Financial and Clinical Impact of Virtual Care During the COVID-19 Pandemic: Difference-in-Differences Analysis.

BACKGROUND: Virtual care (VC) and remote patient monitoring programs were deployed widely during the COVID-19 pandemic. Deployments were heterogeneous and evolved as the pandemic progressed, complicating subsequent attempts to quantify their impact. The unique arrangement of the US Military Health System (MHS) enabled direct comparison between facilities that did and did not implement a standardized VC program. The VC program enrolled patients symptomatic for COVID-19 or at risk for severe disease. Patients' vital signs were continuously monitored at home with a wearable device (Current Health). A central team monitored vital signs and conducted daily or twice-daily reviews (the nurse-to-patient ratio was 1:30). OBJECTIVE: Our goal was to describe the operational model of a VC program for COVID-19, evaluate its financial impact, and detail its clinical outcomes. METHODS: This was a retrospective difference-in-differences (DiD) evaluation that compared 8 military treatment facilities (MTFs) with and 39 MTFs without a VC program. Tricare Prime beneficiaries diagnosed with COVID-19 (Medicare Severity Diagnosis Related Group 177 or International Classification of Diseases-10 codes U07.1/07.2) who were eligible for care within the MHS and aged 21 years and or older between December 2020 and December 2021 were included. Primary outcomes were length of stay and associated cost savings; secondary outcomes were escalation to physical care from home, 30-day readmissions after VC discharge, adherence to the wearable, and alarms per patient-day. RESULTS: A total of 1838 patients with COVID-19 were admitted to an MTF with a VC program of 3988 admitted to the MHS. Of these patients, 237 (13%) were enrolled in the VC program. The DiD analysis indicated that centers with the program had a 12% lower length of stay averaged across all COVID-19 patients, saving US $2047 per patient. The total cost of equipping, establishing, and staffing the VC program was estimated at US $3816 per day. Total net savings were estimated at US $2.3 million in the first year of the program across the MHS. The wearables were activated by 231 patients (97.5%) and were monitored through the Current Health platform for a total of 3474 (median 7.9, range 3.2-16.5) days. Wearable adherence was 85% (IQR 63%-94%). Patients triggered a median of 1.6 (IQR 0.7-5.2) vital sign alarms per patient per day; 203 (85.7%) were monitored at home and then directly discharged from VC; 27 (11.4%) were escalated to a physical hospital bed as part of their initial admission. There were no increases in 30-day readmissions or emergency department visits. CONCLUSIONS: Monitored patients were adherent to the wearable device and triggered a manageable number of alarms/day for the monitoring-team-to-patient ratio. Despite only enrolling 13% of COVID-19 patients at centers where it was available, the program offered substantial savings averaged across all patients in those centers without adversely affecting clinical outcomes.

Malignant Giant Cell Tumor of Bone With a KRAS G12V Mutation.

Malignant giant cell tumor of bone (GCTB) is a rare, aggressive, sarcoma occurring in adolescent and young adults. It is characterized by the presence of multinucleated giant cells and an aggressive clinical course. Because of the rarity of this tumor, no standard therapies have been identified. Current treatment regimens often include osteosarcoma chemotherapy protocols. We present a case of a malignant GCTB with a KRAS G12V mutation. This mutation is a known oncogenic driver that has not previously been reported on patients with malignant GCTB.

Pediatric Myelodysplastic Syndrome With Germline RRAS Mutation: Expanding the Phenotype of RASopathies.

The RAS/mitogen-activated protein kinase pathway plays a significant role in cell cycle regulation. Germline mutation of this pathway leads to overlapping genetic disorders, RASopathies, and is also an important component of tumorigenesis. Here we describe a rare case of myelodysplastic syndrome with monosomy 7 in a pediatric patient with a germline RRAS mutation. RRAS mutations have been implicated in the development of juvenile myelomonocytic leukemia, but our case suggests RRAS mutations display a broader malignant potential. Our case supports the recommendation that genetic testing should include RRAS in suspected RASopathy patients and if identified, these patients undergo surveillance for hematologic malignancy.

