Patient and Parent Experience with Pediatric Care Providers During the COVID-19 Pandemic: A Comparison of Press Ganey Survey Scores for Telehealth and In-Person Encounters.

Background: Prior research suggests that pediatric patients and their parents/guardians are generally satisfied with care provided through telehealth. The objective of this study was to compare Press Ganey provider-oriented experience survey scores between telehealth and in-person patient encounters among a variety of pediatric clinical specialties at a large academic medical center. Methods: We analyzed Press Ganey survey data from pediatric patient encounters from UC Davis Health, collected between August 2020 and February 2022. Survey results analyzed respondents' satisfaction with care providers, including satisfaction with explanations given, discussions led, concern showed, and inclusion by providers; and the likelihood the survey respondent would recommend the provider to others. We used logistic regression models, which included case mix variables and clinical specialty to compare the odds of scoring the highest possible survey response ("top box" score). Results: Of the 6,093 survey responses that met inclusion criteria, 1,157 (19%) were associated with telehealth encounters and 4,936 (81%) were associated with in-person encounters. We found no significant difference in the odds of respondents giving a top box score to rate their satisfaction with their care provider between telehealth and in-person encounters. When respondents were asked whether they would recommend the care provider to others, the odds of giving a top box score following a telehealth encounter relative to an in-person encounter was 1.22 (95% confidence interval [0.97-1.52]; p-value = 0.09). Discussion: We found that survey respondents' experiences with their care provider are high and comparable for telehealth and in-person encounters in a pediatric population.

Implementing the MSFragger Search Engine as a Node in Proteome Discoverer.

Here, we describe the implementation of the fast proteomics search engine MSFragger as a processing node in the widely used Proteome Discoverer (PD) software platform. PeptideProphet (via the Philosopher tool kit) is also implemented as an additional PD node to allow validation of MSFragger open (mass-tolerant) search results. These two nodes, along with the existing Percolator validation module, allow users to employ different search strategies and conveniently inspect search results through PD. Our results have demonstrated the improved numbers of PSMs, peptides, and proteins identified by MSFragger coupled with Percolator and significantly faster search speed compared to the conventional SEQUEST/Percolator PD workflows. The MSFragger-PD node is available at https://github.com/nesvilab/PD-Nodes/releases/.

Adamantylidenecarbene: Photochemical Generation, Trapping, and Theoretical Studies.

Photolysis of 1-(2-adamantylidene)-1a,9b-dihydro-1H-cyclopropa[l]phenanthrene in benzene (or benzene-d6) at ambient temperature produces adamantylidenecarbene. The carbene undergoes dimerization to a cumulene and may also be trapped in a stereospecific fashion by cis- and trans-4-methyl-2-pentene. No products attributable to 4-homoadamantyne, resulting from ring expansion of the carbene, could be detected. Coupled cluster/density functional theory calculations place the singlet carbene ∼49 kcal/mol below the triplet and show that the former must overcome a barrier of ∼13.5 kcal/mol to rearrange into 4-homoadamantyne.

A new continuous glucose monitor for the diagnosis of gestational diabetes mellitus: a pilot study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) incidence and adverse outcomes have increased globally. The validity of the oral glucose tolerance test (OGTT) for GDM diagnosis has long been questioned, with no suitable substitute reported yet. Continuous Glucose Monitoring (CGM) is potentially a more acceptable and comprehensive test. The aim of this study was to assess the Freestyle Libre Pro 2 acceptability as a diagnostic test for GDM, then triangulating its results with OGTT results as well as risk factors and sonographic features of GDM. METHODS: Women wore the CGM device for 7 days at 24-28 weeks, undergoing the OGTT before CGM removal. CGM/OGTT acceptability as well as GDM risk factors evaluation occurred via three online surveys. CGM distribution/variability/time in range parameters, combined in a CGM Score of Variability (CGMSV), were triangulated with OGTT results and a risk-factor-based Total Risk Score (TRS). In a subgroup, GDM ultrasound features (as modified Ultrasound Gestational Diabetes Score - m-UGDS) were also incorporated. RESULTS: Of 107 women recruited, 87 (81%) were included: 74 (85%) with negative OGTT (NGT) and 13 (15%) positive (GDM). No significant difference was found between NGT and GDM in terms of demographics (apart from family history of diabetes mellitus), CGM parameters and perinatal outcomes. Women considered CGM significantly more acceptable than OGTT (81% versus 27% rating 5/5, p < 0.001). Of the 55 NGT with triangulation data, 28 were considered 'true negative' (TRS concordant with OGTT and CGMSV): of these 4/5 evaluated at ultrasound had m-UGDS below the cut-off. Five women were considered 'false negative' (negative OGTT with both TRS and CGMSV above the respective cut-offs). Triangulation identified also six 'false positive' women (positive OGTT but TRS and CGM both below the cut-offs). Only one woman for each of the last two categories had m-UGDS evaluated, with discordant results. CONCLUSIONS: CGM represents a more acceptable alternative for GDM diagnosis to the OGTT. CGM triangulation analysis suggests OGTT screening may result in both false positives and negatives. Further research including larger cohorts of patients, and additional triangulation elements (such as GDM biomarkers/outcomes and expanded m-UGDS) is needed to explore CGM potential for GDM diagnosis.

