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Background Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. Methods One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman’s correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. Results Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. Conclusions The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

States have the latitude to mandate coverage of diabetes self-management education (DSME) services for privately insured and Medicaid patients. The impact of these mandates on the supply of DSME resources is unknown. This study compared changes in the supply of DSME programs and program sites accredited by the American Association for Diabetes Educators (AADE) and certified diabetes educators (CDE) between states that did and did not mandate benefits for DSME. Using a unique combination of legal and programmatic data sources, the authors employed fixed effects regression models with clustered robust standard errors to compare changes in the supply of AADE-accredited DSME programs, program sites, and CDEs in states that mandated benefits with states that did not. Given the variation in state mandates, models also estimated the impact of "flexible" reimbursement provisions on the supply of resources among adopting states. The supply of DSME resources has increased over time, but results indicate that mandated benefits were not a significant driver of these changes in the supply. The impact of flexible reimbursement provisions varied. Interestingly, provisions of the Affordable Care Act were associated with an increased supply of resources. Results suggest that extending benefits to previously insured patients does not increase the supply of DSME resources, but a rapid increase in patients entering the health system does encourage growth.

Many communities are developing innovative forms of collaborative organizations such as multi-sector health care alliances (MHCAs) to address problems of misaligned incentives among providers, payers, and community stakeholders and improve health and health care. Member engagement is essential to the success of these organizations due to their dependence on volunteer members to develop and implement strategy and provide material and in-kind support for alliance efforts, yet relatively little research has examined how alliances can foster engagement. This study examined behavioral indicators of member engagement (e.g., recruitment and retention of organizational and individual members) and how they are related to two foundational dimensions of alliance functioning – alliance leadership and community centrality. Using three rounds of an internet-based survey of alliance members from 14 alliances, the study found that organizational recruitment and retention increased over time, from 26.6% to 41.5% and 56.0% to 65.2%, respectively. Recruitment of individuals increased over the study period (38.3% to 47.2%, while retention of individual members declined over the study period (61.0% to 53.2%). Alliance leadership was associated with lower levels of recruitment (both organizational and individual members) but higher levels of organizational retention (both organizational and individual members). Collectively, our findings suggest that behavioral aspects of alliances are more effective at retaining members than relatively stable characteristics such as size and positioning in the community. Contrasting relationships between recruitment and retention, however, suggest that different forms of leadership may be required to simultaneously attract new members while retaining existing ones.

Objectives This study measured the likelihood of adult patients with diabetes being referred to diabetes self-management education (DSME) when "in need" according to clinical guidelines and identified which types of clinical need predict a greater likelihood of provider referral to DSME. Study design This repeated cross-sectional analysis utilized patient electronic health records (EHRs) and a statewide health information exchange database to examine a 7-year panel (2010-2016) of adult patients with diabetes. Our analytic sample included 8782 adult patients with diabetes with a total of 356,631 encounters. Methods Fixed-effects linear probability models with clustered robust standard errors estimated the association between patients' need for DSME and likelihood of being referred to the service. Models controlled for patients' health status, prior utilization, encounter setting, comorbidity risk scores, the state's expansion of Medicaid, and the count of accredited DSME program sites in the community. Results Most patient encounters indicated at least 1 type of need for DSME, but less than 7% of those encounters with a documented need resulted in a provider referral. In regression analysis, clinical indicators of need increased the likelihood that patients would be referred to DSME. Patients exhibiting multiple types of need were most likely to be referred to DSME. Conclusions Although findings indicate that patient need for DSME does improve the likelihood of being referred, provider referral rates were significantly lower than anticipated. Future research should explore barriers to clinical guideline adherence and whether clinical decision support in EHR systems can facilitate provider referrals.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub ( https://covid19forecasthub.org/ ) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

BNT162b1 is a lipid nanoparticle-formulated, nucleoside-modified mRNA SARS-CoV-2 vaccine. Here, we report safety and immune persistence data following a primary two-dose vaccination schedule administered 21 days apart.Immune persistence was determined at month 3 in 72 younger participants (aged 18-55 years) and at month 6 in 70 younger and 69 older participants (aged 65-85 years).In younger participants, neutralizing antibody (nAb) geometric mean titers (GMTs) for the 10 and 30 µg dose levels declined from 233 and 254 (21 days after dose 2) to 55 and 87 at month 3, respectively, and to 16 and 27 at month 6, respectively. In older participants, nAb GMTs declined from 80 and 160 (21 days after dose 2) to 10 and 21 at month 6. Overall, higher antibody titers were observed in younger participants, and the 30 µg dose induced higher levels of nAb, which declined more slowly by month 6. No serious adverse events were reported in the vaccine group.This study showed BNT162b1 maintains a favorable safety profile in younger and older participants in the 6 months after vaccination. This study further extends our understanding of immune persistence and the safety of the BNT162b1 vaccine as a candidate vaccine in the BioNTech pipeline.NCT04523571, registered August 21, 2020.

Objective To explore why and how health systems are engaging in care delivery redesign (CDR)-defined as the variety of tools and organizational change processes health systems use to pursue the Triple Aim. Study setting A purposive sample of 24 health systems across 4 states as part of the Agency for Healthcare Research and Quality's Comparative Health System Performance Initiative. Study design An exploratory qualitative study design to gain an "on the ground" understanding of health systems' motivations for, and approaches to, CDR, with the goals of identifying key dimensions of CDR, and gauging the depth of change that is possible based on the particular approaches to redesign care being adopted by the health systems. Data collection Semi-structured telephone interviews with health system executives and physician organization leaders from 24 health systems (n = 162). Principal findings We identify and define 13 CDR activities and find that the health systems' efforts are varied in terms of both the combination of activities they are engaging in and the depth of innovation within each activity. Health system executives who report strong internal motivation for their CDR efforts describe more confidence in their approach to CDR than those who report strong external motivation. Health system leaders face uncertainty when implementing CDR due to a limited evidence base and because of the slower than expected pace of payment change. Conclusions The ability to validly and reliably measure CDR activities-particularly across varying organizational contexts and markets-is currently limited but is key to better understanding CDR's impact on intended outcomes, which is important for guiding both health system decision making and policy making.

Background Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. Case presentation This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient’s condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. Conclusions When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

How to overcome multiple obstacles to achieve the efficient and safe delivery of therapeutic genes is still the key to gene therapy. To address this issue, a cationic carrier consisting of polyamide-amine (HPAA-peptide-Fc) modified by an enzyme-responsive polypeptide as the core and hyperbranched polyglycerol derivative (CD-HPG) as the shell was synthesized by self-assembly. The obtained HPAA-peptide-HPG could form the compact nanocomplex with siPlk1, thus confirming the stable load of genes and subsequent targeted gene delivery. And the nanogenes could significantly induce apoptotic effect via the down-expression of Plk1 protein in breast cancer cells. Moreover, compared to polyethylenimine, HPAA-peptide-HPG exhibited superior biocompatibility through hemolysis and cell viability assays because of the shielding function of CD-HPG, thereby being beneficial to increasing the circulation time of the complex when administrated in vivo. Such an efficient and safe gene delivery complex (HPAA-peptide-HPG) presents a good example of rational design of cationic supramolecular vesicles for stimulus-responsive siRNA transport, which should be encouraged in cancer gene therapy.