A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.

PURPOSE: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) PATIENTS & METHODS: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m2/day × 21 days of a 28-day cycle. RESULTS: Twenty-nine patients (age range 4-19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m2/day. Exceptional responses were noted in DIPG and malignant glioma (gliomatosis cerebri) notably at higher dose levels and at higher steady state plasma concentrations. The primary toxicity was myelosuppression. CONCLUSION: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m2/day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response.

Military Telehealth: A Model For Delivering Expertise To The Point Of Need In Austere And Operational Environments.

Austere clinical environments are those in which limited resources hamper the achievement of optimal patient outcomes. Operational environments are those in which caregivers and resources are at risk for harm. Military and civilian caregivers experience these environments in the context of war, natural disasters, humanitarian assistance missions, and mass casualty events. The military has a particular interest in enhancing local caregiver capabilities within austere and operational environments to improve casualty outcomes when evacuation is delayed or impossible, reduce the cost and the risk of unnecessary evacuations, enhance the medical response during aid missions, and increase combat effectiveness by keeping service members in the fight as long as possible. This article describes military telehealth as it relates to care in austere and operational environments, and it suggests implications for policy, particularly with respect to the current emphasis on telehealth solutions that might not be feasible in those settings.

Molecular imaging of pediatric brain tumors: comparison of tumor metabolism using ¹8F-FDG-PET and MRSI.

Magnetic resonance spectroscopic imaging (MRSI) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) are non-invasive imaging techniques routinely used to evaluate tumor malignancy in adults with brain tumors. We compared the metabolic activity of pediatric brain tumors using FDG-PET and MRSI. Children (n = 37) diagnosed with a primary brain tumor underwent FDG-PET and MRSI within two weeks of each other. Tumor metabolism was classified as inactive, active or highly active using the maximum choline:N-acetyl-asparate (Cho:NAA) on MRSI and the highest tumor uptake on FDG-PET. A voxel-wise comparison was used to evaluate the area with the greatest abnormal metabolism. Agreement between methods was assessed using the percent agreement and the kappa statistic (κ). Pediatric brain tumors were metabolically heterogeneous on FDG-PET and MRSI studies. Active tumor metabolism was observed more frequently using MRSI compared to FDG-PET, and agreement in tumor classification was weak (κ = 0.16, p = 0.12), with 42 % agreement (95 % CI = 25-61 %). Voxel-wise comparison for identifying the area of greatest metabolic activity showed overlap in the majority (62 %) of studies, though exact agreement between techniques was low (29.4 %, 95 % CI = 15.1-47.5 %). These results indicate that FDG-PET and MRSI detect similar but not always identical regions of tumor activity, and there is little agreement in the degree of tumor metabolic activity between the two techniques.

Single- and multivoxel proton spectroscopy in pediatric patients with diffuse intrinsic pontine glioma.

PURPOSE: To determine the feasibility of two magnetic resonance spectroscopy (MRS) techniques for treating pediatric patients with diffuse intrinsic pontine gliomas (DIPGs) and to evaluate the relationship of metabolic profiles determined by each technique. Utility of each technique for improving patient management is also discussed. METHODS AND MATERIALS: Children with DIPG (n = 36) were evaluated using single-voxel spectroscopy (SVS) and magnetic resonance spectroscopic imaging (MRSI) during the same imaging session. Patients were followed longitudinally (n = 150 total studies). Technical feasibility was defined by sufficient water and lipid suppression for detection of metabolites. Correlation of metabolic data obtained by SVS and MRSI was determined using the Spearman rank method. Metabolite ratios, including choline:N-acetyl-aspartate (Cho:NAA) and Cho:creatine (Cho:Cr), were obtained from SVS and MRSI. RESULTS: SVS and MRSI acquisitions were feasible in >90% of studies. Maximum Cho:NAA and Cho:Cr from MRSI analysis were strongly associated with Cho:NAA and Cho:Cr obtained by SVS (r = 0.67 and 0.76, respectively). MRSI Cho:NAA values were more heterogeneous than Cho:Cr values within the same lesion, and a strong linear relationship between the range and maximum Cho:NAA values was observed. CONCLUSIONS: SVS and MRSI acquisitions were feasible, with a strong correlation in metabolic data. Both techniques may improve diagnostic evaluation and management of DIPG. SVS is recommended for global assessment of tumor metabolism before and after therapy. MRSI showed heterogeneous patterns of metabolic activity within these tumors and is recommended for planning and monitoring targeted therapies and evaluating nearby tissue for tumor invasion.

