Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

Engaging stakeholders in the use of an interactive simulation tool to support decision-making about the implementation of colorectal cancer screening interventions.

PURPOSE: We aimed to understand how an interactive, web-based simulation tool can be optimized to support decision-making about the implementation of evidence-based interventions (EBIs) for improving colorectal cancer (CRC) screening. METHODS: Interviews were conducted with decision-makers, including health administrators, advocates, and researchers, with a strong foundation in CRC prevention. Following a demonstration of the microsimulation modeling tool, participants reflected on the tool's potential impact for informing the selection and implementation of strategies for improving CRC screening and outcomes. The interviews assessed participants' preferences regarding the tool's design and content, comprehension of the model results, and recommendations for improving the tool. RESULTS: Seventeen decision-makers completed interviews. Themes regarding the tool's utility included building a case for EBI implementation, selecting EBIs to adopt, setting implementation goals, and understanding the evidence base. Reported barriers to guiding EBI implementation included the tool being too research-focused, contextual differences between the simulated and local contexts, and lack of specificity regarding the design of simulated EBIs. Recommendations to address these challenges included making the data more actionable, allowing users to enter their own model inputs, and providing a how-to guide for implementing the simulated EBIs. CONCLUSION: Diverse decision-makers found the simulation tool to be most useful for supporting early implementation phases, especially deciding which EBI(s) to implement. To increase the tool's utility, providing detailed guidance on how to implement the selected EBIs, and the extent to which users can expect similar CRC screening gains in their contexts, should be prioritized.

Cerebral arteriopathy and ischemic stroke in a pediatric MYH11 patient.

OBJECTIVES: Mutations in the MYH11 gene result in smooth muscle cell dysfunction and are associated with familial thoracic aortic aneurysms and dissection. We describe a pediatric patient with a stroke and a pathogenic MYH11 IVS32G>A mutation, and a phenotype similar to ACTA2. METHODS: A proband girl with an acute ischemic stroke underwent genetic analysis and 7T high-resolution MRI. RESULTS: A 12-year-old girl presented with a right middle cerebral artery occlusion. She received thrombolysis and underwent mechanical thrombectomy. An extensive stroke work-up was negative. A three-generation pedigree showed a splice site mutation of MYH11 IVS32G>A of the proband and three more family members. A 7T-MRI showed "broomstick-like" straightening of distal arterial segments, a V-shaped anterior corpus callosum and a post-stroke cystic area of encephalomalacia. This vascular appearance and parenchymal abnormalities typically present in patients with an ACTA2 phenotype. 7T-MRI also demonstrated thickening of the right middle cerebral arterial wall. DISCUSSION: This case suggests that MYH11 patients may have a similar angiographic and brain parenchymal phenotype to patients with ACTA2 mutations. This is the first report of arterial wall thickening in a MYH11 stroke patient using 7T-MRI. Patients with MYH11 mutations may display a focal cerebral steno-occlusive arteriopathy that may lead to stroke.

Assessing the impact of multicomponent interventions on colorectal cancer screening through simulation: What would it take to reach national screening targets in North Carolina?

Healthy People 2020 and the National Colorectal Cancer Roundtable established colorectal cancer (CRC) screening targets of 70.5% and 80%, respectively. While evidence-based interventions (EBIs) have increased CRC screening, the ability to achieve these targets at the population level remains uncertain. We simulated the impact of multicomponent interventions in North Carolina over 5 years to assess the potential for meeting national screening targets. Each intervention scenario is described as a core EBI with additional components indicated by the "+" symbol: patient navigation for screening colonoscopy (PN-for-Col+), mailed fecal immunochemical testing (MailedFIT+), MailedFIT+ targeted to Medicaid enrollees (MailedFIT + forMd), and provider assessment and feedback (PAF+). Each intervention was simulated with and without Medicaid expansion and at different levels of exposure (i.e., reach) for targeted populations. Outcomes included the percent up-to-date overall and by sociodemographic subgroups and number of CRC cases and deaths averted. Each multicomponent intervention was associated with increased CRC screening and averted both CRC cases and deaths; three had the potential to reach screening targets. PN-for-Col + achieved the 70.5% target with 97% reach after 1 year, and the 80% target with 78% reach after 5 years. MailedFIT+ achieved the 70.5% target with 74% reach after 1 year and 5 years. In the Medicaid population, assuming Medicaid expansion, MailedFIT + forMd reached the 70.5% target after 5 years with 97% reach. This study clarifies the potential for states to reach national CRC screening targets using multicomponent EBIs, but decision-makers also should consider tradeoffs in cost, reach, and ability to reduce disparities when selecting interventions.

