictive of allogeneic red blood cell transfusion requirements during the intraoperative period. RESULTS: This study includes 595 patients who underwent open surgery for hip dysplasia, including 297 (52.6%) classified as developmental dysplasia (DD) and 268 (47.3%) as neuromuscular (NM) with a mean age of 9.1 years (interquartile range 3-14). Intraoperative allogeneic transfusion was identified in 26/297 (8.8%) DD and 73/268 (27.2%) NM patients. Adjusted factors associated with increased odds of intraoperative transfusion were NM (odds ratio [OR] = 2.96, 95% confidence interval [CI] [1.76, 5.00]) and the number of osteotomies performed (OR = 1.82/osteotomy, 95% CI [1.40, 2.35]). Adjusted factors that reduced the odds of transfusion were the use of antifibrinolytics (OR = 0.35, 95% CI [0.17, 0.71]) and regional anaesthesia (OR = 0.52, 95% CI [0.29, 0.94]). CONCLUSION: For children undergoing surgery for hip dysplasia, the number of osteotomies performed is predictive of the need for allogeneic blood transfusion. Antifibrinolytics and regional anaesthesia are associated with reduced risk for allogeneic blood transfusion. Blood management initiatives, such a preoperative optimization of haemoglobin and the use of antifibrinolytics, could target patients at increased risk of intraoperative bleeding and transfusion.

The risk of inappropriate empiric treatment and its outcomes based on pathogens in non-ventilated (nvHABP), ventilated (vHABP) hospital-acquired and ventilator-associated (VABP) bacterial pneumonia in the US, 2012-2019.

BACKGROUND: Inappropriate empiric antimicrobial treatment (IET) contributes to worsened outcomes. While IET's differential impact across types of nosocomial pneumonia (NP: non-ventilated [nvHABP], ventilated [vHABP] hospital-acquired and ventilator-associated [VABP] bacterial pneumonia) is established, its potential interaction with the bacterial etiology is less clear. METHODS: We conducted a multicenter retrospective cohort study in the Premier Healthcare Database using an administrative algorithm to identify NP. We paired respective pathogens with empiric treatments. Antimicrobial coverage was appropriate if a drug administered within 2 days of infection onset covered the recovered organism(s). All other treatment was IET. RESULTS: Among 17,819 patients with NP, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Gram-negative (GN) organisms accounted for > 50% of all infections. GN pathogens were ~ 2 × as likely (7.4% vHABP to 10.7% nvHABP) to engender IET than Gram-positive (GP, 2.9% vHABP to 4.9% nvHABP) pathogens. Although rare (5.6% nvHABP to 8.3% VABP), GN + GP infections had the highest rates of IET (6.7% vHABP to 12.9% nvHABP). Carbapenem-resistant GNs were highly likely to receive IET (33.8% nvHABP to 40.2% VABP). Hospital mortality trended higher in the IET group, reaching statistical significance in GN + GP vHABP (47.8% IET vs. 29.3% non-IET, p = 0.016). 30-day readmission was more common with IET (16.0%) than non-IET (12.6%, p = 0.024) in GN VABP. Generally post-infection onset hospital length of stay and costs were higher with IET than non-IET. CONCLUSIONS: IET is ~ 2 × more common in GN than GP infections. Although the magnitude of its impact varies by NP type, IET contributes to worsened clinical and economic outcomes.

Situational Awareness of Opioid Consumption: The Missing Link to Reducing Dependence After Surgery?

A tool for collecting and analyzing morphine milligram equivalents (MMEs) can be used to overcome barriers to situational awareness around opioid utilization in the setting of multimodal pain management. Our software application (App) has facilitated data collection, analysis, and benchmarking in a manner that is not logistically feasible using manual methods. Real-time postoperative tracking of MME over the course of an episode of care can be prohibitively labor-intensive, and teams must have practical strategies to overcome this obstacle. In view of the link between the magnitude of opioid prescriptions at discharge and persistent opioid use after cardiac surgery, we believe that improving situational awareness among the patient care team is a vital first step in reducing opioid dependence after cardiac surgery.

