Search

OBJECTIVE: The objective of this study was to investigate variations across hospitals in infection rates and associated costs, the latter reflected in 90-day Medicare payments. Despite high rates and expenditures of healthcare-associated infections associated with durable ventricular assist device implant, few studies have examined inter-hospital variation and associated costs. METHODS: Clinical data on 8688 patients who received primary durable ventricular assist devices from July 2008 to July 2017 from The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) hospitals (n=120) were merged with post-implant 90-day Medicare claims. Terciles of hospital-specific, risk-adjusted infection rates per 100 patient-months were estimated using Intermacs and associated with Medicare payments (among 5440 Medicare beneficiaries). Primary outcomes included infections within 90 days of implant and Medicare payments. RESULTS: There were 3982 infections identified among 27.8% (2,417/8,688) of patients developing an infection. The median (25(th), 75(th) percentile) adjusted incidence of infections (per 100 patient-months) across hospitals was 14.3 (9.3, 19.5) and varied by hospital (range 0.0 – 35.6). Total Medicare payments from implant to 90-days were 9.0% (absolute difference: $13,652) greater in high versus low infection tercile hospitals, p

The protein histidine phosphatase PHPT1 is implicated in a variety of cellular signaling pathways. However, little is known about the precise biological roles of this enzyme and a dearth of chemical tools for studying histidine phosphorylation and dephosphorylation has hampered progress in the field. With the goal of identifying the first inhibitors of PHPT1 activity, we carried out an inhibitor screen using a facile fluorogenic assay for PHPT1 activity recently developed in our laboratory. From a panel of approximately 4000 compounds obtained from the Microsource Spectrum Collection and the NCI Diversity Set IV, we identified several potential hits with significant selectivity for inhibiting PHPT1 activity over other phosphatases. Of these, norstictic acid was the most potent inhibitor of PHPT1 activity with an IC

BACKGROUND The United States National Organ Procurement Transplant Network (OPTN) implemented changes to the adult heart allocation system to reduce waitlist mortality by improving access for those at greater risk of pre-transplant death, including patients on short-term mechanical circulatory support (sMCS). While sMCS increased, it is unknown whether the increase occurred equitably across centers. METHODS The OPTN database was used to assess changes in use of sMCS at time of transplant in the 12 months before (pre-change) and after (post-change) implementation of the allocation system in October 2018 among 5,477 heart transplant recipients. An interrupted time series analysis comparing use of bridging therapies pre- and post-change was performed. Variability in the proportion of sMCS use at the center level pre- and post-change was determined. RESULTS In the month pre-change, 9.7% of patients were transplanted with sMCS. There was an immediate increase in sMCS transplant the following month to 32.4% - an absolute and relative increase of 22.7% and 312% (p < 0.001). While sMCS use was stable pre-change (monthly change 0.0%, 95% CI [-0.1%,0.1%]), there was a continuous 1.2%/month increase post-change ([0.6%,1.8%], p < 0.001). Center-level variation in sMCS use increased substantially after implementation, from a median (interquartile range) of 3.85% (10%) pre-change to 35.7% (30.6%) post-change (p < 0.001). CONCLUSIONS Use of sMCS at time of transplant increased immediately and continued to expand following heart allocation policy changes. Center-level variation in use of sMCS at the time of transplant increased compared to pre-change, which may have negatively impacted equitable access to heart transplantation.

Background: Older adults may experience a significant digital divide and need support with using technology to transition to telehealth. This study examines the role of social support for telehealt...

Particle suspensions form a fundamental yet complex component of many scientific and engineering endeavours. This paper proposes a numerical coupling between the lattice Boltzmann and discrete element methods that resolves particle suspensions exposed to thermal influences due to temperature-dependent fluid viscosity and conjugate heat transfer between components. Validation of the model was performed via the study of the relative viscosity of suspensions. This numerically corroborated the proposed temperature-dependence of the relative viscosity of suspensions. The model was finally used to interrogate the macroscopic behaviour of sheared suspensions at a range of solid volume fractions. This demonstrated changes in suspension flow behaviour due to temperature related effects. Future work based on these results would examine how particle properties could be modified to exacerbate and control temperature-based phenomena potentially leading to improvements in domains such as industrial material processing and manufacture.

