Characteristics and Health Care Utilization of Patients With Housing Insecurity in the ED.

Importance: Unstable housing and homelessness can exacerbate adverse health outcomes leading to increased risk of chronic disease, injury, and disability. However, emergency departments (EDs) have no universal method to identify those at risk of or currently experiencing homelessness. Objective: To describe the extent of housing insecurity among patients who seek care in an urban ED, including chief concerns, demographics, and patterns of health care utilization. Design, Setting, and Participants: This cross-sectional study included all adult patients presenting to the ED at Vanderbilt University Medical Center (VUMC), an urban tertiary care, level I trauma center in the Southeast US, from January 5 to May 16, 2023. Main Outcomes and Measures: The primary outcome was the proportion of ED visits at which patients screened positive for housing insecurity. Secondary outcomes included prevalence of insecurity by chief concerns, demographics, and patterns of health care utilization. Results: Of all 23 795 VUMC ED visits with screenings for housing insecurity (12 465 visits among women [52%]; median age, 47 years [IQR, 32-48 years]), in 1185 (5%), patients screened positive for current homelessness or housing insecurity (660 unique patients); at 22 610 visits (95%), the screening result was negative. Of visits with positive results, the median age of patients was 46 years (IQR, 36-55 years) and 829 (70%) were among male patients. Suicide and intoxication were more common chief concerns among visits at which patients screened positive (132 [11%] and 118 [10%], respectively) than among those at which patients screened negative (220 [1%] and 335 [2%], respectively). Visits with positive results were more likely to be among patients who were uninsured (395 [33%] vs 2272 [10%]) and had multiple visits during the study period. A higher proportion of positive screening results occurred between 8 pm and 6 am. The social work team assessed patients at 919 visits (78%) with positive screening results. Conclusions and Relevance: In this cross-sectional study of 23 795 ED visits, at 5% of visits, patients screened positive for housing insecurity and were more likely to present with a chief concern of suicide, to be uninsured, and to have multiple visits during the study period. This analysis provides a call for other institutions to introduce screening and create tailored care plans for patients experiencing housing insecurity to achieve equitable health care.

A trial of implementation facilitation to increase timely admission to methadone treatment.

BACKGROUND: During the ongoing opioid epidemic, some Opioid Treatment Programs (OTPs) are unable to admit program applicants in a timely fashion. Interim methadone (IM) treatment (without routine counseling) is an effective approach to overcome this challenge when counseling capacity is inadequate to permit admissions within 14 days of request. It requires both federal and state approval and has been rarely utilized since its incorporation into the federal OTP regulations in 1993. METHODS: We evaluated the impact of Implementation Facilitation (IF) on OTPs providing timely admission to methadone treatment (i.e., within 14 days of request), adopting IM, and changing admissions procedures. IF included data collection on admission processes and an external facilitator who engaged OTP leadership, Local Champions through site visits, remote academic detailing, and feedback. Local Champions and State Opioid Treatment Authorities (SOTAs) participated in learning collaboratives. Using a modified stepped wedge design, six OTPs in four US states on the east and west coasts were randomly assigned to one of two clusters that staggered the timing of IF receipt. Study Phases included: Pre-Implementation, IF, and Sustainability. OTPs submitted data on treatment requests and admissions for 28 months (N = 3108 requests for treatment). RESULTS: Although none of the OTPs adopted IM, all six developed policies and procedures to enable its use. Some OTPs streamlined admissions processes prior to study launch and during the IF intervention. OTPs reduced admission delays over time, although there was substantial site heterogeneity. The IF Phase for the early cluster coincided with the onset of COVID-19, complicating the study. Rates of timely admission within 14 days of request were 56.2 % (Pre-Implementation), 55.8 % (IF), and 78.8 % (Sustainability). Compared to the Pre-Implementation Phase, the odds of timely admission were not significantly different during the IF Phase but significantly higher during the Sustainability Phase (OR = 2.35 [95 % CI = 1.34, 4.12]; p = 0.003). CONCLUSIONS: Committing to study participation and IF activities may have prompted some OTPs to change practices that improved timely admission. Attributing changes to IF should be done with caution considering study limitations. Data collection for the study spanned the COVID-19 pandemic, which complicates interpretation. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT04188977.

Comparison of outcomes in patients with and without neurologic diseases undergoing holmium laser enucleation of the prostate.