Multiple antimicrobial resistance and outcomes among hospitalized patients with complicated urinary tract infections in the US, 2013-2018: a retrospective cohort study.

BACKGROUND: Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes. METHODS: We conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs. RESULTS: Among 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI. CONCLUSIONS: TR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.

The Association of Dexmedetomidine on Perioperative Opioid Consumption in Children Undergoing Adenotonsillectomy With and Without Obstructive Sleep Apnea.

BACKGROUND: Dexmedetomidine is used to reduce opioid consumption in pediatric anesthesia. However, there is conflicting evidence in pediatric adenotonsillectomy literature regarding the total perioperative opioid-sparing effects of dexmedetomidine. The aim of this study was to examine the association between dexmedetomidine and total perioperative opioid consumption in children undergoing adenotonsillectomy. METHODS: This was a retrospective cohort study of the children undergoing adenotonsillectomy surgery at Texas Children's Hospital between November 2017 and October 2018. Intraoperative dexmedetomidine was the exposure of interest. The primary outcome was total perioperative opioid consumption calculated as oral morphine equivalents (OME). Secondary outcomes of interest included opioid consumption and pain scores based on presence and absence of obstructive sleep apnea (OSA) and postanesthesia care unit (PACU) duration. We used multivariable linear regression to estimate the association of dexmedetomidine on the outcomes. RESULTS: A total of 941 patients met inclusion criteria, 697 (74.1%) received intraoperative dexmedetomidine. For every 0.1 µg/kg increase in intraoperative dexmedetomidine, the total perioperative OME (mg/kg) decreases by 0.021 mg/kg (95% CI, -0.027 to -0.015; P < .001). Pain scores did not significantly vary by OSA status. PACU duration increased by 1.14 minutes (95% CI, 0.30-1.99; P = .008) for each 0.1 µg/kg of intraoperative dexmedetomidine. CONCLUSIONS: Dexmedetomidine is associated with an overall perioperative opioid-sparing effect in children undergoing adenotonsillectomy and a small but statistically significant increase in PACU duration. Additionally, children with OSA did not have reduced perioperative opioid consumption.

The association between scene time interval and neurologic outcome following adult bystander witnessed out-of-hospital cardiac arrest.

OBJECTIVE: To analyze the association between Emergency Medical Services (EMS) scene time interval (STI) and survival with functional neurologic recovery following adult out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective analysis of prospectively collected data from the national Cardiac Arrest Registry to Enhance Survival from January 2013 to December 2018. All adult non-traumatic, EMS-treated, bystander-witnessed OHCA with complete data were included. Patients with STI times >60 min, defined as the time from EMS arrival at the patient's side to the time the transport vehicle left the scene, unwitnessed OHCA, nursing home events, EMS-witnessed OHCA, or patients with termination of resuscitation in the field were excluded. The primary outcome was survival with functional recovery (Cerebral Performance Category [CPC] = 1 or 2). Multivariable logistic regression was used to quantify the association of STI with the primary. RESULTS: 67,237 patients met inclusion criteria with 12,098 (18.0%) surviving with functional recovery. Mean STI (SD) for survivors with CPC 1 or 2 was 19 (8.4) and 22.8 (10.5) for those with poor outcomes (death or CPC 3-4; p < 0.001). For every 1-min increase in STI, the adjusted odds of a poor outcome increased by 3.5%; odds ratio = 1.035; 95% CI (1.027, 1.044); p < 0.001. Restricted cubic spline analysis showed increased risk of poor outcome after approximately 20 min. CONCLUSION: Longer STI times are strongly associated with poor neurologic outcome in bystander-witnessed OHCA patients. After a STI duration of approximately 20 min, the associated risk of a poor neurologic outcome increased more rapidly.

