The role of hesitancy and infrastructure in the equity and efficiency of COVID-19 vaccine administration.

After the first COVID-19 vaccines received emergency use authorization from the U.S. FDA in December 2020, U.S. states employed vaccine eligibility and administration plans (VEAPs) that determined when subgroups of residents would become eligible to receive the vaccine while the vaccine supply was still limited. During the implementation of these plans, public concern grew over whether the VEAPs and vaccine allocations from the federal government were resulting in an equitable and efficient vaccine distribution. In this study, we collected data on five states' VEAPs, federal vaccine allocations, vaccine administration, and vaccine hesitancy to assess the equity of vaccine access and vaccine administration efficiency that manifested during the campaign. Our results suggest that residents in states which opened eligibility to the vaccine sooner had more competition among residents to receive the vaccine than occurred in other states. Regardless of states' VEAPs, there was a consistent inefficiency in vaccine administration among all five states that could be attributed to both state and federal infrastructure deficits. A closer examination revealed a misalignment between federal vaccine allocations and the total eligible population in the states throughout the campaign, even when accounting for hesitancy. We conclude that in order to maximize the efficiency of future mass-vaccination campaigns, the federal and state governments should design adaptable allocation policies and eligibility plans that better match the true, real-time supply and demand for vaccines by accounting for vaccine hesitancy and manufacturing capacity. Further, we discuss the challenges of implementing such strategies.

Developing, pilot testing, and refining requirements for 3 EHR-integrated interventions to improve diagnostic safety in acute care: a user-centered approach.

Objective: To describe a user-centered approach to develop, pilot test, and refine requirements for 3 electronic health record (EHR)-integrated interventions that target key diagnostic process failures in hospitalized patients. Materials and Methods: Three interventions were prioritized for development: a Diagnostic Safety Column (DSC) within an EHR-integrated dashboard to identify at-risk patients; a Diagnostic Time-Out (DTO) for clinicians to reassess the working diagnosis; and a Patient Diagnosis Questionnaire (PDQ) to gather patient concerns about the diagnostic process. Initial requirements were refined from analysis of test cases with elevated risk predicted by DSC logic compared to risk perceived by a clinician working group; DTO testing sessions with clinicians; PDQ responses from patients; and focus groups with clinicians and patient advisors using storyboarding to model the integrated interventions. Mixed methods analysis of participant responses was used to identify final requirements and potential implementation barriers. Results: Final requirements from analysis of 10 test cases predicted by the DSC, 18 clinician DTO participants, and 39 PDQ responses included the following: DSC configurable parameters (variables, weights) to adjust baseline risk estimates in real-time based on new clinical data collected during hospitalization; more concise DTO wording and flexibility for clinicians to conduct the DTO with or without the patient present; and integration of PDQ responses into the DSC to ensure closed-looped communication with clinicians. Analysis of focus groups confirmed that tight integration of the interventions with the EHR would be necessary to prompt clinicians to reconsider the working diagnosis in cases with elevated diagnostic error (DE) risk or uncertainty. Potential implementation barriers included alert fatigue and distrust of the risk algorithm (DSC); time constraints, redundancies, and concerns about disclosing uncertainty to patients (DTO); and patient disagreement with the care team's diagnosis (PDQ). Discussion: A user-centered approach led to evolution of requirements for 3 interventions targeting key diagnostic process failures in hospitalized patients at risk for DE. Conclusions: We identify challenges and offer lessons from our user-centered design process.

A structured approach to EHR surveillance of diagnostic error in acute care: an exploratory analysis of two institutionally-defined case cohorts.