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-γ T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population.

Objective We quantify the use of clinical decision support (CDS) and the specific barriers reported by ambulatory clinics and examine whether CDS utilization and barriers differed based on clinics’ affiliation with health systems, providing a benchmark for future empirical research and policies related to this topic. Materials and Methods Despite much discussion at the theoretic level, the existing literature provides little empirical understanding of barriers to using CDS in ambulatory care. We analyze data from 821 clinics in 117 medical groups, based on in Minnesota Community Measurement’s annual Health Information Technology Survey (2014-2016). We examine clinics’ use of 7 CDS tools, along with 7 barriers in 3 areas (resource, user acceptance, and technology). Employing linear probability models, we examine factors associated with CDS barriers. Results Clinics in health systems used more CDS tools than did clinics not in systems (24 percentage points higher in automated reminders), but they also reported more barriers related to resources and user acceptance (26 percentage points higher in barriers to implementation and 33 points higher in disruptive alarms). Barriers related to workflow redesign increased in clinics affiliated with health systems (33 points higher). Rural clinics were more likely to report barriers to training. Conclusions CDS barriers related to resources and user acceptance remained substantial. Health systems, while being effective in promoting CDS tools, may need to provide further assistance to their affiliated ambulatory clinics to overcome barriers, especially the requirement to redesign workflow. Rural clinics may need more resources for training.

Background: Previous infectious or inflammatory events may be involved in the pathogenesis of neuromyelitis optica (NMO), potentially by triggering an autoimmune response. Cytomegalovirus (CMV)-related NMO (CMV-NMO) is rarely reported. Acute hemorrhagic rectal ulcer (AHRU) is a rare disease with a largely unknown pathogenesis. Herein, we reported a co-NMO and AHRU case associated with CMV infection. In addition, we review previously reported cases of CMV-NMO and CMV-AHRU. Case presentation: A 40-year-old female diagnosed with aquaporin4 (AQP4)-IgG+ NMO and a poor response to high-dose intravenous methylprednisolone and immunoglobulin, followed by three rounds of plasma exchange was transferred to Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. She developed repeated acute lower gastrointestinal hemorrhage from the third day of admission. Abdominal computed tomography angiography (CTA) and interventional angiography did not detect any bleeding vessel. Bedside colonoscopy revealed a large ulcer-like lesion at 10 cm above the anus. Rectal biopsy pathology confirmed a CMV infection on day 23 post-admission, and cerebrospinal fluid (CSF) pathogen gene sequencing detected CMV gene copies on day 25 post-admission. After 2 weeks of treatment with ganciclovir and sodium phosphinate, the patient's lower gastrointestinal bleeding stopped, and her limb muscle strength and visual acuity gradually improved. After 4 weeks of antiviral therapy, colonoscopy showed that the intestinal wall of the original lesion was smooth. Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) of a biopsy specimen was negative for CMV, her right eye vision was normal, and limb muscle strength had recovered. Serum AQP4-IgG was negative, and lesions on brain magnetic resonance imaging (MRI) manifested shrinkage. Conclusions: The benefits of antiviral therapy remain unclear; however, clinicians should be aware of the possibility of CMV-related NMO, if NMO was refractory to high-dose intravenous methylprednisolone, immunoglobulin, and plasma exchange. Moreover, clinicians should consider the possibility of CMV-related AHRU when recurrent acute lower gastrointestinal bleeding occurs in a patient.

Feature selection plays a vital role in the detection and discrimination of epileptic seizures in electroencephalogram (EEG) signals. The state-of-the-art EEG classification techniques commonly entail the extraction of the multiple features that would be fed into classifiers. For some techniques, the feature selection strategies have been used to reduce the dimensionality of the entire feature space. However, most of these approaches focus on the performance of classifiers while neglecting the association between the feature and the EEG activity itself. To enhance the inner relationship between the feature subset and the epileptic EEG task with a promising classification accuracy, we propose a machine learning-based pipeline using a novel feature selection algorithm built upon a knockoff filter. First, a number of temporal, spectral, and spatial features are extracted from the raw EEG signals. Second, the proposed feature selection algorithm is exploited to obtain the optimal subgroup of features. Afterwards, three classifiers including [Formula: see text]-nearest neighbor (KNN), random forest (RF) and support vector machine (SVM) are used. The experimental results on the Bonn dataset demonstrate that the proposed approach outperforms the state-of-the-art techniques, with accuracy as high as 99.93% for normal and interictal EEG discrimination and 98.95% for interictal and ictal EEG classification. Meanwhile, it has achieved satisfactory sensitivity (95.67% in average), specificity (98.83% in average), and accuracy (98.89% in average) over the Freiburg dataset.

Background Numerous studies have assessed the association between xeroderma pigmentosum complementation group C (XPC) polymorphisms and susceptibility of prostate cancer (PCa); however, the findings remain inconsistent. Methods We performed an updated analysis utilizing data from electronic databases to obtain a more accurate estimation of the relationship between XPC rs2228001 A/C polymorphism and PCa risk. We further used in silico tools to investigate this correlation. Results Totally, 5,305 PCa cases and 6,499 control subjects were evaluated. When all studies pooled together, we detected no positive result (recessive genetic model: OR = 1.14, 95% CI = 0.93-1.40, Pheterogeneity = 0.001, P = .212); nevertheless, the XPC rs2228001 A/C variant was associated with PCa risk in Asian descendants in the subgroup analysis (OR = 1.21, 95% CI = 1.01-1.43, Pheterogeneity = 0.008, P = .034). In silico tools showed that more than 20 proteins can participate in the protein crosstalk with XPC. The expression of XPC was down-regulated in all Gleason scores of prostate cancer. Conclusions The present study indicated that the XPC rs2228001 A/C variant may be associated with elevated PCa risk in Asian patients.

