Oral microbiome dysbiosis among cigarette smokers and smokeless tobacco users compared to non-users.

Tobacco use significantly influences the oral microbiome. However, less is known about how different tobacco products specifically impact the oral microbiome over time. To address this knowledge gap, we characterized the oral microbiome of cigarette users, smokeless tobacco users, and non-users over 4 months (four time points). Buccal swab and saliva samples (n = 611) were collected from 85 participants. DNA was extracted from all samples and sequencing was carried out on an Illumina MiSeq, targeting the V3-V4 region of the 16S rRNA gene. Cigarette and smokeless tobacco users had more diverse oral bacterial communities, including a higher relative abundance of Firmicutes and a lower relative abundance of Proteobacteria, when compared to non-users. Non-users had a higher relative abundance of Actinomyces, Granulicatella, Haemophilus, Neisseria, Oribacterium, Prevotella, Pseudomonas, Rothia, and Veillonella in buccal swab samples, compared to tobacco users. While the most abundant bacterial genera were relatively constant over time, some species demonstrated significant shifts in relative abundance between the first and last time points. In addition, some opportunistic pathogens were detected among tobacco users including Neisseria subflava, Bulleidia moorei and Porphyromonas endodontalis. Overall, our results provide a more holistic understanding of the structure of oral bacterial communities in tobacco users compared to non-users.

Stacked mutations in wheat homologues of rice SEMI-DWARF1 confer a novel semi-dwarf phenotype.

BACKGROUND: Semi-dwarfing alleles are used widely in cereals to confer improved lodging resistance and assimilate partitioning. The most widely deployed semi-dwarfing alleles in rice and barley encode the gibberellin (GA)-biosynthetic enzyme GA 20-OXIDASE2 (GA20OX2). The hexaploid wheat genome carries three homoeologous copies of GA20OX2, and because of functional redundancy, loss-of-function alleles of a single homoeologue would not be selected in wheat breeding programmes. Instead, approximately 70% of wheat cultivars carry gain-of-function mutations in REDUCED HEIGHT 1 (RHT1) genes that encode negative growth regulators and are degraded in response to GA. Semi-dwarf Rht-B1b or Rht-D1b alleles encode proteins that are insensitive to GA-mediated degradation. However, because RHT1 is expressed ubiquitously these alleles have pleiotropic effects that confer undesirable traits in some environments. RESULTS: We have applied reverse genetics to combine loss-of-function alleles in all three homoeologues of wheat GA20OX2 and its paralogue GA20OX1 and evaluated their performance in three years of field trials. ga20ox1 mutants exhibited a mild height reduction (approximately 3%) suggesting GA20OX1 plays a minor role in stem elongation in wheat. ga20ox2 mutants have reduced GA1 content and are 12-32% shorter than their wild-type segregants, comparable to the effect of the Rht-D1b 'Green Revolution' allele. The ga20ox2 mutants showed no significant negative effects on yield components in the spring wheat variety 'Cadenza'. CONCLUSIONS: Our study demonstrates that chemical mutagenesis can expand genetic variation in polyploid crops to uncover novel alleles despite the difficulty in identifying appropriate mutations for some target genes and the negative effects of background mutations. Field experiments demonstrate that mutations in GA20OX2 reduce height in wheat, but it will be necessary to evaluate the effect of these alleles in different genetic backgrounds and environments to determine their value in wheat breeding as alternative semi-dwarfing alleles.

A randomised clinical trial of awake prone positioning in COVID-19 suspects with acute hypoxemic respiratory failure.

