Background: Global budgets have been proposed as a way to control health care expenditures, but experience with them in the United States is limited. Global budgets for Maryland hospitals, the All-Payer Model, began in January 2014. Objectives: To evaluate the effect of hospital global budgets on health care utilization and expenditures. Research Design: Quantitative analyses used a difference-in-differences design modified for nonparallel baseline trends, comparing trend changes from a 3-year baseline period to the first 3 years after All-Payer Model implementation for Maryland and a matched comparison group. Subjects: Hospitals in Maryland and matched out-of-state comparison hospitals. Fee-for-service Medicare beneficiaries residing in Maryland and comparison hospital market areas. Measures: Medicare claims were used to measure total Medicare expenditures; utilization and expenditures for hospital and nonhospital services; admissions for avoidable conditions; hospital readmissions; and emergency department visits. Qualitative data on implementation were collected through interviews with senior hospital staff, state officials, provider organization representatives, and payers, as well as focus groups of physicians and nurses. Results: Total Medicare and hospital service expenditures declined during the first 3 years, primarily because of reduced expenditures for outpatient hospital services. Nonhospital expenditures, including professional expenditures and postacute care expenditures, also declined. Inpatient admissions, including admissions for avoidable conditions, declined, but, there was no difference in the change in 30-day readmissions. Moreover, emergency department visits increased for Maryland relative to the comparison group. Conclusions: This study provides evidence that hospital global budgets as implemented in Maryland can reduce expenditures and unnecessary utilization without shifting costs to other parts of the health care system.

Background No International Classification of Diseases 10 th revision (ICD-10) diagnosis code exists for injection drug use-associated infective endocarditis (IDU-IE). Instead, public health researchers regularly use combinations of non-specific ICD-10 codes to identify IDU-IE; however, the accuracy of these codes has not been evaluated. Methods We compared commonly used ICD-10 diagnosis codes for IDU-IE to a prospectively collected patient cohort diagnosed with IDU-IE at Barnes-Jewish Hospital to determine the accuracy of ICD-10 diagnosis codes used in IDU-IE research Results ICD-10 diagnosis codes historically used to identify IDU-IE were inaccurate, missing 36.0% and misclassifying 56.4% of patients prospectively identified in this cohort. Use of these non-specific ICD-10 diagnosis codes resulted in substantial biases against the benefit of medications for opioid use disorder (MOUD) with relation to both AMA discharge and all-cause mortality. Specifically, when data from all patients with ICD-10 code combinations suggestive of IDU-IE was used, MOUD was associated with an increased risk of AMA discharge (RR 1.12; 95% CI 0.48 - 2.64). In contrast, when only patients confirmed by chart review as having IDU-IE were analyzed, MOUD was protective (RR 0.49; 95% CI 0.19 - 1.22). Use of MOUD was associated with a protective effect in time to all-cause mortality in Kaplan-Meier analysis only when confirmed IDU-IE cases were analyzed (p=0.007) Conclusions Studies using non-specific ICD-10 diagnosis codes for IDU-IE should be interpreted with caution. In the setting of an ongoing overdose crisis and a syndemic of infectious complications, a specific ICD-10 diagnosis code for IDU-IE is urgently needed

Background. In the United States, patients referred to as high-need, high-cost (HNHC) constitute a very small percentage of the patient population but account for a disproportionally high level of healthcare use and cost. Payers, health systems, and providers would like to improve the quality of care and health outcomes for HNHC patients and reduce their costly use of potentially preventable or modifiable healthcare services, including emergency department (ED) and hospital visits. Methods. We assessed evidence of criteria that identify HNHC patients (best fit framework synthesis); developed program theories on the relationship among contexts, mechanisms, and outcomes of interventions intended to change HNHC patient behaviors (realist review); and assessed the effectiveness of interventions (systematic review). We searched databases, gray literature, and other sources for evidence available from January 1, 2000, to March 4, 2021. We included quantitative and qualitative studies of HNHC patients (high healthcare use or cost) age 18 and over who received intervention services in a variety of settings. Results. We included 110 studies (117 articles). Consistent with our best fit framework, characteristics associated with HNHC include patient chronic clinical conditions, behavioral health factors including depression and substance use disorder, and social risk factors including homelessness and poverty. We also identified prior healthcare use and race as important predictors. We found limited evidence of approaches for distinguishing potentially preventable or modifiable high use from all high use. To understand how and why interventions work, we developed three program theories in our realist review that explain (1) targeting HNHC patients, (2) engaging HNHC patients, and (3) engaging care providers in these interventions. Theories identify the need for individualizing and tailoring services for HNHC patients and the importance of building trusting relationships. For our systematic review, we categorized evidence based on primary setting. We found that ED-, primary care–, and home-based care models result in reduced use of healthcare services (moderate to low strength of evidence [SOE]); ED, ambulatory intensive caring unit, and primary care-based models result in reduced costs (low SOE); and system-level transformation and telephonic/mail models do not result in changes in use or costs (low SOE). Conclusions. Patient characteristics can be used to identify patients who are potentially HNHC. Evidence focusing specifically on potentially preventable or modifiable high use was limited. Based on our program theories, we conclude that individualized and tailored patient engagement and resources to support care providers are critical to the success of interventions. Although we found evidence of intervention effectiveness in relation to cost and use, the studies identified in this review reported little information for determining why individual programs work, for whom, and when.

