Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.

BACKGROUND AND AIMS: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression. APPROACH AND RESULTS: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12 , Allboaculum , and [ Ruminococcus ], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD + ) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype. CONCLUSIONS: Overall, we provide evidence for the relevance of mitochondria-microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.

Hospital Capabilities Associated With Behavioral Health Integration Within Emergency Departments.

OBJECTIVES: To identify hospital capabilities associated with behavioral health (BH) processes in emergency departments (EDs). RESEARCH DESIGN: Six hundred two hospital responses to the 2017/2018 National Survey of Healthcare Organizations and Systems were linked to 2017 American Hospital Association Annual Survey data. Separate multivariable regressions estimated how hospital capabilities (the use of quality improvement methods, approaches to disseminate best patient-care practices, barriers to using care delivery innovations, and inpatient beds for psychiatric or substance use) were associated with each of 4 ED-based BH processes: mental health and substance use disorder screening, team-based approaches to BH, telepsychiatry, and direct referrals to community-based BH clinicians. Models controlled for hospital structural characteristics and area-level socioeconomic factors. RESULTS: Most hospitals screened for BH conditions and provided direct referrals to community-based BH clinicians. Approximately half of the hospitals used a team approach to BH. A minority had implemented telepsychiatry. Each additional process used to disseminate best patient-care practices was associated with more screening for BH conditions (an increase of 4.07 points on the screening index, P <0.01) and greater likelihood of using a team approach to BH [4.41 percentage point ( P <0.01) increase]. Hospitals reporting more barriers to the use of care delivery innovations reported less screening and use of a team approach [a decrease of 0.15 points on the screening index ( P <0.01) and 0.28 percentage points reduction in likelihood of team approach use ( P <0.001) for 1-point increase in the barrier index]. CONCLUSIONS: Research and interventions focused on removing innovation barriers or adding processes to disseminate best practices offer a path to accelerate BH integration in hospital EDs.

Validation of a novel western blot assay to monitor patterns and levels of alpha dystroglycan in skeletal muscle of patients with limb girdle muscular dystrophies.

The cell membrane protein, dystroglycan, plays a crucial role in connecting the cytoskeleton of a variety of mammalian cells to the extracellular matrix. The α-subunit of dystroglycan (αDG) is characterized by a high level of glycosylation, including a unique O-mannosyl matriglycan. This specific glycosylation is essential for binding of αDG to extracellular matrix ligands effectively. A subset of muscular dystrophies, called dystroglycanopathies, are associated with aberrant, dysfunctional glycosylation of αDG. This defect prevents myocytes from attaching to the basal membrane, leading to contraction-induced injury. Here, we describe a novel Western blot (WB) assay for determining levels of αDG glycosylation in skeletal muscle tissue. The assay described involves extracting proteins from fine needle tibialis anterior (TA) biopsies and separation using SDS-PAGE followed by WB. Glycosylated and core αDG are then detected in a multiplexed format using fluorescent antibodies. A practical application of this assay is demonstrated with samples from normal donors and patients diagnosed with LGMD2I/R9. Quantitative analysis of the WB, which employed the use of a normal TA derived calibration curve, revealed significantly reduced levels of αDG in patient biopsies relative to unaffected TA. Importantly, the assay was able to distinguish between the L276I homozygous patients and a more severe form of clinical disease observed with other FKRP variants. Data demonstrating the accuracy and reliability of the assay are also presented, which further supports the potential utility of this novel assay to monitor changes in ⍺DG of TA muscle biopsies in the evaluation of potential therapeutics.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

Primary Care Practice Characteristics Associated With Medical Assistant Staffing Ratios.

This study characterized adult primary care medical assistant (MA) staffing. National Survey of Healthcare Organizations and Systems (n = 1,252) data were analyzed to examine primary care practice characteristics associated with MA per primary care clinician (PCC) staffing ratios. In 2021, few practices (11.4%) had ratios of 2 or more MAs per PCCs. Compared with system-owned practices, independent (odds ratio [OR] = 1.76, P <0.05) and medical group-owned (OR = 2.09, P <0.05) practices were more likely to have ratios of 2 or more MAs per PCCs, as were practices with organizational cultures oriented to innovation (P <0.05). Most primary care practices do not have adequate MA staffing.