Background: Awake prone position (APP) has been reported to improve oxygenation in patients with COVID-19 disease and to reduce the requirement for invasive mechanical ventilation for patients requiring support with high flow nasal cannula. There is conflicting data for patients requiring lower-level oxygen support. Research question: Does APP reduce escalation of oxygen support in COVID-19 patients requiring supplementary oxygen?The primary outcome was defined as an escalation of oxygen support from simple supplementary oxygen (NP, HM, NRB) to NIV (CPAP or BiPAP), HFNC or IMV; OR from NIV (CPAP or BiPAP) or HFNC to IMV by day30. Study design: Two center, prospective, non-blind, randomised controlled trial. Patients with confirmed or suspected COVID-19 pneumonia requiring ≥ 5 liters/min oxygen to maintain saturations ≥ 94 % were randomised to either APP or control group. The APP group received a 3-h APP session three times per day for three days. Results: Between 9 May and July 13, 2021, 89 adults were screened and 61 enrolled, 31 to awake prone position and 30 controls. There was no difference in the primary outcome, 7 (22.6 %) patients randomised to APP and 9 (30.0 %) controls required escalation of oxygen support (OR 0.68 (0.22-2.14), P = 0.51). There were no differences in any secondary outcomes, in APP did not improve oxygenation. Interpretation: In COVID-19 patients, the use of APP did not prevent escalation of oxygen support from supplementary to invasive or non-invasive ventilation or improve patient respiratory physiology. Trial registration: NCT04853979 (clinicaltrials.gov).

Is EGD Needed in all Patients after Suicidal or Exploratory Caustic Ingestions?

BACKGROUND: Caustic ingestions are relatively uncommon, but remain a significant source of morbidity. Patients with caustic injury often undergo an urgent EGD, although it is not clear if an EGD is routinely needed in an asymptomatic patient. The study has two primary objectives; 1) to determine the utility of routine EGD in asymptomatic suicidal caustic ingestions; 2) to determine if asymptomatic unintentional acidic ingestions can be managed with observation alone, similar to basic ingestions. METHODS: This retrospective study, which took place at 14 hospitals in three countries evaluated all patients who presented with a caustic ingestion between 2014-2020. The presence of symptoms and esophageal injury, demographic information, pH of ingested substance, reason for the ingestion, and outcome were recorded. RESULTS: 409 patients were identified; 203 (46.9%) were male. The median (IQR) age was 18 (4-31) years; overall range 10 months to 78 years. Suicidal ingestions accounted for 155 (37.9%) of cases. Dysphagia or dysphonia were more likely in those with significant esophageal injury compared to those without (59.3% vs. 12.6% respectively; OR 10.1; 95% CI 4.43-23.1). Among 27 patients with significant esophageal injury, 48% were found in suicidal patients, compared with 51.9% in non-suicidal patients (p = NS). On multivariate regression, there was no difference in the rate of significant esophageal injury among suicidal vs. non suicidal patients (aOR 1.55; p = 0.45, 95% CI 0.45-5.33). Most ingestions involved basic substances (332/409; 81.2%). Unknown or mixed ingestions accounted for 25 (6.11%) of the ingestions. Significant esophageal burns were found in 6/52 (11.5%) of acid ingestions, compared with 21/332 (6.3%) of basic ingestions. Of the 42 cases of acidic ingestions without dysphagia or odynophagia, 2 (4.8%; 0.58-16.1%) had significant esophageal burns, compared with 9 (3.2%; 95% CI 1.4-5.9%) of the 284 basic ingestions; p = 0.64). On multivariate logistic regression, patients with acidic ingestions were not more likely to experience a significant burn (aOR 1.7; p = 0.11, 95% CI 0.9-3.1) compared to those with basic ingestions. No patient with significant esophageal burns was asymptomatic. CONCLUSION: In this study, there was no statistical differences in the rates of significant burns between acidic and basic caustic ingestions. There were no significant esophageal injuries noted among asymptomatic patients.

Transition Metal-Free Catalytic C-H Zincation and Alumination.