Mailed FIT (fecal immunochemical test), navigation or patient reminders? Using microsimulation to inform selection of interventions to increase colorectal cancer screening in Medicaid enrollees.

Colorectal cancer (CRC) can be effectively prevented or detected with guideline concordant screening, yet Medicaid enrollees experience disparities. We used microsimulation to project CRC screening patterns, CRC cases averted, and life-years gained in the population of 68,077 Oregon Medicaid enrollees 50-64 over a five year period starting in January 2019. The simulation estimated the cost-effectiveness of five intervention scenarios - academic detailing plus provider audit and feedback (Detailing+), patient reminders (Reminders), mailing a Fecal Immunochemical Test (FIT) directly to the patient's home (Mailed FIT), patient navigation (Navigation), and mailed FIT with Navigation (Mailed FIT + Navigation) - compared to usual care. Each intervention scenario raised CRC screening rates compared to usual care, with improvements as high as 11.6 percentage points (Mailed FIT + Navigation) and as low as 2.5 percentage points (Reminders) after one year. Compared to usual care, Mailed FIT + Navigation would raise CRC screening rates 20.2 percentage points after five years - averting nearly 77 cancer cases (a reduction of 113 per 100,000) and exceeding national screening targets. Over a five year period, Reminders, Mailed FIT and Mailed FIT + Navigation were expected to be cost effective if stakeholders were willing to pay $230 or less per additional year up-to-date (at a cost of $22, $59, and $227 respectively), whereas Detailing+ and Navigation were more costly for the same benefits. To approach national CRC screening targets, health system stakeholders are encouraged to implement Mailed FIT with or without Navigation and Reminders.

Estimating the impact of insurance expansion on colorectal cancer and related costs in North Carolina: A population-level simulation analysis.

Although screening is effective in reducing incidence, mortality, and costs of treating colorectal cancer (CRC), it remains underutilized, in part due to limited insurance access. We used microsimulation to estimate the health and financial effects of insurance expansion and reduction scenarios in North Carolina (NC). We simulated the full lifetime of a simulated population of 3,298,265 residents age-eligible for CRC screening (ages 50-75) during a 5-year period starting January 1, 2018, including polyp incidence and progression and CRC screening, diagnosis, treatment, and mortality. Insurance scenarios included: status quo, which in NC includes access to the Health Insurance Exchange (HIE) under the Affordable Care Act (ACA); no ACA; NC Medicaid expansion, and Medicare-for-all. The insurance expansion scenarios would increase percent up-to-date with screening by 0.3 and 7.1 percentage points for Medicaid expansion and Medicare-for-all, respectively, while insurance reduction would reduce percent up-to-date by 1.1 percentage points, compared to the status quo (51.7% up-to-date), at the end of the 5-year period. Throughout these individuals' lifetimes, this change in CRC screening/testing results in an estimated 498 CRC cases averted with Medicaid expansion and 6031 averted with Medicare-for-all, and an additional 1782 cases if health insurance gains associated with ACA are lost. Estimated cost savings - balancing increased CRC screening/testing costs against decreased cancer treatment costs - are approximately $30 M and $970 M for Medicaid expansion and Medicare-for-all scenarios, respectively, compared to status quo. Insurance expansion is likely to improve CRC screening both overall and in underserved populations while saving money, with the largest savings realized by Medicare.

