Billed advance care planning visits may be occurring among older adults with high risk of mortality.

CONTEXT: Advance care planning (ACP) is a process that helps people prepare to make decisions about their future medical care. OBJECTIVES: We sought to understand who was received billed ACP visits and measure the association with health care utilization, cost, and mortality. METHODS: We used a randomly sampled 20 % cohort of Medicare fee-for-service (FFS) beneficiaries' files to conduct a retrospective cohort study. Beneficiaries with a billed ACP visit were matched to controls using a 2-stage propensity score matching process that included assigning a pseudo-ACP visit date for controls. Outcomes included healthcare utilization, mortality, and total medical cost per month. We used descriptive statistics for univariate analysis and fit multilevel logistic regression, multilevel linear regression, or Cox regression models. RESULTS: We identified 183,513 beneficiaries who received any billed ACP visit and 550,539 matched controls. Of those who had a ACP visit, the mean age was 76.5 years and high-risk comorbidities were common: 16 % dementia, 10 % congestive heart failure, 10 % cancer. Beneficiaries who had an ACP visit had slightly more health care utilization than controls. Beneficiaries who had an ACP visit were more likely to die (3.1% vs. 1.0 %, p < 0.01, OR=3.0, 95 %CI 2.9-3.2) in the unadjusted and adjusted analyses compared to matched controls. Total monthly medical costs were 33 % higher among beneficiaries who had an ACP visit. CONCLUSION: Our results suggest that ACP visits may be preferentially utilized amongst individuals with higher risk of mortality. There may be an opportunity to increase ACP visits among older adults at lower risk for mortality. KEY MESSAGE: This article suggests that ACP visits are likely targeted to older adults with a higher risk of mortality than those at lower risk of mortality suggesting an opportunity to reach people before they are facing end-of-life decisions.

CD39 is expressed on functional effector and tissue resident memory CD8+ T cells.

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while it's co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) in vivo . Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory (T RM ) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine T RM across several non-lymphoid tissues and melanoma, while CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ T RM are fully functional when stimulated ex vivo with cognate antigen. This work further expands the identity of CD39 beyond a T cell exhaustion marker.

Dural composite hemangioendothelioma: The first intracranial case.

Background: Composite hemangioendothelioma (CHE) is a rare, locally aggressive neoplasm of intermediate malignant potential. It is composed of a mixture of vascular tumors with a predilection for the dermis and subcutis of the extremities. Case Description: In this report, we describe a 41-year-old man who presented with a 2-month history of headache, dizziness, and intermittent seizures. Magnetic resonance imaging showed a hemorrhagic, multilobulated, and dural-based mass with extension into the calvarium. The mass measured 10.3 × 4.8 × 4 cm along the interhemispheric fissure and encased the superior sagittal sinus. Excision was performed, and histopathologic examination revealed a heterogeneous mixture of vascular components consisting of epithelioid hemangioendothelioma, retiform hemangioendothelioma, and hemangioma. This is the first report of a primary intracranial CHE. Conclusion: The spectrum of mesenchymal neoplasms within the cranium expands to encompass CHE.

Patient Travel Distance to Neurologist Visits.