Monochromic light reduces emergence delirium in children undergoing adenotonsillectomy; a double-blind randomized observational study.

BACKGROUND: Emergence delirium (ED) is common in pediatric anesthesia. This dissociative state in which the patient is confused from their surroundings and flailing can be self-injurious and traumatic for parents. Treatment is by administration of sedatives which can prolong recovery. The aim of this study was to determine if exposure to monochromatic blue light (MBL) in the immediate phase of recovery could reduce the overall incidence of emergence delirium in children following general inhalational anesthesia. METHODS: This double blinded randomized controlled study included patients ages 2-6 undergoing adenotonsillectomy. Postoperatively, 104 patients were randomization (52 in each group) for exposure to sham blue or MBL during the first phase (initial 30 min) of recovery. The primary outcome was the incidence of emergence delirium during the first phase. We also examined Pediatric Anesthesia Emergence Delirium (PAED) scores throughout the first phase. RESULTS: Emergence Delirium was reported in 5.9% of MBL patients versus 33.3% in the sham group, p = 0.001. Using logistic regression adjusting for age, weight, gender, ASA classification and PAED scores provided an adjusted relative risk ratio of 0.18; 95% CI (0.06, 0.54); p = 0.001 for patients in the MBL group. 23.5% of MBL patients versus 52.9% of sham patients had either ED or PAED scores of 12 or more throughout the first phase of recovery, p = 0.002. This produced an adjusted relative risk of 0.46, 95% CI (0.29, 0.75), p = 0.001. CONCLUSIONS: Monochromatic blue light represents a non-pharmacologic method to reduce the incidence of emergence delirium and PAED scores in children. TRIAL REGISTRATION: #NCT03285243 registered on 15/09/2017.

An assessment of opioids on respiratory depression in children with and without obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea is a risk factor for respiratory depression following opioid administration as well as opioid-induced hyperalgesia. Little is known on how obstructive sleep apnea status is associated with central ventilatory depression in pediatric surgical patients given a single dose of fentanyl. METHODS: This was a single-center, prospective trial in children undergoing surgery requiring intubation and opioid administration. Sixty patients between the ages of 2-8 years presenting for surgery at Texas Children's Hospital were recruited. Twenty non-obstructive sleep apnea controls and 30 patients with moderate to severe obstructive sleep apnea met inclusion criteria. Following induction of general anesthesia and establishment of steady-state ventilation, participants received 1 mcg/kg intravenous fentanyl. Ventilatory variables (tidal volume, respiratory rate, end-tidal CO2 , and minute ventilation) were assessed each minute for 10 min. The primary outcome was the extent of opioid-induced central ventilatory depression over time by obstructive sleep apnea status when compared with baseline values. Secondary aims assessed the impact of demographics and SpO2 nadir on ventilatory depression. RESULTS: We found no significant difference in percent decrease in respiratory rate (38.1% and 37.1%; p = .950), tidal volume (6.4% and 5.4%; p = .992), and minute ventilation (35.0 L/min and 35.0 L/min; p = .890) in control and obstructive sleep apnea patients, respectively. Both groups experienced similar percent increases in end-tidal CO2 (4.0% vs. 2.2%; p = .512) in control and obstructive sleep apnea patients, respectively. CONCLUSIONS: In pediatric surgical patients, obstructive sleep apnea status was not associated with significant differences in central respiratory depression following a single dose of fentanyl (1 mcg/kg). These findings can help determine safe opioid doses in future pediatric obstructive sleep apneapatients.

Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

In the face of increasing rates of antimicrobial resistance in complicated urinary tract infections (cUTIs), clinicians need to understand cross-resistance patterns among commonly encountered pathogens. We performed a multicenter, retrospective cohort study in the Premier database of approximately 180 hospitals, from 2013 to 2018. Using an ICD-9/10-based algorithm, we identified all adult patients hospitalized with cUTIs and included those with a positive blood or urine culture. We examined the microbiology and susceptibilities to common cUTI antimicrobials (3rd-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], and nitrofurantoin [NFT]) singly and in groups of two. Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were Escherichia coli (41.0%; C3r, 15.1%), Klebsiella pneumoniae (12.1%; C3r, 13.2%), and Pseudomonas aeruginosa (11.0%; C3r, 12.0%). E. coli was most frequently resistant to FQ (43.5%) and least to NFT (6.7%). K. pneumoniae was most frequently resistant to NFT (60.8%) and least to FFM (0.1%). P. aeruginosa was most frequently resistant to FQ (34.4%) and least to TMP/SMZ (4.2%). Of the C3rE. coli isolates, 87.1% were also FQr, 63.7% were TMP/SMZr, and 13.3% were NFTr C3rK. pneumoniae isolates had a 76.5% chance of being FQr, 78.1% were TMP/SMZr, and 77.6% were NFTr C3rP. aeruginosa coexisted with FQr in 47.3%, TMP/SMZr in 18.9%, and NFTr in 28.7%. Among the most common pathogens isolated from hospitalized patients with cUTIs, the rates of single resistance to common treatments and of cross-resistance to these regimens are substantial. Knowing the patterns of cross-resistance may help clinicians tailor empirical therapy more precisely.

Characteristics, Hospital Course, and Outcomes of Patients Requiring Prolonged Acute Versus Short-Term Mechanical Ventilation in the United States, 2014-2018.

OBJECTIVES: Most patients requiring mechanical ventilation only require it for a short term (< 4 d of mechanical ventilation). Those undergoing prolonged acute mechanical ventilation (≥ 4 d mechanical ventilation) represent a select cohort who face significant morbidity, mortality, and resource utilization. Using administrative codes, we identified prolonged acute mechanical ventilation and short-term mechanical ventilation patients and compared their baseline characteristics, hospital events, and hospital outcomes. DESIGN: Retrospective cohort. SETTING: Seven-hundred eighty-seven acute care hospitals, United States, contributing data to Premier database, 2014-2018. PATIENTS: Patients on mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 691,961 patients meeting the enrollment criteria, 266,374 (38.5%) received prolonged acute mechanical ventilation. At baseline, patients on prolonged acute mechanical ventilation were similar to short-term mechanical ventilation in age (years: 62.0 ± 15.8 prolonged acute mechanical ventilation vs 61.7 ± 17.2 short-term mechanical ventilation), gender (males: 55.6% prolonged acute mechanical ventilation vs 53.9% short-term mechanical ventilation), and race (white: 69.1% prolonged acute mechanical ventilation vs 72.4% short-term mechanical ventilation). The prolonged acute mechanical ventilation group had a higher comorbidity burden than short-term mechanical ventilation (mean Charlson Score 3.5 ± 2.7 vs 3.1 ± 2.7). The prevalence of vasopressors (50.3% vs 36.9%), dialysis (19.4% vs 10.3%), severe sepsis (20.3% vs 10.3%), and septic shock (33.5% vs 15.9%) was higher in prolonged acute mechanical ventilation than short-term mechanical ventilation. Hospital mortality (29.75% vs 21.1%), combined mortality, or discharge to hospice (37.2% vs 25.3%), extubation failure (12.3% vs 6.1%), tracheostomy (21.6% vs 4.5%), development of Clostridium difficile (4.5% vs 1.7%), and incidence density of ventilator-associated pneumonia (2.4/1,000 patient-days vs 0.6/1,000 patient-days) were all higher in the setting of prolonged acute mechanical ventilation than short-term mechanical ventilation. Median (interquartile range) post mechanical ventilation onset length of stay (13 [8-20] vs 4 d [1-8 d]) and hospital costs ($55,014 [$35,051-$88,007] vs $20,120 [$12,071-$34,915] were higher in prolonged acute mechanical ventilation than short-term mechanical ventilation. CONCLUSIONS: Over one-third of all hospitalized patients on mechanical ventilation require it for greater than or equal to 4 days. Prolonged acute mechanical ventilation patients exhibit a higher burden of both chronic and acute illness and experience higher rates than those on short-term mechanical ventilation of hospital-acquired complications and worse clinical and economic outcomes.