C-H metalation is the most efficient method to prepare aryl-zinc and -aluminium complexes that are ubiquitous nucleophiles. Virtually all C-H metalation routes to form Al/Zn organometallics require stoichiometric, strong Brønsted bases with no base-catalyzed reactions reported. Herein we present a catalytic in amine/ammonium salt (Et3N/[(Et3N)H]+) C-H metalation process to form aryl-zinc and aryl-aluminium complexes. Key to this approach is coupling an endergonic C-H metalation step with a sufficiently exergonic dehydrocoupling step between the ammonium salt by-product of C-H metalation ([(Et3N)H]+) and a Zn-H or Al-Me containing complex. This step, forming H2/MeH, makes the overall cycle exergonic while generating more of the reactive metal electrophile. Mechanistic studies supported by DFT calculations revealed metal-specific dehydrocoupling pathways, with the divergent reactivity due to the different metal valency (which impacts the accessibility of amine-free cationic metal complexes) and steric environment. Notably, dehydrocoupling in the zinc system proceeds through a ligand-mediated pathway involving protonation of the ß-diketiminate Cγ position. Given this process is applicable to two disparate metals (Zn and Al), other main group metals and ligand sets are expected to be amenable to this transition metal-free, catalytic C-H metalation.

Catalytic Access to Diastereometrically Pure Four- and Five-Membered Silyl-Heterocycles Using Transborylation.

Silyl-heterocycles offer a unique handle to expand and explore chemical space, reactivity, and functionality. The shortage of catalytic methods for the preparation of diverse and functionalized silyl-heterocycles however limits widespread exploration and exploitation. Herein the borane-catalyzed intramolecular 1,1-carboboration of silyl-alkynes has been developed for the synthesis of 2,3-dihydrosilolyl and silylcyclobut-2-enyl boronic esters. Successful, catalytic carboboration has been achieved on a variety of functionally diverse silyl-alkynes, using a borane catalyst and transborylation-enabled turnover. Mechanistic studies, including 13C-labelling, computational studies, and single-turnover experiments, suggest a reaction pathway proceeding by 1,2-hydroboration, 1,1-carboboration, and transborylation to release the alkenyl boronic ester product and regenerate the borane catalyst.

Low-dose dengue virus 3 human challenge model: a phase 1 open-label study.

Dengue human infection models present an opportunity to explore the potential of a vaccine, anti-viral or immuno-compound for clinical benefit in a controlled setting. Here we report the outcome of a phase 1 open-label assessment of a low-dose dengue virus 3 (DENV-3) challenge model (NCT04298138), in which nine participants received a subcutaneous inoculation with 0.5 ml of a 1.4 × 103 plaque-forming unit per ml suspension of the attenuated DENV-3 strain CH53489. The primary and secondary endpoints of the study were to assess the safety of this DENV-3 strain in healthy flavivirus-seronegative individuals. All participants developed RNAaemia within 7 days after inoculation with peak titre ranging from 3.13 × 104 to 7.02 × 108 genome equivalents per ml. Solicited symptoms such as fever and rash, clinical laboratory abnormalities such as lymphopenia and thrombocytopenia, and self-reported symptoms such as myalgia were consistent with mild-to-moderate dengue in all volunteers. DENV-3-specific seroconversion and memory T cell responses were observed within 14 days after inoculation as assessed by enzyme-linked immunosorbent assay and interferon-gamma-based enzyme-linked immunospot. RNA sequencing and serum cytokine analysis revealed anti-viral responses that overlapped with the period of viraemia. The magnitude and frequency of clinical and immunologic endpoints correlated with an individual's peak viral titre.

Epidemiological profile of stroke in Qatar: Insights from a seven-year observational study.