Objectives The adoption and use of health information technology (IT) by health systems in ambulatory care can be an important driver of care quality. We examine recent trends in health IT adoption by health system-affiliated ambulatory clinics in the context of the federal government's Meaningful Use and Promoting Interoperability programs. Study design We analyzed a national sample of 17,861 ambulatory clinics affiliated with 1711 health systems, using longitudinal data (2014-2016) from the HIMSS Analytics annual surveys. Methods We used descriptive analyses and linear probability models to examine the adoption of electronic health records (EHRs), as well as 16 specific functionalities, at the clinic level and the system level. We compared the differential trends of adoption by various characteristics of health systems. Results We find that the adoption of an EHR certified by the Office of the National Coordinator for Health IT (ONC) increased from 73% to 91%. However, in 2016, only 38% of clinics reported having all 16 health IT functionalities included in this study. Small health systems lag behind large systems in ambulatory health IT adoption. Patient-facing functionalities were less likely to be adopted than those oriented toward physicians. Health information exchange capabilities are still low among ambulatory clinics, pointing to the importance of the ONC's recent Promoting Interoperability initiative. Conclusions The relatively low uptake of health IT functionalities important to care improvement suggests substantial opportunities for further improving adoption of ambulatory health IT even among the current EHR users.

OBJECTIVE The objective of this study was to measure the dissemination of comparative provider quality information (CPQI) and evaluate its impact on consumers' awareness and use of CPQI. DATA SOURCES Two-period, random-digit-dial panel survey of chronically ill consumers residing in 14 regions of the United States; summaries of CPQI dissemination activities of regional multistakeholder alliances; and the LexisNexis Academic and Access World News databases. STUDY DESIGN/METHODS Fixed effects regression to isolate the effect of CPQI producers' dissemination activities and the print media's CPQI coverage on chronically ill consumers' self-reported awareness and use of CPQI. PRINCIPAL FINDINGS Direct CPQI dissemination had no overall effect on either awareness or use of CPQI. One unit increase in the media coverage of an Aligning Forces for Quality (AF4Q) multistakeholder alliance report increased consumer awareness and use of CPQI by 1.4 percentage points (P=0.049) and 1.1 percentage points (P=0.009), respectively. Similar increases for the Centers for Medicare and Medicaid Services (CMS) CPQI and for the nonalliance, non-CMS CPQI improved CPQI use by 1.6 percentage points (P

Background Computerized provider order entry (CPOE) can help providers deliver better quality care. We aimed to understand recent trends in use of CPOE by health system-affiliated ambulatory clinics. Methods We analyzed longitudinal data (2014–2016) for 19,109 ambulatory clinics that participated in all 3 years of the Healthcare Information and Management Systems Society Analytics survey to assess use of CPOE and identify characteristics of clinics associated with CPOE use. We calculated descriptive statistics to examine overall trends in use, location of order entry (bedside vs. clinical station), and system-level use CPOE across all clinics. We used linear probability models to explore the association between clinic characteristics (practice size, practice type, and health system type) and two outcomes of interest: CPOE use at any point between 2014 and 2016, and CPOE use beginning in 2015 or 2016. Results Between 2014 and 2016, use of CPOE increased more than 9 percentage points from 58 to 67%. Larger clinics and those affiliated with multi-hospital health systems were more likely to have reported use of CPOE. We found no difference in CPOE use by primary care versus specialty care clinics. When used, most clinics reported using CPOE for most or all of their orders. Health systems that used CPOE usually did so for all system-affiliated clinics. Conclusions Small practice size or not being part of a multi-hospital system are associated with lower use of CPOE between 2014 and 2016. Less than optimal use in these environments may be harming patient outcomes.

Key Points Question Is the adoption of more advanced electronic health record (EHR) capabilities associated with better ambulatory clinical quality of care? Findings In cross-sectional analyses of 3 states from 2014 to 2017, ambulatory clinics (769-972 per year) with more advanced EHR capabilities had higher scores on a composite measure of ambulatory clinical quality than did other clinics, which translated into an approximately 9% difference in rank order of quality. Across the much smaller number of clinics that gained advanced EHR capabilities between 2014 and 2017 (n = 72), the composite of ambulatory clinical quality improved more than for other clinics, but the difference was not statistically significant. Meaning This study suggests that ambulatory clinics with advanced EHR capabilities were associated with a better performance on a composite measure of ambulatory clinical quality than clinics with less-advanced EHR capabilities; clinics that adopted advanced EHR capabilities during a 3-year period were not associated with significant increases in ambulatory clinical quality performance., Importance Electronic health records (EHRs) are widely promoted to improve the quality of health care, but information about the association of multifunctional EHRs with broad measures of quality in ambulatory settings is scarce. Objective To assess the association between EHRs with different degrees of capabilities and publicly reported ambulatory quality measures in at least 3 clinical domains of care. Design, Setting, and Participants This cross-sectional and longitudinal study was conducted using survey responses from 1141 ambulatory clinics in Minnesota, Washington, and Wisconsin affiliated with a health system that responded to the Healthcare Information and Management Systems Society Annual Survey and reported performance measures in 2014 to 2017. Statistical analysis was performed from July 10, 2019, through February 26, 2021. Main Outcomes and Measures A composite measure of EHR capability that considered 50 EHR capabilities in 7 functional domains, grouped into the following ordered categories: no functional EHR, EHR underuser, EHR, neither underuser or superuser, EHR superuser; as well as a standardized composite of ambulatory clinical performance measures that included 3 to 25 individual measures (median, 13 individual measures). Results In 2014, 381 of 746 clinics (51%) were EHR superusers; this proportion increased in each subsequent year (457 of 846 clinics [54%] in 2015, 510 of 881 clinics [58%] in 2016, and 566 of 932 clinics [61%] in 2017). In each cross-sectional analysis year, EHR superusers had better clinical quality performance than other clinics (adjusted difference in score: 0.39 [95% CI, 0.12-0.65] in 2014; 0.29 [95% CI, −0.01 to 0.59] in 2015; 0.26 [95% CI, –0.05 to 0.56] in 2016; and 0.20 [95% CI, –0.04 to 0.45] in 2017). This difference in scores translates into an approximately 9% difference in a clinic’s rank order in clinical quality. In longitudinal analyses, clinics that progressed to EHR superuser status had only slightly better gains in clinical quality between 2014 and 2017 compared with the gains in clinical quality of clinics that were static in terms of their EHR status (0.10 [95% CI, −0.13 to 0.32]). In an exploratory analysis, different types of EHR capability progressions had different degrees of associated improvements in ambulatory clinical quality (eg, progression from no functional EHR to a status short of superuser, 0.06 [95% CI, −0.40 to 0.52]; progression from EHR underuser to EHR superuser, 0.18 [95% CI, −0.14 to 0.50]). Conclusions and Relevance Between 2014 and 2017, ambulatory clinics in Minnesota, Washington, and Wisconsin with EHRs having greater capabilities had better composite measures of clinical quality than other clinics, but clinics that gained EHR capabilities during this time had smaller increases in clinical quality that were not statistically significant., This cross-sectional study assesses the association between electronic health records with different degrees of capabilities and publicly reported ambulatory quality measures in at least 3 clinical domains of care.