INTRODUCTION: We aimed to compare holmium laser enucleation of the prostate (HoLEP) outcomes in patients with and without neurologic diseases (ND). METHODS: A prospectively maintained database of patients undergoing HoLEP from January 2021 to April 2022 was reviewed. The following NDs were included: diabetes-related neuropathy/neurogenic bladder, Parkinson's disease, dementia, cerebrovascular accident, multiple sclerosis, traumatic brain injury, transient ischemic attack, brain/spinal tumors, myasthenia gravis, spinal cord injury, and other. Statistical analysis was performed using t-tests, Chi-squared, and binomial tests (p<0.05). RESULTS: A total of 118 ND patients were identified with 135 different neurologic diseases. ND patients were more likely to have indwelling catheters (57% vs. 39%, p=0.012) and urinary tract infections (UTIs) preoperatively (32% vs. 19%, p=0.002). Postoperatively, ND patients were more likely to fail initial trial of void (20% vs. 8.1%, p<0.001) and experience an episode of acute urinary retention (16% vs. 8.5%, p=0.024). Within 90 days postoperative, the overall complication rate was higher in the ND group (26% vs. 13%, p=0.001). Within the ND group, 30/118 (25%) had ≥1 UTI within 90 days preoperative, which decreased to 10/118 (8.7%) 90 days postoperative (p<0.001). At last followup (mean 6.7 months [ND] vs. 5.4 months [non-ND], p=0.03), four patients (4.4%) in the ND group required persistent catheter/clean intermittent catheterization compared to none in the non-ND group (p=0.002). CONCLUSIONS: Patients with ND undergoing HoLEP are more likely to experience postoperative retention and higher complication rates compared to non-ND patients. While UTI rates are higher in this population, HoLEP significantly reduced three-month UTI and catheterization rates.

Cloacal Dysgenesis Sequence in a Preterm Neonate.

BACKGROUND Cloaca malformations result from a disproportion of apoptosis, cell growth, and maturation. The range of cloacal malformations is extensive and diverse, with a lack of a straightforward classification system. Cloacal dysgenesis sequence (CDS), also known as urorectal septum malformation sequence, is a rare cloaca variant described as the absence of a perineal orifice. Prenatal magnetic resonance imaging and antenatal ultrasounds may reveal a cloacal malformation; however, many patients are not diagnosed with cloacal malformation until birth. CASE REPORT We present a case of a female neonate delivered by a 23-year-old G2P1T1A0L0 mother who had received comprehensive prenatal care. During pregnancy, bilateral multicystic dysplastic kidneys were identified prenatally, leading to the in utero placement of a vesicoamniotic shunt. The physical exam revealed a distended abdomen with reduced abdominal musculature and laxity, ascites, a vesicoamniotic shunt in place, absent urethra, ambiguous genitalia with no vaginal opening, no perineal opening, and clubfoot. Abdominal radiograph showed findings consistent with significant abdominal ascites. An exploratory laparotomy was performed that included diverting colostomy, mucous fistula creation, tube vaginostomy, removal of the vesicoamniotic shunt, and suprapubic tube placement. The patient recovered well from this operation with no complications. CONCLUSIONS CDS is an uncommon condition in pediatric patients, and although sonographic findings can reveal urinary tract abnormalities, prenatal imaging might not always identify CDS. Our case underscores the uniqueness of the case and the significance of early detection and immediate medical and surgical intervention.

A New Tool for Probabilistic Assessment of MPS Data Associated with mtDNA Mixtures.

Mitochondrial (mt) DNA plays an important role in the fields of forensic and clinical genetics, molecular anthropology, and population genetics, with mixture interpretation being of particular interest in medical and forensic genetics. The high copy number, haploid state (only a single haplotype contributed per individual), high mutation rate, and well-known phylogeny of mtDNA, makes it an attractive marker for mixture deconvolution in damaged and low quantity samples of all types. Given the desire to deconvolute mtDNA mixtures, the goals of this study were to (1) create a new software, MixtureAceMT™, to deconvolute mtDNA mixtures by assessing and combining two existing software tools, MixtureAce™ and Mixemt, (2) create a dataset of in-silico MPS mixtures from whole mitogenome haplotypes representing a diverse set of population groups, and consisting of two and three contributors at different dilution ratios, and (3) since amplicon targeted sequencing is desirable, and is a commonly used approach in forensic laboratories, create biological mixture data associated with two amplification kits: PowerSeq™ Whole Genome Mito (Promega™, Madison, WI, USA) and Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific by AB™, Waltham, MA, USA) to further validate the software for use in forensic laboratories. MixtureAceMT™ provides a user-friendly interface while reducing confounding features such as NUMTs and noise, reducing traditionally prohibitive processing times. The new software was able to detect the correct contributing haplogroups and closely estimate contributor proportions in sequencing data generated from small amplicons for mixtures with minor contributions of ≥5%. A challenge of mixture deconvolution using small amplicon sequencing is the potential generation of spurious haplogroups resulting from private mutations that differ from Phylotree. MixtureAceMT™ was able to resolve these additional haplogroups by including known haplotype/s in the evaluation. In addition, for some samples, the inclusion of known haplotypes was also able to resolve trace contributors (minor contribution 1-2%), which remain challenging to resolve even with deep sequencing.