While left ventricular assist devices (LVADs) increase survival for patients with advanced heart failure (HF), racial and sex access and outcome inequities remain and are poorly understood.To assess risk-adjusted inequities in access and outcomes for both Black and female patients and to examine heterogeneity in treatment decisions among patients for whom clinician discretion has a more prominent role.This retrospective cohort study of 12 310 Medicare beneficiaries used 100% Medicare Fee-for-Service administrative claims. Included patients had been admitted for heart failure from 2008 to 2014. Data were collected from July 2007 to December 2015 and analyzed from August 23, 2020, to May 15, 2022.Beneficiary race and sex.The propensity for LVAD implantation was based on clinical risk factors from the 6 months preceding HF admission using XGBoost and the synthetic minority oversampling technique. Beneficiaries with a 5% or greater probability of receiving an LVAD were included. Logistic regression models were estimated to measure associations of race and sex with LVAD receipt adjusting for clinical characteristics and social determinants of health (eg, distance from LVAD center, Medicare low-income subsidy, neighborhood deprivation). Next, 1-year mortality after LVAD was examined.The analytic sample included 12 310 beneficiaries, of whom 22.9% (n = 2819) were Black and 23.7% (n = 2920) were women. In multivariable models, Black beneficiaries were 3.0% (0.2% to 5.8%) less likely to receive LVAD than White beneficiaries, and women were 7.9% (5.6% to 10.2%) less likely to receive LVAD than men. Individual poverty and worse neighborhood deprivation were associated with reduced use, 2.9% (0.4% to 5.3%) and 6.7% (2.9% to 10.5%), respectively, but these measures did little to explain observed disparities. The racial disparity was concentrated among patients with a low propensity score (propensity score0.52). One-year survival by race and sex were similar on average, but Black patients with a low propensity score experienced improved survival (7.2% [95% CI, 0.9% to 13.5%]).In this cohort study of Medicare beneficiaries hospitalized for HF, disparities in LVAD use by race and sex existed and were not explained by clinical characteristics or social determinants of health. The treatment and post-LVAD survival by race were equivalent among the most obvious LVAD candidates. However, there was differential use and outcomes among less clear-cut LVAD candidates, with lower use but improved survival among Black patients. Inequity in LVAD access may have resulted from differences in clinician decision-making because of systemic racism and discrimination, implicit bias, or patient preference.

Failure to rescue (FTR), defined as death after a complication, is recognized as a principal driver of variation in mortality among hospitals. We evaluated FTR as a quality metric in patients who received durable left ventricular assist devices (LVADs) using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support.Data on 13,617 patients who received primary durable LVADs from April 2012 to October 2017 at 131 hospitals that performed at least 20 implants were analyzed from the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support. Rates of major complications and FTR were compared across risk-adjusted in-hospital mortality terciles (low, medium, high) and hospital volume. Logistic regression was used to estimate expected FTR rates on the basis of patient factors for each major complication.The overall unadjusted in-hospital mortality rate was 6.96%. Risk-adjusted in-hospital mortality rates varied 3.1-fold across terciles (low, 3.3%; high, 10.3%; P trend.001). Rates of major complications varied 1.1-fold (low, 34.0%; high, 38.8%; P .0001). Among patients with a major complication, 854 died in-hospital for an FTR rate of 17.7%, with 2.8-fold variation across mortality terciles (low, 8.5%; high, 23.9%; P .0001). FTR rates were highest for renal dysfunction requiring dialysis (45.3%) and stroke (36.5%). Higher average annual LVAD volume was associated with higher rates of major complications (10 per year, 26.7%; 10-20 per year, 34.0%; 20-30 per year, 34.0%;30 per year, 40.1%; P trend.0001) whereas hospitals implanting10 per year had the highest FTR rate (10 per year, 23.5%; 10-20 per year, 16.5%; 20-30 per year, 17.0%;30 per year, 17.9%; P = .03).FTR might serve as an important quality metric for durable LVAD implant procedures, and identifying strategies for successful rescue after complications might reduce hospital variations in mortality.