As the opioid epidemic has drawn increased attention, many researchers are attempting to estimate the financial burden of opioid misuse. These estimates have become particularly relevant as state and local governments have begun to take legal action against pharmaceutical manufacturers, distributors, and others who are identified as being potentially responsible for the worsening epidemic. An important category of costs includes those related to the effect of opioid misuse on labor market outcomes and productivity. Most published estimates of opioid-attributable productivity losses estimate the financial burden borne by society, failing to distinguish between costs internalized by individuals and those that spill over to third parties, such as state and federal governments. This article provides an overview and a conceptual framework for 2 types of labor market-related costs borne by state and federal governments that typically have not been incorporated into existing estimates, which may represent important categories of expenditures. Because detailed estimates of lost tax revenue are available elsewhere, this article focuses largely on whether, and how, to incorporate opioid-related expenses incurred by means-tested government programs into more general estimates of the economic harm created by the opioid epidemic.

Purpose Multisector health care alliances (alliances) are increasingly viewed as playing an important role in improving the health and health care of local populations, in part by disseminating innovative practices, yet alliances face a number of challenges to disseminating these practices beyond a limited set of initial participants. The purpose of this paper is to examine how alliances attempt to disseminate innovative practices and the facilitating and inhibiting factors that alliances confront when trying to do so. Design/methodology/approach The authors adopted multiple holistic case study design of eight alliances with a maximum variation case selection strategy to reflect a range of structural and geographic characteristics. Semi-structured interviews with staff, leaders and board members were used. Findings The findings show that dissemination is a multidirectional process that is closely if not inextricably intertwined with capacity- and context-related factors (of the alliance, partnering organizations and target organizations). Thus, standardized approaches to dissemination are likely the exception and not the rule, and highlight the value of existing frameworks as a starting point for conceptualizing the important aspects of dissemination, but they are incomplete in their description of the “on-the-ground” dissemination processes that occur in the context of collaborative organizational forms such as alliances. Originality/value Despite a rapidly expanding evidence base to guide clinical and managerial decision making, this knowledge often fails to make its way into routine practice. Consequently, the search for effective strategies to reduce this gap has accelerated in the past decade. This study sheds light on those strategies and the challenges to implementing them.

International audience; Multispectral Imaging (MSI) provides a sequence of en-face fundus spectral slices and allows for the examination of structures and signatures throughout the thickness of retina to characterize diabetic retinopathy (DR) lesions comprehensively. Manual interpretation of MSI images is commonly conducted by qualitatively analyzing both the spatial and spectral properties of multiple spectral slices. Meanwhile, there exist few computerbased algorithms that can effectively exploit the spatial and spectral information of MSI images for the diagnosis of DR. We propose a new approach that can quantify the spatialspectral features of MSI retinal images for automatic DR lesion segmentation. It combines a generalized low-rank approximation of matrices (GLRAM) with a supervised regularization term (SRT) to generate low-dimensional spatial-spectral representations using the feature vectors in all spectral slices. Experimental results showed that the proposed approach is very effective for the segmentation of DR lesions in MSI images, which suggests it as an interesting tool for assisting ophthalmologists in diagnosing, analyzing, and managing DR lesions in MSI.

The main purpose of this study was to estimate the tax revenue lost by state and federal governments as a result of adverse labor market outcomes attributable to opioid misuse.We pair existing, plausibly causal estimates of the effect of opioid misuse on the decline in the labor force from 2000 to 2016 with a variety of data sources to compute tax revenues lost by state and federal governments using the online TAXSIM calculator.We find that between 2000 and 2016, opioid misuse cost state governments $11.8 billion, including $1.7 billion in lost sales tax revenue and $10.1 billion in lost income tax revenue. In addition, the federal government lost $26.0 billion in income tax revenue.By omitting lost tax revenue due to labor force exits, prior studies have missed an important component of opioid-related costs borne by state and federal governments.As more states and the federal government contemplate litigation for opioid-related damages, lost tax revenue represents an important cost that could be recouped and allocated to opioid prevention and treatment programs.

There is growing interest in the use of intersectoral collaboration (e.g., alliances, coalitions, partnerships) to address complex, health-related issues in local communities. Relatively little empirical research, however, has examined how to foster and sustain collaboration across sectors during later stages of development, despite a recognition that the needs and goals for collaboration may change over time. The purpose of this study was to address this gap by examining the perceptions of alliance participants regarding the importance of collaborating with different industry sectors as alliances transitioned from stable, prescriptive foundation support to a more uncertain future. Our findings suggest that, in addition to the contextual characteristics highlighted in previous research, the perceived importance of intersectoral collaboration varies for different types of alliances and participants. Moreover, the salience of these characteristics varied for different types of collaboration, in our case, collaboration with nonmedical health care sectors and nonhealth care sectors. Collectively, our findings point to the importance of thinking more comprehensively, across multiple levels of influence, when considering ways to foster or sustain intersectoral collaboration.

Background Ara h 1 is a major food allergen in peanuts. Recently, many studies have revealed that the Maillard reaction (MR) affects the allergenicity of food proteins. Results To investigate the influence of the MR on the allergenicity of Ara h 1, R-Ara h 1 was processed with glucose in dry heating conditions for different periods. The extent of the MR was assessed by four methods. The changes in secondary and tertiary structures were characterized through spectroscopy assays. Advanced glycation end products (AGE) structures were identified by protein sample dry heating for 60 min, indicating the formation of AGE-Ara h 1. Simulated gastric fluid (SGF) digestion analysis showed that AGE-Ara h 1 has higher resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model was also utilized to explore the effect of the MR on the allergenicity of Ara h 1, and the results showed that the Th2-type cytokines, antibodies, and histamine content increased, and there was a greater degree of degranulation of rat basophilic leukemia (RBL) cells in the AGE-Ara h 1 group compared with the R-Ara h 1 group. Conclusion During the process of dry heating, proteins participated in the MR with changes in secondary and tertiary structures. The condition applying a temperature of 100 °C for 60 min caused the formation of AGE-Ara h 1. Simulated gastric fluid digestion analysis showed that AGE-Ara h 1 had a greater resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model showed that AGE-Ara h 1 had more allergenicity, indicating that the MR could enhance the allergenicity of Ara h 1. © 2020 Society of Chemical Industry.

Background Despite significant investments in health information technology (IT), the technology has not yielded the intended performance effects or transformational change. We describe activities that health systems are pursuing to better leverage health IT to improve performance. Methods We conducted semi-structured telephone interviews with C-suite executives from 24 U.S. health systems in four states during 2017–2019 and analyzed the data using a qualitative thematic approach. Results Health systems reported two broad categories of activities: laying the foundation to improve performance with IT and using IT to improve performance. Within these categories, health systems were engaged in similar activities but varied greatly in their progress. The most substantial effort was devoted to the first category, which enabled rather than directly improved performance, and included consolidating to a single electronic health record (EHR) platform and common data across the health system, standardizing data elements, and standardizing care processes before using the EHR to implement them. Only after accomplishing such foundational activities were health systems able to focus on using the technology to improve performance through activities such as using data and analytics to monitor and provide feedback, improving uptake of evidence-based medicine, addressing variation and overuse, improving system-wide prevention and population health management, and making care more convenient. Conclusions and implications Leveraging IT to improve performance requires significant and sustained effort by health systems, in addition to significant investments in hardware and software. To accelerate change, better mechanisms for creating and disseminating best practices and providing advanced technical assistance are needed.

