United States

Background
High-deductible health plans (HDHPs) have grown rapidly in recent years, and now cover more than half of U.S. workers. Patients in HDHPs are liable for the costs of all cancer-related care until their annual deductible is met, with the exception of screening tests such as colonoscopy and mammography. Due to higher out-of-pocket costs, patients may postpone presenting for concerning symptoms or diagnostic testing, leading to delayed diagnosis. We sought to assess the impacts of HDHPs on the timing of metastatic cancer detection in a nationally representative cohort of cancer patients.

Methods
Using a cohort of privately insured patients age 18-64 in a national commercial and Medicare Advantage database (2003-2017), we studied 2,703 individuals with cancer whose employers mandated a switch from a low-deductible (≤$500) plan to a high-deductible (≥$1,000) plan. Our control group consisted of 43,005 contemporaneous individuals with cancer whose employers offered only low-deductible plans. Both groups had a 1-year baseline period when all members were enrolled in low-deductible plans. Members were followed for a maximum of 4 years. To address potential confounding, HDHP and control participants were matched on demographic variables, morbidity score, baseline health care utilization, cancer type and timing, follow-up duration, and employer characteristics. We assessed time to metastatic cancer diagnosis in the baseline and follow-up periods using a weighted Cox proportional hazards model. 

Results
The mean age of participants was 53; 59% were female. We detected 4,741 cases of metastatic progression. There were no differences in time to metastatic diagnosis in the baseline year, prior to the HDHP switch (HR 0.99, p = 0.93). After employer-mandated HDHP switch, cancer patients enrolled in HDHPs experienced later detection of metastatic cancer (HR 0.70, p = 0.04), equivalent to a delay of 8.5 months relative to the control group. 

Conclusion
Compared with conventional insurance, HDHPs are associated with delayed detection of metastatic cancer. These findings imply that cancer patients postpone seeking care for concerning symptoms or defer diagnostic testing when exposed to high cost-sharing. Future policy efforts should aim to protect cancer patients from burdensome costs-sharing requirements to ensure timely detection and treatment of metastatic cancer.

AMA Research Challenge 2022

Impact of high-deductible health plans on delays in metastatic cancer diagnosis

We are inviting nursing administrators, faculty members, instructors, and students to attend this conference, which will feature current directions and priorities for the Uvic and College Partners BSN curriculum, and feature scholarship from throughout our partnership.


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### Situating Ourselves in Nursing Education: Exploring Emerging Directions
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University of Victoria and College Partners BSN Virtual Conference

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Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
The 2022 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. Log in at any time throughout the event to:
* **View posters and presentations** on a variety of topics and specialties
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At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges and compete to win a $10,000 grand prize sponsored by Laurel Road.
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Ricardo Correa, MD, EdD
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Stuart M. Greenstein, MD
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Stephanie Strohbeen, MD
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

### Sponsor
AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on Dec. 7 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Background: The annual bleeding risk for a brain arteriovenous malformation (AVM) is 2-8%, but obliterating the nidus reduces the risk to near population levels. We evaluate the outcomes of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in the treatment of brain AVMs in our institutional cohort.
Methods: The study comprises patients treated with SRS for AVMs with follow-up care greater than one month from 2014-2021. Baseline characteristics were compared between pediatric and adults in the sample. Time-to-event analyses were conducted using the Kaplan-Meier survival method. Statistical significance is defined as P<0.05; all tests were two-tailed; no adjustments were made for multiple comparisons. Influences of baseline characteristics were evaluated using simple or multiple logistic regression.
Results: Among 29 qualifying patients with SRS-treated AVMs, a mean nidus volume of 6.26cm3 (SD=9.12, Range=0.13-40.2) and nidus max diameter of 24.8mm (SD=15.9, Range=2- 60) were observed. The distribution of Spetzler-Martin (SM) grades were SM1 (3.3%), SM2 (23.3%), SM3 (50%), SM4 (16.7%) and SM5 (6.7%). Pretreatment included intervention for hemorrhage (65.5%), embolization (43.3%), and microsurgery (13.3%). SRS for the AVM involved VMAT approach (50%), conformal arc (36.7%) and step-and-shoot IMRT (10%). The mean target dose was 18.72Gy (SD=1.7, Range=13.5-22) and delivered primarily in one fraction (86.7%). Obliteration occurred in 53.3% of patients and median time to obliteration was 27.1 months. Mortality was 10.3% with only one-cause specific death (AVM hemorrhage). Median follow-up was 23.6 months (Range=3-50.7). Comparing adult and pediatric patients, significant factors affecting likelihood of SRS delivery were sex (p=0.05), race (p=0.0089), nidus max diameter (p=0.033), pre-treatment SRS (p=0.027) and neurological deficits at presentation (p=0.0169). Likelihood of obliteration decreased with increasing nidus volume with an estimated 10% for each additional cm3 (OR=0.90, 95% CI=0.82-0.99, p=0.027). Adverse Events (AE) were observed in 55.2% of patients with a median time to AE of 11.4 months. Nidus max diameter significantly affected rate of AE (HR=1.36, 95% CI=1.03-1.8, p=0.031).
Conclusion: SRS resulted in 53.3% of our cohort achieving obliteration (mean follow-up: 23.6mos). Adverse events occurred in 55.2% of patients, but most were mild and resolved. Pediatric patients obliterate at similar rates to their adult counterparts but on an accelerated time course.

