Maternal Perceptions of Evidence-Based Early Childhood Sleep Health Promotion Recommendations: An Explanatory Sequential Study.

OBJECTIVES: The purpose of this explanatory sequential design study was to better understand caregivers' perceptions about and interest in evidence-based early childhood sleep health promotion recommendations. METHOD: A purposeful sample of mothers of 20 1-5-year-old children (10 children exhibiting optimal sleep and 10 children exhibiting insufficient/fragmented sleep) attending a preschool serving a low socio-economic (SES) status metropolitan community were invited to participate in qualitative interviews. Data were coded according to a grounded theory approach and themes were identified within the optimal and suboptimal sleeper groups. RESULTS: Mothers reported different approaches to managing electronics by optimal/suboptimal sleeper group, with mothers of optimal sleepers limiting access to electronics more than mothers in the suboptimal sleep group. Other themes of sleep health practices did not differ meaningfully between groups. CONCLUSIONS: Maternal perspectives about early childhood sleep health were similar across optimal and suboptimal sleepers on most elements of child sleep health. Managing child sleep was contextually influenced and these results highlight the complexities of how families living in lower SES environments perceive common sleep recommendations. Thus, sleep health education efforts should be tailored to the needs and values of specific families and communities.

Development and evaluation of a concise nurse-driven non-pharmacological delirium reduction workflow for hospitalized patients: An interrupted time series study.

We created a concise nurse-driven delirium reduction workflow with the aim of reducing delirium rates and length of stay for hospitalized adults. Our nurse-driven workflow included five evidence-based daytime "sunrise" interventions (patient room lights on, blinds up, mobilization/out-of-bed, water within patient's reach and patient awake) and five nighttime "turndown" interventions (patient room lights off, blinds down, television off, noise reduction and pre-set bedtime). Interventions were also chosen because fidelity could be quickly monitored twice daily without patient interruption from outside the room. To evaluate the workflow, we used an interrupted time series study design between 06/01/17 and 05/30/22 to determine if the workflow significantly reduced the unit's delirium rate and average length of stay. Our workflow is feasible to implement and monitor and initially significantly reduced delirium rates but not length of stay. However, the reduction in delirium rates were not sustained following the emergence of the COVID-19 pandemic.

Developing electronic health record-based measures of the 4Ms to support implementation and evidence generation for Age-Friendly Health Systems.

BACKGROUND: To support implementation of the 4Ms framework and more rigorous evidence of 4Ms impact, we translated Institute for Healthcare Improvement's (IHI's) recommended 4Ms routine care practices into electronic health record-based, encounter-level adherence measures and then implemented measures at a large academic medical center. METHODS: We started with the 19 care practices in IHI's 4Ms implementation guide and developed encounter-level adherence measures using structured EHR data. We also developed overall 4Ms-level and M-level composite measures. Next, we operationalized measures at UCSF Health-an academic medical center that has implemented the 4Ms using the IHI guide. We identified UCSF Health patients who should have received 4Ms care during their inpatient admission (19,335 individuals 65 years and older with an admission between January 1, 2019 and December 31, 2021), then implemented the individual measures and composite measures (all at the encounter level) using Epic EHR data. We focused on 4Ms inpatient care processes, but similar approaches can be followed for ambulatory, post-acute, and other settings. RESULTS: We developed 18 EHR-based measures that captured all IHI care practices, 16 of which could be implemented using UCSF Health EHR data. For example, the EHR-based measure for the Medication care practice "deprescribe high risk medications" was measured using EHR data as "Patient had no previously existing prescriptions for high-risk medications OR patient had ≥1 previously existing prescriptions for high-risk medications deprescribed during the encounter," and 29.5% of UCSF Health encounters met this measure. For composite measures, on average, UCSF Health encounters had 61.1% adherence to the 4Ms (SD = 14.4%), with the lowest average adherence to What Matters (50.9%; SD = 44.3%) and the highest for Mentation (68.4%; SD = 13.4%). CONCLUSIONS: It is feasible to construct encounter-level measures of 4Ms adherence using EHR data and derive insights to guide ongoing implementation efforts. Future efforts should refine measures based on assessments of reliability and validity.

Development of the Groundwater Concept Inventory to Measure Groundwater Knowledge in a General Audience.