A Metabolomics Assay to Diagnose Citrus Huanglongbing Disease and to Aid in Assessment of Treatments to Prevent or Cure Infection.

Citrus greening disease, or Huanglongbing (HLB), has devastated citrus crops globally in recent years. The causal bacterium, 'Candidatus Liberibacter asiaticus', presents a sampling issue for qPCR diagnostics and results in a high false negative rate. In this work, we compared six metabolomics assays to identify HLB-infected citrus trees from leaf tissue extracted from 30 control and 30 HLB-infected trees. A liquid chromatography-mass spectrometry-based assay was most accurate. A final partial least squares-discriminant analysis (PLS-DA) model was trained and validated on 690 leaf samples with corresponding qPCR measures from three citrus varieties (Rio Red grapefruit, Hamlin sweet orange, and Valencia sweet orange) from orchards in Florida and Texas. Trees were naturally infected with HLB transmitted by the insect vector Diaphorina citri. In a randomized validation set, the assay was 99.9% accurate to classify diseased from nondiseased samples. This model was applied to samples from trees receiving plant defense-inducer compounds or biological treatments to prevent or cure HLB infection. From two trials, HLB-related metabolite abundances and PLS-DA scores were tracked longitudinally and compared with those of control trees. We demonstrate how our assay can assess tree health and the efficacy of HLB treatments and conclude that no trialed treatment was efficacious.

Data-Driven Approach to Modeling Microfabricated Chemical Sensor Manufacturing.

We have developed a statistical model-based approach to the quality analysis (QA) and quality control (QC) of a gas micro pre-concentrator chip (µPC) performance when manufactured at scale for chemical and biochemical analysis of volatile organic compounds (VOCs). To test the proposed model, a medium-sized university-led production batch of 30 wafers of chips were subjected to rigorous chemical performance testing. We quantitatively report the outcomes of each manufacturing process step leading to the final functional chemical sensor chip. We implemented a principal component analysis (PCA) model to score individual chip chemical performance, and we observed that the first two principal components represent 74.28% of chemical testing variance with 111 of 118 viable chips falling into the 95% confidence interval. Chemical performance scores and chip manufacturing data were analyzed using a multivariate regression model to determine the most influential manufacturing parameters and steps. In our analysis, we find the amount of sorbent mass present in the chip (variable importance score = 2.6) and heater and the RTD resistance values (variable importance score = 1.1) to be the manufacturing parameters with the greatest impact on chemical performance. Other non-obvious latent manufacturing parameters also had quantified influence. Statistical distributions for each manufacturing step will allow future large-scale production runs to be statistically sampled during production to perform QA/QC in a real-time environment. We report this study as the first data-driven, model-based production of a microfabricated chemical sensor.

A Pediatric Patient with Severe Obstructive Sleep Apnea and Comorbid Depression and Substance Abuse.

Obstructive sleep apnea (OSA), depression, and substance abuse problems share similar symptomatology and have significant interplay. An underlying diagnosis of OSA can often be overlooked in patients with significant psychiatric illness and polysubstance use. Pediatric OSA is often associated with adenotonsillar hypertrophy and frequently requires surgical intervention for resolution of symptoms. Untreated OSA can worsen mental status and encourage polysubstance abuse as a form of self-medication. Proper identification and management of OSA plays an important role in treating psychiatric conditions. We report a 16-year-old with major depressive disorder (MDD), suicide attempts, polysubstance use disorder, and severe OSA admitted to an inpatient psychiatric facility. History included sleep and mood disturbances started at age 12. Patient presented with apnea-hypopnea index greater than 50 and started on bilevel-positive airway pressure (BiPAP) prior to admission. Management of OSA led to significant improvement of MDD, insomnia, and polysubstance abuse. OSA can often be overlooked in patients with MDD or substance abuse. Among adolescent patients with poorly managed psychiatric conditions, significant sleep disturbances, and polysubstance abuse, providers should maintain a high degree of suspicion for OSA, as its proper management will aid in the management of the other conditions.