Colorectal cancer screening in newly insured Medicaid members: a review of concurrent federal and state policies.

BACKGROUND: Colorectal cancer (CRC) screening is underutilized by Medicaid enrollees and the uninsured. Multiple national and state policies were enacted from 2010 to 2014 to increase access to Medicaid and to promote CRC screening among Medicaid enrollees. We aimed to determine the impact of these policies on screening initiation among newly enrolled Oregon Medicaid beneficiaries age-eligible for CRC screening. METHODS: We identified national and state policies affecting Medicaid coverage and preventive services in Oregon during 2010-2014. We used Oregon Medicaid claims data from 2010 to 2015 to conduct a cohort analysis of enrollees who turned 50 and became age-eligible for CRC screening (a prevention milestone, and an age at which guideline-concordant screening can be assessed within a single year) during each year from 2010 to 2014. We calculated risk ratios to assess whether first year of Medicaid enrollment and/or year turned 50 was associated with CRC screening initiation. RESULTS: We identified 14,576 Oregon Medicaid enrollees who turned 50 during 2010-2014; 2429 (17%) completed CRC screening within 12 months after turning 50. Individuals newly enrolled in Medicaid in 2013 or 2014 were 1.58 and 1.31 times more likely, respectively, to initiate CRC screening than those enrolled by 2010. A primary care visit in the calendar year, having one or more chronic conditions, and being Hispanic was also associated with CRC screening initiation. DISCUSSION: The increased uptake of CRC screening in 2013 and 2014 is associated with the timing of policies such as Medicaid expansion, enhanced federal matching for preventive services offered to Medicaid enrollees without cost sharing, and formation of Medicaid accountable care organizations, which included CRC screening as an incentivized quality metric.

Objective measures of workload in healthcare: a narrative review.

PURPOSE: Workload is a critical concept in the evaluation of performance and quality in healthcare systems, but its definition relies on the perspective (e.g. individual clinician-level vs unit-level workload) and type of available metrics (e.g. objective vs subjective measures). The purpose of this paper is to provide an overview of objective measures of workload associated with direct care delivery in tertiary healthcare settings, with a focus on measures that can be obtained from electronic records to inform operationalization of workload measurement. DESIGN/METHODOLOGY/APPROACH: Relevant papers published between January 2008 and July 2018 were identified through a search in Pubmed and Compendex databases using the Sample, Phenomenon of Interest, Design, Evaluation, Research Type framework. Identified measures were classified into four levels of workload: task, patient, clinician and unit. FINDINGS: Of 30 papers reviewed, 9 used task-level metrics, 14 used patient-level metrics, 7 used clinician-level metrics and 20 used unit-level metrics. Key objective measures of workload include: patient turnover (n=9), volume of patients (n=6), acuity (n=6), nurse-to-patient ratios (n=5) and direct care time (n=5). Several methods for operationalization of these metrics into measurement tools were identified. ORIGINALITY/VALUE: This review highlights the key objective workload measures available in electronic records that can be utilized to develop an operational approach for quantifying workload. Insights gained from this review can inform the design of processes to track workload and mitigate the effects of increased workload on patient outcomes and clinician performance.

Threshold responses of Amazonian stream fishes to timing and extent of deforestation.

Deforestation is a primary driver of biodiversity change through habitat loss and fragmentation. Stream biodiversity may not respond to deforestation in a simple linear relationship. Rather, threshold responses to extent and timing of deforestation may occur. Identification of critical deforestation thresholds is needed for effective conservation and management. We tested for threshold responses of fish species and functional groups to degree of watershed and riparian zone deforestation and time since impact in 75 streams in the western Brazilian Amazon. We used remote sensing to assess deforestation from 1984 to 2011. Fish assemblages were sampled with seines and dip nets in a standardized manner. Fish species (n = 84) were classified into 20 functional groups based on ecomorphological traits associated with habitat use, feeding, and locomotion. Threshold responses were quantified using threshold indicator taxa analysis. Negative threshold responses to deforestation were common and consistently occurred at very low levels of deforestation (<20%) and soon after impact (<10 years). Sensitive species were functionally unique and associated with complex habitats and structures of allochthonous origin found in forested watersheds. Positive threshold responses of species were less common and generally occurred at >70% deforestation and >10 years after impact. Findings were similar at the community level for both taxonomic and functional analyses. Because most negative threshold responses occurred at low levels of deforestation and soon after impact, even minimal change is expected to negatively affect biodiversity. Delayed positive threshold responses to extreme deforestation by a few species do not offset the loss of sensitive taxa and likely contribute to biotic homogenization.