Thermotolerance capabilities, blood metabolomics, and mammary gland hemodynamics and transcriptomic profiles of slick-haired Holstein cattle during mid lactation in Puerto Rico.

Holstein cattle carrying a prolactin receptor gene mutation (SLICK) exhibit short and sleek hair coats (short-haired Holstein [SLK]) enhancing thermotolerance and productivity compared with wild type-haired Holstein (WT) under tropical conditions. The objectives were to unravel the physiological and molecular mechanisms that confer an advantage to this slick genotype in Puerto Rico and determine potential correlations between metabolites and physiological variables. At 160 ± 3 DIM we compared vaginal temperatures (VT) and voluntary solar radiation exposure (VSRE) during 48 h between 9 SLK and 9 WT Holsteins, whereas a subsample of 7 SLK and 7 WT were used to assess udder skin temperature, mammary gland hemodynamics and transcriptomics, and blood plasma untargeted metabolomics at a single time point. The SLK cattle showed lower VT throughout the day and greater VSRE at 1000 h and 1100 h compared with their WT counterparts. Total mammary blood flow (MBF) was greater in SLK Holsteins compared with WT. The metabolite 9-nitrooctadecenoic acid was identified as a potential biomarker for MBF; moreover, SLK cattle had greater amounts of this metabolite in their plasma. Prostaglandin D2 synthase (PTGS) was upregulated in the slick mammary gland, while plasma prostaglandin D2 was positively correlated with milk yield and increased in SLK Holsteins compared with WT. Interestingly, the arachidonic acid metabolism pathway was enriched in the mammary gland transcriptome and perturbed in the blood metabolome in the SLK Holsteins. In conclusion, SLK Holsteins exhibited lower body temperatures, greater VSRE, enhanced blood supply to the mammary gland, and alterations in genes and metabolites involved in arachidonic acid metabolism at the mammary gland and blood plasma. The usage of the SLK Holstein cattle genetics in dairy operations could be a feasible alternative to mitigate the adverse consequences of heat stress.

Conjoint Analysis of Telemedicine Preferences for Hypertension Management Among Adult Patients.

Background: Telemedicine has been differentially utilized by different demographic groups during COVID-19, exacerbating inequities in health care. We conducted conjoint and latent class analyses to understand factors that shape patient preferences for hypertension management telemedicine appointments. Methods: We surveyed 320 adults, oversampling participants from households that earned <$50K per year (77.2%) and speak a language other than English at home (68.8%). We asked them to choose among 2 hypothetical appointments through 12 conjoint tasks measuring 6 attributes. Individual utilities for attributes were constructed using logit estimation, and latent classes were identified and compared by demographic and clinical characteristics. Results: Respondents preferred in-person visits (0.353, standard error [SE] = 0.039) and video appointments conducted through a secure patient portal (0.002, SE = 0.040). Respondents also preferred seeing a clinician with whom they have an established relationship (0.168, SE = 0.021). We found four latent classes: "in-person" (26.5% of participants) who strongly weighted in-person appointments, "cost conscious" (8.1%) who prioritized the lowest copay ($0 to $10), "expedited" (19.7%) who prioritized getting the earliest appointment possible (same/next day or at least within the next week), and "comprehensive" (45.6%) who had preferences for in-person care and telemedicine appointments through a secure portal, low copayments, and the ability to see a familiar clinician. Conclusions: Appointment preferences for hypertension management can be segmented into four groups that prioritize (1) in-person care, (2) low copayments, (3) expedited care, and (4) balanced preferences for in-person and telemedicine appointments. Evidence is needed to clarify whether aligning appointment offerings with patients' preferences can improve care quality, equity, and efficiency.

Telemedicine Implementation for Safety Net Populations: A Systematic Review.