Characterization of the microbiome and volatile compounds in anal gland secretions from domestic cats (Felis catus) using metagenomics and metabolomics.

Many mammals rely on volatile organic chemical compounds (VOCs) produced by bacteria for their communication and behavior, though little is known about the exact molecular mechanisms or bacterial species that are responsible. We used metagenomic sequencing, mass-spectrometry based metabolomics, and culturing to profile the microbial and volatile chemical constituents of anal gland secretions in twenty-three domestic cats (Felis catus), in attempts to identify organisms potentially involved in host odor production. We found that the anal gland microbiome was dominated by bacteria in the genera Corynebacterium, Bacteroides, Proteus, Lactobacillus, and Streptococcus, and showed striking variation among individual cats. Microbiome profiles also varied with host age and obesity. Metabolites such as fatty-acids, ketones, aldehydes and alcohols were detected in glandular secretions. Overall, microbiome and metabolome profiles were modestly correlated (r = 0.17), indicating that a relationship exists between the bacteria in the gland and the metabolites produced in the gland. Functional analyses revealed the presence of genes predicted to code for enzymes involved in VOC metabolism such as dehydrogenases, reductases, and decarboxylases. From metagenomic data, we generated 85 high-quality metagenome assembled genomes (MAGs). Of importance were four MAGs classified as Corynebacterium frankenforstense, Proteus mirabilis, Lactobacillus johnsonii, and Bacteroides fragilis. They represent strong candidates for further investigation of the mechanisms of volatile synthesis and scent production in the mammalian anal gland.

Assessment of implementation methods in sepsis: study protocol for a cluster-randomized hybrid type 2 trial.

BACKGROUND: Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis "bundles" (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle. METHOD: The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes. DISCUSSION: This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles. FUNDING: NHLBI R01HL162954. TRIAL REGISTRATION: ClinicalTrials.gov NCT05491941. Registered on August 8, 2022.

Massively Parallel Sequencing of the Mitogenome from Human Hair Shafts in Forensic Investigations.

This article highlights methods used to perform DNA extraction, mitochondrial DNA quantification, multiplex PCR amplification, amplicon-based massively parallel sequencing, and data analysis of the mitochondrial genome (mitogenome) from human hair shafts. The focus is on applications to forensic casework, but this set of protocols can be used for any purpose involving small cuttings (as small as 1 to 5 mm) of human hair shafts up to 40 years from the time of collection. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Extraction of mitochondrial DNA from human hair shafts Basic Protocol 2: Quantification of mitochondrial DNA (copies/µl) Basic Protocol 3: Multiplex amplification of the mitogenome Basic Protocol 4: Library preparation and sequencing of mitogenome amplicons Basic Protocol 5: Data analysis of mitogenome haplotypes.

Oxylipin concentration shift in exhaled breath condensate (EBC) of SARS-CoV-2 infected patients.

Infection of airway epithelial cells with severe acute respiratory coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and lung injury with hypoxia. It is challenging to sample the lower airways non-invasively and the capability to identify a highly representative specimen that can be collected in a non-invasive way would provide opportunities to investigate metabolomic consequences of COVID-19 disease. In the present study, we performed a targeted metabolomic approach using liquid chromatography coupled with high resolution chromatography (LC-MS) on exhaled breath condensate (EBC) collected from hospitalized COVID-19 patients (COVID+) and negative controls, both non-hospitalized and hospitalized for other reasons (COVID-). We were able to noninvasively identify and quantify inflammatory oxylipin shifts and dysregulation that may ultimately be used to monitor COVID-19 disease progression or severity and response to therapy. We also expected EBC-based biochemical oxylipin changes associated with COVID-19 host response to infection. The results indicated ten targeted oxylipins showing significative differences between SAR-CoV-2 infected EBC samples and negative control subjects. These compounds were prostaglandins A2 and D2, LXA4, 5-HETE, 12-HETE, 15-HETE, 5-HEPE, 9-HODE, 13-oxoODE and 19(20)-EpDPA, which are associated with specific pathways (i.e. P450, COX, 15-LOX) related to inflammatory and oxidative stress processes. Moreover, all these compounds were up-regulated by COVID+, meaning their concentrations were higher in subjects with SAR-CoV-2 infection. Given that many COVID-19 symptoms are inflammatory in nature, this is interesting insight into the pathophysiology of the disease. Breath monitoring of these and other EBC metabolites presents an interesting opportunity to monitor key indicators of disease progression and severity.