Objective To determine if the release of health care report cards focused on physician practice quality measures leads to changes in consumers’ awareness and use of this information. Primary Data Sources Data from two rounds of a survey of the chronically ill adult population conducted in 14 regions across the United States, combined with longitudinal information from a public reporting tracking database. Both data were collected as part of the evaluation for Aligning Forces for Quality, a nationwide quality improvement initiative funded by the Robert Wood Johnson Foundation. Study Design Using a longitudinal design and an individual-level fixed effects modeling approach, we estimated the impact of community public reporting efforts, measured by the availability and applicability of physician quality reports, on consumers’ awareness and use of physician quality information (PQI). Principal Findings The baseline level of awareness was 12.6 percent in our study sample, drawn from the general population of chronically ill adults. Among those who were not aware of PQI at the baseline, when PQI became available in their communities for the first time, along with quality measures that are applicable to their specific chronic conditions, the likelihood of PQI awareness increased by 3.8 percentage points. For the same group, we also find similar increases in the uses of PQI linked to newly available physician report cards, although the magnitudes are smaller, between 2 and 3 percentage points. Conclusions Specific contents of physician report cards can be an important factor in consumers’ awareness and use of PQI. Policies to improve awareness and use of PQI may consider how to customize quality report cards and target specific groups of consumers in dissemination.

Background Multi-stakeholder alliances – groups of payers, purchasers, providers, and consumers that work together to address local health goals – are frequently used to improve health care quality within communities. Under the Aligning Forces for Quality (AF4Q) initiative, multi-stakeholder alliances were given funding and technical assistance to encourage the use of health information technology (HIT) to improve quality. We investigated whether HIT adoption was greater in AF4Q communities than in other communities. Methods Drawing upon survey data from 782 small and medium-sized physician practices collected as part of the National Study of Physician Organizations during July 2007 – March 2009 and January 2012—November 2013, we used weighted fixed effects models to detect relative changes in four measures representing three domains: use of electronic health records (EHRs), receipt of electronic information from hospitals, and patients’ online access to their medical records. Results Improvement on a composite EHR adoption measure was 7.6 percentage points greater in AF4Q communities than in non-AF4Q communities, and the increase in the probability of adopting all five EHR capabilities was 23.9 percentage points greater in AF4Q communities. There was no significant difference in improvement in receipt of electronic information from hospitals or patients’ online access to medical records between AF4Q and non-AF4Q communities. Conclusion By linking HIT to quality improvement efforts, AF4Q alliances may have facilitated greater adoption of EHRs in small and medium-sized physician practices, but not receipt of electronic information from hospitals or patients’ online access to medical records. Implications Multi-stakeholder alliances charged with promoting HIT to advance quality improvement may accelerate adoption of EHRs.

To improve health care quality within communities, increasing numbers of multistakeholder alliances-groups of payers, purchasers, providers, and consumers-have been created. We used data from two rounds (conducted in July 2007-March 2009 and January 2012-November 2013) of a large nationally representative survey of small and medium-size physician practices. We examined whether the adoption of patient-centered medical home processes spread more rapidly in fourteen Robert Wood Johnson Foundation Aligning Forces for Quality communities, where multistakeholder health care alliances promoted their use, than in other communities. We found no difference in the overall growth of adoption of the processes between the two types of communities. However, improvement on a care coordination subindex was 7.17 percentage points higher in Aligning Forces for Quality communities than in others. Despite the enthusiasm for quality improvement led by multistakeholder alliances, such alliances may not be a panacea for spreading patient-centered medical home processes across a community.

Background: Collaborative forms of organizations such as multisectoral health care alliances play an increasingly prominent role in the U.S. health care system. A key feature of these organizations highlighted in previous research is leadership, yet little research has examined what happens when there is a change in leadership. Purpose: The aim of this study was to examine the relationship between leadership transitions in an alliance and member assessments of the benefits and costs of participation, indicators of the value that members derive from their involvement in the alliance. Methodology/Approach: The study used quantitative data collected from three rounds of surveys of alliance members participating in the Robert Wood Johnson Foundation’s Aligning Forces for Quality Program. Qualitative interview data supplemented this analysis by providing examples of why leadership transitions may affect participation benefits and costs. Findings: Quantitative analysis indicated that alliance members who experienced a change in leadership reported both higher and lower levels of participation benefits and costs, depending on the type of leadership change (i.e., alliance leader vs. programmatic leader). Qualitative analysis suggested that the scope of responsibilities of different types of leaders plays an important role in how members perceive changes. Likewise, interviews indicated that timing influences how disruptive a leadership transition is and whether it is perceived positively or negatively. Practice Implications: Leadership transitions present both challenges and opportunities; whether the effects are felt positively or negatively depends on when a transition occurs and how it is handled by incoming leaders and remaining members. Furthermore, different types of members report higher levels of participation benefits and lower levels of participation costs, suggesting that efforts to maintain a sense of alliance value during times of transitions may be able to target certain types of individuals.

Purpose The purpose of this paper is to examine the relationship between different aspects of alliance funding profiles (e.g. range of sources, dependence on specific sources) and participant’ perceptions of how well the organization is positioned for the future. Design/methodology/approach A mixed method study in the context of eight alliances participating in the Robert Wood Johnson Foundation’s Aligning Forces for Quality program. Data collection approaches included surveys of alliance participants and semi-structured interviews with alliance leaders. Findings The findings indicate that dependence on grant revenues, in particular, may be problematic for how well alliances are positioned for sustainability. While a number of approaches were identified to reduce dependence on grants, implementing these strategies presented more of a challenge for alliances due to the contextual demands of their external environment and a need to strike a balance between pursuing alternative revenue sources and fidelity to the mission and identity of the organization. Practical implications Alliance leaders need to have not only a broad and accurate understanding of their external environment, but also an appreciation of the alliance’s identity in that environment. Collectively, the findings can help organizational leaders be more informed about their funding choices and the implications those choices have for the future of their organization. Originality/value Collaborative forms of organizations (e.g. alliances, coalitions, networks) are increasingly viewed as an effective means of addressing complex, multifaceted health, and social challenges. For collaborative organizations that depend on the coordinated efforts of volunteers, addressing such complex issues is predicated on sustaining programmatic activities as well as the interest and participation of stakeholders over extended periods of time. This study sheds light on how leaders of these organizations may improve their prospects for sustainability.

