Search

Purpose To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis. Design Retrospective, interventional case series. Methods Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from 1/1/2018 to 1/1/2020 included: demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥ 2 lines, change in lens status or cataract surgery, and IOP ≥24 mm Hg. Results Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were Caucasian. Forty percent had bilateral disease; 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, p=0.02). Nine eyes had IOP elevation. Four eyes lost two lines or more of BCVA, one due to cataract progression. One eye underwent cataract surgery. Conclusions Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt’s lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin’s lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt’s (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade.

To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART).Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0-12.9 g/dl men, 11.0-11.9 g/dl women), moderate (8.0-10.9 g/dl regardless of sex) and severe (8.0 g/dl regardless of sex) anemia. Poisson regression models with robust variance and general estimating equations estimated crude and adjusted prevalence ratios (aPR) with 95% confidence intervals ([-]) comparing risk factors for moderate/severe vs. no/mild anemia between 2007 and 2017.Among 73 898 PWH we observed 366 755 hemoglobin measurements following ART initiation, 37 301 (50%) had one or more measures of anemia during follow-up (mild = 17 743 [24%]; moderate = 13 383[18%]; severe = 6175 [8%]). Moderate/severe anemia was more prevalent among women, non-Hispanic Black and Hispanic PWH (vs. non-Hispanic white), those with underweight body mass index (18.5 kg/m2) and with comorbidities and coinfections. Older age had increased prevalence of moderate/severe anemia among males and decreased prevalence among females. Prevalence of moderate/severe anemia was greater among those with lower CD4+ cell count (≤200 cells/μl) [aPR = 2.11 (2.06-2.17)] unsuppressed HIV viral load (200 copies/ml) [aPR = 1.26 (1.23-1.29)] and within the first 6 months of ART initiation (vs.1 year of ART) [aPR = 1.66 (1.61-1.72)].The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.

OBJECTIVE To project the future age distribution of people with HIV using antiretroviral therapy (ART) in the US, under expected trends in HIV diagnosis and survival (baseline scenario) and achieving the Ending the HIV Epidemic (EHE) goals of a 75% reduction in HIV diagnoses from 2020-25 and sustaining levels to 2030 (EHE75% scenario). DESIGN An agent-based simulation model with mathematical functions estimated from North American AIDS Cohort Collaboration on Research and Design data and parameters from the US Centers for Disease Control and Prevention's annual HIV surveillance reports. METHODS The PEARL (ProjEcting Age, multimoRbidity, and poLypharmacy in adults with HIV) model simulated individuals in 15 subgroups of sex-and-HIV acquisition risk and race/ethnicity. Simulation outcomes from the baseline scenario are compared with outcomes from the EHE75% scenario. RESULTS Under the baseline scenario, PEARL projects a substantial increase in number of ART-users over time, reaching a population of 909,638 [95%uncertaintyrange(UR):878,449-946,513] by 2030. The overall median age increased from 50 years (y) in 2020 to 52y in 2030, with 23% of ART-users age ≥65y in 2030. Under the EHE75% scenario, the projected number of ART-users was 718,348 [703,044-737,817] (median age=56y) in 2030, with a 70% relative reduction in ART-users

Background Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population. Objective To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time. Design Observational cohort study. Setting Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design. Participants 82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics. Measurements Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function. Results Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017. Limitation Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors. Conclusion Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population. Primary funding source National Institutes of Health.

The uveitides are a collection of over 30 diseases characterised by intraocular inflammation. Previous work demonstrated that the agreement among uveitis experts on diagnosis was modest at best with some pairs of experts having chance alone agreement on selected diseases. The Standardisation of Uveitis Nomenclature (SUN) is a17-year collaboration among experts in uveitis, ocular image grading, informatics, and machine learning to improve clinical and translational uveitis research. The SUN "Developing Classification Criteria for the Uveitides" project used a rigorous, multi-phase approach to develop classification criteria for 25 of the most common uveitic diseases. The project's phases were: (1) informatics; (2) case collection; (3) case selection; (4) machine learning; and (5) consensus review and publication. The results were classification criteria with a high degree of accuracy (93.3%-99.3% depending on anatomic class of the uveitis), the goal of which is to form the basis for future uveitis research.