BACKGROUND AND OBJECTIVES: The density of neurologists within a given geographic region varies greatly across the United States. We aimed to measure patient travel distance and travel time to neurologist visits, across neurologic conditions and subspecialties. Our secondary goal was to identify factors associated with long-distance travel for neurologic care. METHODS: We performed a cross-sectional analysis using a 2018 Medicare sample of patients with at least 1 outpatient neurologist visit. Long-distance travel was defined as driving distance ≥50 miles 1-way to the visit. Travel time was measured as driving time in minutes. Multilevel generalized linear mixed models with logistic link function, which accounted for clustering of patients within hospital referral region and allowed modeling of region-specific random effects, were used to determine the association of patient and regional characteristics with long-distance travel. RESULTS: We identified 563,216 Medicare beneficiaries with a neurologist visit in 2018. Of them, 96,213 (17%) traveled long distance for care. The median driving distance and time were 81.3 (interquartile range [IQR]: 59.9-144.2) miles and 90 (IQR: 69-149) minutes for patients with long-distance travel compared with 13.2 (IQR: 6.5-23) miles and 22 (IQR: 14-33) minutes for patients without long-distance travel. Comparing across neurologic conditions, long-distance travel was most common for nervous system cancer care (39.6%), amyotrophic lateral sclerosis [ALS] (32.1%), and MS (22.8%). Many factors were associated with long-distance travel, most notably low neurologist density (first quintile: OR 3.04 [95% CI 2.41-3.83] vs fifth quintile), rural setting (4.89 [4.79-4.99]), long-distance travel to primary care physician visit (3.6 [3.51-3.69]), and visits for ALS and nervous system cancer care (3.41 [3.14-3.69] and 5.27 [4.72-5.89], respectively). Nearly one-third of patients bypassed the nearest neurologist by 20+ miles, and 7.3% of patients crossed state lines for neurologist care. DISCUSSION: We found that nearly 1 in 5 Medicare beneficiaries who saw a neurologist traveled ≥50 miles 1-way for care, and travel burden was most common for lower-prevalence neurologic conditions that required coordinated multidisciplinary care. Important potentially addressable predictors of long-distance travel were low neurologist density and rural location, suggesting interventions to improve access to care such as telemedicine or neurologic subspecialist support to local neurologists. Future work should evaluate differences in clinical outcomes between patients with long-distance travel and those without.

Predictors of referral for long-term EEG monitoring for Medicare beneficiaries with drug-resistant epilepsy.

OBJECTIVE: For people with drug-resistant epilepsy, the use of epilepsy surgery is low despite favorable odds of seizure freedom. To better understand surgery utilization, we explored factors associated with inpatient long-term EEG monitoring (LTM), the first step of the presurgical pathway. METHODS: Using 2001-2018 Medicare files, we identified patients with incident drug-resistant epilepsy using validated criteria of ≥2 distinct antiseizure medication (ASM) prescriptions and ≥1 drug-resistant epilepsy encounter among patients with ≥2 years pre- and ≥1 year post-diagnosis Medicare enrollment. We used multilevel logistic regression to evaluate associations between LTM and patient, provider, and geographic factors. We then analyzed neurologist-diagnosed patients to further evaluate provider/environmental characteristics. RESULTS: Of 12 044 patients with incident drug-resistant epilepsy diagnosis identified, 2% underwent surgery. Most (68%) were diagnosed by a neurologist. In total, 19% underwent LTM near/after drug-resistant epilepsy diagnosis; another 4% only underwent LTM much prior to diagnosis. Patient factors most strongly predicting LTM were age <65 (adjusted odds ratio 1.5 [95% confidence interval 1.3-1.8]), focal epilepsy (1.6 [1.4-1.9]), psychogenic non-epileptic spells diagnosis (1.6 [1.1-2.5]) prior hospitalization (1.7, [1.5-2]), and epilepsy center proximity (1.6 [1.3-1.9]). Additional predictors included female gender, Medicare/Medicaid non-dual eligibility, certain comorbidities, physician specialties, regional neurologist density, and prior LTM. Among neurologist-diagnosed patients, neurologist <10 years from graduation, near an epilepsy center, or epilepsy-specialized increased LTM likelihood (1.5 [1.3-1.9], 2.1 [1.8-2.5], 2.6 [2.1-3.1], respectively). In this model, 37% of variation in LTM completion near/after diagnosis was explained by individual neurologist practice and/or environment rather than measurable patient factors (intraclass correlation coefficient 0.37). SIGNIFICANCE: A small proportion of Medicare beneficiaries with drug-resistant epilepsy completed LTM, a proxy for epilepsy surgery referral. While some patient factors and access measures predicted LTM, non-patient factors explained a sizable proportion of variance in LTM completion. To increase surgery utilization, these data suggest initiatives targeting better support of neurologist referral.

A Validated Method to Identify Neuro-Ophthalmologists in a Large Administrative Claims Database.