Despite growing investment in producing and releasing comparative provider quality information (CQI), consumer use of CQI has remained poor. We offer a framework to interpret and synthesize the existing literature’s diverse approaches to explaining the CQI’s low appeal for consumers. Our framework cautions CQI stakeholders against forming unrealistic expectations of pervasive consumer use and suggests that they focus their efforts more narrowly on consumers who may find CQI more salient for choosing providers. We review the consumer impact of stakeholder efforts to apply the burgeoning knowledge of consumers’ cognitive limitations to the design and dissemination of the new generation of report cards; we conclude that while it is too limited to draw firm conclusions, early evidence suggests consumers are responding to the novel design and dissemination strategies. We find that consumers continue to have difficulty accessing reliable report cards, while the media remains underused in the dissemination of report cards.

Peanut allergy is one of the most common food allergies worldwide. Studies have shown that the incidence of peanut allergies in Western-born Asians is higher than that in Asia-born Asians. Notably, Europeans and Americans mostly eat roasted peanuts, whereas Asians mostly eat boiled or fried peanuts.BALB/c mice were sensitized using purified protein from raw, roasted or boiled peanuts, then fed the same by oral gavage. The relevant allergic reactions were studied using BALB/c mice model, including a rat basophilic leukemia (RBL) cell model, simulated gastric fluid experiments, and ultraviolet (UV) and circular dichroism (CD) spectral analysis. Serological studies showed increased levels of immunoglobulin E, interleukin-4 and interleukin-5, and pathological studies showed mast cell degranulation and inflammatory changes in jejunal tissues, with an increase in thymic stromal lymphopoietin (TSLP) gene expression in all treatment groups compared with the control group (phosphate-buffered saline). Compared with the raw peanut group, sera from the roasted peanut group produced a significant increase in RBL β-hexosaminidase A release in vitro, and roasted peanuts showed increased resistance to digestion in simulated gastric fluid experiments. Ultraviolet and CD spectral analyses showed that the roasting and boiling processes altered the structure of the major peanut allergens, which may have contributed to the differences observed in peanut allergenicity.Our findings indicate that peanut allergies are related to peanut thermal processing methods. In our mouse model, the raw, roasted and boiled peanuts elicited different degrees of allergic response. Compared with raw peanut, roasted peanuts show a higher allergenicity, whereas the boiled peanuts show a lower allergenicity. © 2018 Society of Chemical Industry.

Although intervention dose—defined as the quality and quantity of an intervention and participation—might be key to understanding why some multisite quality improvement (QI) initiatives work and others do not, evaluations rarely consider dose, and there is no widely accepted method for measuring it. In this exploratory study, the authors examined the literature on QI dose, identified four methods for measuring QI dose, applied them to 14 communities participating in a QI initiative, examined whether the dose scores aligned with perceptions of QI dose among individuals knowledgeable of the initiative, and report on lessons learned. They conclude it is feasible to measure QI dose and found a high level of concordance between scores on a comprehensive dose measure and knowledgeable informants’ perceptions. However, measuring QI dose presents many challenges, including subjective decisions about the elements of dose to include in a measure and the need for extensive data collection.

Public reporting of health care provider quality is intended to spark consumer informed decision-making, yet there is concern that it might exacerbate disparities. This study explores the extent to which people with chronic conditions are aware of and using comparative quality information (CQI) on hospitals and doctors, and how awareness and use of the information differs by individuals' socio-demographic characteristics. Using a large 2011/2012 survey of adults with chronic conditions, we find low awareness of hospital and doctor CQI (26% and 16% respectively), and lower CQI use (8% and 6% respectively). Findings related to equity in awareness and use by socio-demographic subgroups was mixed. Higher education and income were related to greater CQI awareness, however Whites were less likely to be aware of and use CQI than African Americans and Latinos. The magnitudes of these differences, however, were not large; all groups had modest levels of CQI awareness and use.

To examine the impact of prescription drug monitoring programs (PDMPs) on drug overdose deaths.We used variation in the timing of state PDMP legislation and implementation to estimate the impact of these programs on drug overdose mortality rates across all drug categories from 1999 to 2014 and separately for each category from 1999 to 2010. Data used include US all-jurisdiction mortality data, estimated population data, and sociodemographic data from the CDC and the US Census Bureau.Multivariate regression models were applied to state panel data, including state and year fixed effects and state-specific linear time trends. Preprogram tests were used to assess the common trends assumption underlying our empirical approach.The implementation of PDMPs was not associated with reductions in overall drug overdose or prescription opioid overdose mortality rates relative to expected rates in the absence of PDMPs. For most categories, PDMPs were associated with increased mortality rates, but the associations were statistically insignificant. In a subsample analysis of states with PDMPs in operation for 5 or more years, the programs were found to be associated with significantly higher mortality rates in legal narcotics, illicit drugs, and other and unspecified drugs.PDMPs were not associated with reductions in drug overdose mortality rates and may be related to increased mortality from illicit drugs and other, unspecified drugs. More comprehensive and prevention-oriented approaches may be needed to effectively reduce drug overdose deaths and avoid fatal overdoses from other drugs used as substitutes for prescription opioids.

Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells.

The objective of this study was to examine racial-ethnic disparities in the use of antidepressants among people with private coverage and people with public insurance or no coverage.Data were from Medical Expenditure Panel Surveys (2006-2010), and logistic regression was used for the analysis.Among persons with depression and private coverage, racial-ethnic minority groups were significantly less likely than non-Hispanic whites to use antidepressants (N=4,468; adjusted odds ratio [AOR]=.50, 95% confidence interval [CI]=.33-.66 for non-Hispanic blacks; AOR=.70, CI=.55-.89 for Hispanics). No significant racial-ethnic disparity in the use of antidepressants was found in Medicare (N=1,944), Medicaid (N=2,125), and uninsured populations (N=1,679). For all racial-ethnic groups, persons with no insurance coverage had much lower rates of antidepressant use than their insured counterparts.A wide racial-ethnic gap in the use of antidepressants existed in private coverage. As the nation continues to implement the Affordable Care Act, which will increase the number of enrollees from racial-ethnic minority groups in private plans, continuing efforts will be needed to reduce racial-ethnic disparities in the use of antidepressants.

