Identifying Individuals with Highest Social Risk in Adults with Type 2 Diabetes Using Item Response Theory.

OBJECTIVE: The aim of this analysis was to create a parsimonious tool to screen for high social risk using item response theory to discriminate across social risk factors in adults with type 2 diabetes. METHODS: Cross-sectional data of 615 adults with diabetes recruited from two primary care clinics were used. Participants completed assessments including validated scales on economic instability (financial hardship), neighborhood and built environment (crime, violence, neighborhood rating), education (highest education, health literacy), food environment (food insecurity), social and community context (social isolation), and psychological risk factors (perceived stress, depression, serious psychological distress, diabetes distress). Item response theory (IRT) models were used to understand the association between a participant's underlying level of a particular social risk factor and the probability of that response. A two-parameter logistic IRT model was used with each of the 12 social determinant factors being added as a separate parameter in the model. Higher values in item discrimination indicate better ability of a specific social risk factor in differentiating participants from each other. RESULTS: Rate of crime reported in a neighborhood (discrimination 3.13, SE 0.50; item difficulty - 0.68, SE 0.07) and neighborhood rating (discrimination 4.02, SE 0.87; item difficulty - 1.04, SE 0.08) had the highest discrimination. CONCLUSIONS: Based on these findings, crime and neighborhood rating discriminate best between individuals with type 2 diabetes who have high social risk and those with low social risk. These two questions can be used as a parsimonious social risk screening tool to identify high social risk.

Historic Residential Redlining and Present-Day Social Determinants of Health, Home Evictions, and Food Insecurity within US Neighborhoods.

OBJECTIVE: Examine the association between historic residential redlining and present-day racial/ethnic composition of neighborhoods, racial/ethnic differences in social determinant of health domains, and risk of home evictions and food insecurity. RESEARCH DESIGN AND METHODS: We examined data on 12,334 (for eviction sample), and 8996 (for food insecurity sample), census tracts in 213 counties across 37 states in the USA with data on exposure to historic redlining. First, we examined relationships between Home Owners' Loan Corporation (HOLC) redlining grades (A="Best", B="Still Desirable", C="Definitely Declining", D="Hazardous") and present-day racial/ethnic composition and racial/ethnic differences in social determinant of health domains of neighborhoods. Second, we examined whether historic redlining is associated with present-day home eviction rates (measured across eviction filings rates, and eviction judgment rates for 12,334 census tracts in 2018) and food insecurity (measured across low supermarket access, low supermarket access and income, low supermarket access and low car ownership for 8996 census tracts in 2019). Multivariable regression models were adjusted for census tract population, urban/rural designation, and county level fixed effects. RESULTS: Relative to areas with a historic HOLC grading of "A (Best)", areas with a "D (Hazardous)" grading had a 2.59 (95%CI=1.99-3.19; p-value<0.01) higher rate of eviction filings, and a 1.03 (95%CI=0.80-1.27; p-value<0.01) higher rate of eviction judgments. Compared to areas with a historic HOLC grading of "A (Best)", areas rated with a "D (Hazardous)" had a 16.20 (95%CI=15.02-17.79; p-value<0.01) higher rate of food insecurity based on supermarket access and income, and a 6.15 (95%CI =5.53-6.76; p-value<0.01) higher rate of food insecurity based on supermarket access and car ownership. CONCLUSIONS: Historic residential redlining is significantly associated with present-day home evictions and food insecurity, highlighting persistent associations between structural racism and present-day social determinants of health.

Modern Day Consequences of Historic Redlining: Finding a Path Forward.

There is emerging evidence that structural racism is a major contributor to poor health outcomes for ethnic minorities. Structural racism captures upstream historic racist events (such as slavery, black code, and Jim Crow laws) and more recent state-sanctioned racist laws in the form of redlining. Redlining refers to the practice of systematically denying various services (e.g., credit access) to residents of specific neighborhoods, often based on race/ethnicity and primarily within urban communities. Historical redlining is linked to increased risk of diabetes, hypertension, and early mortality due to heart disease with evidence suggesting it impacts health through suppressing economic opportunity and human capital, or the knowledge, skills, and value one contributes to society. Addressing structural racism has been a rallying call for change in recent years-drawing attention to the racialized impact of historical policies in the USA. Unfortunately, the enormous scope of work has also left people feeling incapable of effecting the very change they seek. This paper highlights a path forward by briefly discussing the origins of historical redlining, highlighting the modern-day consequences both on health and at the societal level, and suggest promising initiatives to address the impact.