BACKGROUND: Validated methods to identify neuro-ophthalmologists in administrative data do not exist. The development of such method will facilitate research on the quality of neuro-ophthalmic care and health care utilization for patients with neuro-ophthalmic conditions in the United States. METHODS: Using nationally representative, 20% sample from Medicare carrier files from 2018, we identified all neurologists and ophthalmologists billing at least 1 office-based evaluation and management (E/M) outpatient visit claim in 2018. To isolate neuro-ophthalmologists, the National Provider Identifier numbers of neuro-ophthalmologists in the North American Neuro-Ophthalmology Society (NANOS) directory were collected and linked to Medicare files. The proportion of E/M visits with International Classification of Diseases-10 diagnosis codes that best distinguished neuro-ophthalmic care ("neuro-ophthalmology-specific codes" or NSC) was calculated for each physician. Multiple logistic regression models assessed predictors of neuro-ophthalmology specialty designation after accounting for proportion of ophthalmology, neurology, and NSC claims and primary specialty designation. Sensitivity, specificity, and positive predictive value (PPV) for varying proportions of E/M visits with NSC were calculated. RESULTS: We identified 32,293 neurologists and ophthalmologists who billed at least 1 outpatient E/M visit claim in 2018 in Medicare. Of the 472 NANOS members with a valid individual National Provider Identifier, 399 (84.5%) had a Medicare outpatient E/M visit in 2018. The model containing only the proportion of E/M visits with NSC best predicted neuro-ophthalmology specialty designation (odds ratio 1.05 [95% confidence interval 1.04, 1.05]; P < 0.001; area under the receiver operating characteristic [AUROC] = 0.91). Model predictiveness for neuro-ophthalmology designation was maximized when 6% of all billed claims were for NSC (AUROC = 0.89; sensitivity: 84.0%; specificity: 93.9%), but PPV was low (14.9%). The threshold was unchanged when limited only to neurologists billing ≥1% ophthalmology claims or ophthalmologists billing ≥1% neurology claims, but PPV increased (33.3%). CONCLUSIONS: Our study provides a validated method to identify neuro-ophthalmologists who can be further adapted for use in other administrative databases to facilitate future research of neuro-ophthalmic care delivery in the United States.

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma.

Diffusely infiltrating gliomas are associated with high morbidity and mortality due to the infiltrative nature of tumor spread. They are morphologically complex tumors, with a high degree of proteomic variability across both the tumor itself and its heterogenous microenvironment. The malignant potential of these tumors is enhanced by the dysregulation of proteins involved in several key pathways, including processes that maintain cellular stability and preserve the structural integrity of the microenvironment. Although there have been numerous bulk and single-cell glioma analyses, there is a relative paucity of spatial stratification of these proteomic data. Understanding differences in spatial distribution of tumorigenic factors and immune cell populations between the intrinsic tumor, invasive edge, and microenvironment offers valuable insight into the mechanisms underlying tumor proliferation and propagation. Digital spatial profiling (DSP) represents a powerful technology that can form the foundation for these important multilayer analyses. DSP is a method that efficiently quantifies protein expression within user-specified spatial regions in a tissue specimen. DSP is ideal for studying the differential expression of multiple proteins within and across regions of distinction, enabling multiple levels of quantitative and qualitative analysis. The DSP protocol is systematic and user-friendly, allowing for customized spatial analysis of proteomic data. In this experiment, tissue microarrays are constructed from archived glioblastoma core biopsies. Next, a panel of antibodies is selected, targeting proteins of interest within the sample. The antibodies, which are preconjugated to UV-photocleavable DNA oligonucleotides, are then incubated with the tissue sample overnight. Under fluorescence microscopy visualization of the antibodies, regions of interest (ROIs) within which to quantify protein expression are defined with the samples. UV light is then directed at each ROI, cleaving the DNA oligonucleotides. The oligonucleotides are microaspirated and counted within each ROI, quantifying the corresponding protein on a spatial basis.

Pineal region ganglioglioma: A neoplasm with a bimodal age distribution.

Background: Gangliogliomas arise very rarely in the pineal region, where their natural histories and pathologic features are poorly understood. Case Description: In this report, we describe a 36-year-old woman who presented with a seizure followed by worsening headache, dizziness, confusion, and intermittent left facial numbness over the next few weeks. A head CT scan showed a partially calcified pineal region mass with hydrocephalus. After an endoscopic third ventriculostomy, the patient underwent a resection of the tumor that contained dysplastic ganglion cells and piloid glial cells. Molecular profiling of this CNS WHO Grade 1 ganglioglioma revealed polysomies of chromosomes 7 and 9, and a BUB1 variant of uncertain significance, without known MAP kinase pathway alterations. From a review of the literature, we found two distinct age distributions for pineal ganglioglioma, with modes at 1 and 36 years of age. Conclusion: Although very rare, this tumor should be considered in the differential diagnosis of pineal region tumors in children and young adults.

