Informative missingness: What can we learn from patterns in missing laboratory data in the electronic health record?

BACKGROUND: In electronic health records, patterns of missing laboratory test results could capture patients' course of disease as well as ​​reflect clinician's concerns or worries for possible conditions. These patterns are often understudied and overlooked. This study aims to identify informative patterns of missingness among laboratory data collected across 15 healthcare system sites in three countries for COVID-19 inpatients. METHODS: We collected and analyzed demographic, diagnosis, and laboratory data for 69,939 patients with positive COVID-19 PCR tests across three countries from 1 January 2020 through 30 September 2021. We analyzed missing laboratory measurements across sites, missingness stratification by demographic variables, temporal trends of missingness, correlations between labs based on missingness indicators over time, and clustering of groups of labs based on their missingness/ordering pattern. RESULTS: With these analyses, we identified mapping issues faced in seven out of 15 sites. We also identified nuances in data collection and variable definition for the various sites. Temporal trend analyses may support the use of laboratory test result missingness patterns in identifying severe COVID-19 patients. Lastly, using missingness patterns, we determined relationships between various labs that reflect clinical behaviors. CONCLUSION: In this work, we use computational approaches to relate missingness patterns to hospital treatment capacity and highlight the heterogeneity of looking at COVID-19 over time and at multiple sites, where there might be different phases, policies, etc. Changes in missingness could suggest a change in a patient's condition, and patterns of missingness among laboratory measurements could potentially identify clinical outcomes. This allows sites to consider missing data as informative to analyses and help researchers identify which sites are better poised to study particular questions.

SurvMaximin: Robust federated approach to transporting survival risk prediction models.

OBJECTIVE: For multi-center heterogeneous Real-World Data (RWD) with time-to-event outcomes and high-dimensional features, we propose the SurvMaximin algorithm to estimate Cox model feature coefficients for a target population by borrowing summary information from a set of health care centers without sharing patient-level information. MATERIALS AND METHODS: For each of the centers from which we want to borrow information to improve the prediction performance for the target population, a penalized Cox model is fitted to estimate feature coefficients for the center. Using estimated feature coefficients and the covariance matrix of the target population, we then obtain a SurvMaximin estimated set of feature coefficients for the target population. The target population can be an entire cohort comprised of all centers, corresponding to federated learning, or a single center, corresponding to transfer learning. RESULTS: Simulation studies and a real-world international electronic health records application study, with 15 participating health care centers across three countries (France, Germany, and the U.S.), show that the proposed SurvMaximin algorithm achieves comparable or higher accuracy compared with the estimator using only the information of the target site and other existing methods. The SurvMaximin estimator is robust to variations in sample sizes and estimated feature coefficients between centers, which amounts to significantly improved estimates for target sites with fewer observations. CONCLUSIONS: The SurvMaximin method is well suited for both federated and transfer learning in the high-dimensional survival analysis setting. SurvMaximin only requires a one-time summary information exchange from participating centers. Estimated regression vectors can be very heterogeneous. SurvMaximin provides robust Cox feature coefficient estimates without outcome information in the target population and is privacy-preserving.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask.

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.

International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study.

BACKGROUND: Many countries have experienced 2 predominant waves of COVID-19-related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and health care dynamics of the COVID-19 pandemic. OBJECTIVE: In this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating health care systems representing 315 hospitals across 6 countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic. METHODS: Using a federated approach, each participating health care system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were adopted at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual health care system effect sizes and synthesizing these using random effect meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19. RESULTS: Data were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50 to 69 years decreased significantly between the first and second waves. Patients hospitalized in the second wave had a 9.9% reduction in the risk of severe COVID-19 compared to patients hospitalized in the first wave (95% CI 8.5%-11.3%). Demographic subgroup analyses indicated that patients aged 26 to 49 years and 50 to 69 years; male and female patients; and black patients had significantly lower risk for severe disease in the second wave than in the first wave. At admission, the mean values of CRP were significantly lower in the second wave than in the first wave. On the seventh hospital day, the mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave than in the first wave. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain. CONCLUSIONS: Patients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international health care systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve.

Authorship Correction: International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: Retrospective Cohort Study.

[This corrects the article DOI: 10.2196/31400.].

Impact of a health information technology tool addressing information needs of caregivers of adult and pediatric hematopoietic stem cell transplantation patients.