Do Chargemaster Prices Matter?: An Examination of Acute Care Hospital Profitability.

BACKGROUND: It remains widely debated whether chargemaster price markups are tied to hospital profitability. OBJECTIVE: To evaluate the effect of chargemaster markups on hospital profitability in the presence of unobserved hospital-specific (time-invariant) confounders, and cross-sectional dependence due to latent (common) policy shocks. DESIGN: We use interactive fixed effects methods to address concerns of unobserved hospital-specific (time-invariant) confounders, and cross-sectional dependence. SETTING: US acute care hospitals, 1996 through 2017 (ie, 22 y). PARTICIPANTS: Using primarily Medicare cost report data, we construct an unbalanced panel of 3499 acute care hospitals per year, or a total of 76,972 hospital-year observations. MEASUREMENTS: Chargemaster markups (above cost), profits per hospital inpatient discharge. RESULTS: Between 1996 and 2017, chargemaster markups increased (on average) by 155%, and the SD of the chargemaster markup distribution increased by 324%-indicating growing variability in the average markup strategies pursued by hospitals. Our preferred model specification implies that a unit increase of the hospital chargemaster markup is associated with a $261 ( P <0.01; 95% confidence interval: $232-$291) increase in profits per hospital inpatient discharge. These results are robust to a wide set of model specifications, the use of alternative profitability measurements, and the use of an alternative instrumental variable identification strategy. Additional subsample analysis that controls for a rich set of hospital quality measures and system affiliation information also yields similar results. CONCLUSION: We show that higher chargemaster markups are associated with higher hospital profitability. Additional research is needed to understand how chargemaster pricing impact health outcomes and health care disparities.

Hospital Price Transparency in the United States: An Examination of Chargemaster, Cash, and Negotiated, Price Variation for 14 Common Procedures.

BACKGROUND: Effective January 1, 2021, US hospitals were required to upload information on their chargemaster prices (database of list prices), discounted cash prices (commonly charged to self-pay patients), and payer-specific negotiated prices. OBJECTIVE: Examine how prices vary and are associated with hospital characteristics, market competition, and hospital quality. DESIGN SETTING AND PARTICIPANTS: This observational study used data on 14 common medical services across 1599 hospitals in 2021. Descriptive and regression analyses were used to study price variation. Analyses adjust for hospital characteristics, market competition and state fixed effects. RESULTS: Ninetieth -to-10th-percentile price markups factors (ratios) range between 3.2 and 11.5 for chargemaster; 6.1 and 19.7 for cash; and 6.6 and 30.0 for negotiated prices. Adjusted regression results indicate that hospitals' cash prices are on average 60% ( P <0.01) higher, and list prices are on average 164% ( P <0.01) higher, than negotiated prices. Systematic pricing differences across hospitals were noted, with urban hospitals having 14% ( P <0.01) lower prices than rural hospitals, teaching hospitals having 3% ( P <0.01) higher prices than nonteaching hospitals, and nonprofit hospitals pricing 9% ( P <0.01), and for-profit hospitals 39% ( P <0.01), higher than government owned hospitals. In addition, hospitals that contract with more insurance plans have higher prices, hospitals in more competitive markets have lower prices, and higher quality hospitals have on average 5% ( P <0.01) lower prices than lower quality hospitals. CONCLUSIONS: Prices all vary considerably across US hospitals. High quality hospitals are associated with lower pricing across all three sets of prices examined. Hospital price transparency may help consumers better identify hospitals that provide both high quality, and low cost, care.

Provider Network Structure and Black-to-White Disparity Gaps for Medicare Patients with Diabetes: County-Level Analysis of Cost, Utilization, and Clinical Care.