OBJECTIVES: Stroke prevalence is progressively increasing in developing countries due to increased vascular risk factors. This study aims to describe the epidemiology, prevalent risk factors, and outcomes of stroke in a multi-ethnic society of Qatar. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients with suspected stroke admitted to stroke services between January 2014 and September 2020. RESULTS: A total of 11,892 patients were admitted during this period with suspected stroke. Of these, the diagnosis was ischemic stroke (48.8 %), transient ischemic attack (10.3 %), intracerebral hemorrhage (10.9 %), cerebral venous sinus thrombosis (1.3 %), and stroke mimics (28.6 %). The median age was 52 (43-62), with a male-female ratio of 3:1. The study population was predominantly Asian (56.8 %) and Arab (36 %). The majority of the patients were hypertensive (66.8 %), diabetic (47.9 %), and dyslipidemic (45.9 %). A history of prior stroke was observed in 11.7 %, while 0.9 % had prior transient ischemic attack. Among ischemic strokes, 31.7 % arrived within 4.5 h, 12.5 % received thrombolysis, and 4.6 % underwent thrombectomy. Median Door-to-Needle time was 51 (33-72) minutes. The average length of stay was 5.2 ± 9.0 days, with 71.5 % discharged home, 13.8 % transferred to rehabilitation, 9.3 % to other specialties, 3 % to long-term care, and 2.4 % suffered in-hospital mortality. CONCLUSION: Stroke in Qatar is characterized by a younger, expatriate-dominant cohort, with notable prevalence of ischemic and hemorrhagic stroke and a distinct risk factor profile. Further analysis of epidemiological differences among different population groups can inform targeted policies for prevention and management to reduce the burden of disease.

What is the environmental impact of a blood transfusion? A life cycle assessment of transfusion services across England.

BACKGROUND: Healthcare activities significantly contribute to greenhouse gas (GHG) emissions. Blood transfusions require complex, interlinked processes to collect, manufacture, and supply. Their contribution to healthcare emissions and avenues for mitigation is unknown. STUDY DESIGN AND METHODS: We performed a life cycle assessment (LCA) for red blood cell (RBC) transfusions across England where 1.36 million units are transfused annually. We defined the process flow with seven categories: donation, transportation, manufacturing, testing, stockholding, hospital transfusion, and disposal. We used direct measurements, manufacturer data, bioengineering databases, and surveys to assess electrical power usage, embodied carbon in disposable materials and reagents, and direct emissions through transportation, refrigerant leakage, and disposal. RESULTS: The central estimate of carbon footprint per unit of RBC transfused was 7.56 kg CO2 equivalent (CO2eq). The largest contribution was from transportation (2.8 kg CO2eq, 36% of total). The second largest was from hospital transfusion processes (1.9 kg CO2eq, 26%), driven mostly by refrigeration. The third largest was donation (1.3 kg CO2eq, 17%) due to the plastic blood packs. Total emissions from RBC transfusion are ~10.3 million kg CO2eq/year. DISCUSSION: This is the first study to estimate GHG emissions attributable to RBC transfusion, quantifying the contributions of each stage of the process. Primary areas for mitigation may include electric vehicles for the blood service fleet, improving the energy efficiency of refrigeration, using renewable sources of electricity, changing the plastic of blood packs, and using methods of disposal other than incineration.

Assessing the one-month mortality impact of civilian-setting prehospital transfusion: A systematic review and meta-analysis.

BACKGROUND: Based on convincing evidence for outcomes improvement in the military setting, the past decade has seen evaluation of prehospital transfusion (PHT) in the civilian emergency medical services (EMS) setting. Evidence synthesis has been challenging, due to study design variation with respect to both exposure (type of blood product administered) and outcome (endpoint definitions and timing). The goal of the current meta-analysis was to execute an overarching assessment of all civilian-arena randomized controlled trial (RCT) evidence focusing on administration of blood products compared to control of no blood products. METHOD: The review structure followed the Cochrane group's Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Using the Transfusion Evidence Library (transfusionevidencelibrary.com), the multidatabase (e.g. PubMed, EMBASE) Harvard On-Line Library Information System (HOLLIS), and GoogleScholar, we accessed many databases and gray literature sources. RCTs of PHT in the civilian setting with a comparison group receiving no blood products with 1-month mortality outcomes were identified. RESULTS: In assessing a single patient-centered endpoint-1-month mortality-we calculated an overall risk ratio (RR) estimate. Analysis of three RCTs yielded a model with acceptable heterogeneity (I2 = 48%, Q-test p = 0.13). Pooled estimate revealed civilian PHT results in a statistically nonsignificant (p = 0.38) relative mortality reduction of 13% (RR 0.87, 95% CI 0.63-1.19). CONCLUSIONS: Current evidence does not demonstrate 1-month mortality benefit of civilian-setting PHT. This should give pause to EMS systems considering adoption of civilian-setting PHT programs. Further studies should not only focus on which formulations of blood products might improve outcomes but also focus on which patients are most likely to benefit from any form of civilian-setting PHT.