Sepsis is a major cause of morbidity and mortality in critically ill patients. MD-2 is a 25-kDa lipopolysaccharide (LPS)-binding protein that forms a heterodimer with TLR42, but its regulation in sepsis is not clear. This study aims to investigate the molecular mechanism of regulation of MD-2. Inflammation cytokines in monocytes were analyzed by real-time RT-PCR and ELISA, and it was found that IL-10 was elevated significantly in the monocytes with LPS treatment. And then, when the cells were treated with IL-10, STAT1 was activated in the monocytes using Western blotting. It was also found that STAT1 could enhance MD-2 expression on transcriptional and posttranscriptional levels. Finally, miR-30a was predicted to the molecule that may regulate STAT1 expression. It was verified that STAT1 was a new target gene of miR-30a. miR-30a could inhibit IL-10-induced cytokine release by targeting STAT1-MD-2 in monocytes. In conclusion, this study for the first time demonstrated that miR-30a inhibits MD-2 expression by targeting of STAT1 in human monocytes.

A key component of efforts to improve the quality of care in the United States is the use of public reporting and pay-for-performance programs. Little is known, however, about the extent to which small- and medium-sized physician practices are participating in these programs. This study examined the participation of small- and medium-sized physician practices in pay-for-performance and public reporting programs and the characteristics of the participating practices. Using cross-sectional data from a national sample of 1,734 small- and medium-sized physician practices throughout the United States, we found that many practices (61.2%) were participating in at least one program, while far fewer (19.2%) were participating in multiple programs. Among practices participating in multiple programs, relatively few (21.9%) reported high levels of administrative problems due to a lack of standardization on performance measures. The study also suggests that some structural features are associated with participation and may provide leverage points for fostering participation.

Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.

A novel star-shaped polymer, porphyrin-poly(L-lysine) dendrons (PP-PLLD), is synthesized by the click reaction between azido-modified porphyrin and propargyl focal point poly(L-lysine) dendrons. Its chemical structure is characterized by (1) H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and gel permeation chromatography (GPC) is analyses etc. Due to its amphiphilic property, the obtained PP-PLLD has a low critical micelle concentration in an aqueous solution, and can load doxorubicin (DOX) with a loading amount of 64 μg mg(-1) . By in vitro toxicity assay, PP-PLLD has no dark cytotoxicity but has significant phototoxicity. Moreover, DOX-loaded PP-PLLD shows a higher cytotoxicity under the light condition than PP-PLLD or DOX alone, suggesting PP-PLLD has a potential application in combined photodynamic therapy and chemotherapy.

A key component of the Aligning Forces for Quality (AF4Q) program was engaging consumers in their health and healthcare. We examined the extent to which the alliances embraced 4 areas of consumer engagement: self-management, consumer friendliness of reports of healthcare provider quality, involvement of consumers in alliance governance, and the integration of consumers into quality improvement teams.We used a largely qualitative approach. The evaluation team conducted 1100 in-depth interviews with alliance stakeholders. Two authors reviewed the consumer engagement data for each alliance to assess its level of embrace in the 4 consumer engagement areas. For consumer friendliness of public reporting websites, we also assessed alliance public reports for reading level, technical language, and evaluable displays. Population-level effects were also examined for self-management and public reporting.Consumer engagement was new to most alliances, and few had staff with consumer engagement expertise or existing consumer constituencies. For each area of consumer engagement, some alliances enthusiastically embraced the work, other alliances made a concerted but limited effort to develop programs, and a third group of alliances did the minimum work required. Integrating consumers into governance was the area most often embraced, followed by making public reports consumer friendly. Two alliances strongly embraced both self-management and integrating patients into quality improvement efforts. The AF4Q program did not have greater population level effects from self-management or public reporting than were those observed in a national comparison sample.The AF4Q program sparked a few alliances to develop robust consumer engagement programming, while most alliances tried consumer engagement efforts for the first time and developed an appreciation for integrating consumer perspectives into their work.

To report summative evaluation results from the Aligning Forces for Quality (AF4Q) initiative, the Robert Wood Johnson Foundation's (RWJF's) signature effort to improve quality of care from 2005 to 2015.This was a longitudinal mixed methods program evaluation (ie, multiphase triangulated evaluation) of 16 grantee "alliances" from across the country, funded by RWJF as part of the AF4Q initiative. Grantees were selected in a nonexperimental manner and were charged with deploying interventions in 5 main programmatic areas to improve health and healthcare in their communities.Except for a small proportion of outcomes, there were no major differences in the rate of longitudinal improvement in AF4Q communities, compared with control communities, on quantitative outcomes related to the Triple Aim. Although the majority of the measures improved in both AF4Q and non-AF4Q communities, there were some exceptions to this improving trend, most noticeably in the cost of care and population health. There was also considerable heterogeneity across communities in terms of programmatic areas and the scale and scope of interventions in these areas. Although a number of AF4Q alliances implemented robust interventions in specific areas, often advancing strategies useful for others in the field, no AF4Q alliance pursued and aligned all 5 AF4Q programmatic areas in a robust way. In addition, whereas all alliances were able to garner the participation of multiple stakeholders initially, sustaining this participation and securing new sources of funding after RWJF support ended proved challenging for many alliances. Conclusion and Policy and Practice Implications: While the AF4Q program did not attain the ambitious community-level changes predicted by its sponsor at the program's outset, it did produce pockets of success on some dimensions for particular alliances. A number of factors explain the less-than-expected impact of the AF4Q initiative on community health and the observed variation in alliance sustainability and intervention strength. These include differing acceptance of the AF4Q initiative's theory of change, variation in the experience and capacity of the alliance communities selected for the program, differences in alliances' local healthcare market context, and the changing programmatic requirements for alliances participating in the AF4Q initiative. The variation in AF4Q program outcomes offers important lessons for those engaged in regional health improvement work.

The Aligning Forces for Quality (AF4Q) initiative was the Robert Wood Johnson Foundation's (RWJF's) signature effort to increase the overall quality of healthcare in targeted communities throughout the country. In addition to sponsoring this 16-site complex program, RWJF funded an independent scientific evaluation to support objective research on the initiative's effectiveness and contributions to basic knowledge in 5 core programmatic areas. The research design, data, and challenges faced during the summative evaluation phase of this near decade-long program are discussed.A descriptive overview of the summative research design and its development for a multi-site, community-based, healthcare quality improvement initiative is provided.The summative research design employed by the evaluation team is discussed.The evaluation team's summative research design involved a data-driven assessment of the effectiveness of the AF4Q program at large, assessments of the impact of AF4Q in the specific programmatic areas, and an assessment of how the AF4Q alliances were positioned for the future at the end of the program.The AF4Q initiative was the largest privately funded community-based healthcare improvement initiative in the United States to date and was implemented at a time of rapid change in national healthcare policy. The implementation of large-scale, multi-site initiatives is becoming an increasingly common approach for addressing problems in healthcare. The summative evaluation research design for the AF4Q initiative, and the lessons learned from its approach, may be valuable to others tasked with evaluating similarly complex community-based initiatives.