Background: Telemedicine systems were rapidly implemented in response to COVID-19. However, little is known about their effectiveness, acceptability, and sustainability for safety net populations. This study systematically reviewed primary care telemedicine implementation and effectiveness in safety net settings. Methods: We searched PubMed for peer-reviewed articles on telemedicine implementation from 2013 to 2021. The search was done between June and December 2021. Included articles focused on health care organizations that primarily serve low-income and/or rural populations in the United States. We screened 244 articles from an initial search of 343 articles and extracted and analyzed data from N = 45 articles. Results: Nine (20%) of 45 articles were randomized controlled trials. N = 22 reported findings for at least one marginalized group (i.e., racial/ethnic minority, 65 years+, limited English proficiency). Only n = 19 (42%) included African American/Black patients in demographics descriptions, n = 14 (31%) LatinX/Hispanic patients, n = 4 (9%) Asian patients, n = 4 (9%) patients aged 65+ years, and n = 4 (9%) patients with limited English proficiency. Results show telemedicine can provide high-quality primary care that is more accessible and affordable. Fifteen studies assessed barriers and facilitators to telemedicine implementation. Common barriers were billing/administrative workflow disruption (n = 9, 20%), broadband access/quality (n = 5, 11%), and patient preference for in-person care (n = 4, 9%). Facilitators included efficiency gains (n = 6, 13%), patient acceptance (n = 3, 7%), and enhanced access (n = 3, 7%). Conclusions: Telemedicine is an acceptable care modality to deliver primary care in safety net settings. Future studies should compare telemedicine and in-person care quality and test strategies to improve telemedicine implementation in safety net settings.

A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in ≥12-Year-Olds.

BACKGROUND: Protection against contemporary SARS-CoV-2 variants requires sequence-adapted vaccines. METHODS: In this ongoing phase 2/3 trial, 12-17-year-olds (n=108), 18-55-year-olds (n=313), and >55-year-olds (n=306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-BA.4/BA.5-adapted BNT162b2 (BNT162b2-Omi.BA.4/BA.5). For comparisons with original BNT162b2, participants were selected from another phase 3 trial. Immunologic superiority 1-month post-vaccination, with respect to 50% neutralizing titers (GMR lower bound [LB] 2-sided 95%CI >1), and noninferiority with respect to seroresponse rates (rate-difference LB 2-sided 95%CI >-5%), for Omicron BA.4/BA.5 were assessed in >55-year-olds versus original BNT162b2 as a second booster. Noninferiority with respect to neutralizing titer level (GMR LB 2-sided 95%CI >0.67) and seroresponse rate (rate-difference LB 2-sided 95%CI >-10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds versus >55-year-olds was assessed. RESULTS: One-month post-vaccination in >55-year-olds, model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 group (2.91; 95%CI 2.45-3.44) demonstrated superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in percentages of >55-year-olds with seroresponse (26.77%; 95%CI 19.59-33.95) showed noninferiority of BNT162b2-Omi.BA.4/BA.5 to BNT162b2. Noninferiority of BNT162b2-Omi.BA.4/BA.5 in 18‒55-year-olds to >55-year-olds was met for model-adjusted GMR and seroresponse. GMTs in 12-17-year-olds increased from baseline to 1-month post-vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to booster doses of bivalent Omicron BA.1-modified BNT162b2 and original BNT162b2 reported in previous studies. CONCLUSIONS: Based on immunogenicity and safety data up to 1-month post-vaccination in participants who previously received 3 original BNT162b2 doses, a BNT162b2-Omi.BA.4/BA.5 30 µg booster has a favorable benefit-risk profile. CLINICAL TRIAL REGISTRATION: NCT05472038.

Assessing the Impact of Telemedicine Implementation in Diverse Health Care Systems.

Health care organizations and systems can have a large impact on how extensively telemedicine and virtual visits are used by medical practices and individual clinicians. This supplemental issue of medical care aims to advance evidence about how health care organizations and systems can best support telemedicine and virtual visit implementation. This issue includes 10 empirical studies examining the impact of telemedicine on quality of care, utilization, and/or patient care experiences, of which 6 are studies of Kaiser Permanente patients; 3 are studies of Medicaid, Medicare, and community health center patients; and 1 is a study of PCORnet primary care practices. The Kaiser Permanente studies find that ancillary service orders resulting from telemedicine encounters were not placed as often as in-person encounters for urinary tract infections, neck, and back pain, but there were no significant changes in patient fulfillment of ordered antidepressant medications. Studies focused on diabetes care quality among community health center patients and Medicare and Medicaid beneficiaries highlight that telemedicine helped maintain continuity of primary care and diabetes care quality during the COVID-19 pandemic. The research findings collectively demonstrate high variation in telemedicine implementation across systems and the important role that telemedicine had in maintaining the quality of care and utilization for adults with chronic conditions when in-person care was less accessible.