Substantial effort is being invested in the creation of a virtual human — a model which will improve our understanding of human physiology and diseases and assist clinicians in the design of personalised medical treatments. A central challenge of achieving blood flow simulations at full-human scale is the development of an efficient and accurate approach to imposing boundary conditions on many outlets. A previous study proposed an efficient method for implementing the two-element Windkessel model to control the flow rate ratios at outlets. However, no study to date has examined the conditions for this approach to hold in complex geometries. Here we clarify the general role of the resistance and capacitance in this approach. We show that the error of the flow rate ratios decreases exponentially as the resistance increases. The errors fall below 4% in a simple five-outlets model and 7% in a human artery model comprising 10 outlets. Moreover, the flow rate ratios converge faster and suffer from weaker fluctuations as the capacitance decreases. Our findings also establish constraints on the parameters controlling the numerical stability of the simulations. The findings from this work are directly applicable to larger and more complex vascular domains encountered at full-human scale.

OBJECTIVE: The 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease. RESEARCH DESIGN AND METHODS: We used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005–2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes. RESULTS: Overall rates of pneumococcal polysaccharide vaccination among adults 30–60 years old were

During the COVID-19 pandemic, many primary care practices adopted telehealth in place of in-person care to preserve access to care for patients with acute and chronic conditions. The extent to which this change was associated with their rates of acute care visits (ie, emergency department visits and hospitalizations) for these conditions is unknown.To examine whether a primary care practice's level of telehealth use is associated with a change in their rate of acute care visits for ambulatory care-sensitive conditions (ACSC visits).This retrospective cohort analysis used a difference-in-differences study design to analyze insurance claims data from 4038 Michigan primary care practices from January 1, 2019, to September 30, 2020.Low, medium, or high tertile of practice-level telehealth use based on the rate of telehealth visits from March 1 to August 31, 2020, compared with prepandemic visit volumes.Risk-adjusted ACSC visit rates before (June to September 2019) and after (June to September 2020) the start of the COVID-19 pandemic, reported as an annualized average marginal effect. The study examined overall, acute, and chronic ACSC visits separately and controlled for practice size, in-person visit volume, zip code-level attributes, and patient characteristics.A total of nearly 1.5 million beneficiaries (53% female; mean [SD] age, 40 [22] years) were attributed to 4038 primary care practices. Compared with 2019 visit volumes, median telehealth use was 0.4% for the low telehealth tertile, 14.7% for the medium telehealth tertile, and 39.0% for the high telehealth tertile. The number of ACSC visits decreased in all tertiles, with adjusted rates changing from 24.3 to 14.9 per 1000 patients per year (low), 23.9 to 15.3 per 1000 patients per year (medium), and 27.5 to 20.2 per 1000 patients per year (high). In difference-in-differences analysis, high telehealth use was associated with a higher ACSC visit rate (2.10 more visits per 1000 patients per year; 95% CI, 0.22-3.97) compared with low telehealth practices; practices in the middle tertile did not differ significantly from the low tertile. No difference was found in ACSC visits across tertiles when acute and chronic ACSC visits were examined separately.In this cohort study that used a difference-in-differences analysis, the association between practice-level telehealth use and ACSC visits was mixed. High telehealth use was associated with a slightly higher overall ACSC visit rate than low telehealth practices. The association of telehealth with downstream care use should be closely monitored going forward.

There is increasing awareness of the importance of nutritional support in cancer treatment including the interaction with immunity. Immunonutrition is the provision of one or more nutrients (e.g. Vitamins A, D, or E, omega-3 fatty acids, arginine and glutamine) known to modulate immune function when given at levels above those normally encountered in the diet in order to support immune system function or modulate its activity, including control of inflammation. We reviewed the role of oral or enteral immunonutrition versus standard nutrition on infection and infection-related biomarkers in adult cancer patients undergoing chemotherapy.A systematic search of oral or enteral immunonutrition versus standard nutrition in adult cancer patients during chemotherapy with or without radiotherapy or haematopoietic stem cell transplant was conducted in MEDLINE, EMBASE and CENTRAL. The search was limited to randomised controlled trials. Our primary outcome was infectious episodes or immune-related biomarkers (e.g. immune cell numbers, inflammatory markers). Secondary outcomes included incidence of malnutrition or cachexia, non-infection related adverse events (AEs), rate of remission, survival, and delays or incomplete cycles of chemotherapy. Risk of bias was assessed using ROB 2.0 and study quality was assessed using CASP for RCTs.The search yielded seven studies involving 521 patients (261 immunonutrition, 260 control) for analysis. All studies enrolled patients with solid tumours (no haematological malignancies). Studies were heterogenous for cancer type (upper gastrointestinal, head and neck, pancreatic and lung), immunonutrient composition (omega-3 fatty acids, vitamin A, E, glutamine, arginine or nucleotides), delivery route (enteral nutrition or oral nutritional supplement) and control used. Intervention period ranged from 4 to 14 weeks. No study reported absolute number of infections. Three studies reported AEs including potential infectious episodes of febrile neutropenia, pneumonitis and mucositis with oral candidiasis. Some studies report a decrease in blood concentrations of CRP and TNF-α with immunonutrition.There is currently insufficient evidence to define a role for immunonutrition on infectious episodes during chemotherapy in adult cancer patients. Further well-defined studies that account for degree of malnutrition, dose, timing and duration of immunonutrition in specific well-defined cancer groups using a standardised outcome framework are needed.