OBJECTIVES: To test a structured electronic health record (EHR) case review process to identify diagnostic errors (DE) and diagnostic process failures (DPFs) in acute care. METHODS: We adapted validated tools (Safer Dx, Diagnostic Error Evaluation Research [DEER] Taxonomy) to assess the diagnostic process during the hospital encounter and categorized 13 postulated e-triggers. We created two test cohorts of all preventable cases (n=28) and an equal number of randomly sampled non-preventable cases (n=28) from 365 adult general medicine patients who expired and underwent our institution's mortality case review process. After excluding patients with a length of stay of more than one month, each case was reviewed by two blinded clinicians trained in our process and by an expert panel. Inter-rater reliability was assessed. We compared the frequency of DE contributing to death in both cohorts, as well as mean DPFs and e-triggers for DE positive and negative cases within each cohort. RESULTS: Twenty-seven (96.4%) preventable and 24 (85.7%) non-preventable cases underwent our review process. Inter-rater reliability was moderate between individual reviewers (Cohen's kappa 0.41) and substantial with the expert panel (Cohen's kappa 0.74). The frequency of DE contributing to death was significantly higher for the preventable compared to the non-preventable cohort (56% vs. 17%, OR 6.25 [1.68, 23.27], p<0.01). Mean DPFs and e-triggers were significantly and non-significantly higher for DE positive compared to DE negative cases in each cohort, respectively. CONCLUSIONS: We observed substantial agreement among final consensus and expert panel reviews using our structured EHR case review process. DEs contributing to death associated with DPFs were identified in institutionally designated preventable and non-preventable cases. While e-triggers may be useful for discriminating DE positive from DE negative cases, larger studies are required for validation. Our approach has potential to augment institutional mortality case review processes with respect to DE surveillance.

Analyzing diagnostic errors in the acute setting: a process-driven approach.

OBJECTIVES: We describe an approach for analyzing failures in diagnostic processes in a small, enriched cohort of general medicine patients who expired during hospitalization and experienced medical error. Our objective was to delineate a systematic strategy for identifying frequent and significant failures in the diagnostic process to inform strategies for preventing adverse events due to diagnostic error. METHODS: Two clinicians independently reviewed detailed records of purposively sampled cases identified from established institutional case review forums and assessed the likelihood of diagnostic error using the Safer Dx instrument. Each reviewer used the modified Diagnostic Error Evaluation and Research (DEER) taxonomy, revised for acute care (41 possible failure points across six process dimensions), to characterize the frequency of failure points (FPs) and significant FPs in the diagnostic process. RESULTS: Of 166 cases with medical error, 16 were sampled: 13 (81.3%) had one or more diagnostic error(s), and a total of 113 FPs and 30 significant FPs were identified. A majority of significant FPs (63.3%) occurred in "Diagnostic Information and Patient Follow-up" and "Patient and Provider Encounter and Initial Assessment" process dimensions. Fourteen (87.5%) cases had a significant FP in at least one of these dimensions. CONCLUSIONS: Failures in the diagnostic process occurred across multiple dimensions in our purposively sampled cohort. A systematic analytic approach incorporating the modified DEER taxonomy, revised for acute care, offered critical insights into key failures in the diagnostic process that could serve as potential targets for preventative interventions.

Pan-Cancer Transcriptional Models Predicting Chemosensitivity in Human Tumors.

MOTIVATION: Despite increasing understanding of the molecular characteristics of cancer, chemotherapy success rates remain low for many cancer types. Studies have attempted to identify patient and tumor characteristics that predict sensitivity or resistance to different types of conventional chemotherapies, yet a concise model that predicts chemosensitivity based on gene expression profiles across cancer types remains to be formulated. We attempted to generate pan-cancer models predictive of chemosensitivity and chemoresistance. Such models may increase the likelihood of identifying the type of chemotherapy most likely to be effective for a given patient based on the overall gene expression of their tumor. RESULTS: Gene expression and drug sensitivity data from solid tumor cell lines were used to build predictive models for 11 individual chemotherapy drugs. Models were validated using datasets from solid tumors from patients. For all drug models, accuracy ranged from 0.81 to 0.93 when applied to all relevant cancer types in the testing dataset. When considering how well the models predicted chemosensitivity or chemoresistance within individual cancer types in the testing dataset, accuracy was as high as 0.98. Cell line-derived pan-cancer models were able to statistically significantly predict sensitivity in human tumors in some instances; for example, a pan-cancer model predicting sensitivity in patients with bladder cancer treated with cisplatin was able to significantly segregate sensitive and resistant patients based on recurrence-free survival times (P = .048) and in patients with pancreatic cancer treated with gemcitabine (P = .038). These models can predict chemosensitivity and chemoresistance across cancer types with clinically useful levels of accuracy.

Effects of trust-based decision making in disrupted supply chains.