The utility of the bilateral temporal artery biopsy for diagnosis of giant cell arteritis.

OBJECTIVE: A surgical temporal artery biopsy (TAB) is the gold standard for diagnosis of giant cell arteritis (GCA). The necessity of performing a bilateral biopsy remains under debate. The primary objective of this study was to assess the rate of discordance between pathology results in patients who underwent bilateral TAB for suspected GCA. METHODS: We performed a retrospective review of patients who underwent bilateral TAB for the diagnosis of GCA between 2011 and 2020. The primary end point was the rate of discordance between specimens for patients with pathology positive GCA. Secondary end points included assessments of the sensitivity of preoperative temporal artery duplex and the effects of specimen length and specialty of referring provider on the diagnostic yield of the biopsy. RESULTS: During the study period, 310 patients underwent bilateral TAB for the diagnosis of GCA. These patients were primarily female (73.9%), elderly (mean age, 70.8 years), and Caucasian (95.8%). Preoperative symptoms for patients were typically bilateral (59%) and included headache (81%), vision changes (45.2%), and temporal tenderness (32.6%). Most patients (85.2%) were on preoperative steroid therapy at the time of surgical biopsy with a mean preoperative duration of steroid therapy of 15.1 days. Overall, 91 patients (29.4%) had a positive pathologic diagnosis after bilateral TAB. Of these patients, 11 had a positive pathology result in only a single specimen, resulting in a discordance rate of 12.1%. Preoperative temporal artery duplex demonstrated a low sensitivity (27.3%) for identifying patients with pathologic positive disease. There were no significant differences between the pathology-positive and -negative patients in terms of mean surgical specimen length (1.67 cm vs 1.64 cm; P = .67) or the specialty of the referring provider (P = .73). CONCLUSIONS: At our institution, we observed a 12.1% discordance rate between pathology results in patients who underwent bilateral TAB for diagnosis of GCA. A preoperative temporal artery duplex provided little value in identifying patients with biopsy-proven GCA.

Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients.

PURPOSE: To evaluate targetable mutations and molecular genetic pathways in conjunctival melanoma with clinical correlation. DESIGN: Observational case series. PARTICIPANTS: Patients with conjunctival melanoma. MAIN OUTCOME MEASURES: Mutational profile of the tumor by next-generation sequencing (NGS), alternative lengthening of telomeres (ALT) by fluorescence in situ hybridization (FISH), and ATRX immunohistochemistry. Outcomes at 2 years and 5 years of tumor-related metastasis and death were recorded. RESULTS: Of the 101 patients, mean age at presentation was 60 years, 52% were male, and 88% were White. The NGS panels initially targeted BRAF only (n = 6, 6%), BRAF/NRAS (n = 17, 17%), and BRAF/NRAS/NF1 (n = 10, 10%). Sixty-eight tumors were tested with the expanded 592-gene panel. Next-generation sequencing identified high-frequency mutations in NF1 (29/74, 39%), BRAF (31/101, 31%), NRAS (25/95, 26%), and ATRX (17/68, 25%). Of those with an ATRX mutation, 12 (71%) had an additional NF1 mutation. A subset analysis of 21 melanomas showed that the ATRX mutation was associated with loss of ATRX protein expression and ALT. Loss of ATRX expression and ALT were present in both intraepithelial and invasive tumors, suggesting that an ATRX mutation is an early event in conjunctival melanoma progression. The NF1 and ATRX mutations were associated with tarsal (vs. nontarsal) tumors (NF1: 28% vs. 9%, P = 0.035, ATRX: 41% vs. 14%, P = 0.021) and orbital (vs. nonorbital) tumors (ATRX: 24% vs. 2%, P = 0.007). ATRXMUT (vs. ATRXWT) tumors were associated with a lower 2-year rate of metastasis (0% vs. 24%, P = 0.005). NRASMUT (vs. NRASWT) tumors were associated with a greater 2-year rate of metastasis (28% vs. 14%, P = 0.07) and death (16% vs. 4%, P = 0.04), with a 5-fold increased risk of death (relative risk, 5.45 [95% confidence interval, 1.11-26.71], P = 0.039). CONCLUSIONS: This study confirms the high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma. An NRAS mutation implied increased risk for metastasis and death. Loss of ATRX and ALT may be early events in conjunctival melanoma development.