Institutional Experience of Linear Accelerator-Based Stereotactic Radiosurgery For Brain Arteriovenous Malformations 


Compassionate behavior, or the ability to help others in need, is a cornerstone of prosocial interactions. To benefit others, it is necessary for individuals not only to perceive the internal states or emotions of others but also to take appropriate actions. Yet, how mammalian neurons precisely link social-specific information with adaptive behavior has been a major challenge to understand. Here, we developed a place-preference assay that allowed mice to directly control in real-time the experience of a nearby conspecific partner while also allowing the animal’s own actions to be dissociated from the other’s identity. Behaviorally, we found that wild-type male mice consistently chose to reduce aversive experiences of familiar but not unfamiliar partners, actions not observed when visual and olfactory cues were blocked. By recording from anterior insular (AI) neurons, we identified cells that encoded task relevant information, including the social identity of the animal’s partners and their specific experiences. Dorsal anterior cingulate (dACC) neurons, by contrast, preferentially encoded information about the act of helping their partners, displaying changes in activity prior to making their decisions. Further, whereas information about the experience of others could be predominantly decoded from AI activity, information about the animal’s prosocial actions could be predominantly decoded from dACC activity; demonstrating a partitioning of information within the insular-prefrontal circuit. Finally, chemogenetic excitation of AI-to-dACC projectors but not dACC-to-AI projections increased compassionate behavior while inhibitions of both dACC to AI as well as AI to dACC projectors, on the other hand, decreased this behavior with familiar partners. Taken together, these findings identify a putative insular-prefrontal circuit for driving compassionate behavior and a mechanism that could allow insular neurons to instruct social-specific actions through prefrontal control.

Insular-prefrontal circuit driving compassionate social behavior

Background: Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients and to propose a novel mechanism explaining corticosteroid benefits in patients regardless of HIV status. 
Methods: We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected from 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality. 
Results: Common underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. We propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents. 
Conclusions: We found substantial mortality among HIV-negative patients with PJP, and adjuvant corticosteroid use was associated with decreased mortality. Decreased PJP lysis reduces surfactant disruption resulting from pneumocystis internal substances. Suppressing pneumocystis lysis best explains the adjuvant corticosteroid mortality-lowering effect.


Lower mortality associated with adjuvant corticosteroid therapy in non-HIV infected patients with pneumocystis jirovecii pneumonia

Background: Total knee arthroplasty (TKA) was removed from the “Inpatient Only List”(IOL) in 2018, enabling access to outpatient TKA for a broader cohort of beneficiaries. The effect of this reimbursement policy across the U.S. has yet to be fully explored. Therefore, we aimed to: 1) quantify the annual volume of inpatient/outpatient primary TKAs; 2) compare patient characteristics before/after 2018; and 3) compare annual trends in 30-day-readmissions, 30-day- complications, and healthcare utilization parameters for inpatient/outpatient TKAs.

Methods: The American College of Surgeons-National Surgical Quality Improvement Program was reviewed (January 2010 - December 2020) for patients who underwent primary TKA (n=470,456). The primary outcome was annual volumes of inpatient/outpatient TKA. Secondary outcomes included 30-day-readmissions, 30-day-reoperations, and 30-day-major/minor complications. Demographic characteristics and healthcare utilization parameters were compared between cohorts via Chi-square goodness of fit tests. All analyses were performed using R version 4.2.1.

Results: Overall, 89% had inpatient TKA (n=416,972) and 11% had outpatient TKA (n=53,854). Between 2017 and 2020, the volume of outpatient TKA grew by 2,025% (1,019 to 20,633), while inpatient TKA decreased by 47% (61,874 to 29,280). Patients who had outpatient TKA after 2018 were older (p<0.001), predominantly male (p<0.001), more commonly White (p<0.001), and had a greater proportion of ASA class III (p<0.001). Overall, patients who had inpatient TKA had higher rates of 30-day readmissions, reoperations, and complications. Average LOS and non-home discharges decreased for both cohorts.

Conclusion: Outpatient TKA increased exponentially since its removal from the IOL. The observed changes in comorbidity profiles and the increase in volumes of outpatient TKA were not associated with a rise in cumulative 30-day readmissions and complications, supporting the continued implementation of outpatient TKA. Further research and policy endeavors should focus on enhancing outpatient care pathways and building tools to identify patients who would benefit from inpatient TKA.