Groundwater is a critical resource globally, and understanding groundwater processes is vital to ensure sustainable management practices. However, there are many widely held misconceptions and inaccuracies about groundwater, and we currently lack tools to measure groundwater knowledge across large populations and measure how groundwater knowledge relates to management decisions or behaviors. Here, we present a survey instrument, the Groundwater Concept Inventory (GWCI), that has been designed for general audiences to measure groundwater knowledge comparable to that in an introductory geoscience curriculum. The GWCI was developed using ∼1200 responses using an online platform, Amazon Mechanical Turks, to represent a general population. Responses were evaluated using the Rasch model that configures a relationship between person-ability and item-difficulty. We found that the study population displayed similar misconceptions about groundwater compared with previous literature, and that age and education were not strong predictors of GWCI scores. The GWCI can be used by researchers to understand links between knowledge and behavior, and also by other stakeholders to quantify misconceptions about groundwater and target resources for a more informed public.

Investigating the Relationship between Surface Water Pollution and Onsite Wastewater Treatment Systems.

Onsite wastewater treatment systems (OWTSs) are important nonpoint sources (NPSs) of pollution to consider in watershed management. However, limited OWTS data availability makes it challenging to account for them as an NPS of water pollution. In this study, we succeeded in obtaining OWTS permits and integrated them with environmental data to model the pollution potential from OWTSs at the watershed scale using GIS-based multicriteria decision analysis. Then, in situ water quality parameters─Escherichia coli (E. coli), total nitrogen, total phosphorus, temperature, and pH─were measured along the main tributary at base-flow conditions. Three general linear models were developed to relate E. coli to water quality parameters and OWTS pollution indicators. It was found that the model with the OWTS pollution potential had the lowest corrected Akaike information criterion (AICc) value (35.01) compared to the models that included classified OWTS pollution potential input criteria (AICc = 36.76) and land cover (AICc = 36.74). These results demonstrate that OWTSs are a significant contributor to surface water pollution, and future efforts should be made to improve access to OWTS data (i.e., location and age) to account for these systems as an NPS of water pollution.

Lost in Transition: Missed Opportunities for the 4 Ms to Support Post-Acute Care Transitions.

Thousands of health systems have adopted the 4 Ms framework, a set of evidence-based practices specific to older adults, as part of the Age-Friendly Health Systems (AFHS) initiative. However, implementation efforts have largely been setting-specific and approaches to achieve continuity of the 4 Ms during care transitions are nascent. Transitions from hospitals to skilled nursing facilities (SNFs) are one type of care transition that would greatly benefit from continuity of 4 Ms practices. Drawing from the authors' insights and 5 exploratory interviews at 3 health systems that implemented the 4 Ms in the inpatient setting, we describe a set of current-state challenges when trying to extend specific inpatient 4 Ms practices (eg, deprescribing of high-risk medications) as well as the nuanced understanding of the individual's clinical trajectory developed during an inpatient stay. We also offer concrete opportunities, such as developing 4 Ms-centric discharge summary templates, to address the challenges. With the large investment in AFHS transformation and associated efforts to implement the 4 Ms framework in all care settings used by older adults, it is critical to raise awareness of the specific obstacles to promoting continuity of successful 4 Ms practices during care transitions and work to overcome them. Our insights from hospital-to-SNF transitions offer a starting point.

Health system approaches and experiences implementing the 4Ms: Insights from 3 early adopter health systems.

BACKGROUND: Redesigning the healthcare system to consistently provide effective and tailored care to older adults is needed. The 4Ms (What Matters, Mobility, Medication, and Mentation) offer a framework to guide health systems' efforts to deliver Age-Friendly care. We use an implementation science framework to characterize and assess real-world implementation experiences with the 4Ms across varied health systems. METHODS: With expert input, we selected three health systems that were early adopters of the 4Ms and engaged in different implementation support models through the Institute for Healthcare Improvement. We conducted 29 semi-structured interviews with diverse stakeholders from each site. Stakeholders ranged from hospital leadership to frontline clinicians. Interviews covered each site's approach to and experiences with implementation, including facilitators and barriers. Interviews were recorded, transcribed, and deductively coded using the Consolidated Framework for Implementation Research. We characterized each site's implementation decisions and then inductively identified overarching themes and subthemes with supporting quotes. RESULTS: Health systems varied in their implementation approach, including the implementation order of each of the 4Ms. We identified three overarching themes: (1) the 4Ms offered a compelling conceptual framework for advancing Age-Friendly care, but implementation was complex and fragmented; (2) complete and sustained implementation of the 4Ms required multidisciplinary and multilevel leadership and engagement; (3) strategies that facilitate implementation success and support frontline culture change included top-down communication and infrastructure alongside hands-on clinical education and support. Common barriers are siloed implementation efforts across settings that impeded synergies and scaling; disengaged physicians; and difficulty implementing What Matters in a meaningful way. CONCLUSIONS: Similar to other implementation studies, we identified multifactorial domains impacting 4Ms implementation. To achieve Age-Friendly transformation, health systems must plan for and attend to multiple phases of implementation while ensuring that the work coheres under a unified vision that spans disciplines and settings.

Physiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function.

Human trophoblast cultures provide powerful tools to model key processes of placental development. In vitro trophoblast studies to date have relied on commercial media that contains nonphysiological levels of nutrients, and the impact of these conditions on trophoblast metabolism and function is unknown. Here, we show that the physiological medium (Plasmax) with nutrient and metabolite concentrations recapitulating human plasma improves human trophoblast stem cell (hTSC) proliferation and differentiation compared with standard medium (DMEM-F12). hTSCs cultured in Plasmax-based medium also show altered glycolytic and mitochondrial metabolism, as well as reduced S-adenosylmethionine/S-adenosyl-homocysteine ratio compared with DMEM-F12-based medium. These findings demonstrate the importance of the nutritional environment for phenotyping cultured human trophoblasts.

Honey bee colony loss linked to parasites, pesticides and extreme weather across the United States.

Honey bee (Apis mellifera) colony loss is a widespread phenomenon with important economic and biological implications, whose drivers are still an open matter of investigation. We contribute to this line of research through a large-scale, multi-variable study combining multiple publicly accessible data sources. Specifically, we analyzed quarterly data covering the contiguous United States for the years 2015-2021, and combined open data on honey bee colony status and stressors, weather data, and land use. The different spatio-temporal resolutions of these data are addressed through an up-scaling approach that generates additional statistical features which capture more complex distributional characteristics and significantly improve modeling performance. Treating this expanded feature set with state-of-the-art feature selection methods, we obtained findings that, nation-wide, are in line with the current knowledge on the aggravating roles of Varroa destructor and pesticides in colony loss. Moreover, we found that extreme temperature and precipitation events, even when controlling for other factors, significantly impact colony loss. Overall, our results reveal the complexity of biotic and abiotic factors affecting managed honey bee colonies across the United States.

The current landscape of Acute Care for Elders units in the United States.

BACKGROUND: The clinical benefits of Acute Care for Elders (ACE) units have been established for over 25 years. However, how widely disseminated ACE units are in the United States and the degree of fidelity to the key elements of this model of care are unknown. Our objective was to identify all existing ACE units in the United States and to obtain detailed information about variations in implementation. METHODS: The strategy to identify current ACE units began with online searches and snowball sampling using contacts from professional societies and workgroups. Next, a request for information regarding the existence of ACE units was sent to the remaining US hospitals listed in a national hospital database. An online survey was sent to identified ACE unit contacts to capture information on implementation characteristics and the five key elements of ACE units. RESULTS: There were 3692 hospitals in the database with responses from 2055 (56%) hospitals reporting the presence or absence of an ACE unit. We identified 68 hospitals (3.3%) with an existing or previous ACE unit. Of these 68 hospitals, 50 (74%) completed the survey and reported that 43 ACE units were currently open and 7 had been closed. Of the 43 currently open ACE units, most are affiliated with an academic hospital and there is variable implementation of each of the five key ACE elements (from 69% to 98%). CONCLUSIONS: Among the 50 hospitals to complete the survey, 43 current ACE units were identified, with variable fidelity to the key elements. Estimates of prevalence of ACE units and fidelity to key elements are limited by nonresponses to the national survey request by nearly half of hospitals.

Spatial distribution and mass transport of Perfluoroalkyl Substances (PFAS) in surface water: A statewide evaluation of PFAS occurrence and fate in Alabama.