IonQuant Enables Accurate and Sensitive Label-Free Quantification With FDR-Controlled Match-Between-Runs.

Missing values weaken the power of label-free quantitative proteomic experiments to uncover true quantitative differences between biological samples or experimental conditions. Match-between-runs (MBR) has become a common approach to mitigate the missing value problem, where peptides identified by tandem mass spectra in one run are transferred to another by inference based on m/z, charge state, retention time, and ion mobility when applicable. Though tolerances are used to ensure such transferred identifications are reasonably located and meet certain quality thresholds, little work has been done to evaluate the statistical confidence of MBR. Here, we present a mixture model-based approach to estimate the false discovery rate (FDR) of peptide and protein identification transfer, which we implement in the label-free quantification tool IonQuant. Using several benchmarking datasets generated on both Orbitrap and timsTOF mass spectrometers, we demonstrate superior performance of IonQuant with FDR-controlled MBR compared with MaxQuant (19-38 times faster; 6-18% more proteins quantified and with comparable or better accuracy). We further illustrate the performance of IonQuant and highlight the need for FDR-controlled MBR, in two single-cell proteomics experiments, including one acquired with the help of high-field asymmetric ion mobility spectrometry separation. Fully integrated in the FragPipe computational environment, IonQuant with FDR-controlled MBR enables fast and accurate peptide and protein quantification in label-free proteomics experiments.

Patient Satisfaction with Care Providers During the COVID-19 Pandemic: An Analysis of Consumer Assessment of Healthcare Providers and Systems Survey Scores for In-Person and Telehealth Encounters at an Academic Medical Center.

Background: Previous research has demonstrated high patient satisfaction with telehealth encounters. The objective of this study was to compare patient satisfaction scores regarding their physician using the Consumer Assessment of Healthcare Providers and Systems (CAHPS®) surveys between in-person and telehealth outpatient encounters during the pandemic at a large academic health center. Methods: We analyzed CAHPS patient satisfaction survey data within the UC Davis Health system between August 2020 and February 2022. The questions analyzed pertained to patients' satisfaction with their care provider; whether they felt included in discussions, would recommend their physician, received clear explanations, and that their concerns were heard. Using logistic regression models adjusting for confounders, we compared CAHPS care provider top box scores-a score of 4 or 5 on the 5-point scale-for 5 survey items. Results: Survey results from 76,687 (84.2%) in-person encounters and 14,404 (15.8%) telehealth encounters were evaluated. The odds of a telehealth patient giving a top box score for whether they would recommend their care provider to others were 0.97 those of an in-person patient (95% confidence interval [0.87-1.06]; p = 0.494). Similarly, there was no significant difference in odds of giving a top box score between telehealth and in-person patients for the other four questions analyzed. Discussion: Our findings indicate that patient experience and care provider rankings for in-person care and telehealth care are comparable across a variety of specialties and conditions at a large academic health center. Future studies should investigate patient satisfaction with in-person and telehealth encounters by diagnosis and specialty.

Economic Evaluation of Telemedicine Consultations to Reduce Unnecessary Neonatal Care Transfers.