The United States has experienced prolonged severe shortages of vital medications over the past two decades. The causes underlying the severity and prolongation of these shortages are complex, in part due to the complexity of the underlying supply chain networks, which involve supplier-buyer interactions across multiple entities with competitive and cooperative goals. This leads to interesting challenges in maintaining consistent interactions and trust among the entities. Furthermore, disruptions in supply chains influence trust by inducing over-reactive behaviors across the network, thereby impacting the ability to consistently meet the resulting fluctuating demand. To explore these issues, we model a pharmaceutical supply chain with boundedly rational artificial decision makers capable of reasoning about the motivations and behaviors of others. We use multiagent simulations where each agent represents a key decision maker in a pharmaceutical supply chain. The agents possess a Theory-of-Mind capability to reason about the beliefs, and past and future behaviors of other agents, which allows them to assess other agents' trustworthiness. Further, each agent has beliefs about others' perceptions of its own trustworthiness that, in turn, impact its behavior. Our experiments reveal several counter-intuitive results showing how small, local disruptions can have cascading global consequences that persist over time. For example, a buyer, to protect itself from disruptions, may dynamically shift to ordering from suppliers with a higher perceived trustworthiness, while the supplier may prefer buyers with more stable ordering behavior. This asymmetry can put the trust-sensitive buyer at a disadvantage during shortages. Further, we demonstrate how the timing and scale of disruptions interact with a buyer's sensitivity to trustworthiness. This interaction can engender different behaviors and impact the overall supply chain performance, either prolonging and exacerbating even small local disruptions, or mitigating a disruption's effects. Additionally, we discuss the implications of these results for supply chain operations.

Improving patient timeliness of care through efficient outpatient clinic layout design using data-driven simulation and optimisation.

With greater demand for outpatient services, the importance of patient-centric clinic layout design that improves timeliness of patient care has become more elucidated. In this paper, a novel simulation-optimisation (SO) framework is proposed focusing on the physical and process flows of patients in the design of a paediatric orthopaedic outpatient clinic. A discrete-event simulation model is used to estimate the frequency of movements between clinic units. The resulting information is utilised as input to a mixed integer programming (MIP) model, optimising the clinic layout design. In order to solve the MIP model, Particle Swarm Optimisation (PSO), a metaheuristic approach enhanced with several heuristics is utilised. Finally, the optimisation model outputs are evaluated with the simulation model. The results demonstrate that improvements to the quality of the patient experience can be achieved through incorporating SO methods into the clinic layout design process.

Analysis of the effects of EHR implementation on timeliness of care in a dermatology clinic: a simulation study.

Objective: Quantify the downstream impact on patient wait times and overall length of stay due to small increases in encounter times caused by the implementation of a new electronic health record (EHR) system. Methods: A discrete-event simulation model was created to examine the effects of increasing the provider-patient encounter time by 1, 2, 5, or 10 min, due to an increase in in-room documentation as part of an EHR implementation. Simulation parameters were constructed from an analysis of 52 000 visits from a scheduling database and direct observation of 93 randomly selected patients to collect all the steps involved in an outpatient dermatology patient care visit. Results: Analysis of the simulation results demonstrates that for a clinic session with an average booking appointment length of 15 min, the addition of 1, 2, 5, and 10 min for in-room physician documentation with an EHR system would result in a 5.2 (22%), 9.8 (41%), 31.8 (136%), and 87.2 (373%) minute increase in average patient wait time, and a 6.2 (12%), 11.7 (23%), 36.7 (73%), and 96.9 (193%) minute increase in length of stay, respectively. To offset the additional 1, 2, 5, or 10 min, patient volume would need to decrease by 10%, 20%, 40%, and >50%, respectively. Conclusions: Small changes to processes, such as the addition of a few minutes of extra documentation time in the exam room, can cause significant delays in the timeliness of patient care. Simulation models can assist in quantifying the downstream effects and help analyze the impact of these operational changes.

Decreasing patient length of stay via new flexible exam room allocation policies in ambulatory care clinics.