PURPOSE: We developed BMT Roadmap, a health information technology (HIT) application on a tablet, to address caregivers' unmet needs with patient-specific information from the electronic health record. We conducted a preliminary feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT patients. The study was registered on ClinicalTrials.gov (NCT03161665; NCT02409121). METHODS: BMT Roadmap was delivered to 39 caregivers of adult and pediatric patients undergoing first-time HSCT at a single study site. We assessed person-reported outcome measures (PROMs) at baseline (hospital admission), discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness); activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health ([POMS-2®]: depression, distress, vigor, and fatigue); anxiety (State-Trait Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer [CQOLC]). To identify determinants of caregiver activation and quality of life, we used linear mixed models. RESULTS: BMT Roadmap was perceived useful and activation increased from baseline to discharge (p = 0.001). Further, burden decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor and decreasing depression, distress, fatigue, and anxiety was apparent from baseline to discharge. However, overall quality of life lowered at discharge after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p = 0.04). CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in HSCT caregivers. BMT Roadmap was associated with increased activation and decreased burden, but quality of life lowered across hospitalization. Findings support the need to further develop caregiver-specific self-directed resources and provide them both inpatient and outpatient across the HSCT trajectory.

Complexities, variations, and errors of numbering within clinical notes: the potential impact on information extraction and cohort-identification.

BACKGROUND: Numbers and numerical concepts appear frequently in free text clinical notes from electronic health records. Knowledge of the frequent lexical variations of these numerical concepts, and their accurate identification, is important for many information extraction tasks. This paper describes an analysis of the variation in how numbers and numerical concepts are represented in clinical notes. METHODS: We used an inverted index of approximately 100 million notes to obtain the frequency of various permutations of numbers and numerical concepts, including the use of Roman numerals, numbers spelled as English words, and invalid dates, among others. Overall, twelve types of lexical variants were analyzed. RESULTS: We found substantial variation in how these concepts were represented in the notes, including multiple data quality issues. We also demonstrate that not considering these variations could have substantial real-world implications for cohort identification tasks, with one case missing > 80% of potential patients. CONCLUSIONS: Numbering within clinical notes can be variable, and not taking these variations into account could result in missing or inaccurate information for natural language processing and information retrieval tasks.

Development and empirical user-centered evaluation of semantically-based query recommendation for an electronic health record search engine.

OBJECTIVE: The utility of biomedical information retrieval environments can be severely limited when users lack expertise in constructing effective search queries. To address this issue, we developed a computer-based query recommendation algorithm that suggests semantically interchangeable terms based on an initial user-entered query. In this study, we assessed the value of this approach, which has broad applicability in biomedical information retrieval, by demonstrating its application as part of a search engine that facilitates retrieval of information from electronic health records (EHRs). MATERIALS AND METHODS: The query recommendation algorithm utilizes MetaMap to identify medical concepts from search queries and indexed EHR documents. Synonym variants from UMLS are used to expand the concepts along with a synonym set curated from historical EHR search logs. The empirical study involved 33 clinicians and staff who evaluated the system through a set of simulated EHR search tasks. User acceptance was assessed using the widely used technology acceptance model. RESULTS: The search engine's performance was rated consistently higher with the query recommendation feature turned on vs. off. The relevance of computer-recommended search terms was also rated high, and in most cases the participants had not thought of these terms on their own. The questions on perceived usefulness and perceived ease of use received overwhelmingly positive responses. A vast majority of the participants wanted the query recommendation feature to be available to assist in their day-to-day EHR search tasks. DISCUSSION AND CONCLUSION: Challenges persist for users to construct effective search queries when retrieving information from biomedical documents including those from EHRs. This study demonstrates that semantically-based query recommendation is a viable solution to addressing this challenge.

User-Centered Design Groups to Engage Patients and Caregivers with a Personalized Health Information Technology Tool.

Health information technology (IT) has opened exciting avenues for capturing, delivering and sharing data, and offers the potential to develop cost-effective, patient-focused applications. In recent years, there has been a proliferation of health IT applications such as outpatient portals. Rigorous evaluation is fundamental to ensure effectiveness and sustainability, as resistance to more widespread adoption of outpatient portals may be due to lack of user friendliness. Health IT applications that integrate with the existing electronic health record and present information in a condensed, user-friendly format could improve coordination of care and communication. Importantly, these applications should be developed systematically with appropriate methodological design and testing to ensure usefulness, adoption, and sustainability. Based on our prior work that identified numerous information needs and challenges of HCT, we developed an experimental prototype of a health IT tool, the BMT Roadmap. Our goal was to develop a tool that could be used in the real-world, daily practice of HCT patients and caregivers (users) in the inpatient setting. Herein, we examined the views, needs, and wants of users in the design and development process of the BMT Roadmap through user-centered Design Groups. Three important themes emerged: 1) perception of core features as beneficial (views), 2) alerting the design team to potential issues with the user interface (needs); and 3) providing a deeper understanding of the user experience in terms of wider psychosocial requirements (wants). These findings resulted in changes that led to an improved, functional BMT Roadmap product, which will be tested as an intervention in the pediatric HCT population in the fall of 2015 (ClinicalTrials.govNCT02409121).