Versatile genetic assembly system (VEGAS) to assemble pathways for expression in S. cerevisiae.

We have developed a method for assembling genetic pathways for expression in Saccharomyces cerevisiae. Our pathway assembly method, called VEGAS (Versatile genetic assembly system), exploits the native capacity of S. cerevisiae to perform homologous recombination and efficiently join sequences with terminal homology. In the VEGAS workflow, terminal homology between adjacent pathway genes and the assembly vector is encoded by 'VEGAS adapter' (VA) sequences, which are orthogonal in sequence with respect to the yeast genome. Prior to pathway assembly by VEGAS in S. cerevisiae, each gene is assigned an appropriate pair of VAs and assembled using a previously described technique called yeast Golden Gate (yGG). Here we describe the application of yGG specifically to building transcription units for VEGAS assembly as well as the VEGAS methodology. We demonstrate the assembly of four-, five- and six-gene pathways by VEGAS to generate S. cerevisiae cells synthesizing ß-carotene and violacein. Moreover, we demonstrate the capacity of yGG coupled to VEGAS for combinatorial assembly.

Cost-Effectiveness Analysis of Four Simulated Colorectal Cancer Screening Interventions, North Carolina.

INTRODUCTION: Colorectal cancer (CRC) screening rates are suboptimal, particularly among the uninsured and the under-insured and among rural and African American populations. Little guidance is available for state-level decision makers to use to prioritize investment in evidence-based interventions to improve their population's health. The objective of this study was to demonstrate use of a simulation model that incorporates synthetic census data and claims-based statistical models to project screening behavior in North Carolina. METHODS: We used individual-based modeling to simulate and compare intervention costs and results under 4 evidence-based and stakeholder-informed intervention scenarios for a 10-year intervention window, from January 1, 2014, through December 31, 2023. We compared the proportion of people living in North Carolina who were aged 50 to 75 years at some point during the window (that is, age-eligible for screening) who were up to date with CRC screening recommendations across intervention scenarios, both overall and among groups with documented disparities in receipt of screening. RESULTS: We estimated that the costs of the 4 intervention scenarios considered would range from $1.6 million to $3.75 million. Our model showed that mailed reminders for Medicaid enrollees, mass media campaigns targeting African Americans, and colonoscopy vouchers for the uninsured reduced disparities in receipt of screening by 2023, but produced only small increases in overall screening rates (0.2-0.5 percentage-point increases in the percentage of age-eligible adults who were up to date with CRC screening recommendations). Increased screenings ranged from 41,709 additional life-years up to date with screening for the voucher intervention to 145,821 for the mass media intervention. Reminders mailed to Medicaid enrollees and the mass media campaign for African Americans were the most cost-effective interventions, with costs per additional life-year up to date with screening of $25 or less. The intervention expanding the number of endoscopy facilities cost more than the other 3 interventions and was less effective in increasing CRC screening. CONCLUSION: Cost-effective CRC screening interventions targeting observed disparities are available, but substantial investment (more than $3.75 million) and additional approaches beyond those considered here are required to realize greater increases population-wide.

Declining liver graft quality threatens the future of liver transplantation in the United States.

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level.

COVSIM: A stochastic agent-based COVID-19 SIMulation model for North Carolina.