Hospital Characteristics Associated With Clinically Integrated Network Participation.

BACKGROUND: Increased integration of physician organizations and hospitals into health systems has not necessarily improved clinical integration or patient outcomes. However, federal regulators have issued favorable opinions for clinically integrated networks (CINs) as a way to pursue coordination between hospitals and physicians. Hospital organizational affiliations, including independent practice associations (IPA), physician-hospital organizations (PHOs), and accountable care organizations (ACOs), may support CIN participation. No empirical evidence, however, exists about factors associated with CIN participation. METHODS: Data from the 2019 American Hospital Association survey (n = 4405) were analyzed to quantify hospital CIN participation. Multivariable logistic regression models were estimated to examine whether IPA, PHO, and ACO affiliations were associated with CIN participation, controlling for market factors and hospital characteristics. RESULTS: In 2019, 34.6% of hospitals participated in a CIN. Larger, not-for-profit, and metropolitan hospitals were more likely to participate in CINs. In adjusted analyses, hospitals participating in CINs were more likely to have an IPA (9.5% points, P < 0.001), a PHO (6.1% points, P < 0.001), and ACO (19.3% points, P < 0.001) compared with hospitals not participating in a CIN. CONCLUSIONS: Over one-third of hospitals participate in a CIN, despite limited evidence about their effectiveness in delivering value. Results suggest that CIN participation may be a response to integrative norms. Future work should attempt to better define CIN participation and strive to disentangle overlapping organizational participation.

Telehealth Use, Care Continuity, and Quality: Diabetes and Hypertension Care in Community Health Centers Before and During the COVID-19 Pandemic.

BACKGROUND: Community health centers (CHCs) pivoted to using telehealth to deliver chronic care during the coronavirus COVID-19 pandemic. While care continuity can improve care quality and patients' experiences, it is unclear whether telehealth supported this relationship. OBJECTIVE: We examine the association of care continuity with diabetes and hypertension care quality in CHCs before and during COVID-19 and the mediating effect of telehealth. RESEARCH DESIGN: This was a cohort study. PARTICIPANTS: Electronic health record data from 166 CHCs with n=20,792 patients with diabetes and/or hypertension with ≥2 encounters/year during 2019 and 2020. METHODS: Multivariable logistic regression models estimated the association of care continuity (Modified Modified Continuity Index; MMCI) with telehealth use and care processes. Generalized linear regression models estimated the association of MMCI and intermediate outcomes. Formal mediation analyses assessed whether telehealth mediated the association of MMCI with A1c testing during 2020. RESULTS: MMCI [2019: odds ratio (OR)=1.98, marginal effect=0.69, z=165.50, P<0.001; 2020: OR=1.50, marginal effect=0.63, z=147.73, P<0.001] and telehealth use (2019: OR=1.50, marginal effect=0.85, z=122.87, P<0.001; 2020: OR=10.00, marginal effect=0.90, z=155.57, P<0.001) were associated with higher odds of A1c testing. MMCI was associated with lower systolic (ß=-2.90, P<0.001) and diastolic blood pressure (ß=-1.44, P<0.001) in 2020, and lower A1c values (2019: ß=-0.57, P=0.007; 2020: ß=-0.45, P=0.008) in both years. In 2020, telehealth use mediated 38.7% of the relationship between MMCI and A1c testing. CONCLUSIONS: Higher care continuity is associated with telehealth use and A1c testing, and lower A1c and blood pressure. Telehealth use mediates the association of care continuity and A1c testing. Care continuity may facilitate telehealth use and resilient performance on process measures.

Shared Decision-making Lowers Medical Expenditures and the Effect Is Amplified in Racially-Ethnically Concordant Relationships.