Rosette-Forming Glioneuronal Tumor in the Pineal Region: A Series of 6 Cases and Literature Review.

Resected lesions from the pineal region are rare specimens encountered by surgical pathologists, and their heterogeneity can pose significant diagnostic challenges. Here, we reviewed 221 pineal region lesions resected at New York-Presbyterian Hospital/Columbia University Irving Medical Center from 1994 to 2019 and found the most common entities to be pineal parenchymal tumors (25.3%), glial neoplasms (18.6%), and germ cell tumors (17.6%) in this predominantly adult cohort of patients. Six cases of a rare midline entity usually found exclusively in the fourth ventricle, the rosette-forming glioneuronal tumor, were identified. These tumors exhibit biphasic morphology, with a component resembling pilocytic astrocytoma admixed with variable numbers of small cells forming compact rosettes and perivascular pseudorosettes. Targeted sequencing revealed a 100% co-occurrence of novel and previously described genetic alterations in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways, suggesting a synergistic role in tumor formation. The most common recurrent mutation, PIK3CA H1047R, was identified in tumor cells forming rosettes and perivascular pseudorosettes. A review of the literature revealed 16 additional cases of rosette-forming glioneuronal tumors in the pineal region. Although rare, this distinctive low-grade tumor warrants consideration in the differential diagnosis of pineal region lesions.

Definitions of Drug-Resistant Epilepsy for Administrative Claims Data Research.

BACKGROUND AND OBJECTIVE: To assess the accuracy of definitions of drug-resistant epilepsy applied to administrative claims data. METHODS: We randomly sampled 450 patients from a tertiary health system with ≥1 epilepsy/convulsion encounter, ≥2 distinct antiseizure medications (ASMs) from 2014 to 2020, and ≥2 years of electronic medical records (EMR) data. We established a drug-resistant epilepsy diagnosis at a specific visit by reviewing EMR data and using a rubric based on the 2010 International League Against Epilepsy definition. We performed logistic regressions to assess clinically relevant predictors of drug-resistant epilepsy and to inform claims-based definitions. RESULTS: Of 450 patients reviewed, 150 were excluded for insufficient EMR data. Of the 300 patients included, 98 (33%) met criteria for current drug-resistant epilepsy. The strongest predictors of current drug-resistant epilepsy were drug-resistant epilepsy diagnosis code (odds ratio [OR] 16.9, 95% confidence interval [CI] 8.8-32.2), ≥2 ASMs in the prior 2 years (OR 13.0, 95% CI 5.1-33.3), ≥3 nongabapentinoid ASMs (OR 10.3, 95% CI 5.4-19.6), neurosurgery visit (OR 45.2, 95% CI 5.9-344.3), and epilepsy surgery (OR 30.7, 95% CI 7.1-133.3). We created claims-based drug-resistant epilepsy definitions (1) to maximize overall predictiveness (drug-resistant epilepsy diagnosis; sensitivity 0.86, specificity 0.74, area under the receiver operating characteristics curve [AUROC] 0.80), (2) to maximize sensitivity (drug-resistant epilepsy diagnosis or ≥3 ASMs; sensitivity 0.98, specificity 0.47, AUROC 0.72), and (3) to maximize specificity (drug-resistant epilepsy diagnosis and ≥3 nongabapentinoid ASMs; sensitivity 0.42, specificity 0.98, AUROC 0.70). DISCUSSION: Our findings provide validation for several claims-based definitions of drug-resistant epilepsy that can be applied to a variety of research questions.

Suppression of Experimental Autoimmune Encephalomyelitis by ILT3.Fc.

Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS that is characterized by demyelination, axonal loss, gliosis, and inflammation. The murine model of MS is the experimental autoimmune encephalopathy (EAE) induced by immunization of mice with myelin oligodendrocyte glycoprotein (MOG)35-55 Ig-like transcript 3 (ILT3) is an inhibitory cell surface receptor expressed by tolerogenic human dendritic cells. In this study, we show that the recombinant human ILT3.Fc protein binds to murine immune cells and inhibits the release of proinflammatory cytokines that cause the neuroinflammatory process that result in paralysis. Administration of ILT3.Fc prevents the rapid evolution of the disease in C57BL/6 mice and is associated with a profound reduction of proliferation of MOG35-55-specific Th1 and Th17 cells. Inhibition of IFN-γ and IL-17A in mice treated with ILT3.Fc is associated with delayed time of onset of the disease and its evolution to a peak clinical score. Neuropathological analysis shows a reduction in inflammatory infiltrates and demyelinated areas in the brains and spinal cords of treated mice. These results indicate that inhibition of Th1 and Th17 development provides effective suppression of EAE and suggests the feasibility of a clinical approach based on the use of ILT3.Fc for treatment of MS. Furthermore, our results open the way to further studies on the effect of the human ILT3.Fc protein in murine experimental models of autoimmunity and cancer.

Institutional-Level Differences in Quality and Outcomes of Lung Cancer Resections in the United States.

BACKGROUND: Institutional-level disparities in non-small cell lung cancer (NSCLC) survival may be driven by reversible differences in care-delivery processes. We quantified the impact of differences in readily identifiable quality metrics on long-term survival disparities in resected NSCLC. RESEARCH QUESTION: How do reversible differences in oncologic quality of care contribute to institutional-level disparities in early-stage NSCLC survival? STUDY DESIGN AND METHODS: We retrospectively analyzed patients in the National Cancer Data Base who underwent NSCLC resection from 2004 through 2015 within institutions categorized as Community, Comprehensive Community, Integrated Network, Academic, and National Cancer Institute (NCI)-Designated Cancer Programs. We estimated percentages and adjusted ORs for six potentially avoidable poor-quality markers: incomplete resection, nonexamination of lymph nodes, nonanatomic resection, non-evidence-based use of adjuvant chemotherapy, non-evidence-based use of adjuvant radiation therapy, and 60-day postoperative mortality. By sequentially eliminating patients with poor-quality markers and calculating adjusted hazard ratios, we quantified their overall survival impact. RESULTS: Of 169,775 patients, 7%, 46%, 10%, 24%, and 12% underwent surgery at Community, Comprehensive Community, Integrated Network, Academic, and NCI-Designated Cancer Programs, with 5-year overall survival rates of 52%, 56%, 58%, 60% and 66%, respectively. After the sequential elimination process, using NCI-Designated Cancer Centers as a reference, the adjusted hazard ratio for 5-year overall survival changed from 1.47 (95% CI, 1.41-1.53), 1.29 (95% CI, 1.25-1.33), 1.18 (95% CI, 1.14-1.23), and 1.20 (95% CI, 1.16-1.24) for Community, Comprehensive Community, Integrated Networks, and Academic Cancer Programs to 1.35 (95% CI, 1.28-1.42), 1.22 (95% CI, 1.17-1.26), 1.16 (95% CI, 1.11-1.22), and 1.17 (95% CI, 1.12-1.21), respectively (P < .001 for all comparisons with NCI-designated programs). Differences in quality of surgical resection and postoperative care accounted for 11% to 26% of the interinstitutional survival disparities. INTERPRETATION: Targeting six readily identified poor-quality markers narrowed, but did not eliminate, institutional survival disparities. The greatest impact was in community programs. Residual factors driving persistent institution-level long-term NSCLC survival disparities must be characterized to eliminate them.

Association Between Steroid-Sparing Therapy and the Risk of Perianal Fistulizing Complications Among Young Patients With Crohn Disease.