OBJECTIVES: To perform an economic evaluation to estimate the return on investment (ROI) of making available telemedicine consultations from a healthcare payer perspective, and to estimate the economic impacts of telemedicine under a hypothetical scenario in which all rural hospitals providing level I neonatal care in California had access to telemedicine consultations from neonatologists at level III and level IV neonatal intensive care units (NICUs). STUDY DESIGN: We developed standard decision models with assumptions derived from primary data and the literature. Telemedicine costs included equipment installation and operation costs. Probabilistic analysis with Monte Carlo simulation was performed to address model uncertainties and to estimate 95% probabilistic confidence intervals (PCIs). All costs were adjusted to 2017 US dollars using the Consumer Price Index. RESULTS: Our probabilistic analysis estimated the ROI to have a mean value of 2.23 (95% PCI, -0.7 to 6.0). That is, a $1 investment in this telemedicine model would yield a net medical expenditure saving of $1.23. "Cost saving" was observed for 75% of the hypothetical 1000 Monte Carlo simulations. For the state of California, the estimated mean annual net savings was $661 000. CONCLUSIONS: Providing telemedicine and making available consultations to rural hospitals providing level I neonatal care are likely to reduce medical expenditures by reducing potentially avoidable transfers of newborns to level III and IV NICUs, offsetting all telemedicine-related costs.

Maternal body weight and estimated circulating blood volume: a review and practical nonlinear approach.

Postpartum haemorrhage continues to be a leading cause of morbidity and mortality in the obstetric population worldwide, especially in patients at extremes of body weight. Quantification of blood loss has been considered extensively in the literature. However, these volumes must be contextualised to appreciate the consequences of blood loss for individual parturients. Knowledge of a patient's peripartum circulating blood volume is essential to allow accurate interpretation of the significance of haemorrhage and appropriate resuscitation. Greater body weight in obesity can lead to overestimation of blood volume, resulting in inappropriately high thresholds for blood product transfusion and delays in treatment. The most recent Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK) surveillance report demonstrated the risk to this population, with more than half of all maternal mortality recorded in parturients who were either overweight or obese. Current linear calculations used to estimate circulating blood volumes based on patients' weights could be contributing to this phenomenon, as blood volume increases at a disproportional rate to body composition. In this review, we summarise the relevant physiology and explore the existing literature on the estimation of circulating blood volume, both during pregnancy and in obesity. Building on key works and principal findings, we present a practical, nonlinear approach to the adjustment of estimated blood volume with increasing body mass. This clinical tool aims to reduce the clinical bias influencing the management of obstetric haemorrhage in a population already at increased risk of morbidity and mortality. Discussion of the limitations of this approach and the call for further research within this field completes this review.

Telemedicine use for pediatric asthma care: a mixed methods study.

OBJECTIVES: To identify factors associated with telemedicine use for asthma care among children and young adults, and to describe the parent and patient experience of asthma care over telemedicine. METHODS: Our mixed methods study consisted of an electronic health record analysis and a qualitative focus group analysis. We analyzed records for all patients aged 2-24 seen at UC Davis Health between March 19, 2020 and September 30, 2020 for a primary diagnosis of asthma. We performed multivariable logistic regression to quantify the relationships between patient characteristics and telemedicine use. We also conducted focus groups with parents and patients who received asthma care during the study period and used qualitative content analysis to identify themes from the transcripts. RESULTS: 502 patients met the inclusion criteria. Telemedicine use was significantly lower among patients with a primary language other than English (OR = 0.12, 95% CI: 0.025-0.54, p = 0.006), school-aged children (OR = 0.43, 95% CI: 0.24-0.77, p = 0.005), and patients who received asthma care from a primary care provider instead of a specialist (OR = 0.55, 95% CI: 0.34-0.91, p = 0.020). Six thematic categories emerged from focus groups: engaging with the patient, improving access to care, experience of visit, measurements, scheduling, and the future of telemedicine in asthma care. CONCLUSIONS: Alternating telemedicine with in-person visits for asthma care may result in improved access to care and reduced burdens on patients and families. Providers and researchers should work to understand the specific reasons for low telemedicine use among non-English speaking patients so that these patients receive equitable access to care.

Fast Quantitative Analysis of timsTOF PASEF Data with MSFragger and IonQuant.