Hyperlocal lessons from the COVID-19 pandemic: Toward an equity-centered implementation science approach.

COVID-19 vaccination campaigns across the US were implemented to mitigate the disproportionate hospitalizations and unnecessary deaths across many communities that experienced unequal gaps in initial vaccine distribution rollout and uptake. In parallel, the COVID-19 pandemic created declines in routine vaccination coverage for adults, adolescents, and children; particularly, in communities experiencing overlapping social disadvantage. Community-based efforts offer a solution to narrow immunization gaps but have not been replicated consistently nor demonstrated widespread success during the pandemic as evidenced by prevailing disparities in immunization uptake. We offer an equity centered implementation science approach that involves co-designing, co-implementing, and co-evaluating solutions with the community and all partners investing in the shared goal of sustainable improvement in health outcomes.

Natural Experiment Outcomes Studies in Rotor Wing Air Medical Transport: Systematic Review and Meta-Analysis of Before-and-After and Helicopter-Unavailable Publications From 1970 to 2022.

OBJECTIVE: Helicopter emergency medical services (HEMS) is widely used for prehospital and interfacility transport, but there is a paucity of HEMS outcomes data from studies using randomized controlled trial designs. In the absence of robust randomized controlled trial evidence, judgments regarding HEMS potential benefit must be informed by observational data. Within the study design set of observational analyses, the natural experiment (NE) is notable for its high potential methodologic quality; NE designs are occasionally denoted "quasi-experimental." The aim of this study is to examine all NE outcomes studies in the HEMS literature and to discern what lessons can be learned from these potentially high-quality observational data. METHODS: HEMS NE studies were identified during the development of a new HEMS Outcomes Assessment Research Database (HOARD). HOARD was constructed using a broad-ranging search of published and gray literature resources (eg, PubMed, Embase, and Google Scholar) that used variations of the terms "helicopter EMS," "air ambulance," and "air medical transport." Among the 221 studies ultimately included in HOARD, 16 NE publications describing 13 sets of observational data comprising myriad diagnostic groups were identified. Of these 16 HEMS NEs, 4 HEMS NE studies assessing trauma outcomes were used in a meta-analysis. A meta-analysis was also performed of 4 HEMS NE studies. RESULTS: Although the disparity of studies (in terms of both case mix and end points) precluded the generation of a pooled effect estimate of an adjusted mortality benefit of HEMs versus ground emergency medical services, HEMS was found to be associated with outcomes improvement in 8 of the 13 cohorts. CONCLUSION: The weight of the NE evidence supports a conclusion of some form of HEMS-mediated outcomes improvement in a variety of patient types. Meta-analysis of 4 HEMS NE studies assessing trauma outcomes generated a model with acceptable heterogeneity (I2 = 43%, Q test: P = .16), which significantly (P < .01) favored HEMS use with a pooled HEMS survival odd ratio estimate of 1.66 (95% confidence interval, 1.23-2.22).

Applications of Artificial Intelligence in Helicopter Emergency Medical Services: A Scoping Review.