Predicting outcome of children with diffuse intrinsic pontine gliomas using multiparametric imaging.

Noninvasive evaluation using MRI is the primary means to routinely assess children with diffuse intrinsic pontine gliomas (DIPGs). However, no standard MR sequence has correlated with outcome in these patients. In this study, patients with DIPGs were assessed to determine the combined prognostic value via dynamic susceptibility contrast (DSC) MRI, single-voxel spectroscopy (SVS), multivoxel MR spectroscopy (MRS), and T1-weighted post-gadolinium imaging. Eligible patients had clinical and radiographic findings consistent with a DIPG. Imaging studies were acquired on a 1.5T MRI at various time points during each patient's course. Data were evaluated using a Cox proportional hazard model, a time-dependent covariant Cox model, a Wald test, and a Kaplan-Meier analysis. Ninety-eight studies were performed on 34 patients of median age 5.5 years. Median survival from diagnosis was 468 days. At baseline imaging only, increased ratio of choline to n-acetylaspartate (Cho:NAA) on SVS and increased perfusion on DSC-MRI each predicted shorter survival (relative risk [RR] = 1.48, P = .015 and RR = 4.91, P = .0012, respectively). When analyzing all subsequent time points, increased maximum Cho:NAA on MRS (RR = 1.45, P = .042), increased Cho:NAA on SVS (RR = 1.69, P = .003), increased perfusion (RR = 4.68, P = .0016), and the presence of enhancement (RR = 5.69, P = .022) each predicted shorter survival. Kaplan-Meier analysis showed shorter survival associated with increased perfusion at baseline (P = .0004). Increased perfusion at any time point predicts a significantly shorter survival in children with DIPG. In addition, enhancement, increased Cho:NAA on SVS, and increased maximum Cho:NAA on chemical shift imaging are predictive of shorter survival over time. Routine baseline and subsequent imaging for children with DIPG should, at minimum, incorporate DSC-MRI and SVS.

Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma.

Patients with diffuse intrinsic pontine glioma (DIPG) face a grim prognosis with limited treatment options. Many patients will enroll on investigational trials though the role of chemotherapy or immunotherapy is unclear. Radiographic changes on conventional MRI are used to evaluate tumor response and progression, but are not predictive of outcome in these patients. More sensitive measures of tumor biology are needed to improve patient management. We evaluated changes in magnetic resonance spectroscopy (MRS) biomarkers in patients with DIPG. Thirty-eight patients were enrolled prospectively on an IRB-approved protocol, which included standard MRI, single voxel spectroscopy (SVS) and multi-slice multi-voxel spectroscopy (MRSI). Scans were performed at multiple time points during each patient's clinical course, with a total of 142 scans. The prognostic values of Choline:N-acetylaspartate (Cho:NAA), Cho:Creatine (Cho:Cr) and the presence of lactate and lipids (+Lac/Lip) were evaluated. Cho:NAA and variance in Cho:NAA values among different voxels within a tumor were each predictive of shorter survival. This prospective study shows that MRS can be used to identify high-risk patients and monitor changes in tumor metabolism, which may reflect changes in tumor behavior.

Multifocal bone marrow involvement in cat-scratch disease.

We describe 2 children with prolonged fever of unknown origin and prominent skeletal pain who had multifocal bone disease caused by Bartonella infection. Initial radiologic studies, including plain films, radionuclide scintigraphy and computed tomography, yielded negative results. In both cases, magnetic resonance imaging revealed multiple enhancing bone marrow lesions consistent with clinical symptoms. Microbiologic diagnoses were established serologically.