Time dependent patient no-show predictive modelling development.

Purpose - The purpose of this paper is to develop evident-based predictive no-show models considering patients' each past appointment status, a time-dependent component, as an independent predictor to improve predictability. Design/methodology/approach - A ten-year retrospective data set was extracted from a pediatric clinic. It consisted of 7,291 distinct patients who had at least two visits along with their appointment characteristics, patient demographics, and insurance information. Logistic regression was adopted to develop no-show models using two-thirds of the data for training and the remaining data for validation. The no-show threshold was then determined based on minimizing the misclassification of show/no-show assignments. There were a total of 26 predictive model developed based on the number of available past appointments. Simulation was employed to test the effective of each model on costs of patient wait time, physician idle time, and overtime. Findings - The results demonstrated the misclassification rate and the area under the curve of the receiver operating characteristic gradually improved as more appointment history was included until around the 20th predictive model. The overbooking method with no-show predictive models suggested incorporating up to the 16th model and outperformed other overbooking methods by as much as 9.4 per cent in the cost per patient while allowing two additional patients in a clinic day. Research limitations/implications - The challenge now is to actually implement the no-show predictive model systematically to further demonstrate its robustness and simplicity in various scheduling systems. Originality/value - This paper provides examples of how to build the no-show predictive models with time-dependent components to improve the overbooking policy. Accurately identifying scheduled patients' show/no-show status allows clinics to proactively schedule patients to reduce the negative impact of patient no-shows.

Supporting information retrieval from electronic health records: A report of University of Michigan's nine-year experience in developing and using the Electronic Medical Record Search Engine (EMERSE).

OBJECTIVE: This paper describes the University of Michigan's nine-year experience in developing and using a full-text search engine designed to facilitate information retrieval (IR) from narrative documents stored in electronic health records (EHRs). The system, called the Electronic Medical Record Search Engine (EMERSE), functions similar to Google but is equipped with special functionalities for handling challenges unique to retrieving information from medical text. MATERIALS AND METHODS: Key features that distinguish EMERSE from general-purpose search engines are discussed, with an emphasis on functions crucial to (1) improving medical IR performance and (2) assuring search quality and results consistency regardless of users' medical background, stage of training, or level of technical expertise. RESULTS: Since its initial deployment, EMERSE has been enthusiastically embraced by clinicians, administrators, and clinical and translational researchers. To date, the system has been used in supporting more than 750 research projects yielding 80 peer-reviewed publications. In several evaluation studies, EMERSE demonstrated very high levels of sensitivity and specificity in addition to greatly improved chart review efficiency. DISCUSSION: Increased availability of electronic data in healthcare does not automatically warrant increased availability of information. The success of EMERSE at our institution illustrates that free-text EHR search engines can be a valuable tool to help practitioners and researchers retrieve information from EHRs more effectively and efficiently, enabling critical tasks such as patient case synthesis and research data abstraction. CONCLUSION: EMERSE, available free of charge for academic use, represents a state-of-the-art medical IR tool with proven effectiveness and user acceptance.

Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P < .001) and higher nonrelapse mortality at 2 years (38% versus 19%, P < .001) compared with non-ES patients, resulting in lower overall survival at 2 years (38% versus 54%, P < .001). There was no significant difference in relapse at 2 years (26% versus 31%, P = .772). Suppression of tumorigenicity 2, interleukin 2 receptor alpha, and tumor necrosis factor receptor 1 plasma biomarker levels were significantly elevated in ES patients. Our results illustrate the clinical significance and prognostic impact of ES on allogeneic HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES.

Osteochondromas after radiation for pediatric malignancies: a role for expanded counseling for skeletal side effects.