BACKGROUND: Racial-ethnic disparities are pervasive in health care. One mechanism that may underlie disparities is variation in shared decision-making (SDM), which encompasses high-quality clinician-patient communication, including deliberative discussions about treatment options. OBJECTIVES: To determine whether SDM has causal effects on outcomes and whether these effects are stronger within racial-ethnic concordant clinician-patient relationships. RESEARCH DESIGN: We use instrumental variables to estimate the causal effect of SDM on outcomes. SUBJECTS: A total of 60,584 patients from the 2003-2017 Integrated Public Use Microdata Series Medical Expenditure Panel Survey. Years 2018 and 2019 were excluded due to changes in the Medical Expenditure Panel Survey that omitted essential parts of the SDM index. MEASURES: Our key variable of interest is the SDM index. Outcomes included total, outpatient, and drug expenditures; physical and mental health; and the utilization of inpatient and emergency services. RESULTS: SDM lowers annual total health expenditures for all racial-ethnic groups, but this effect is only moderated among Black patients seen by Black clinicians, more than doubling in size relative to Whites. A similar SDM moderation effect also occurs for both Black patients seen by Black clinicians and Hispanic patients seen by Hispanic clinicians with regard to annual outpatient expenditures. There was no significant effect of SDM on self-reported physical or mental health. CONCLUSIONS: High-quality SDM can reduce health expenditures without negatively impacting overall physical or mental health, supporting a business case for health care organizations and systems to improve racial-ethnic clinician-patient concordance for Black and Hispanic patients.

Racial-Ethnic Composition of Primary Care Practices and Comprehensive Primary Care Plus Initiative Participation.

BACKGROUND: It remains unclear whether the racial-ethnic composition or the socioeconomic profiles of eligible primary care practices better explain practice participation in the Centers for Medicare and Medicaid Services' (CMS) Comprehensive Primary Care Plus (CPC+) program. OBJECTIVE: To examine whether practices serving high proportions of Black or Latino Medicare fee-for-service (FFS) beneficiaries were less likely to participate in CPC+ in 2021 compared to practices serving lower proportions of these populations. DESIGN: 2019 IQVIA OneKey data on practice characteristics was linked with 2018 CMS claims data and 2021 CMS CPC+ participation data. Medicare FFS beneficiaries were attributed to practices using CMS's primary care attribution method. PARTICIPANTS: 11,718 primary care practices and 7,264,812 attributed Medicare FFS beneficiaries across 18 eligible regions. METHODS: Multivariable logistic regression models examined whether eligible practices with relatively high shares of Black or Latino Medicare FFS beneficiaries were less likely to participate in CPC+ in 2021, controlling for the clinical and socioeconomic profiles of practices. MAIN MEASURES: Proportion of Medicare FFS beneficiaries attributed to each practice that are (1) Latino and (2) Black. KEY RESULTS: Of the eligible practices, 26.9% were CPC+ participants. In adjusted analyses, practices with relatively high shares of Black (adjusted odds ratio, aOR = 0.62, p < 0.05) and Latino (aOR = 0.32, p < 0.01) beneficiaries were less likely to participate in CPC+ compared to practices with lower shares of these beneficiary groups. State differences in CPC+ participation rates partially explained participation disparities for practices with relatively high shares of Black beneficiaries, but did not explain participation disparities for practices with relatively high shares of Latino beneficiaries. CONCLUSIONS: The racial-ethnic composition of eligible primary care practices is more strongly associated with CPC+ participation than census tract-level poverty. Practice eligibility requirements for CMS-sponsored initiatives should be reconsidered so that Black and Latino beneficiaries are not left out of the benefits of practice transformation.

Solubility of Amino Acids in the Eutectic Solvent Constituted by Sodium Acetate Trihydrate and Urea and in Its Mixture with Water.

Industrial fish and aquaculture processing leads to the generation of a huge quantity of by-products, whose accumulation and mismanagement involve serious environmental consequences as well as high economic losses. Taking advantage of these residues as a source of added-value compounds must be a priority in a circular economy. This work is a preliminary study to analyze the possibility of using the eutectic mixture of urea and sodium acetate trihydrate as a solvent for collagen extraction. To that end, the solid-liquid equilibrium of the system was determined in order to define the exact composition and temperature of the eutectic. The solubility in this solvent of the main amino acids that constitute fish collagen was studied at several temperatures and atmospheric pressure. At 308.15 K, solubilities of the major constituents of the target protein, namely L-proline, trans-4-hydroxy-L-proline, and glycine, were 0.19, 0.16, and 0.12 (mass fraction), respectively. These values increased with temperature. Dilution with water (50 wt%) allowed operation at lower temperature and led to an increase in the solubilities. The van 't Hoff model was satisfactorily used to correlate the experimental data and to calculate apparent properties of dissolution. All the dissolution processes studied herein are endothermic, non-spontaneous, and enthalpy-driven. Both the eutectic and its mixture with water are promising solvents for the design of an environmentally benign process for collagen extraction.