Patients undergoing left ventricular assist device (LVAD) implantation are at risk for death and postoperative adverse outcomes. Interhospital variability and concordance of quality metrics were assessed using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs).A total of 22 173 patients underwent primary, durable LVAD implantation across 160 hospitals from 2012 to 2020, excluding hospitals performing10 implant procedures. Observed and risk-adjusted operative mortality rates were calculated for each hospital. Outcomes included operative and 90-day mortality, a composite of adverse events (operative mortality, bleeding, stroke, device malfunction, renal dysfunction, respiratory failure), and secondarily failure to rescue. Rates are presented as median (interquartile range [IQR]). Hospital performance was evaluated using observed-to-expected (O/E) ratios for mortality and the composite outcome.Interhospital variability existed in observed (median, 7.2% [IQR, 5.1%-9.6%]) mortality. The rates of adverse events varied across hospitals: major bleeding, 15.6% (IQR, 11.4%-22.4%); stroke, 3.1% (IQR, 1.6%-4.7%); device malfunction, 2.4% (IQR, 0.8%-3.7%); respiratory failure, 10.5% (IQR, 4.6%-15.7%); and renal dysfunction, 6.4% (IQR, 3.2%-9.6%). The O/E ratio for operative mortality varied from 0.0 to 6.1, whereas the O/E ratio for the composite outcome varied from 0.28 to 1.99. Hospital operative mortality O/E ratios were more closely correlated with the 90-day mortality O/E ratio (r = 0.74) than with the composite O/E ratio (r = 0.12).This study reported substantial interhospital variability in performance for hospitals implanting durable LVADs. These findings support the need to (1) report hospital-level performance (mortality, composite) and (2) undertake benchmarking activities to reduce unwarranted variability in outcomes.

The ability to visualize enzyme activity in a cell, tissue, or living organism can greatly enhance our understanding of the biological roles of that enzyme. While many aspects of cellular signaling are controlled by reversible protein phosphorylation, our understanding of the biological roles of the protein phosphatases involved is limited. Here, we provide an overview of progress toward the development of fluorescent probes that can be used to visualize the activity of protein phosphatases. Significant advances include the development of probes with visible and near-infrared (near-IR) excitation and emission profiles, which provides greater tissue and whole-animal imaging capabilities. In addition, the development of peptide-based probes has provided some selectivity for a phosphatase of interest. Key challenges involve the difficulty of achieving sufficient selectivity for an individual member of a phosphatase enzyme family and the necessity of fully validating the best probes before they can be adopted widely.

Background:Thirst is a sensation normally aroused by a lack of water and associated with a desire to drink more fluid.Aim:The aims of this brief review are twofold: (a) to summarize the thirst mechanism in how it is initiated and diminished, and (b) to describe techniques to assess human thirst accurately in a variety of situations.Discussion:Thirst is maintained via a feedback-controlled mechanism, regulated by central and peripheral factors, as well as social and psychological cues. Most studies of thirst have focused on the initiation of water intake and the neural mechanisms responsible for this vital behavior. Less attention has been paid to the stimuli and mechanisms that terminate a bout of drinking and limit fluid ingestion, such as oropharyngeal and gastric signals, coupled with osmotic sensations. Thirst perception is typically assessed by subjective ratings using a variety of questionnaires, rankings, or visual analog scales. However, the appropriate perceptual tool may not always be used for the correct assessment of thirst perception.Conclusions:In considering the many factors involved in thirst arousal and inhibition, similar questions need to be considered for the correct assessment of this ingestive behavior.