Ion mobility brings an additional dimension of separation to LC-MS, improving identification of peptides and proteins in complex mixtures. A recently introduced timsTOF mass spectrometer (Bruker) couples trapped ion mobility separation to TOF mass analysis. With the parallel accumulation serial fragmentation (PASEF) method, the timsTOF platform achieves promising results, yet analysis of the data generated on this platform represents a major bottleneck. Currently, MaxQuant and PEAKS are most used to analyze these data. However, because of the high complexity of timsTOF PASEF data, both require substantial time to perform even standard tryptic searches. Advanced searches (e.g. with many variable modifications, semi- or non-enzymatic searches, or open searches for post-translational modification discovery) are practically impossible. We have extended our fast peptide identification tool MSFragger to support timsTOF PASEF data, and developed a label-free quantification tool, IonQuant, for fast and accurate 4-D feature extraction and quantification. Using a HeLa data set published by Meier et al. (2018), we demonstrate that MSFragger identifies significantly (∼30%) more unique peptides than MaxQuant (1.6.10.43), and performs comparably or better than PEAKS X+ (∼10% more peptides). IonQuant outperforms both in terms of number of quantified proteins while maintaining good quantification precision and accuracy. Runtime tests show that MSFragger and IonQuant can fully process a typical two-hour PASEF run in under 70 min on a typical desktop (6 CPU cores, 32 GB RAM), significantly faster than other tools. Finally, through semi-enzymatic searching, we significantly increase the number of identified peptides. Within these semi-tryptic identifications, we report evidence of gas-phase fragmentation before MS/MS analysis.

Parent Experience and Cost Savings Associated With a Novel Tele-physiatry Program for Children Living in Rural and Underserved Communities.

OBJECTIVE: The aim of this study was to investigate parent and therapist experience and cost savings from the payer perspective associated with a novel tele-physiatry program for children living in rural and underserved communities. DESIGN: We designed a noninferiority, cluster-randomized crossover study at 4 school-based clinics to evaluate parent experience and perceived quality of care between a telemedicine-based approach in which the physiatrist conducts the visit remotely with an in-person therapist and a traditional in-person physiatrist clinic. SETTING: Four school-based clinics in Northern California. PARTICIPANTS: A total of 268 encounters (124 telemedicine and 144 in-person) were completed by 200 unique patients (N=200). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Parent and therapist experience scores. RESULTS: For parents and therapists, experience and perceived quality of care were high with no significant differences between telemedicine and in-person encounters. For parents whose children received a telemedicine encounter, 40 (54.8%) reported no preference for their child's subsequent encounter, 21 (28.8%) preferred a physiatrist telemedicine visit, and 12 (16.4%) preferred a physiatrist in-person visit. From the payer perspective, costs were $100 higher for in-person clinics owing to physician mileage reimbursement. CONCLUSIONS: We found that school-based tele-physiatry for children with special health care needs is not inferior to in-person encounters with regard to parent and provider experience and perceived quality of care. Tele-physiatry was also associated with an average cost savings of $100 per clinic to the payer.

Resources for Improving Pediatric Readiness and Quality of Care in Rural Communities and Emergency Departments.

OBJECTIVES: To share the process and products of an 8-year, federally funded grant from the Health Resources and Services Administration Emergency Medical Services for Children program to increase pediatric emergency readiness and quality of care provided in rural communities located within 2 underserved local emergency medical services agencies (LEMSAs) in Northern California. METHODS: In 2 multicounty LEMSAs with 24 receiving hospital emergency departments, we conducted focus groups and interviews with patients and parents, first responders, receiving hospital personnel, and other community stakeholders. From this, we (a regional, urban children's hospital) provided a variety of resources for improving the regionalization and quality of pediatric emergency care provided by prehospital providers and healthcare staff at receiving hospitals in these rural LEMSAs. RESULTS: From this project, we provided resources that included regularly scheduled pediatric-specific training and education programs, pediatric-specific quality improvement initiatives, expansion of telemedicine services, and cultural competency training. We also enhanced community engagement and investment in pediatric readiness. CONCLUSIONS: The resources we provided from our regional, urban children's hospital to 2 rural LEMSAs facilitated improvements in a regionalized system of care for critically ill and injured children. Our shared resources framework can be adapted by other regional children's hospitals to increase readiness and quality of pediatric emergency care in rural and underserved communities and LEMSAs.