Purpose To determine classification criteria for Fuchs uveitis syndrome. Design Machine learning of cases with Fuchs uveitis syndrome and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 146 cases of Fuchs uveitis syndrome, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for Fuchs uveitis syndrome included unilateral anterior uveitis with or without vitritis and either: 1) heterochromia or 2) unilateral diffuse iris atrophy and stellate keratic precipitates. The overall accuracy for anterior uveitides was 97.5% in the training set (95% confidence interval [CI] 96.3, 98.4) and 96.7% in the validation set (95% CI 92.4, 98.6). The misclassification rates for FUS were 4.7% in the training set and 5.5% in the validation set, respectively. Conclusions The criteria for Fuchs uveitis syndrome had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Purpose To determine classification criteria for Vogt-Koyanagi-Harada (VKH) disease Design Machine learning of cases with VKH disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve cases of panuveitides, including 156 cases of early-stage VKH and 103 cases of late-stage VKH, were evaluated. Overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for early-stage VKH included: 1) exudative retinal detachment with characteristic appearance on fluorescein angiogram or optical coherence tomography or 2) panuveitis with ≥2 of 5 neurologic symptoms/signs. Key criteria for late-stage VKH included history of early-stage VKH and either: 1) sunset glow fundus or 2) uveitis and ≥1 of 3 cutaneous signs. The misclassification rates in the learning and validation sets for early-stage VKH were 8.0% and 7.7%, respectively, and for late-stage VKH 1.0% and 12%, respectively. Conclusions The criteria for VKH had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis (CAU). Design Machine learning of cases with JIA CAU and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 202 cases of JIA CAU, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for JIA CAU included 1) chronic anterior uveitis (or if newly diagnosed insidious onset) and 2) JIA, except for the systemic, rheumatoid factor-positive polyarthritis, and enthesitis related arthritis variants. The misclassification rates for JIA CAU were 2.4% in the training set and 0% in the validation set, respectively. Conclusions The criteria for JIA CAU had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.

Purpose To determine classification criteria for tubercular uveitis DESIGN: Machine learning of cases with tubercular uveitis and 14 other uveitides. Methods Cases of non-infectious posterior or panuveitis, and of infectious posterior or panuveitis were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation sets. Results Two hundred seventy-seven cases of tubercular uveitis were evaluated by machine learning against other uveitides. Key criteria for tubercular uveitis were a compatible uveitic syndrome, including: 1) anterior uveitis with iris nodules, 2) serpiginous-like tubercular choroiditis, 3) choroidal nodule (tuberculoma), 4) occlusive retinal vasculitis, and 5) in hosts with evidence of active systemic tuberculosis, multifocal choroiditis; and evidence of tuberculosis, including: 1) histologically- or microbiologically-confirmed infection, 2) positive interferon-Ɣ release assay test, or 3) positive tuberculin skin test. The overall accuracy of the diagnosis of tubercular uveitis versus other uveitides in the validation set was 98.2% (95% CI 96.5, 99.1). The misclassification rates for tubercular uveitis were: training set 3.4%; and validation set 3.6%. Conclusions The criteria for tubercular uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for varicella zoster virus (VZV) anterior uveitis DESIGN: Machine learning of cases with VZV anterior uveitis and 8 other anterior uveitides. Methods Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand eighty-three cases of anterior uveitides, including 123 cases of VZV anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for VZV anterior uveitis included unilateral anterior uveitis with either 1) positive aqueous humor polymerase chain reaction assay for VZV; 2) sectoral iris atrophy in a patient ≥60 years of age; or 3) concurrent or recent dermatomal herpes zoster. The misclassification rates for VZV anterior uveitis were 0.9% in the training set and 0% in the validation set, respectively. Conclusions The criteria for VZV anterior uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU) DESIGN: : Machine learning of cases with MFCPU and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included: 1) multifocal choroiditis with the predominant lesions size >125 µm in diameter; 2) lesions outside the posterior pole (with or without posterior involvement); and either 3) punched-out atrophic chorioretinal scars or 4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set. Conclusions The criteria for MFCPU had a reasonably low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