Importance: Perianal fistulizing complications (PFCs) develop in 15% to 30% of patients with Crohn disease (CD), are difficult to treat, worsen quality of life, increase cost of care, and commonly recur. Evidence-based strategies to prevent PFCs are lacking. Objectives: To investigate the effectiveness of medical therapy for reducing risk of PFCs among young people with CD and to test the hypothesis that steroid-sparing therapy (SST) use would be associated with reduced risk of PFC development. Design, Setting, and Participants: In this comparative effectiveness analysis of commercial administrative claims from January 1, 2001, through June 30, 2016, patients who did or did not initiate SST were matched via propensity score to adjust for all available confounders. Using Optum's Clinformatics Data Mart, a deidentified database of US commercial administrative claims, all patients aged 5 to 24 years with CD (January 1, 2001, through June 30, 2016) were identified. The index date was the CD diagnosis date. Patients with PFCs or SST use at or before CD diagnosis were excluded. The dates of analysis were October 2017 to February 2020. Exposures: The primary exposure of interest was SST initiation, including immunomodulators and/or anti-tumor necrosis factor α (anti-TNFα) medications, initiated before either PFC development or the end of the study period. Main Outcomes and Measures: The primary outcome was PFC development. Propensity score matching was used to balance baseline characteristics. Cox proportional hazards multivariable regression analyses were used to estimate hazard ratios (HRs) with 95% CIs for PFC development. Results: Among 2214 young people with CD without PFCs identified, the mean (SD) age at CD diagnosis was 17.0 (4.5) years, and 1151 (52.0%) were male. Among the cohort, 1242 patients (56.1%) initiated SST before PFC development or the end of 24-month follow-up. After propensity score matching, 972 patients remained in each treatment group. Overall, 384 of 1944 (19.8%) developed PFCs within 2 years of the index date. The use of SST was associated with a 59% decreased risk of PFC development (hazard ratio [HR], 0.41; 95% CI, 0.33-0.52; P < .001) in 2 years compared with no SST use. Among those who developed PFCs, 55% fewer SST users underwent ostomy than SST nonusers. The use of immunomodulators alone, anti-TNFα alone, and combination therapy was associated with 52% (HR, 0.48; 95% CI, 0.37-0.62; P < .001), 47% (HR, 0.53; 95% CI, 0.36-0.78; P = .001), and 83% (HR, 0.17; 95% CI, 0.09-0.30; P < .001) reductions in the risk of 2-year PFC development, respectively, compared with no SST use. Conclusions and Relevance: In this study, PFC development was common among young patients with CD. The use of SST was lower than expected. Compared with no SST, patients who initiated SST were 59% less likely to develop PFCs and fewer underwent ostomy. These results indicate that PFCs may be preventable and emphasize the importance of considering SST for all patients with CD.

The impact of the Patient Protection and Affordable Care Act on insurance coverage and cancer-directed treatment in HIV-infected patients with cancer in the United States.

BACKGROUND: To the authors' knowledge, little is known regarding the impact of the Patient Protection and Affordable Care Act (ACA) on people living with HIV and cancer (PLWHC), who have lower cancer treatment rates and worse cancer outcomes. To investigate this research gap, the authors examined the effects of the ACA on insurance coverage and receipt of cancer treatment among PLWHC in the United States. METHODS: HIV-infected individuals aged 18 to 64 years old with cancer diagnosed between 2011 and 2015 were identified in the National Cancer Data Base. Health insurance coverage and cancer treatment receipt were compared before and after implementation of the ACA in non-Medicaid expansion and Medicaid expansion states using difference-in-differences analysis. RESULTS: Of the 4794 PLWHC analyzed, approximately 49% resided in nonexpansion states and were more often uninsured (16.7% vs 4.2%), nonwhite (65.2% vs 60.2%), and of low income (36.3% vs 26.9%) compared with those in Medicaid expansion states. After 2014, the percentage of uninsured individuals decreased in expansion states (from 4.9% to 3%; P = .01) and nonexpansion states (from 17.6% to 14.6%; P = .06), possibly due to increased Medicaid coverage in expansion states (from 36.9% to 39.2%) and increased private insurance coverage in nonexpansion states (from 29.5% to 34.7%). There was no significant difference in cancer treatment receipt noted between Medicaid expansion and nonexpansion states. However, the percentage of PLWHC treated at academic facilities increased significantly only in expansion states (from 40.2% to 46.7% [P < .0001]; difference-in-differences analysis: 7.2 percentage points [P = .02]). CONCLUSIONS: The implementation of the ACA was associated with improved insurance coverage among PLWHC. Lack of insurance still is common in non-Medicaid expansion states. Patients with minority or low socioeconomic status more often resided in nonexpansion states, thereby highlighting the need for further insurance expansion.