BACKGROUND: Prior work has shown that provider network structures correlate with outcomes such as patient costs, utilization, and care. However, it remains unknown whether certain provider networks are associated with reduced disparity gaps. METHODS: We study the population of Medicare beneficiaries with diabetes who were continuously enrolled in Medicare FFS in 2016. Using multivariable regression analysis of county-level risk adjusted cost, hospitalization, emergency department visits, A1c testing, and preventable diabetes-related hospitalizations, we measure the effect that the relative network connectivity of primary care providers (PCPs) in relation to medical and surgical specialists (PCP/Specialist degree centrality ratio), derived from Medicare patient sharing data, has on non-Hispanic black-to-white disparity gaps controlling for county-level socioeconomic and demographic variables and state fixed effects. RESULTS: Relative to non-Hispanic white, our adjusted results show that non-Hispanic black beneficiaries have $1673 (p<0.001) higher risk adjusted total costs, 2.6 (p<0.001) more hospitalizations (per 1000 beneficiaries), 11.6 (p<0.001) more ED visits (per 1000 beneficiaries), receive 2.2% (p<0.001) less A1c testing, and have 69.4 (p<0.01) more (per 100,000) avoidable diabetes-related hospital admissions. Our main results show that increasing the PCP/Specialist degree centrality ratio by one standard deviation is associated with a disparity gap decrease of 25.3% (p<0.01) in hospitalizations, 8.3% (p<0.05) in ED visits, 2.8% (p<0.01) in A1c testing, and 26.9% (p<0.1) in the volume of preventable diabetes-related hospital admissions. CONCLUSIONS: Network structures where PCPs are more central relative to medical and surgical specialists are associated with reduced non-Hispanic black-to-white disparity gaps, suggesting that how we organize and structure our health systems has implications for disparity gaps between non-Hispanic black and white Medicare beneficiaries with diabetes.

Pharmaceutical opioid marketing and physician prescribing behavior.

Physicians' relationships with the pharmaceutical industry have recently come under public scrutiny, particularly in the context of opioid drug prescribing. This study examines the effect of doctor-industry marketing interactions on subsequent prescribing patterns of opioids using linked Medicare Part D and Open Payments data for the years 2014-2017. Results indicate that both the number and the dollar-value of marketing visits increase physicians' patented opioid claims. Furthermore, direct-to-physician marketing of safer abuse-deterrent formulations of opioids is the primary driver of positive and persistent spillovers on the prescribing of less safe generic opioids - a result that we show appears to be driven by insurance coverage policies. These findings suggest that pharmaceutical marketing efforts may have unintended public health implications.

Photometry unlocks 3D information from 2D localization microscopy data.

We developed a straightforward photometric method, temporal, radial-aperture-based intensity estimation (TRABI), that allows users to extract 3D information from existing 2D localization microscopy data. TRABI uses the accurate determination of photon numbers in different regions of the emission pattern of single emitters to generate a z-dependent photometric parameter. This method can determine fluorophore positions up to 600 nm from the focal plane and can be combined with biplane detection to further improve axial localization.

The formation of physician patient sharing networks in medicare: Exploring the effect of hospital affiliation.

This study explores the forces that drive the formation of physician patient sharing networks. In particular, I examine the degree to which hospital affiliation drives physicians' sharing of Medicare patients. Using a revealed preference framework where observed network links are taken to be pairwise stable, I estimate the physicians' pair-specific values using a tetrad maximum score estimator that is robust to the presence of unobserved physician specific characteristics. I also control for a number of potentially confounding patient sharing channels, such as (a) common physician group or hospital system affiliation, (b) physician homophily, (c) knowledge complementarity, (d) patient side considerations related to both geographic proximity and insurance network participation, and (e) spillover from other collaborations. Focusing on the Chicago hospital referral region, I find that shared hospital affiliation accounts for 36.5% of the average pair-specific utility from a link. Implications for reducing care fragmentation are discussed.

Speech Production Skills in Children With Cleft Palate Who Were Internationally Adopted.

OBJECTIVE: The objective of this study was to investigate the impact of international adoption (IA), age at palatoplasty (PR age), and velopharyngeal sufficiency (VPS) on articulation outcomes. DESIGN: This was a cross-sectional, prospective, observational study. SETTING: Outpatient hospital clinic. PARTICIPANTS: Fifty-one IA and 65 not-adopted (NA) children between the ages of 3 and 9 with nonsyndromic cleft palate with or without cleft lip. MAIN OUTCOME MEASURE(S): The Goldman-Fristoe Test of Articulation-2nd Edition (GFTA-2) standard score and cleft-related articulation errors (CREs). RESULTS: Articulation impairment was observed for 40% to 76% of NA children and 71% to 92% IA children, depending on age. PR age mean IA = 2.07 (0.86) years; NA = 1.23 (0.71) years. Children who were IA had poorer performance on the GFTA-2 ( B = -13.82, P = .015). Children who were IA were not significantly more likely to make CRE; rather, age at the time of assessment ( B = -.10, P = .002) and VPS ( B = .24, P = .021) were associated with CRE. CONCLUSIONS: Children who were IA demonstrated poorer articulation skills. Although primary palatoplasty was accomplished later among children who were IA, age at assessment and VP status (not PR age) were significantly correlated with articulation outcomes. Implications for timing of surgical intervention are discussed.

Correlative super-resolution fluorescence and electron microscopy of the nuclear pore complex with molecular resolution.