The protein tyrosine phosphatase (PTP) family of enzymes includes many attractive therapeutic targets, such as those in the leukocyte common antigen-related (LAR) subfamily of receptor PTPs. Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether are described, with a focus on selective inhibition of LAR PTP relative to a small collection of other representative PTPs. The synthesis comprises 16 steps and provides illudalic acid in up to 12% overall yield from neopentylene-fused benzoate 1 (20 steps from commercial materials). Illudalic acid dose-dependently (measured IC50 = 2.1 ± 0.2 μM) and time-dependently inhibits LAR consistent with previous reports of covalent binding. The kinetics of LAR inhibition by illudalic acid are consistent with a two-step mechanism in which the inhibitor and enzyme first interact noncovalently (KI = 130 ± 50 μM), followed by covalent ligation at a rate kinact = 1.3 ± 0.4 min-1. The kinact/KI ratio of 104 corresponds to a t∞1/2 of 0.5 min, as discussed herein. The phenol methyl ether of illudalic acid was found to be less potent in our dose-response assays (measured IC50 = 55 ± 6 μM) but more selective for LAR, with a weaker initial noncovalent interaction and faster covalent ligation of LAR as compared to illudalic acid itself. A truncated analogue of illudalic acid that lacks the neopentylene ring fusion was found to be devoid of significant activity under our assay conditions, in contrast to previous reports. These observations collectively help inform further development of illudalic acid analogues as potent and selective inhibitors of the LAR subfamily of tyrosine phosphatases.

Background Public reporting of transcatheter aortic valve replacement (TAVR) claims–based outcome measures is used to identify high‐ and low‐performing centers. Whether claims‐based TAVR outcomes can reliably be used for center‐level comparisons is unknown. In this study, we sought to evaluate center variability in claims‐based TAVR outcomes used in public reporting. Methods and Results The study sample included 119 554 Medicare beneficiaries undergoing TAVR between January 2014 and October 2018 based on procedure codes in 100% Medicare inpatient claims. Multivariable hierarchical logistic regression was used to estimate center‐specific adjusted rates and reliability (R) of 30‐day mortality, discharge not to home/self‐care, 30‐day stroke, and 30‐day readmission. Reliability was defined as the ratio of between‐hospital variation to the sum of the between‐ and within‐hospital variation. The median (interquartile range [IQR]) center‐level adjusted outcome rates were 3.1% (2.9%–3.4%) for 30‐day mortality, 41.4% (31.3%–53.4%) for discharge not to home, 2.5% (2.3%–2.7%) for 30‐day stroke, and 14.9% (14.4%–15.5%) for 30‐day readmission. Median reliability was highest for the discharge not to home measure (R=0.95; IQR, 0.94–0.97), followed by the 30‐day stroke (R=0.92; IQR, 0.87–0.94), 30‐day mortality (R=0.86; IQR, 0.81–0.91), and 30‐day readmission measures (R=0.42; IQR, 0.35–0.51). Across outcomes, there was an inverse relationship between center volume and measure reliability. Conclusions Claims‐based TAVR outcome measures for mortality, discharge not to home, and stroke were reliable measures for center‐level comparisons, but readmission measures were unreliable. Stakeholders should consider these findings when evaluating claims‐based measures to compare center‐level TAVR performance.