Per- and polyfluoroalkyl substances (PFAS) have been previously detected near suspected sources in Alabama, but the overall extent of contamination across the state is unknown. This study evaluated the spatial distribution of 17 PFAS within the ten major river basins in Alabama and provided insights into their transport and fate through a mass flux analysis. Six PFAS were identified in 65 out of the 74 riverine samples, with mean ∑6PFAS levels of 35.2 ng L-1. The highest ∑6PFAS concentration of 237 ng L-1 was detected in the Coosa River, a transboundary river that receives discharges from multiple sources in Alabama and Georgia. PFAS distribution was not observed to be uniform across the state: while the Coosa, Alabama, and Chattahoochee rivers presented relatively high mean ∑6PFAS concentrations of 191, 100 and 28.8 ng L-1, respectively, PFAS were not detected in the Conecuh, Escatawpa, and Yellow rivers. Remaining river systems presented mean ∑6PFAS concentrations between 7.94 and 24.7 ng L-1. Although the short-chain perfluoropentanoic acid (PFPeA) was the most detected analyte (88%), perfluorobutanesulfonic acid (PFBS) was the substance with the highest individual concentration of 79.4 ng L-1. Consistent increases in the mass fluxes of PFAS were observed as the rivers flowed through Alabama, reaching up to 63.3 mg s-1, indicating the presence of numerous sources across the state. Most of the mass inputs would not have been captured if only aqueous concentrations were evaluated, since concentration is usually heavily impacted by environmental conditions. Results of this study demonstrate that mass flux is a simple and powerful complementary approach that can be used to broadly understand trends in the transport and fate of PFAS in large river systems.

Operative Management of Hip Fractures Within 24 Hours in the Elderly is Achievable and Associated With Reduced Opiate Use.

Introduction: Morbidity and mortality benefits have been associated with prompt surgical treatment of geriatric hip fractures. The purpose of this study was to evaluate the impact of early (≤24 hr) vs delayed (>24 hr) time to operating room (TTOR) on 1) hospital length of stay and 2) total and post-operative opiate use in geriatric hip fractures. Materials and Methods: This study was a retrospective review of patients ≥65 years-old at the time of admission for surgery for hip fracture at a Level II academic trauma center. Outcome measures were length of stay (LOS), oral morphine equivalents (OME) throughout hospitalization. Patients were stratified into early and delayed TTOR groups and comparisons were made between groups. Results: Between the early (n = 75, 80.6%) and late (n = 18, 19.4%) groups, there were no differences in age, fracture pattern, type of treatment, preoperative opiate use, and perioperative non-oral pain management. The early group trended toward shorter total LOS (108.0 ± 67.2 hours vs 144.8 ± 103.7 hours, P = .066), but not post-operative LOS. Total OME usage was less in the early intervention group (92.5 ± 188.0 vs 230.2 ± 296.7, P = .015), in addition to reduced post-operative OME (81.3 ± 174.9 vs 213.3 ± 271.3, P = .012). There were no differences in evaluated potential delay sources such as primary language, use of surrogate decision makers, or need for advanced imaging. Discussion: Surgical treatment of geriatric hip/femur fractures in ≤24 hours from presentation is achievable and may be associated with reduced total inpatient opiate use, although daily use did not differ. Conclusion: Establishing institutional TTOR goals as part of an interdisciplinary hip fracture co-management clinical pathway can facilitate prompt care and contribute to recovery and less opiate use in these patients with highly morbid injuries.

Protocol-based interdisciplinary co-management for hip fracture care: 3 years of experience at an academic medical center.

BACKGROUND: Interdisciplinary standardized protocols for the care of patients with hip fractures have been shown to improve outcomes. A hip fracture protocol was implemented at our institution to standardize care, focusing on emergency care, pre-operative medical management, operative timing, and geriatrics co-management. The aim of this study was to evaluate the efficacy of this protocol. METHODS: We conducted a retrospective review of adult patients admitted to a single tertiary care institution who underwent operative management of a hip fracture between July 2012 and March 2020. Comparison of patient characteristics, hospitalization characteristics, and outcomes were performed between patients admitted before and after protocol implementation in 2017. RESULTS: A total of 517 patients treated for hip fracture were identified: 313 before and 204 after protocol implementation. Average age, average Charlson Comorbidity Index, percent female gender, and distribution of hip fracture diagnosis did not vary significantly between groups. There was a significant reduction in time from admission to surgical management, from 37.0 ± 47.7 to 28.5 ± 27.1 h (p = 0.0016), and in the length of hospital stay, from 6.3 ± 6.5 to 5.4 ± 4.0 days (p = 0.0013). The percentage of patients whose surgeries were performed under spinal anesthesia increased from 12.5 to 26.5% (p = 0.016). There was no difference in 90-day readmission rate or mortality at 30 days, 90 days, or 1 year between groups. CONCLUSION: With the implementation of an interdisciplinary hip fracture protocol, we observed significant and sustained reductions in time to surgery and hospital length of stay, important metrics in hip fracture management, without increased readmission or mortality. This has implications to minimize health care costs and improve outcomes for our aging population. LEVEL OF EVIDENCE: III, therapeutic.