OBJECTIVE: Recent systematic reviews of acute care medicine applications of artificial intelligence (AI) have focused on hospital and general prehospital uses. The purpose of this scoping review was to identify and describe the literature on AI use with a focus on applications in helicopter emergency medical services (HEMS). METHODS: A literature search was performed with specific inclusion and exclusion criteria. Articles were grouped by characteristics such as publication year and general subject matter with categoric and temporal trend analyses. RESULTS: We identified 21 records focused on the use of AI in HEMS. These applications included both clinical and triage uses and nonclinical uses. The earliest study appeared in 2006, but over one third of the identified studies have been published in 2021 or later. The passage of time has seen an increased likelihood of HEMS AI studies focusing on nonclinical issues; for each year, the likelihood of a nonclinical focus had an odds ratio of 1.3. CONCLUSION: This scoping review provides overview and hypothesis-generating information regarding AI applications specific to HEMS. HEMS AI may be ultimately deployed in nonclinical arenas as much as or more than for clinical decision support. Future studies will inform future decisions as to how AI may improve HEMS systems design, asset deployment, and clinical care.

Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity.

The differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross-validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric significantly improved model performance.

Zika purified inactivated virus (ZPIV) vaccine reduced vertical transmission in pregnant immunocompetent mice.

Zika virus (ZIKV) is a significant threat to pregnant women and their fetuses as it can cause severe birth defects and congenital neurodevelopmental disorders, referred to as congenital Zika syndrome (CZS). Thus, a safe and effective ZIKV vaccine for pregnant women to prevent in utero ZIKV infection is of utmost importance. Murine models of ZIKV infection are limited by the fact that immunocompetent mice are resistant to ZIKV infection. As such, interferon-deficient mice have been used in some preclinical studies to test the efficacy of ZIKV vaccine candidates against lethal virus challenge. However, interferon-deficient mouse models have limitations in assessing the immunogenicity of vaccines, necessitating the use of immunocompetent mouse pregnancy models. Using the human stat2 knock-in (hSTAT2KI) mouse pregnancy model, we show that vaccination with a purified formalin-inactivated Zika virus (ZPIV) vaccine prior to pregnancy successfully prevented vertical transmission. In addition, maternal immunity protected offspring against postnatal challenge for up to 28 days. Furthermore, passive transfer of human IgG purified from hyper-immune sera of ZPIV vaccinees prevented maternal and fetal ZIKV infection, providing strong evidence that the neutralizing antibody response may serve as a meaningful correlate of protection.

Protective efficacy of a Zika purified inactivated virus vaccine candidate during pregnancy in marmosets.

Zika virus (ZIKV) infection during pregnancy poses significant threats to maternal and fetal health, leading to intrauterine fetal demise and severe developmental malformations that constitute congenital Zika syndrome (CZS). As such, the development of a safe and effective ZIKV vaccine is a critical public health priority. However, the safety and efficacy of such a vaccine during pregnancy remain uncertain. Historically, the conduct of clinical trials in pregnant women has been challenging. Therefore, clinically relevant animal pregnancy models are in high demand for testing vaccine efficacy. We previously reported that a marmoset pregnancy model of ZIKV infection consistently demonstrated vertical transmission from mother to fetus during pregnancy. Using this marmoset model, we also showed that vertical transmission could be prevented by pre-pregnancy vaccination with Zika purified inactivated virus (ZPIV) vaccine. Here, we further examined the efficacy of ZPIV vaccination during pregnancy. Vaccination during pregnancy elicited virus neutralizing antibody responses that were comparable to those elicited by pre-pregnancy vaccination. Vaccination also reduced placental pathology, viral burden and vertical transmission of ZIKV during pregnancy, without causing adverse effects. These results provide key insights into the safety and efficacy of ZPIV vaccination during pregnancy and demonstrate positive effects of vaccination on the reduction of ZIKV infection, an important advance in preparedness for future ZIKV outbreaks.

Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines.

BACKGROUND & AIMS: Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study's aim was to assess the current status of states' OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States. METHODS: Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher's exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols. RESULTS: Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%). CONCLUSION: There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.

A five-year quasi-experimental study to evaluate the impact of empiric antibiotic order sets on antibiotic use metrics among hospitalized adult patients.

OBJECTIVE: Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase. DESIGN: This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31. SETTING: The study was conducted in a 752-bed tertiary care, academic medical center. INTERVENTION: Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults. RESULTS: For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics. CONCLUSIONS: Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.