Major National Shifts to Outpatient Total Knee Arthroplasties in The United States: A 10-year Trends Analysis Of Procedure Volumes, Complications, and Healthcare Utilizations (2010 to 2020)

Characterization of Salivary Extracellular Vesicles in Preterm Infants

Mosaic Chromosomal Alterations Increase Risk of MGUS and Multiple Myeloma

The aim of this study was to create an accurate risk stratification tool for Covid-19 admissions. We looked at data from 1093 patients admitted to a regional hospital in Michigan with the primary diagnosis of Covid-19. Through various statistical approaches we analyzed factors that lead to worse outcomes. We then combined our analysis to determine which predictive factor had a stronger influence on Covid-19 mortality. Our end goal is to use this data to drive clinical decision making by identifying patients at greater risk of worse outcomes.

Multifaceted, Data-Driven Approach for Characterization and Prediction of Covid-19 Morbidity and Mortality in Rural Health Care Facilities

Background: The purpose of this study was to define the prevalence of orthopaedic knee scooter (OKS)-related injuries, describe the patient perceptions of OKS safety and identify potential risk factors.
Methods: This single-surgeon prospective study enrolled 134 patients at a community-based orthopaedic clinic from 6/2020 to 4/2021. Our primary outcome informed an a priori power analysis. The prevalence of OKS-related injury, patient perceptions, and riskfactors were analyzed.
Results: The prevalence of patient falls was 37% (44/118, 95CI 29-46%), and the prevalence of patient injury was 15% (18/118, 95CI 10-23%). Sedentary lifestyle increased odds (OR = 4.67, 1.52-14.35 95CI) of OKS-related injury.
Conclusion: Despite a high prevalence of patient falls (37%), there is a low prevalence of injury (15%) and a favorable perception of OKS safety. Sedentary lifestyles may be a risk factor for OKS-related injury.

Orthopaedic Knee Scooter-Related Injury: Prevalence and Patient Safety Perception in a Prospective Cohort with Exploratory Risk Factor Analysis

Orthopaedic surgery, the NFL's biggest gateway drug: a case study

Background
Colorectal adenomas are precursors of colorectal cancer (CRC). Pro-inflammatory states associated with colorectal adenomas significantly predispose for colorectal tumorigenesis via upregulation of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis. The PGE2/COX-2 axis allows cancer cells to progress and evade attack from immune cells via increasing immunosuppressive cell activity, disrupting antigen-presenting and T-cell functions, and interrupting innate leukocyte responses. The purpose of this study was to demonstrate that PGE2 can upregulate expression of PD-1, an immunosuppressive signaling receptor, on THP-1-derived macrophages and CD8+ T-cells. 

Methods
THP-1 cells were differentiated into macrophages via phorbol 12-myristate-13-acetate (PMA) administration. Following serum starvation and incubation with three different concentrations of PGE2 (0.1μM, 0.3μM, and 1μM), the cells were analyzed with western blot and qRT-PCR. CD8+ T-cells were isolated from mice spleens using biotin-antibody cocktail and anti-biotin microbeads and then stimulated with rIL-2 and CD3/CD28 Dynabeads. The cells were serum starved, incubated with two different concentrations of PGE2 (0.1μM and 0.3μM), and analyzed utilizing flow cytometry and qRT-PCR.

Results
Western blot analysis of THP-1-derived macrophages incubated in 0.1μM, 0.3μM, and 1.0μM PGE2 demonstrated increased PD-1 expression. qRT-PCR analysis of THP-1-derived macrophages incubated in 0.1μM, 0.3μM, and 1.0μM PGE2 demonstrated 3.030-fold, 5.712-fold, and 2.683-fold increased PD-1 mRNA expression, respectively. qRT-PCR of mouse CD8+ T-cells incubated in 0.1μM and 0.3μM PGE2 demonstrated 1.874-fold and 9.594-fold increased PD-1 mRNA expression, respectively. Flow cytometry demonstrated that 9.14% and 9.35% of mouse CD8+ T-cells incubated in 0.1μM and 0.3μM PGE2 expressed PD-1, respectively, while 4.65% of control cells expressed PD-1. 

Conclusion
Our in vitro data shows PGE2 inducing PD-1 expression in THP-1-derived macrophages and mouse CD8+ T-cells. Greater PD-1 expression would allow cancer cells to progress safe from the host immune system. These data demonstrate that PGE2 produced in the colorectal tumor microenvironment promotes immune evasion by suppressing tumor-infiltrating CD8+ T-cell cytotoxicity and macrophage phagocytosis via induction of PD-1. Because of PGE2’s immunosuppressive effects, NSAIDs and COXIBs are effective at preventing and treating CRC by inhibiting PGE2 synthesis via COX-2 blockade.

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Impact of high-deductible health plans on delays in metastatic cancer diagnosis

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