To address prolonged lengths of stay (LOS) in ambulatory care clinics, we analyze the impact of implementing flexible and dynamic policies for assigning exam rooms to providers. In contrast to the traditional approaches of assigning specific rooms to each provider or pooling rooms among all practitioners, we characterize the impact of alternate compromise policies that have not been explored in previous studies. Since ambulatory care patients may encounter multiple different providers in a single visit, room allocation can be determined separately for each encounter accordingly. For the first phase of the visit, conducted by the medical assistant, we define a dynamic room allocation policy that adjusts room assignments based on the current state of the clinic. For the second phase of the visit, conducted by physicians, we define a series of room sharing policies which vary based on two dimensions, the number of shared rooms and the number of physicians sharing each room. Using a discrete event simulation model of an outpatient cardiovascular clinic, we analyze the benefits and costs associated with the proposed room allocation policies. Our findings show that it is not necessary to fully share rooms among providers in order to reduce patient LOS and physician idle time. Instead, most of the benefit of pooling can be achieved by implementation of a compromise room allocation approach, limiting the need for significant organizational changes within the clinic. Also, in order to achieve most of the benefits of room allocation policies, it is necessary to increase flexibility in the two dimensions simultaneously. These findings are shown to be consistent in settings with alternate patient scheduling and distinctions between physicians.

Onset of white striping and progression into wooden breast as defined by myopathic changes underlying Pectoralis major growth. Estimation of growth parameters as predictors for stage of myopathy progression.

The broiler industry has incurred significant economic losses due to two muscle myopathies, white striping (WS) and wooden breast (WB), affecting the Pectoralis major (P. major) of commercial broilers. The present study documented macroscopic changes occurring with age/growth in the P. major and P. minor muscles of commercial broilers from day 2 through day 46 (n = 27/day). Distinct myopathic aberrations observed in both breast muscles corresponded to the onset of WB. These distinct morphological changes were used as determinants in developing a ranking system, defining the ontogeny of WB as the following four stages: (1) WS, (2) petechial epimysium haemorrhages, (3) intramuscular haemorrhages and (4) ischaemia. A cumulative logit proportional odds model was used to relate the rank probabilities with the following growth parameters: body weight, P. major and P. minor weight/yield/length/width/depth. The best-fit model included P. major length/width/depth, P. minor width, P. major and P. minor yield as predictors for rank. Increasing P. major depth, P. minor width and P. major yield increased the odds of falling into higher ranks (more severe myopathy). Conversely, increasing P. major length, P. major width and P. minor yield increased the odds of falling into smaller ranks (less severe myopathy). This study describes the macroscopic changes associated with WB ontogeny in the development of a ranking system and the contribution of growth parameters in the determination of rank (WB severity). Results suggest that physical measurements inherent to selection for high-yielding broiler genotypes are contributing to the occurrence and severity of WS and WB.

Improving patient flow in an obstetric unit.

Hospitals have become increasingly interested in maximizing patient throughput and bed utilization in all units to improve efficiency. To study tradeoffs in blocking and system efficiency, a simulation model using a path-based approach is developed for an obstetric unit. The model focuses on patient flow, considering patient classification, blocking effects, time dependent arrival and departure patterns, and statistically supported distributions for length of stay (LOS). The model is applied to DeKalb Medical's Women's Center, a large obstetrics hospital in Atlanta, GA, to analyze the hospital's readiness for potential changes to patient mix and patient volume. A comparison of results predicted by the simulation model and actual performance after implementation of "swing" rooms is presented, suggesting the value of implementing "swing" rooms to balance bed allocation.

A framework for assessing patient crossover and health information exchange value.

OBJECTIVE: To evaluate the benefit of a health information exchange (HIE) between hospitals, we examine the rate of crossover among neurosurgical inpatients treated at Emory University Hospital (EUH) and Grady Memorial Hospital (GMH) in Atlanta, Georgia. To inform decisions regarding investment in HIE, we develop a methodology analyzing crossover behavior for application to larger more general patient populations. DESIGN: Using neurosurgery inpatient visit data from EUH and GMH, unique patients who visited both hospitals were identified through classification by name and age at time of visit. The frequency of flow patterns, including time between visits, and the statistical significance of crossover rates for patients with particular diagnoses were determined. MEASUREMENTS: The time between visits, flow patterns, and proportion of patients exhibiting crossover behavior were calculated for the total population studied as well as subpopulations. RESULTS: 5.25% of patients having multiple visits over the study period visited the neurosurgical departments at both hospitals. 77% of crossover patients visited the level 1 trauma center (GMH) before visiting EUH. LIMITATIONS: The true patient crossover may be under-estimated because the study population only consists of neurosurgical inpatients at EUH and GMH. CONCLUSION: We demonstrate that detailed analysis of crossover behavior provides a deeper understanding of the potential value of HIE.