Challenges in Using Ionic Liquids for Cellulosic Ethanol Production.

The growing need to expand the use of renewable energy sources in a sustainable manner, providing greater energy supply security and reducing the environmental impacts associated with fossil fuels, finds in the agricultural by-product bioethanol an economically viable alternative with significant expansion potential. In this regard, a dramatic boost in the efficiency of processes already in place is required, reducing costs, industrial waste, and our carbon footprint. Biofuels are one of the most promising alternatives to massively produce energy sustainably in a short-term period. Lignocellulosic biomass (LCB) is highly recalcitrant, and an effective pretreatment strategy should also minimize carbohydrate degradation by diminishing enzyme inhibitors and other products that are toxic to fermenting microorganisms. Ionic liquids (ILs) have been playing an important role in achieving cleaner processes as a result of their excellent physicochemical properties and outstanding performance in the dissolution and fractionation of lignocellulose. This review provides an analysis of recent advances in the production process of biofuels from LCB using ILs as pretreatment and highlighting techniques for optimizing and reducing process costs that should help to develop robust LCB conversion processes.

Ex vivo effect of JAK inhibition on JAK-STAT1 pathway hyperactivation in patients with dominant-negative STAT3 mutations.

PURPOSE: STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted treatment with Janus-kinase (JAK) inhibitors shows promising results in treating STAT1 GOF-associated symptoms while management of DN STAT3 patients has been largely supportive. We here assessed the impact of ruxolitinib on the JAK-STAT1/3 pathway in DN STAT3 patients' cells. METHODS: Using flow cytometry, immunoblot, qPCR, and ELISA techniques, we examined the levels of basal STAT1 and phosphorylated STAT1 (pSTAT1) of cells obtained from DN STAT3, STAT1 GOF patients, and healthy donors following stimulation with type I/II interferons (IFNs) or interleukin (IL)-6. We also describe the impact of ruxolitinib on cytokine-induced STAT1 signaling in these patients. RESULTS: DN STAT3 and STAT1 GOF resulted in a similar phenotype characterized by increased STAT1 and pSTAT1 levels in response to IFNα (CD3+ cells) and IFNγ (CD14+ monocytes). STAT1-downstream gene expression and C-X-C motif chemokine 10 secretion were higher in most DN STAT3 patients upon stimulation compared to healthy controls. Ex vivo treatment with the JAK1/2-inhibitor ruxolitinib reduced cytokine responsiveness and normalized STAT1 phosphorylation in DN STAT3 and STAT1 GOF patient' cells. In addition, ex vivo treatment was effective in modulating STAT1 downstream signaling in DN STAT3 patients. CONCLUSION: In the absence of effective targeted treatment options for AD-HIES at present, modulation of the JAK/STAT1 pathway with JAK inhibitors may be further explored particularly in those AD-HIES patients with autoimmune and/or autoinflammatory manifestations.

Adoption of Patient Engagement Strategies by Physician Practices in the United States.

BACKGROUND: Patient engagement strategies can equip patients with tools to navigate treatment decisions and improve patient-centered outcomes. Despite increased recognition about the importance of patient engagement, little is known about the extent of physician practice adoption of patient engagement strategies nationally. METHODS: We analyzed data collected from the National Survey of Healthcare Organizations and Systems (NSHOS) on physician practice adoption of patient engagement strategies. Stratified-cluster sampling was used to select physician practices operating under different organizational structures. Multivariable linear regression models estimated the association of practice ownership, health information technology functionality, use of screening activities, patient responsiveness, chronic care management processes, and the adoption of patient engagement strategies, including shared decision-making, motivational interviewing, and shared medical appointments. All regression models controlled for participation in payment reforms, practice size, Medicaid revenue percentage, and geographic region. RESULTS: We found modest and varied adoption of patient engagement strategies by practices of different ownership types, with health system-owned practices having the lowest adoption of ownership types. Practice capabilities, including chronic care management processes, routine screening of medical and social risks, and patient care dissemination strategies were associated with greater practice-level adoption of patient engagement strategies. CONCLUSIONS: This national study is the first to characterize the adoption of patient engagement strategies by US physician practices. We found modest adoption of shared decision-making and motivational interviewing, and low adoption of shared medical appointments. Risk-based payment reform has the potential to motivate greater practice-level patient engagement, but the extent to which it occurs may depend on internal practice capabilities.