ImportanceNonadherence to buprenorphine may increase patient risk of opioid overdose and increase health care spending. Quantifying the impacts of nonadherence can help inform clinician practice and policy.ObjectiveTo estimate the association between buprenorphine treatment gaps, opioid overdose, and health care spending.Design, Setting, and ParticipantsThis longitudinal case-control study compared patient opioid overdose and health care spending in buprenorphine-treated months with treatment gap months. Individuals who were US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder who received at least 1 two-week period of continuous buprenorphine treatment between 2010 and 2017 were included. Analysis took place between January 2010 and December 2017.InterventionsA gap in buprenorphine treatment in a month lasting more than 15 consecutive days.Main Outcomes and MeasuresOpioid overdose and total, medical, and drug spending (combined patient out-of-pocket and Medicare spending).ResultsOf 34 505 Medicare beneficiaries (17 927 [520%] male; 16 578 [48.1%] female; mean [SD] age, 49.5 [12.7] years; 168 [0.5%] Asian; 2949 [8.5%] Black; 2089 [6.0%] Hispanic; 266 [0.8%] Native American; 28 525 [82.7%] White; 508 [1.5%] other race), 11 524 beneficiaries (33.4%) experienced 1 or more buprenorphine treatment gaps. Treatment gap beneficiaries, compared with nontreatment gap beneficiaries, were more likely to be younger, be male, have a disability, and be Medicaid dual-eligible while less likely to be White, close to a buprenorphine prescriber, and treated with buprenorphine monotherapy (ie, buprenorphine hydrochloride). Beneficiaries were 2.89 (95% CI, 2.20-3.79) times more likely to experience an opioid overdose during buprenorphine treatment gap months compared with treated months. During treatment gap months, spending was $196.41 (95% CI, $110.53-$282.30) more than in treated months. Patients who continued to take buprenorphine dosages of greater than 8 mg/d and 16 mg/d were 2.61 and 2.84 times more likely to overdose in a treatment gap month, respectively, while patients taking buprenorphine dosages of 8 mg/d or less were 3.62 times more likely to overdose in a treatment gap month (maintenance of >16 mg/d: hazard ratio (HR), 2.64 [95% CI, 1.80-3.87]; maintenance of >8 mg/d: HR, 2.84 [95% CI, 2.13-3.78]; maintenance of ≤8 mg/d: HR, 3.62 [95% CI, 1.54-8.50]). Buprenorphine monotherapy was associated with greater risk of overdose and higher spending during treatment gaps months than buprenorphine/naloxone.Conclusions and RelevanceMedicare patients treated with buprenorphine between 2010 and 2017 had a lower associated opioid overdose risk and spending during treatment months than treatment gap months.

ImportanceIn 2020, the Centers for Medicare & Medicaid Services revised its national coverage determination, removing the requirement to obtain review from a Medicare-approved heart transplant center to implant a durable left ventricular assist device (LVAD) for bridge-to-transplant (BTT) intent at an LVAD-only center. The association between center-level transplant availability and access to heart transplant, the gold-standard therapy for advanced heart failure (HF), is unknown.ObjectiveTo investigate the association of center transplant availability with LVAD implant strategies and subsequent heart transplant following LVAD implant before the Centers for Medicare & Medicaid Services policy change.Design, Setting, and ParticipantsA retrospective cohort study of the Society of Thoracic Surgeons Intermacs multicenter US registry database was conducted from April 1, 2012, to June 30, 2020. The population included patients with HF receiving a primary durable LVAD.ExposuresLVAD center transplant availability (LVAD/transplant vs LVAD only).Main Outcomes and MeasuresThe primary outcomes were implant strategy as BTT and subsequent transplant by 2 years. Covariates that might affect listing strategy and outcomes were included (eg, patient demographic characteristics, comorbidities) in multivariable models. Parameters for BTT listing were estimated using logistic regression with center-level random effects and for receipt of a transplant using a Cox proportional hazards regression model with death as a competing event.ResultsThe sample included 22 221 LVAD recipients with a median age of 59.0 (IQR, 50.0-67.0) years, of whom 17 420 (78.4%) were male and 3156 (14.2%) received implants at LVAD-only centers. Receiving an LVAD at an LVAD/transplant center was associated with a 79% increased adjusted odds of BTT LVAD designation (odds ratio, 1.79; 95% CI, 1.35-2.38; P Conclusions and RelevanceReceiving an LVAD at an LVAD-transplant center was associated with increased odds of BTT intent at implant and subsequent transplant receipt for patients at 2 years. The findings of this study suggest that Centers for Medicare & Medicaid Services policy change may have the unintended consequence of further increasing inequities in access to transplant among patients at LVAD-only centers.