We document the evolution and use of the stochastic agent-based COVID-19 simulation model (COVSIM) to study the impact of population behaviors and public health policy on disease spread within age, race/ethnicity, and urbanicity subpopulations in North Carolina. We detail the methodologies used to model the complexities of COVID-19, including multiple agent attributes (i.e., age, race/ethnicity, high-risk medical status), census tract-level interaction network, disease state network, agent behavior (i.e., masking, pharmaceutical intervention (PI) uptake, quarantine, mobility), and variants. We describe its uses outside of the COVID-19 Scenario Modeling Hub (CSMH), which has focused on the interplay of nonpharmaceutical and pharmaceutical interventions, equitability of vaccine distribution, and supporting local county decision-makers in North Carolina. This work has led to multiple publications and meetings with a variety of local stakeholders. When COVSIM joined the CSMH in January 2022, we found it was a sustainable way to support new COVID-19 challenges and allowed the group to focus on broader scientific questions. The CSMH has informed adaptions to our modeling approach, including redesigning our high-performance computing implementation.

Evaluating the potential impact of rubella-containing vaccine introduction on congenital rubella syndrome in Afghanistan, Dem. Republic of Congo, Ethiopia, Nigeria, and Pakistan: A mathematical modeling study.

We assessed the potential impact of introducing rubella-containing vaccine (RCV) on congenital rubella syndrome (CRS) incidence in Afghanistan (AFG), Democratic Republic of Congo (COD), Ethiopia (ETH), Nigeria (NGA), and Pakistan (PAK). We simulated several RCV introduction scenarios over 30 years using a validated mathematical model. Our findings indicate that RCV introduction could avert between 86,000 and 535,000 CRS births, preventing 2.5 to 15.8 million disability-adjusted life years. AFG and PAK could reduce about 90% of CRS births by introducing RCV with current measles routine coverage and executing supplemental immunization activities (SIAs). However, COD, NGA, and ETH must increase their current routine vaccination coverage to reduce CRS incidence significantly. This study showcases the potential benefits of RCV introduction and reinforces the need for global action to strengthen immunization programs.

A proposed modification to the Kellgren and Lawrence classification for knee osteoarthritis using a compartment-specific approach.

Purpose: Since Kellgren and Lawrence (KL) originally classified knee osteoarthritis, several authors have reported varying levels of reliability and a lack of uniformity in the use of this classification system. We propose several modifications to the KL classification including the use of a compartment-specific approach that we hypothesize will lead to a better understanding of knee OA while maintaining an adequate interobserver and intraobserver reliability. Methods: We propose the addition of the lateral and skyline-view radiographs to the standard anteroposterior (AP) and lateral projections in the evaluation. Also suggest a more precise definition of the evaluated parameters; the addition of the subchondral cancellous bone as parameter of evaluation; and the assessment of medial tibiofemoral compartment (MTFC), lateral tibiofemoral compartment (LTFC) and patellofemoral compartment (PFC) separately resulting in a compartment-specific KL staging score rather than a single overall KL score. Six evaluators (two knee surgeons, two radiologists and two knee fellows) used the modified KL classification to classify 230 randomly selected knees on two separate occasions. Reliabilities were assessed by calculating Krippendorff's ⍺ coefficients. Results: Two hundred and ten knees were included for final evaluation and analyses (53% left knees; 65% females; mean age 56 years old). Average interobserver reliability was moderate for all compartments (0.51 for the MTFC; 0.51 for the LTFC; and 0.56 for the PFC). Average intraobserver reliability was substantial for all compartments (0.63 for the MTFC; 0.65 for the LTFC; and 0.7 for the PFC). Experienced evaluators showed a higher intraobserver reliability than less-experienced evaluators. Conclusions: A modified compartment-specific KL classification enables a practical and detailed description of knee OA involvement and demonstrates acceptable interobserver and intraobserver reliability. Level of Evidence: Level III.

Estimated number of preterm births and low birth weight children born in the United States due to maternal binge drinking.