Building Optimal Three-Drug Combination Chemotherapy Regimens To Eradicate Mycobacterium tuberculosis in Its Slow-Growth Acid Phase.

Mycobacterium tuberculosis metabolic state affects the response to therapy. Quantifying the effect of antimicrobials in the acid and nonreplicating metabolic phases of M. tuberculosis growth will help to optimize therapy for tuberculosis. As a brute-force approach to all possible drug combinations against M. tuberculosis in all different metabolic states is impossible, we have adopted a model-informed strategy to accelerate the discovery. Using multiple concentrations of each drug in time-kill studies, we examined single drugs and two- and three-drug combinations of pretomanid, moxifloxacin, and bedaquiline plus its active metabolite against M. tuberculosis in its acid-phase metabolic state. We used a nonparametric modeling approach to generate full distributions of interaction terms between pretomanid and moxifloxacin for susceptible and less susceptible populations. From the model, we could predict the 95% confidence interval of the simulated total bacterial population decline due to the 2-drug combination regimen of pretomanid and moxifloxacin and compare this to observed declines with 3-drug regimens. We found that the combination of pretomanid and moxifloxacin at concentrations equivalent to average or peak human concentrations effectively eradicated M. tuberculosis in its acid growth phase and prevented emergence of less susceptible isolates. The addition of bedaquiline as a third drug shortened time to total and less susceptible bacterial suppression by 8 days compared to the 2-drug regimen, which was significantly faster than the 2-drug kill.

2021 John Charnley Award: A protocol-based strategy when using hemiarthroplasty or total hip arthroplasty for femoral neck fractures decreases mortality, length of stay, and complications.

AIMS: While interdisciplinary protocols and expedited surgical treatment improve the management of hip fractures in the elderly, the impact of such interventions on patients specifically undergoing arthroplasty for a femoral neck fracture is not clear. We sought to evaluate the efficacy of an interdisciplinary protocol for the management of patients with a femoral neck fracture who are treated with an arthroplasty. METHODS: In 2017, our institution introduced a standardized interdisciplinary hip fracture protocol. We retrospectively reviewed adult patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fracture between July 2012 and March 2020, and compared patient characteristics and outcomes between those treated before and after the introduction of the protocol. RESULTS: A total of 157 patients were treated before the introduction of the protocol (35 (22.3%) with a THA), and 114 patients were treated after its introduction (37 (32.5%) with a THA). The demographic details and medical comorbidities were similar in the two groups. Patients treated after the introduction of the protocol had a significantly reduced median time between admission and surgery (22.8 hours (interquartile range (IQR) 18.8 to 27.7) compared with 24.8 hours (IQR 18.4 to 43.3) (p = 0.042), and a trend towards a reduced mean time to surgery (24.1 hours (SD 10.7) compared with 46.5 hours (SD 165.0); p = 0.150), indicating reduction in outliers. Patients treated after the introduction of the protocol had a significantly decreased rate of major complications (4.4% vs 17.2%; p = 0.005), decreased median hospital length of stay in hospital (4.0 days vs 4.8 days; p = 0.008), increased rate of discharge home (26.3% vs 14.7%; p = 0.030), and decreased one-year mortality (14.7% vs 26.3%; p = 0.049). The 90-day readmission rate (18.2% vs 21.7%; p = 0.528) and 30-day mortality (3.7% vs 5.1%; p = 0.767) did not significantly differ. Patients who underwent HA were significantly older than those who underwent THA (82.1 years (SD 10.4) vs 71.1 years (SD 9.5); p < 0.001), more medically complex (mean Charlson Comorbidity Index 6.4 (SD 2.6) vs 4.1 (SD 2.2); p < 0.001), and more likely to develop delirium (8.5% vs 0%; p = 0.024). CONCLUSION: The introduction of an interdisciplinary protocol for the management of elderly patients with a femoral neck fracture was associated with reduced time to surgery, length of stay, complications, and one-year mortality. Such interventions are critical in improving outcomes and reducing costs for an ageing population. Cite this article: Bone Joint J 2021;103-B(7 Supple B):3-8.