To summarize the results from the quantitative analyses conducted during the summative evaluation of the Aligning Forces for Quality (AF4Q) initiative.Longitudinal design using linear difference-in-difference (DD) regression models with fixed effects. Outcomes were selected based on the AF4Q program logic model and organized according to the categories of the Triple Aim: improving population health, improving quality and experience of care, and reducing the cost of care.Two primary data sources: the AF4Q Consumer Survey and the National Study of Physician Organizations (NSPO); and 4 secondary data sources: the Dartmouth Atlas Medicare claims database, the Truven Health MarketScan commercial claims database, the Behavioral Risk Factor Surveillance System (BRFSS), and the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS).In total, 144 outcomes were analyzed, 27 were associated with improving population health, 87 were associated with improving care quality and experience, and 30 were associated with reducing the cost of care. Based on the estimated DD coefficients, there is no consistent evidence that AF4Q regions, over the life of the program, showed greater improvement in these measures compared with the rest of the United States. For less than 12% of outcomes (17/144), the AF4Q initiative was associated with a significant positive impact (P ≤.05), although the magnitude of the impact was often small. Among the remaining outcomes, with some exceptions, similarly improving trends were observed in both AF4Q and non-AF4Q areas over the period of intervention. Conclusion and Policy and Practice Implications: Our quantitative findings, which suggest that the AF4Q initiative had less impact than expected, are potentially due to the numerous other efforts to improve healthcare across the United States, including regions outside the AF4Q program over the same period of time. The limited overall impact may also be due to the variability in the "dose" of the interventions across AF4Q regions. However, these results should not be interpreted as a conclusive statement about the AF4Q initiative. More nuanced discussions of the implementation of interventions in the specific AF4Q programmatic areas and their potential success (or lack thereof) in the participating communities are included in other articles in this supplement.

We describe an electrostatic droplet generation method to prepare a novel carboxymethyl chitosan−graphene oxide hybrid particles for delivery purpose. Under an adjustable electrostatic field, graphene oxide and carboxymethyl chitosan mixed solution was sprayed as uniform micro-droplets, which were solidified as particles in CaCl2 solution. Such hybrid particles are wished to have excellent stability in saline solution, and better delivery properties than pristine carboxymethyl chitosan particles. The effects of micro-droplets generation conditions on particles formation were systematically investigated. At conditions of 40 mg/ml of carboxymethyl chitosan, 2 mg/ml of graphene oxide, 3 ml/h of feed speed, electrostatic field parameters was 9 kV and 20 cm, uniformly sized carboxymethyl chitosan–graphene oxide particles in the diameter range of 250–300 μm was successfully prepared. In NaCl saline, these particles could maintain stable for at least a week, while pristine carboxymethyl chitosan particles quickly collapsed within an hour. The results of loading experiments showed that carboxymethyl chitosan–graphene oxide particles could effectively adsorb gatifloxacin, ofloxacin, bovine serum albumin, lysozyme, doxorubicin hydrochloride. And gatifloxacin was chosen as a model drug to study the exact effect of graphene oxide content on the loading and release properties. In 40:2 group, the highest loading capacity of 0.45 ± 0.19 mg/mg was achieved, and also a good sustained release was available. Above all, we believed that carboxymethyl chitosan–graphene oxide particles as a versatile carrier, has great potential in Medicine and Pharmacy.

Objective To determine whether chronically ill adults from communities participating in a community-level quality improvement effort reported greater improvement on four domains of patient experience: care coordination, patient satisfaction, provider interaction and support, and receipt of recommended care for diabetes. Study Setting The Robert Wood Johnson Foundation's Aligning Forces for Quality (AF4Q) initiative provides multistakeholder alliances with funding and technical assistance to improve quality in their communities. Study Design This is a quasi-experimental, pre-post study. We used a difference-in-difference approach to detect relative changes over time on 16 survey-based outcome measures representing the four patient experience domains. Data Collection We surveyed adults with chronic illness(es) in 14 AF4Q communities and a national comparison group. Wave 1 was completed in 2008 (8,140 respondents) and wave 2 in 2012 (9,565 respondents). Principal Findings Respondents from AF4Q communities reported modestly greater improvement on patient satisfaction and receipt of recommended care for diabetes. Conclusions Results suggest that community-level QI efforts led by multistakeholder alliances hold the potential to improve patient satisfaction and receipt of recommended care for diabetes, but the magnitude of the effect may be limited. However, there is less evidence that community-level QI can improve patient perceptions of care coordination or provider interaction and support.

Significant investments have been made to provide comparative healthcare quality information (CQI) to the public, but whether these efforts are increasing awareness of CQI is unknown.To provide regional estimates of change in awareness of CQI among the chronically ill population residing in 14 geographic regions of the United States between 2008 and 2012. Additionally, to examine its correlation with the changes in the availability of quality reports.Data from 2 waves (2008 and 2012) of a random-digit dial survey of 11,896 adults with chronic illness.Regression-adjusted change in the percentage of respondents aware of physician and hospital CQI, and Pearson correlations between regional change in awareness of CQI and regional change in availability of quality reports.While the number of reports on both hospital quality and physician quality increased between 2008 and 2012, there was significant change in awareness of only physician CQI (12.8% to 16.2%, regression-adjusted change of 3.7 percentage points; P.05). No significant correlation was found between the change in awareness of CQI and the change in availability of hospital quality reports or physician quality reports.Awareness of physician CQI among the chronically ill increased modestly between 2008 and 2012, but no significant increase in awareness of hospital quality was observed. As efforts to report CQI accelerate, more attention to approaches to dissemination may be warranted in order to increase awareness in the chronically ill population.

Patient activation is an important predictor of health outcomes and health care usage, yet we do not know how enduring the benefits of greater patient activation are. This study uses a large panel survey of people with chronic conditions ( n = 4,865) to examine whether a baseline patient activation measure predicts outcomes 4 years later, and whether changes in patient activation measure scores are associated with changes in outcomes. The findings indicate that the benefits of health activation are enduring, yielding benefits in the form of better self-management, improved functioning, and lower use of costly health care services over time. Furthermore, the findings indicate that when activation levels change, many outcomes change in the same direction. Patient activation seems to be an important and modifiable factor for influencing chronic disease outcomes; health care delivery systems can use this information to personalize and improve care.

Consumers facing barriers to healthcare access may use online health information seeking and online communication with physicians, but the empirical relationship has not been sufficiently analyzed. Our study examines the association of barriers to healthcare access with consumers' health-related information searching on the internet, use of health chat groups, and email communication with physicians, using data from 27 210 adults from the 2009 National Health Interview Survey. Individuals with financial barriers to healthcare access, difficulty getting timely appointments with doctors, and conflicts in scheduling during clinic hours are more likely to search for general health information online than those without these access barriers. Those unable to get timely appointments with physicians are more likely to participate in health chat groups and email physicians. The internet may offer a low-cost source of health information and could help meet the heightened demand for health-related information among those facing access barriers to care.