BACKGROUND: A relationship has been reported between total body irradiation (TBI) and later development of osteochondromas in children who receive radiation therapy as conditioning before hematopoietic stem cell transplantation (HSCT). The goal of this study was to better characterize osteochondromas occurring in these children. METHODS: We identified all children (0 to 18 y) who received an allogeneic HSCT and TBI from 2000 to 2012 from a blood and marrow transplant (BMT) database. Thereafter, we identified those who developed osteochondromas through a chart review. In addition, we searched for diagnosis and operative codes from 1996 to 2012 in our pediatric orthopaedic clinical records, isolating osteochondroma patients with a history of radiation exposure. RESULTS: Four patients who underwent allogeneic HSCT and were later diagnosed with osteochondromas were identified from the BMT database (N=233 children); all 4 were among a group of 72 patients who received TBI. Three patients were identified from orthopaedic records. The cohort included 5 boys and 2 girls with acute lymphoblastic leukemia (N=5) or neuroblastoma (N=2), diagnosed at a median age of 2.0 years. Therapy for all patients included chemotherapy, radiation therapy (TBI, N=5; abdominal, N=2), and HSCT. A diagnosis of osteochondroma was made at a median age of 11.7 years (range, 5 to 16 y), on average 8.6 years after radiation therapy. Diagnosis was incidental in 2 patients and secondary to symptoms (pain or genu valgum) in 5. Locations of osteochondromas were the proximal tibia (N=3), distal tibia, distal femur, distal ulna, and the distal phalanx (N=1 each). Three patients underwent surgical resection. CONCLUSIONS: Children may be more likely to develop osteochondromas after early exposure to radiation therapy, which may cause pain and require surgical resection. To the best of our knowledge, this is the first reported case of a radiation-induced osteochondroma causing lower extremity malalignment. Patients typically present to the pediatric orthopaedist's attention when symptomatic, but there may be an expanded role for counseling for potential for long-term skeletal effects in this group. LEVEL OF EVIDENCE: Level IV, case series.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods.

BACKGROUND: Pediatric hematology-oncology (PHO) patients are at significant risk for developing central line-associated bloodstream infections (CLA-BSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospital-acquired CLA-BSIs. MATERIALS AND METHODS: CLA-BSI rates were analyzed within a single-institution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using time-series methods to evaluate the pre- and post-intervention effect of the practice changes. RESULTS: The pre-intervention CLA-BSI incidence was 2.92 per 1,000-patient days (PD) and coagulase-negative Staphylococcus was the most prevalent pathogen (29%). In the post-intervention period, the CLA-BSI rate decreased substantially (45%) to 1.61 per 1,000-PD (P < 0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLA-BSI rate compared to non-BMT patients (P < 0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLA-BSI rate reduction such that BMT and non-BMT CLA-BSI rates were not significantly different post-intervention. CONCLUSIONS: By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLA-BSI incidence in our study population was significantly reduced and maintained.

A pilot intervention of using a mobile health app (ONC Roadmap) to enhance health-related quality of life in family caregivers of pediatric patients with cancer.

Background: The Roadmap mobile health (mHealth) app was developed to provide health-related quality of life (HRQOL) support for family caregivers of patients with cancer. Methods: Eligibility included: family caregivers (age ≥18 years) who self-reported as the primary caregiver of their pediatric patient with cancer; patients (age ≥5 years) who were receiving cancer care at the University of Michigan. Feasibility was calculated as the percentage of caregivers who logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the 120-day study duration. Feasibility and acceptability was also assessed through a Feasibility and Acceptability questionnaire and the Mobile App Rating Scale to specifically assess app-quality. Exploratory analyses were also conducted to assess HRQOL self- or parent proxy assessments and physiological data capture. Results: Between September 2020-September 2021, 100 participants (or 50 caregiver-patient dyads) consented and enrolled in the ONC Roadmap study for 120-days. Feasibility of the study was met, wherein the majority of caregivers (N=32; 65%) logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the study duration (defined a priori in the Protocol). The Feasibility and Acceptability questionnaire responses indicated that the study was feasible and acceptable with the majority (>50%) reporting Agree or Strongly Agree with positive Net Favorability [(Agree + Strongly Agree) - (Disagree + Totally Disagree)] in each of the domains (e.g., Fitbit use, ONC Roadmap use, completing longitudinal assessments, engaging in similar future study, study expectations). Improvements were seen across the majority of the mental HRQOL domains across all groups; even though underpowered, there were significant improvements in caregiver-specific aspects of HRQOL and anxiety and in depression and fatigue for children (ages 8-17 years), and a trend toward improvement in depression for children ages 8-17 years and in fatigue for adult patients. Conclusions: This study supports that mHealth technology may be a promising platform to provide HRQOL support for caregivers of pediatric patients with cancer. Importantly, the findings suggest that the study protocol was feasible, and participants were favorable to participate in future studies of this intervention alongside routine cancer care delivery.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years. Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months. Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Article Summary: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months. What's Known on This Subject: Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID. What This Study Adds: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months. Contributors' Statement: Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Authorship statement: Authorship has been determined according to ICMJE recommendations.