Knowledge of the intrinsic variability of radiomic features is essential to the proper interpretation of changes in these features over time. The primary aim of this study was to assess the test-retest repeatability of radiomic features extracted from 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) images of cervical tumors. The impact of different image pre-processing methods was also explored.Methods: Patients with cervical cancer underwent baseline and repeat FDG PET/CT imaging within 7 days. PET images were reconstructed using 2 methods: ordered subset expectation maximization (PETOSEM) or OSEM with point-spread function (PETPSF). Tumors were segmented to produce whole-tumor volumes of interest (VOIWT) and 40% isocontours (VOI40). Voxels were either left at the default size or resampled to 3 mm isotropic voxels. SUV was discretized to a fixed number of bins (32, 64, or 128).Radiomic features were extracted from both VOIs and repeatability was then assessed using Lin's concordance correlation coefficient (CCC). Results: Eleven patients were enrolled and completed the test-retest PET/CT imaging protocol. Shape, neighborhood gray-level difference matrix (NGLDM), and gray-level cooccurence matrix (GLCM) features were repeatable with mean CCC values of 0.81. Radiomic features extracted from PETOSEM images showed significantly better repeatability than features extracted from PETPSF images (P < 0.001). Radiomic features extracted from VOI40 were more repeatable than features extracted from VOIWT (P < 0.001). For most features (78.4%), a change in bin number or voxel size resulted in less than 10% change in feature value.All gray-level emphasis and gray-level run emphasis features showed poor repeatability (CCC values < 0.52) when extracted from VOIWT, but were highly repeatable (mean 4 CCC values > 0.96) when extracted from VOI40. Conclusion: Shape, GLCM, and NGLDM radiomic features were consistently repeatable while gray-level run length matrix (GLRLM) and gray-level zone length matrix (GLZLM) features were highly variable. Radiomic features extracted from 40% isocontours were more repeatable than features extracted from whole-tumor contours. Changes in voxel size or SUV discretization parameters typically resulted in relatively small differences in feature value, though several features were highly sensitive to these changes.

As a single polypeptide, cytochrome P450 BM3 fuses oxidase and reductase domains and couples each domain's function to perform catalysis with exceptional activity upon binding of substrate for hydroxylation. Mutations introduced into the enzyme to change its substrate specificity often decrease coupling efficiency between the two domains, resulting in unproductive consumption of cofactors and formation of water and/or reactive species. This phenomenon can correlate with leakage, in which P450 BM3 uses electrons from NADPH to reduce oxygen to water and/or reactive species even without bound substrate. The physical basis for leakage is not yet well understood in this particular member of the cytochrome P450 family. To clarify the relationship between leakage and coupling, we used simulations to illustrate how different combinations of kinetic parameters related to substrate-free consumption of NADPH and substrate hydroxylation can lead to either minimal effects on coupling or a dramatic decrease in coupling as a result of leakage. We explored leakage in P450 BM3 by introducing leakage-enhancing mutations and combining these mutations to assess whether doing so increases leakage further. The variants in this study provide evidence that while a transition to high spin may be vital for coupled hydroxylation, it is not required for enhanced leakage; substrate binding and the consequent shift in spin state are not necessary as a redox switch for catalytic oxidation of NADPH. Additionally, the variants in this study suggest a tradeoff between leakage and stability and thus evolvability, as the mutations we Abbreviations: P450 BM3, cytochrome P450 monooxygenase from B. megaterium; P450 cam, cytochrome P450 monooxygenase from P. putida; WT, wild type; k cat , R-H, turnover rate constant with respect to hydroxylation; K m , R-H, Michaelis constant with respect to hydroxylation; k cat , leakage, turnover rate constant with respect to leakage; K m , leakage, Michaelis constant with respect to leakage; K d , dissociation equilibrium constant; k on , association rate constant; k off , dissociation rate constant; T 50 , incubation temperature at which half of protein becomes denatured after 10 min; NADPH, nicotinamide adenine dinucleotide phosphate; ROS, reactive oxygen species; H 2 O 2 , hydrogen peroxide; O 2 2 , superoxide; IPTG, isopropyl b-d-1-thiogalactopyranoside; KPi, potassium phosphate; HRP, horseradish peroxidase; ABTS, 2,2 0 -azino-bis(3-ethylbenzothiazoline-6-sulphonic acid); CO, carbon monoxide; Tris, tris(hydroxyl)aminomethane; SDS, sodium dodecyl sulfate; PAGE, polyacrylamide gel electrophoresis Additional Supporting Information may be found in the online version of this article. Published by Wiley-Blackwell. V C 2015 The Protein Society investigated were far more deleterious than other mutations that have been used to change substrate specificity.