Here, we combine super-resolution fluorescence localization microscopy with scanning electron microscopy to map the position of proteins of nuclear pore complexes in isolated Xenopus laevis oocyte nuclear envelopes with molecular resolution in both imaging modes. We use the periodic molecular structure of the nuclear pore complex to superimpose direct stochastic optical reconstruction microscopy images with a precision of <20 nm on electron micrographs. The correlative images demonstrate quantitative molecular labeling and localization of nuclear pore complex proteins by standard immunocytochemistry with primary and secondary antibodies and reveal that the nuclear pore complex is composed of eight gp210 (also known as NUP210) protein homodimers. In addition, we find subpopulations of nuclear pore complexes with ninefold symmetry, which are found occasionally among the more typical eightfold symmetrical structures.

Instant live-cell super-resolution imaging of cellular structures by nanoinjection of fluorescent probes.

Labeling internal structures within living cells with standard fluorescent probes is a challenging problem. Here, we introduce a novel intracellular staining method that enables us to carefully control the labeling process and provides instant access to the inner structures of living cells. Using a hollow glass capillary with a diameter of <100 nm, we deliver functionalized fluorescent probes directly into the cells by (di)electrophoretic forces. The label density can be adjusted and traced directly during the staining process by fluorescence microscopy. We demonstrate the potential of this technique by delivering and imaging a range of commercially available cell-permeable and nonpermeable fluorescent probes to cells.

The chlamydial organism Simkania negevensis forms ER vacuole contact sites and inhibits ER-stress.

Most intracellular bacterial pathogens reside within membrane-surrounded host-derived vacuoles. Few of these bacteria exploit membranes from the host's endoplasmic reticulum (ER) to form a replicative vacuole. Here, we describe the formation of ER-vacuole contact sites as part of the replicative niche of the chlamydial organism Simkania negevensis. Formation of ER-vacuole contact sites is evolutionary conserved in the distantly related protozoan host Acanthamoeba castellanii. Simkania growth is accompanied by mitochondria associating with the Simkania-containing vacuole (SCV). Super-resolution microscopy as well as 3D reconstruction from electron micrographs of serial ultra-thin sections revealed a single vacuolar system forming extensive ER-SCV contact sites on the Simkania vacuolar surface. Simkania infection induced an ER-stress response, which was later downregulated. Induction of ER-stress with Thapsigargin or Tunicamycin was strongly inhibited in cells infected with Simkania. Inhibition of ER-stress was required for inclusion formation and efficient growth, demonstrating a role of ER-stress in the control of Simkania infection. Thus, Simkania forms extensive ER-SCV contact sites in host species evolutionary as diverse as human and amoeba. Moreover, Simkania is the first bacterial pathogen described to interfere with ER-stress induced signalling to promote infection.

How to switch a fluorophore: from undesired blinking to controlled photoswitching.

Molecular optical photoswitches based on fluorescent proteins and organic dyes are fundamental for super-resolution fluorescence imaging and tracking methods. Precise control of switching, bio-labeling compatibility, and high brightness make photoswitches broadly applicable. This review emphasizes the design and development of photoswitches and the requirements they need to fulfill for their successful application in single-molecule localization microscopy. Furthermore, we discuss recent developments in improving the photoswitching performance with a special focus on organic dyes.

Super-resolution imaging visualizes the eightfold symmetry of gp210 proteins around the nuclear pore complex and resolves the central channel with nanometer resolution.

One of the most complex molecular machines of cells is the nuclear pore complex (NPC), which controls all trafficking of molecules in and out of the nucleus. Because of their importance for cellular processes such as gene expression and cytoskeleton organization, the structure of NPCs has been studied extensively during the last few decades, mainly by electron microscopy. We have used super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) to investigate the structure of NPCs in isolated Xenopus laevis oocyte nuclear envelopes, with a lateral resolution of ~15 nm. By generating accumulated super-resolved images of hundreds of NPCs we determined the diameter of the central NPC channel to be 41 ± 7 nm and demonstrate that the integral membrane protein gp210 is distributed in an eightfold radial symmetry. Two-color dSTORM experiments emphasize the highly symmetric NPCs as ideal model structures to control the quality of corrections to chromatic aberration and to test the capability and reliability of super-resolution imaging methods.

Cubic B-spline calibration for 3D super-resolution measurements using astigmatic imaging.