Bleeding After Musculoskeletal Surgery in Hospitals That Switched From Hydroxyethyl Starch to Albumin Following a Food and Drug Administration Warning.

BACKGROUND: While US Food and Drug Administration (FDA) black box warnings are common, their impact on perioperative outcomes is unclear. Hydroxyethyl starch (HES) is associated with increased bleeding and kidney injury in patients with sepsis, leading to an FDA black box warning in 2013. Among patients undergoing musculoskeletal surgery in a subset of hospitals where colloid use changed from HES to albumin following the FDA warning, we examined the rate of major perioperative bleeding post- versus pre-FDA warning. METHODS: The authors of this article used a retrospective, quasi-experimental, repeated cross-sectional, interrupted time series study of patients undergoing musculoskeletal surgery in hospitals within the Premier Healthcare Database, in the year before and year after the 2013 FDA black box warning. We examined patients in 23 "switcher" hospitals (where the percentage of colloid recipients receiving HES exceeded 50% before the FDA warning and decreased by at least 25% in absolute terms after the FDA warning) and patients in 279 "nonswitcher" hospitals. Among patients having surgery in "switcher" and "nonswitcher" hospitals, we determined monthly rates of major perioperative bleeding during the 12 months after the FDA warning, compared to 12 months before the FDA warning. Among patients who received surgery in "switcher" hospitals, we conducted a propensity-weighted segmented regression analysis assessing differences-in-differences (DID), using patients in "nonswitcher" hospitals as a control group. RESULTS: Among 3078 patients treated at "switcher" hospitals (1892 patients treated pre-FDA warning versus 1186 patients treated post-FDA warning), demographic and clinical characteristics were well-balanced. Two hundred fifty-one (13.3%) received albumin pre-FDA warning, and 900 (75.9%) received albumin post-FDA warning. Among patients undergoing surgery in "switcher" hospitals during the pre-FDA warning period, 282 of 1892 (14.9%) experienced major bleeding during the hospitalization, compared to 149 of 1186 (12.6%) following the warning. In segmented regression, the adjusted ratio of slopes for major perioperative bleeding post- versus pre-FDA warning was 0.98 (95% confidence interval [CI], 0.93-1.04). In the DID estimate using "nonswitcher" hospitals as a control group, the ratio of ratios was 0.93 (95% CI, 0.46-1.86), indicating no significant difference. CONCLUSIONS: We identified a subset of hospitals where colloid use for musculoskeletal surgery changed following a 2013 FDA black box warning regarding HES use in sepsis. Among patients undergoing musculoskeletal surgery at these "switcher" hospitals, there was no significant decrease in the rate of major perioperative bleeding following the warning, possibly due to incomplete practice change. Evaluation of the impact of systemic changes in health care may contribute to the understanding of patient outcomes in perioperative medicine.

Derivation and validation of a prognostic model to predict mortality in patients with advanced chronic kidney disease.