Analyzing a Cost-Effectiveness Dataset: A Speech and Language Example for Clinicians.

Cost-effectiveness analysis, the most common type of economic evaluation, estimates a new option's additional outcome in relation to its extra costs. This is crucial to study within the clinical setting because funding for new treatments and interventions is often linked to whether there is evidence showing they are a good use of resources. This article describes how to analyze a cost-effectiveness dataset using the framework of a net benefit regression. The process of creating estimates and characterizing uncertainty is demonstrated using a hypothetical dataset. The results are explained and illustrated using graphs commonly employed in cost-effectiveness analyses. We conclude with a call to action for researchers to do more person-level cost-effectiveness analysis to produce evidence of the value of new treatments and interventions. Researchers can utilize cost-effectiveness analysis to compare new and existing treatment mechanisms.

Emergency Department Pediatric Readiness and Potentially Avoidable Transfers.

OBJECTIVE: To determine the association between potentially avoidable transfers (PATs) and emergency department (ED) pediatric readiness scores and the score's associated components. STUDY DESIGN: This cross-sectional study linked the 2012 National Pediatric Readiness Project assessment with individual encounter data from California's statewide ED and inpatient databases during the years 2011-2013. A probabilistic linkage, followed by deterministic heuristics, linked pretransfer, and post-transfer encounters. Applying previously published definitions, a transferred child was considered a PAT if they were discharged within 1 day from the ED or inpatient care and had no specialized procedures. Analyses were stratified by injured and noninjured children. We compared PATs with necessary transfers using mixed-effects logistic regression models with random intercepts for hospital and adjustment for patient and hospital covariates. RESULTS: After linkage, there were 6765 injured children (27% PATs) and 18 836 noninjured children (14% PATs) who presented to 283 hospitals. In unadjusted analyses, a 10-point increase in pediatric readiness was associated with lower odds of PATs in both injured (OR 0.93, 95% CI 0.90-0.96) and noninjured children (OR 0.90, 95% CI 0.88-0.93). In adjusted analyses, a similar association was detected in injured patients (aOR 0.92, 95% CI 0.86-0.98) and was not detected in noninjured patients (aOR 0.94, 95% CI 0.88-1.00). Components associated with decreased PATs included having a nurse pediatric emergency care coordinator and a quality improvement plan. CONCLUSIONS: Hospital ED pediatric readiness is associated with lower odds of a PAT. Certain pediatric readiness components are modifiable risk factors that EDs could target to reduce PATs.

The Effect of Rehospitalization and Emergency Department Visits on Subsequent Adherence to Weight Telemonitoring.

BACKGROUND: Weight telemonitoring may be an effective way to improve patients' ability to manage heart failure and prevent unnecessary utilization of health services. However, the effectiveness of such interventions is dependent upon patient adherence. OBJECTIVE: The purpose of this study was to determine how adherence to weight telemonitoring changes in response to 2 types of events: hospital readmissions and emergency department visits. METHODS: The Better Effectiveness After Transition-Heart Failure trial examined the effectiveness of a remote telemonitoring intervention compared with usual care for patients discharged to home after hospitalization for decompensated heart failure. Participants were followed for 180 days and were instructed to transmit weight readings daily. We used Poisson regression to determine the within-person effects of events on subsequent adherence. RESULTS: A total of 625 events took place during the study period. Most of these events were rehospitalizations (78.7%). After controlling for the number of previous events and discharge to a skilled nursing facility, the rate for adherence decreased by nearly 20% in the 2 weeks after a hospitalization compared with the 2 weeks before (adjusted rate ratio, 0.81; 95% confidence interval: 0.77-0.86; P < .001). CONCLUSIONS: Experiencing a rehospitalization had the effect of diminishing adherence to daily weighing. Providers using telemonitoring to monitor decompensation and manage medications should take advantage of the potential "teachable moment" during hospitalization to reinforce the importance of adherence.

The Use of Telemedicine for Stabilization of Neonates Transferred from Rural Community Hospitals.