Outcomes Following Implementation of a Hospital-Wide, Multicomponent Delirium Care Pathway.

BACKGROUND: Delirium is associated with poor clinical outcomes that could be improved with targeted interventions. OBJECTIVE: To determine whether a multicomponent delirium care pathway implemented across seven specialty nonintensive care units is associated with reduced hospital length of stay (LOS). Secondary objectives were reductions in total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. METHODS: This retrospective cohort study included 22,708 hospitalized patients (11,018 preintervention) aged ≥50 years encompassing seven nonintensive care units: neurosciences, medicine, cardiology, general and specialty surgery, hematology-oncology, and transplant. The multicomponent delirium care pathway included a nurse-administered delirium risk assessment at admission, nurse-administered delirium screening scale every shift, and a multicomponent delirium intervention. The primary study outcome was LOS for all units combined and the medicine unit separately. Secondary outcomes included total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. RESULTS: Adjusted mean LOS for all units combined decreased by 2% post intervention (proportional change, 0.98; 95% CI, 0.96-0.99; P = .0087). Medicine unit adjusted LOS decreased by 9% (proportional change, 0.91; 95% CI, 0.83-0.99; P = .028). For all units combined, adjusted odds of 30-day readmission decreased by 14% (odds ratio [OR], 0.86; 95% CI, 0.80-0.93; P = .0002). Medicine unit adjusted cost decreased by 7% (proportional change, 0.93; 95% CI, 0.89-0.96; P = .0002). CONCLUSION: This multicomponent hospital-wide delirium care pathway intervention is associated with reduced hospital LOS, especially for patients on the medicine unit. Odds of 30-day readmission decreased throughout the entire cohort.

Postnatal Arx transcriptional activity regulates functional properties of PV interneurons.

The transcription factor Aristaless-related X-linked gene (Arx) is a monogenic factor in early onset epileptic encephalopathies (EOEEs) and a fundamental regulator of early stages of brain development. However, Arx expression persists in mature GABAergic neurons with an unknown role. To address this issue, we generated a conditional knockout (CKO) mouse in which postnatal Arx was ablated in parvalbumin interneurons (PVIs). Electroencephalogram (EEG) recordings in CKO mice revealed an increase in theta oscillations and the occurrence of occasional seizures. Behavioral analysis uncovered an increase in anxiety. Genome-wide sequencing of fluorescence activated cell sorted (FACS) PVIs revealed that Arx impinged on network excitability via genes primarily associated with synaptic and extracellular matrix pathways. Whole-cell recordings revealed prominent hypoexcitability of various intrinsic and synaptic properties. These results revealed important roles for postnatal Arx expression in PVIs in the control of neural circuits and that dysfunction in those roles alone can cause EOEE-like network abnormalities.

Dose Fractionation of Moxifloxacin for Treatment of Tuberculosis: Impact of Dosing Interval and Elimination Half-Life on Microbial Kill and Resistance Suppression.

The repurposed agent moxifloxacin has become an important addition to the physician's armamentarium for the therapy of Mycobacterium tuberculosis When a drug is administered, we need to have metrics for success. As for most antimicrobial chemotherapy, we contend that for Mycobacterium tuberculosis therapy, these metrics should be a decline in the susceptible bacterial burden and the suppression of amplification of less-susceptible populations. To achieve optimal outcomes relative to these metrics, a dose and schedule of administration need to be chosen. For large populations of patients, there are true between-patient differences in important pharmacokinetic parameters. These distributions of parameter values may have an impact on these metrics, depending on what measure of drug exposure drives the metrics. To optimize dose and schedule choice of moxifloxacin, we performed a dose fractionation experiment in the hollow fiber infection model. We examined 12-, 24-, and 48-h dosing intervals with doses of 200, 400, and 800 mg for each interval, respectively. Within each interval, we had an arm where half-lives of 12, 8, and 4 h were simulated. We attempted to keep the average concentration (Cavg) or area under the concentration-time curve (AUC) constant across arms. We found that susceptible bacterial load decline was linked to Cavg, as we had indicated previously. Resistance suppression, a nonmonotonic function, had minimum concentration (Cmin) as the linked index. The 48-h interval with the 4-h half-life had the largest less-susceptible population. Balancing bacterial kill, resistance suppression, toxicity (linked to peak concentration [Cpeak]), and adherence, we conclude that the dose of 400 mg daily is optimal for moxifloxacin.