The objective of this study was to estimate the aggregate burden of maternal binge drinking on preterm birth (PTB) and low birth weight (LBW) across American sociodemographic groups in 2008. To estimate the aggregate burden of maternal binge drinking on preterm birth (PTB) and low birth weight (LBW) across American sociodemographic groups in 2008. A simulation model was developed to estimate the number of PTB and LBW cases due to maternal binge drinking. Data inputs for the model included number of births and rates of preterm and LBW from the National Center for Health Statistics; female population by childbearing age groups from the U.S. Census; increased relative risks of preterm and LBW deliveries due to maternal binge drinking extracted from the literature; and adjusted prevalence of binge drinking among pregnant women estimated in a multivariate logistic regression model using Behavioral Risk Factor Surveillance System survey. The most conservative estimates attributed maternal binge drinking to 8,701 (95% CI: 7,804-9,598) PTBs (1.75% of all PTBs) and 5,627 (95% CI 5,121-6,133) LBW deliveries in 2008, with 3,708 (95% CI: 3,375-4,041) cases of both PTB and LBW. The estimated rate of PTB due to maternal binge drinking was 1.57% among all PTBs to White women, 0.69% among Black women, 3.31% among Hispanic women, and 2.35% among other races. Compared to other age groups, women ages 40-44 had the highest adjusted binge drinking rate and highest PTB rate due to maternal binge drinking (4.33%). Maternal binge drinking contributed significantly to PTB and LBW differentially across sociodemographic groups.

Maternal pre-pregnancy weight and gestational weight gain and their association with birthweight with a focus on racial differences.

Our objectives were to examine the interaction between maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) and their association with birthweight, with a focus on racial differences. We used birth certificate data from live singleton births of South Carolina resident mothers, who self-reported their race as non-Hispanic white (NHW, n = 140, 128) or non-Hispanic black (NHB, n = 82,492) and who delivered at 34-44 weeks of gestation between 2004 and 2008 to conduct a cross-sectional study. Linear regression was used to examine the relationship between our exposures (i.e., race, BMI and GWG) and our outcome birthweight. Based on 2009 Institute of Medicine guidelines, the prevalence of adequate, inadequate and excessive GWG was 27.1, 24.2 and 48.7%, respectively, in NHW women and 24.2, 34.8 and 41.0%, respectively, in NHB women. Adjusting for infant sex, gestational age, maternal age, tobacco use, education, prenatal care, and Medicaid, the difference in birthweight between excessive and adequate GWG at a maternal BMI of 30 kg/m(2) was 118 g (95% CI: 109, 127) in NHW women and 101 g (95% CI: 91, 111) in NHB women. Moreover, excessive versus adequate GWG conveyed similar protection from having a small for gestational age infant in NHW [OR = 0.64 (95% CI 0.61, 0.67)] and NHB women [OR = 0.68 (95% CI: 0.65, 0.72)]. In conclusion, we report a strong association between excessive GWG and higher infant birthweight across maternal BMI classes in NHW and NHB women. Given the high prevalence of excessive GWG even a small increase in birthweight may have considerable implications at the population level.

Squamous Cell Carcinoma In Situ of the Breast With the Configuration of an Intraductal Papilloma.

A 64-year-old woman presented to our institution with a palpable and painful left breast mass. She denied any other breast symptoms. Subsequent imaging classified it as a US Breast Imaging-Reporting and Data System (BI-RADS) 4A lesion. A core needle biopsy was performed showing atypical proliferating fragments of squamous epithelium suspicious for malignant neoplasm. An excisional biopsy was recommended. Gross examination showed a well-circumscribed pink soft mass measuring 2.0 x 1.4 x 1.3 cm. The entire lesion was submitted for histologic evaluation, demonstrating a neoplasm with branching stroma and exuberant squamous differentiation. The lesion exhibited obvious cytologic features of malignancy like mitotic figures, prominent nucleoli, irregular nuclei, and multinucleation. Collagen IV stain ruled out invasion. The lesion was finally classified as squamous cell carcinoma (SCC) in situ with the configuration of an intraductal papilloma. The possibility of metastatic disease was suggested. A PET scan was negative, and no other foci of disease were found in the remainder of the specimen. The mass was also independent of nipple and skin. Based on the architectural features, we believe that this is a case of an intraductal papilloma that underwent complete squamous metaplasia with no residual adenomyoepithelial components and transformation into an SCC in situ demonstrated by stains. Papillomas can undergo reactive metaplastic changes, usually benign and in small foci. This is the first reported case of exuberant squamous epithelium that transformed into carcinoma in situ with papillary architecture in the breast.