Highlights • Post-TAVR HRQOL shows more rapid short-term improvement than SAVR within trials. • Higher TAVR use requires better real-world TAVR/SAVR cost-effectiveness comparisons. • Wearable devices should be used in real-world settings to compare TAVR/SAVR HRQOL., Background Aortic stenosis is a prevalent valvular heart disease that is treated primarily by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR), which are common treatments for addressing symptoms secondary to valvular heart disease. This narrative review article focuses on the existing literature comparing recovery and cost-effectiveness for SAVR and TAVR. Methods Major databases were searched for relevant literature discussing HRQOL and cost-effectiveness of TAVR and SAVR. We also searched for studies analyzing the use of wearable devices to monitor post-discharge recovery patterns. Results The literature focusing on quality-of-life following TAVR and SAVR has been limited primarily to single-center observational studies and randomized controlled trials. Studies focused on TAVR report consistent and rapid improvement relative to baseline status. Common HRQOL instruments (SF-36, EQ-5D, KCCQ, MLHFQ) have been used to document that TF-TAVR is advantageous over SAVR at 1-month follow-up, with the benefits leveling off following 1 year. TF-TAVR is economically favorable relative to SAVR, with estimated incremental cost-effectiveness ratio values ranging from $50,000 to $63,000/QALY gained. TA-TAVR has not been reported to be advantageous from an HRQOL or cost-effectiveness perspective. Conclusions While real-world experiences are less described, large-scale trials have advanced our understanding of recovery and cost-effectiveness of aortic valve replacement treatment strategies. Future work should focus on scalable wearable device technology, such as smartwatches and heart-rate monitors, to facilitate real-world evaluation of TAVR and SAVR to support clinical decision-making and outcomes ascertainment.

Background: MicroRNAs (miRNAs) are important regulators of molecular pathways in psychiatric disease. Here, we examine differential miRNAs expression in lymphoblastoid cell lines (LCLs) derived from 10 individuals with autism spectrum disorder (ASD) and compare them to seven typically developing unrelated age- and gender-matched controls and 10 typically developing siblings. Small RNAseq analysis identified miRNAs, and selected miRNAs were validated using quantitative real-time polymerase reaction (qRT-PCR). KEGG analysis identified target pathways, and selected predicted mRNAs were validated using qRT-PCR. Results: Small RNAseq analysis identified that multiple miRNAs differentiated ASD from unrelated controls and ASD from typically developing siblings, with only one, hsa-miR-451a_R-1, being in common. Verification with qRT-PCR showed that miR-320a differentiated ASD from both sibling and unrelated controls and that several members of the miR-181 family differentiated ASD from unrelated controls. Differential expression of AKT2, AKT3, TNF α and CamKinase II predicted by KEGG analysis was verified by qRT-PCR. Expression of CamKinase II βwas found to be correlated with the severity of stereotyped behavior of the ASD participants. Conclusions: This study provides insight into the mechanisms regulating molecular pathways in individuals with ASD and identifies differentiated regulated genes involved in both the central nervous system and the immune system.

Current guidelines recommend restricting acetaminophen (APAP) use in patients with cirrhosis, but evidence to support that recommendation is lacking. Prior studies focused on pharmacokinetics (PK) of APAP in cirrhosis but did not rigorously examine clinical outcomes, sensitive biomarkers of liver damage, or serum APAP‐protein adducts, which are a specific marker of toxic bioactivation. Hence, the goal of this pilot study was to test the effects of regularly scheduled APAP dosing in a well‐defined compensated cirrhosis group compared to control subjects without cirrhosis, using the abovementioned outcomes. After a 2‐week washout, 12 subjects with and 12 subjects without cirrhosis received 650 mg APAP twice per day (1.3 g/day) for 4 days, followed by 650 mg on the morning of day 5. Patients were assessed in‐person at study initiation (day 1) and on days 3 and 5. APAP‐protein adducts and both conventional (alanine aminotransferase) and sensitive (glutamate dehydrogenase [GLDH], full‐length keratin 18 [K18], and total high‐mobility group box 1 protein) biomarkers of liver injury were measured in serum on the mornings of days 1, 3, and 5, with detailed PK analysis of APAP, metabolites, and APAP‐protein adducts throughout day 5. No subject experienced adverse clinical outcomes. GLDH and K18 were significantly different at baseline but did not change in either group during APAP administration. In contrast, clearance of APAP‐protein adducts was dramatically delayed in the cirrhosis group. Minor differences for other APAP metabolites were also detected. Conclusion: Short‐term administration of low‐dose APAP (650 mg twice per day, The safety of acetaminophen (APAP) use in cirrhosis is highly controversial. In this study, we compared novel, sensitive biomarkers of liver injury and pharmacokinetics between non‐cirrhotic and cirrhotic subjects with repeated APAP use over 5 days. There was no APAP‐induced liver damage in either group, but there was evidence of greater APAP‐protein binding and reduced APAP‐protein adduct clearance in the cirrhosis group that warrants caution and further study.