BACKGROUND: Guiding patients with advanced chronic kidney disease (CKD) through advance care planning about future treatment obliges an assessment of prognosis. A patient-specific integrated model to predict mortality could inform shared decision-making for patients with CKD. METHODS: Patients with Stages 4 and 5 CKD from Massachusetts (749) and West Virginia (437) were prospectively evaluated for clinical parameters, functional status [Karnofsky Performance Score (KPS)] and their provider's response to the Surprise Question (SQ). A predictive model for 12-month mortality was derived with the Massachusetts cohort and then validated externally on the West Virginia cohort. Logistic regression was used to create the model, and the c-statistic and Hosmer-Lemeshow statistic were used to assess model discrimination and calibration, respectively. RESULTS: In the derivation cohort, the SQ, KPS and age were most predictive of 12-month mortality with odds ratios (ORs) [95% confidence interval (CI)] of 3.29 (1.87-5.78) for a 'No' response to the SQ, 2.09 (95% CI 1.19-3.66) for fair KPS and 1.41 (95% CI 1.15-1.74) per 10-year increase in age. The c-statistic for the 12-month mortality model for the derivation cohort was 0.80 (95% CI 0.75-0.84) and for the validation cohort was 0.74 (95% CI 0.66-0.83). CONCLUSIONS: Our integrated prognostic model for 12-month mortality in patients with advanced CKD had good discrimination and calibration. This model provides prognostic information to aid nephrologists in identifying and counseling advanced CKD patients with poor prognosis who are facing the decision to initiate dialysis or pursue medical management without dialysis.

Epidemiology and Outcomes of Hospitalizations With Invasive Aspergillosis in the United States, 2009-2013.

Background: Though invasive aspergillosis (IA) complicates care of up to 13% of patients with immunocompromise, little is known about its morbidity and mortality burden in the United States. Methods: We analyzed the Health Care Utilization Project's data from the Agency for Healthcare Research and Quality for 2009-2013. Among subjects with high-risk conditions for IA, IA was identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). Using propensity score matching, we calculated the IA-associated excess mortality and 30-day readmission rates, length of stay, and costs. Results: Of the 66634683 discharged patients meeting study inclusion criteria, 154888 (0.2%) had a diagnosis of IA. The most common high-risk conditions were major surgery (50.1%) in the non-IA and critical illness (41.0%) in the IA group. After propensity score matching, both mortality (odds ratio, 1.43; 95% confidence interval, 1.36-1.51) and 30-day readmission (1.39; 1.34-1.45) rates were higher in the IA group. IA was associated with 6.0 (95% confidence interval, 5.7-6.4) excess days in the hospital and $15542 ($13869-$17215) in excess costs per hospitalization. Conclusions: Although rare even among high-risk groups, IA is associated with increased hospital mortality and 30-day readmission rates, excess duration of hospitalization, and costs. Given nearly 40000 annual admissions for IA in the United States, the aggregate IA-attributable excess costs may reach $600 million annually.

The dangers of extreme body mass index values in patients with Clostridium difficile.

PURPOSE: To examine the association between body mass index (BMI) and in-hospital mortality in patients presenting with Clostridium difficile infections in emergency department visits (ED) in the USA. Infected patients with extreme BMIs may have an elevated mortality risk, but prior studies examining this question have been too small to reach definitive conclusions. METHODS: Data were from the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality during 2012. NEDS records emergency department (ED) visits across the USA and provides statistical sampling weights to approximate a nationally representative sample of US hospital-based EDs. Inclusion criteria were adults age 18 or older with an ICD-9 code for C. difficile infection (008.45) and a documented body mass index ICD-9 V code (V85.x). Logistic regression was used to predict mortality after adjusting for demographic variables and chronic comorbidities defined by Elixhauser. RESULTS: A weighted sample of 22,937 ED visits met all inclusion criteria. The cohort's mean age was 66. 64.6% were female. The unadjusted mortality rate was 6.5%. Patients with a BMI < 19 kg/m2 had an adjusted odds ratio of 2.73; 95% CI (1.80, 4.16), p < 0.001 compared to patients with a BMI of 19.0-4.9 kg/m2 (the referent category). In obese patients, only BMI values >40 kg/m2 were associated with significantly greater mortality risk. CONCLUSION: Being underweight (BMI < 19) or morbidly obese (BMI > 40) was associated with increased risk of in-hospital mortality in patients presenting with C. difficile infections.