Quantifying association and disparities between diabetes complications and COVID-19 outcomes: A retrospective study using electronic health records.

BACKGROUND: Despite established relationships between diabetic status and an increased risk for COVID-19 severe outcomes, there is a limited number of studies examining the relationships between diabetes complications and COVID-19-related risks. We use the Adapted Diabetes Complications Severity Index to define seven diabetes complications. We aim to understand the risk for COVID-19 infection, hospitalization, mortality, and longer length of stay of diabetes patients with complications. METHODS: We perform a retrospective case-control study using Electronic Health Records (EHRs) to measure differences in the risks for COVID-19 severe outcomes amongst those with diabetes complications. Using multiple logistic regression, we calculate adjusted odds ratios (OR) for COVID-19 infection, hospitalization, and in-hospital mortality of the case group (patients with diabetes complications) compared to a control group (patients without diabetes). We also calculate adjusted mean difference in length of stay between the case and control groups using multiple linear regression. RESULTS: Adjusting demographics and comorbidities, diabetes patients with renal complications have the highest odds for COVID-19 infection (OR = 1.85, 95% CI = [1.71, 1.99]) while those with metabolic complications have the highest odds for COVID-19 hospitalization (OR = 5.58, 95% CI = [3.54, 8.77]) and in-hospital mortality (OR = 2.41, 95% CI = [1.35, 4.31]). The adjusted mean difference (MD) of hospital length-of-stay for diabetes patients, especially those with cardiovascular (MD = 0.94, 95% CI = [0.17, 1.71]) or peripheral vascular (MD = 1.72, 95% CI = [0.84, 2.60]) complications, is significantly higher than non-diabetes patients. African American patients have higher odds for COVID-19 infection (OR = 1.79, 95% CI = [1.66, 1.92]) and hospitalization (OR = 1.62, 95% CI = [1.39, 1.90]) than White patients in the general diabetes population. However, White diabetes patients have higher odds for COVID-19 in-hospital mortality. Hispanic patients have higher odds for COVID-19 infection (OR = 2.86, 95% CI = [2.42, 3.38]) and shorter mean length of hospital stay than non-Hispanic patients in the general diabetes population. Although there is no significant difference in the odds for COVID-19 hospitalization and in-hospital mortality between Hispanic and non-Hispanic patients in the general diabetes population, Hispanic patients have higher odds for COVID-19 hospitalization (OR = 1.83, 95% CI = [1.16, 2.89]) and in-hospital mortality (OR = 3.69, 95% CI = [1.18, 11.50]) in the diabetes population with no complications. CONCLUSIONS: The presence of diabetes complications increases the risks of COVID-19 infection, hospitalization, and worse health outcomes with respect to in-hospital mortality and longer hospital length of stay. We show the presence of health disparities in COVID-19 outcomes across demographic groups in our diabetes population. One such disparity is that African American and Hispanic diabetes patients have higher odds of COVID-19 infection than White and Non-Hispanic diabetes patients, respectively. Furthermore, Hispanic patients might have less access to the hospital care compared to non-Hispanic patients when longer hospitalizations are needed due to their diabetes complications. Finally, diabetes complications, which are generally associated with worse COVID-19 outcomes, might be predominantly determining the COVID-19 severity in those infected patients resulting in less demographic differences in COVID-19 hospitalization and in-hospital mortality.

Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub.

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.