In recent years three-dimensional (3D) super-resolution fluorescence imaging by single-molecule localization (localization microscopy) has gained considerable interest because of its simple implementation and high optical resolution. Astigmatic and biplane imaging are experimentally simple methods to engineer a 3D-specific point spread function (PSF), but existing evaluation methods have proven problematic in practical application. Here we introduce the use of cubic B-splines to model the relationship of axial position and PSF width in the above mentioned approaches and compare the performance with existing methods. We show that cubic B-splines are the first method that can combine precision, accuracy and simplicity.

A blueprint for cost-efficient localization microscopy.

Crystal clear: The authors introduce a miniaturized localization microscopy setup based on cost-effective components. They demonstrate its feasibility for subdiffraction resolution fluorescence imaging in resolving different cellular nanostructures. The setup can be used advantageously in practical courses for training students in super-resolution fluorescence microscopy.

Catastrophic health expenditures: a disproportionate risk in uninsured ethnic minorities with diabetes.

BACKGROUND: Chargemaster prices are the list prices that providers and health systems assign to each of their medical services in the US. These charges are often several factors of magnitude higher than those extended to individuals with either private or public insurance, however, these list prices are billed in full to uninsured patients, putting them at increased risk of catastrophic health expenditures (CHE). The objective of this study was to examine the risk of CHE across insurance status, diabetes diagnosis and to examine disparity gaps across race/ethnicity. METHODS: We perform a retrospective observational study on a nationally representative cohort of adult patients from the Medical Expenditure Panel Survey for the years 2002-2017. Using logistic regression models we estimate the risk of CHE across insurance status, diabetes diagnosis and explore disparity gaps across race/ethnicity. RESULTS: Our fully adjusted results show that the relative odds of having CHE if uninsured is 5.9 (p < 0.01) compared to if insured, and 1.1 (p < 0.01) for patients with a diabetes diagnosis (compared to those without one). We note significant interactions between insurance status and diabetes diagnosis, with uninsured patients with a diabetes diagnosis being 9.5 times (p < 0.01) more likely to experience CHE than insured patients without a diabetes diagnosis. In terms of racial/ethnic disparities, we find that among the uninsured, non-Hispanic blacks are 13% (p < 0.05), and Hispanics 14.2% (p < 0.05), more likely to experience CHE than non-Hispanic whites. Among uninsured patients with diabetes, we further find that Hispanic patients are 39.3% (p < 0.05) more likely to have CHE than non-Hispanic white patients. CONCLUSIONS: Our findings indicate that uninsured patients with diabetes are at significantly elevated risks for CHE. These risks are further found to be disproportionately higher among uninsured racial/ethnic minorities, suggesting that CHE may present a channel through which structural economic and health disparities are perpetuated.

Historic Redlining and Impact of Structural Racism on Diabetes Prevalence in a Nationally Representative Sample of U.S. Adults.

OBJECTIVE: We investigated direct and indirect relationships between historic redlining and prevalence of diabetes in a U.S. national sample. RESEARCH DESIGN AND METHODS: Using a previously validated conceptual model, we hypothesized pathways between structural racism and prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing, education, unemployment, and food access. We combined census tract-level data, including diabetes prevalence from the Centers for Disease Control and Prevention PLACES 2019 database, redlining using historic Home Owners' Loan Corporation (HOLC) maps from the Mapping Inequality project, and census data from the Opportunity Insights database. HOLC grade (a score between 1 [best] and 4 [redlined]) for each census tract was based on overlap with historically HOLC-graded areas. The final analytic sample consisted of 11,375 U.S. census tracts. Structural equation modeling was used to investigate direct and indirect relationships adjusting for the 2010 population. RESULTS: Redlining was directly associated with higher crude prevalence of diabetes within a census tract (r = 0.01; P = 0.008) after adjusting for the 2010 population (χ2(54) = 69,900.95; P < 0.001; root mean square error of approximation = 0; comparative fit index = 1). Redlining was indirectly associated with diabetes prevalence via incarceration (r = 0.06; P < 0.001), poverty (r = -0.10; P < 0.001), discrimination (r = 0.14; P < 0.001); substance use (measured by binge drinking: r = -0.65, P < 0.001; and smoking: r = 0.35, P < 0.001), housing (r = 0.06; P < 0.001), education (r = -0.17; P < 0.001), unemployment (r = -0.17; P < 0.001), and food access (r = 0.14; P < 0.001) after adjusting for the 2010 population. CONCLUSIONS: Redlining has significant direct and indirect relationships with diabetes prevalence. Incarceration, poverty, discrimination, substance use, housing, education, unemployment, and food access may be possible targets for interventions aiming to mitigate the impact of structural racism on diabetes.