Portable chemical detection platform for on-site monitoring of odorant levels in natural gas.

The adequate odorization of natural gas is critical to identify gas leaks and to reduce accidents. To ensure odorization, natural gas utility companies collect samples to be processed at core facilities or a trained human technician smells a diluted natural gas sample. In this work, we report a detection platform that addresses the lack of mobile solutions capable of providing quantitative analysis of mercaptans, a class of compounds used to odorize natural gas. Detailed description of the platform hardware and software components is provided. Designed to be portable, the platform hardware facilitates extraction of mercaptans from natural gas, separation of individual mercaptan species, and quantification of odorant concentration, with results reported at point-of-sampling. The software was developed to accommodate skilled users as well as minimally trained operators. Detection and quantification of six commonly used mercaptan compounds (ethyl mercaptan, dimethyl sulfide, n-propylmercaptan, isopropyl mercaptan, tert­butyl mercaptan, and tetrahydrothiophene) at typical odorizing concentrations of 0.1-5 ppm was performed using the device. We demonstrate the potential of this technology to ensure natural gas odorizing concentrations throughout distribution systems.

What animal model should I use to study necrotizing enterocolitis?

Unfortunately, we are all too familiar with the statement: "Necrotizing enterocolitis remains the leading cause of gastrointestinal surgical emergency in preterm neonates". It's been five decades since the first animal models of necrotizing enterocolitis (NEC) were described. There remains much investigative work to be done on identifying various aspects of NEC, ranging from the underlying mechanisms to treatment modalities. Experimental NEC is mainly focused on a rat, mouse, and piglet models. Our aim is to not only highlight the pros and cons of these three main models, but to also present some of the less-used animal models that have contributed to the body of knowledge about NEC. Choosing an appropriate model is essential to conducting effective research and answering the questions asked. As such, this paper reviews some of the variations that come with each model.

Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

Time to treatment and mortality for clinical sepsis subtypes.

BACKGROUND: Sepsis is common, deadly, and heterogenous. Prior analyses of patients with sepsis and septic shock in New York State showed a risk-adjusted association between more rapid antibiotic administration and bundled care completion, but not an intravenous fluid bolus, with reduced in-hospital mortality. However, it is unknown if clinically identifiable sepsis subtypes modify these associations. METHODS: Secondary analysis of patients with sepsis and septic shock enrolled in the New York State Department of Health cohort from January 1, 2015 to December 31, 2016. Patients were classified as clinical sepsis subtypes (α, ß, γ, δ-types) using the Sepsis ENdotyping in Emergency CAre (SENECA) approach. Exposure variables included time to 3-h sepsis bundle completion, antibiotic administration, and intravenous fluid bolus completion. Then logistic regression models evaluated the interaction between exposures, clinical sepsis subtypes, and in-hospital mortality. RESULTS: 55,169 hospitalizations from 155 hospitals were included (34% α, 30% ß, 19% γ, 17% δ). The α-subtype had the lowest (N = 1,905, 10%) and δ-subtype had the highest (N = 3,776, 41%) in-hospital mortality. Each hour to completion of the 3-h bundle (aOR, 1.04 [95%CI, 1.02-1.05]) and antibiotic initiation (aOR, 1.03 [95%CI, 1.02-1.04]) was associated with increased risk-adjusted in-hospital mortality. The association differed across subtypes (p-interactions < 0.05). For example, the outcome association for the time to completion of the 3-h bundle was greater in the δ-subtype (aOR, 1.07 [95%CI, 1.05-1.10]) compared to α-subtype (aOR, 1.02 [95%CI, 0.99-1.04]). Time to intravenous fluid bolus completion was not associated with risk-adjusted in-hospital mortality (aOR, 0.99 [95%CI, 0.97-1.01]) and did not differ among subtypes (p-interaction = 0.41). CONCLUSION: Timely completion of a 3-h sepsis bundle and antibiotic initiation was associated with reduced risk-adjusted in-hospital mortality, an association modified by clinically identifiable sepsis subtype.