Background: For newborns requiring transfer to a higher level of care, stabilization before the arrival of the transport team is essential. Telemedicine consultations with a neonatologist may improve local providers' ability to stabilize a newborn during this critical interval. The purpose of this study was to describe the use of telemedicine for stabilizing newborns who were transferred from one of six rural hospitals to a regional neonatal intensive care unit in northern California and to examine the association between telemedicine use and time needed to stabilize the newborn. Materials and Methods: We collected data on all newborns who were transferred after either a telemedicine or telephone consultation with a neonatologist between April 2014 and June 2018. We used multiple regression to examine the association between the use of telemedicine and stabilization time, adjusting for gestational age, 5-min Apgar score, birth weight, site, and primary reason for consultation. Results: In total, 162 infants (77.5%) received a telephone consultation and 47 (22.5%) received a telemedicine consultation. Neonates who received telemedicine had a significantly greater severity of illness, as measured by mean 5-min Apgar score (6.9 vs. 7.8, p = 0.008) and Transport Risk Index of Physiologic Stability version II (TRIPS-II) score (14.4 vs. 6.0, p < 0.001). There was no significant difference in stabilization time for telemedicine consultations compared with telephone consultations in the adjusted analysis (adjusted mean difference: -1.80, 95% confidence interval: -16.0 to 12.4, p = 0.802). Conclusions: Although we found no difference in stabilization times between modes of consultation, telemedicine may be helpful for stabilizing infants with a higher severity of illness, particularly those in respiratory distress. Future studies should examine the impact of telemedicine on specific interventions.

Crystal-C: A Computational Tool for Refinement of Open Search Results.

Shotgun proteomics using liquid chromatography coupled to mass spectrometry (LC-MS) is commonly used to identify peptides containing post-translational modifications. With the emergence of fast database search tools such as MSFragger, the approach of enlarging precursor mass tolerances during the search (termed "open search") has been increasingly used for comprehensive characterization of post-translational and chemical modifications of protein samples. However, not all mass shifts detected using the open search strategy represent true modifications, as artifacts exist from sources such as unaccounted missed cleavages or peptide co-fragmentation (chimeric MS/MS spectra). Here, we present Crystal-C, a computational tool that detects and removes such artifacts from open search results. Our analysis using Crystal-C shows that, in a typical shotgun proteomics data set, the number of such observations is relatively small. Nevertheless, removing these artifacts helps to simplify the interpretation of the mass shift histograms, which in turn should improve the ability of open search-based tools to detect potentially interesting mass shifts for follow-up investigation.

DIA-SIFT: A Precursor and Product Ion Filter for Accurate Stable Isotope Data-Independent Acquisition Proteomics.

Quantitative mass spectrometry-based protein profiling is widely used to measure protein levels across different treatments or disease states, yet current mass spectrometry acquisition methods present distinct limitations. While data-independent acquisition (DIA) bypasses the stochastic nature of data-dependent acquisition (DDA), fragment spectra derived from DIA are often complex and challenging to deconvolve. In-line ion mobility separation (IMS) adds an additional dimension to increase peak capacity for more efficient product ion assignment. As a similar strategy to sequential window acquisition methods (SWATH), IMS-enabled DIA methods rival DDA methods for protein annotation. Here we evaluate IMS-DIA quantitative accuracy using stable isotope labeling by amino acids in cell culture (SILAC). Since SILAC analysis doubles the sample complexity, we find that IMS-DIA analysis is not sufficiently accurate for sensitive quantitation. However, SILAC precursor pairs share common retention and drift times, and both species cofragment to yield multiple quantifiable isotopic y-ion peak pairs. Since y-ion SILAC ratios are intrinsic for each quantified precursor, combined MS1 and y-ion ratio analysis significantly increases the total number of measurements. With increased sampling, we present DIA-SIFT ( SILAC Intrinsic Filtering Tool), a simple statistical algorithm to identify and eliminate poorly quantified MS1 and/or MS2 events. DIA-SIFT combines both MS1 and y-ion ratios, removes outliers, and provides more accurate and precise quantitation (<15% CV) without removing any proteins from the final analysis. Overall, pooled MS1 and MS2 quantitation increases sampling in IMS-DIA SILAC analyses for accurate and precise quantitation.