Survey of Information Exchange and Advanced Use of Other Health Information Technology in Primary Care Settings: Capabilities In and Outside of the Safety Net.

BACKGROUND: Advanced use of health information technology (IT) functionalities can support more comprehensive, coordinated, and patient-centered primary care services. Safety net practices may benefit disproportionately from these investments, but it is unclear whether IT use in these settings has kept pace and what organizational factors are associated with varying use of these features. OBJECTIVE: The aim was to estimate advanced use of health IT use in safety net versus nonsafety net primary care practices. We explore domains of patient engagement, population health management (decision support and registries), and electronic information exchange. We examine organizational characteristics that may differentially predict advanced use of IT across these settings, with a focus on health system ownership and/or membership in an independent practice network as key factors that may indicate available incentives and resources to support these efforts. RESEARCH DESIGN: We conduct cross-sectional analysis of a national survey of physician practices (n=1776). We use logistic regression to predict advanced IT use in each of our domains based on safety net status and other organizational characteristics. We then use interaction models to assess whether ownership or network membership moderate the relationship between safety net status and advanced use of health IT. RESULTS: Health IT use was common across primary care practices, but advanced use of health IT functionalities ranged only from 30% to 50% use. Safety net settings have kept pace with adoption of features for patient engagement and population management, yet lag in information exchange capabilities compared with nonsafety net practices (odds ratio=0.52 for federally qualified health centers, P<0.001; odds ratio=0.66 for other safety net, P=0.03). However, when safety net practices are members of a health system or practice network, health IT capabilities are comparable to nonsafety net sites. CONCLUSIONS: All outpatient settings would benefit from improved electronic health record usability and implementation support that facilitates advanced use of health IT. Safety net practices, particularly those without other sources of centralized support, need targeted resources to maintain equitable access to information exchange capabilities.

Adoption of Patient-Reported Outcomes by Health Systems and Physician Practices in the USA.

BACKGROUND: Patient-reported outcome measures (PROs) can help clinicians adjust treatments and deliver patient-centered care, but organizational adoption of PROs remains low. OBJECTIVE: This study examines the extent of PRO adoption among health systems and physician practices nationally and examines the organizational capabilities associated with more extensive PRO adoption. DESIGN: Two nationally representative surveys were analyzed in parallel to assess health system and physician practice capabilities associated with adoption of PROs of disability, pain, and depression. PARTICIPANTS: A total of 323 US health system and 2,190 physician practice respondents METHODS: Multivariable regression models separately estimated the association of health system and physician practice capabilities associated with system-level and practice-level adoption of PROs. MAIN MEASURES: Health system and physician practice adoption of PROs for depression, pain, and disability. KEY RESULTS: Pain (50.6%) and depression (43.8%) PROs were more commonly adopted by all hospitals and medical groups within health systems compared to disability PROs (26.5%). In adjusted analyses, systems with more advanced health IT functions were more likely to use disability (p<0.05) and depression (p<0.01) PROs than systems with less advanced health IT. Practice-level advanced health IT was positively associated with use of depression PRO (p<0.05), but not disability or pain PRO use. Practices with more chronic care management processes, broader medical and social risk screening, and more processes to support patient responsiveness were more likely to adopt each of the three PROs. Compared to independent physician practices, system-owned practices and community health centers were less likely to adopt PROs. CONCLUSIONS: Chronic care management programs, routine screening, and patient-centered care initiatives can enable PRO adoption at the practice level. Developing these practice-level capabilities may improve PRO adoption more than solely expanding health IT functions.