To determine classification criteria for acute retinal necrosis (ARN).Machine learning of cases with ARN and 4 other infectious posterior uveitides / panuveitides.Cases of infectious posterior uveitides / panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.Eight hundred three cases of infectious posterior uveitides / panuveitides, including 186 cases of ARN, were evaluated by machine learning. Key criteria for ARN included (1) peripheral necrotizing retinitis and either (2) polymerase chain reaction assay of an intraocular fluid specimen positive for either herpes simplex virus or varicella zoster virus or (3) a characteristic clinical appearance with circumferential or confluent retinitis, retinal vascular sheathing and/or occlusion, and more than minimal vitritis. Overall accuracy for infectious posterior uveitides / panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for ARN were 15% in the training set and 11.5% in the validation set.The criteria for ARN had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for Behcet disease uveitis. Design Machine learning of cases with Behcet disease and 5 other panuveitides. Methods Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. Results One thousand twelve of cases panuveitides, including 194 cases of Behcet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behcet disease uveitis were a diagnosis of Behcet disease using the International Study Group for Behcet Disease criteria and a compatible uveitis, including: 1) anterior uveitis; 2) anterior chamber and vitreous inflammation; 3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or 4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behcet disease uveitis were 0.6 % in the training set and 0% in the validation set, respectively. Conclusions The criteria for Behcet disease uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for cytomegalovirus (CMV) retinitis. DESIGN: Machine learning of cases with CMV retinitis and 4 other infectious posterior/panuveitides. METHODS: Cases of infectious posterior/panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: Eight hundred three cases of infectious posterior/panuveitides, including 211 cases of CMV retinitis, were evaluated by machine learning. Key criteria for CMV retinitis included: 1) necrotizing retinitis with indistinct borders due to numerous small satellites; 2) evidence of immune compromise; and either 3) a characteristic clinical appearance or 4) positive polymerase chain assay for CMV from an intraocular specimen. Characteristic appearances for CMV retinitis included: 1) wedge-shaped area of retinitis; 2) hemorrhagic retinitis; or 3) granular retinitis. Overall accuracy for infectious posterior/panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for CMV retinitis were 6.9% in the training set and 6.3% in the validation set. CONCLUSIONS: The criteria for CMV retinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for sarcoidosis-associated uveitis DESIGN: Machine learning of cases with sarcoid uveitis and 15 other uveitides. Methods Cases of anterior, intermediate, and panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training sets to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation sets. Results One thousand eighty-three anterior uveitides, 589 intermediate uveitides, and 1012 panuveitides, including 278 cases of sarcoidosis-associated uveitis, were evaluated by machine learning. Key criteria for sarcoidosis-associated uveitis included a compatible uveitic syndrome of any anatomic class and evidence of sarcoidosis, either 1) a tissue biopsy demonstrating non-caseating granulomata or 2) bilateral hilar adenopathy on chest imaging. The overall accuracy of the diagnosis of sarcoidosis-associated uveitis in the validation set was 99.7% (95% confidence interval 98.8, 99.9).The misclassification rates for sarcoidosis-associated uveitis in the training sets were: anterior uveitis 3.2%, intermediate uveitis 2.6%, and panuveitis 1.2%; in the validation sets the misclassification rates were: anterior uveitis 0%, intermediate uveitis 0%, and panuveitis 0%, respectively. Conclusions The criteria for sarcoidosis-associated uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

Purpose To determine classification criteria for birdshot chorioretinitis. Design Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides. Methods Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. Results One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with: 1) the characteristic appearance a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); 2) absent to mild anterior chamber inflammation; and 3) absent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either: 1) classic "birdshot spots" or 2) characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set. Conclusions The criteria for birdshot chorioretinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for syphilitic uveitis DESIGN: Machine learning of cases with syphilitic uveitis and 24 other uveitides. METHODS: Cases of anterior, intermediate, posterior, and panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were analyzed by anatomic class, and each class was split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the different uveitic classes. The resulting criteria were evaluated on the validation set. RESULTS: Two hundred twenty-two cases of syphilitic uveitis were evaluated by machine learning with cases evaluated against other uveitides in the relevant uveitic class. Key criteria for syphilitic uveitis included a compatible uveitic presentation, (1) anterior uveitis, 2) intermediate uveitis, or 3) posterior or panuveitis with retinal, retinal pigment epithelial, or retinal vascular inflammation) and evidence of syphilis infection with a positive treponemal test. The Centers for Disease Control and Prevention reverse screening algorithm for syphilis testing is recommended. The misclassification rates for syphilitic uveitis in the training sets were: anterior uveitides 0%, intermediate uveitides 6.0%, posterior uveitides 0%, panuveitides 0%, and infectious posterior/panuveitides 8.6%. The overall accuracy of the diagnosis of syphilitic uveitis in the validation set was 100% (99% CI 99.5, 100) – i.e. the validation sets misclassification rates were 0% for each uveitic class. CONCLUSIONS: The criteria for syphilitic uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III).PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis).METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug.MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids.RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively.CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab.

The purpose of this study was to present a case of diffuse noncaseating granulomas involving the corneal stroma in a patient with ocular and pulmonary sarcoidosis.This was a single case report.A 31-year-old female patient presented with a 6-year history of panuveitis of the right eye along with a history of pulmonary sarcoidosis and a conjunctival biopsy of the right eye that was reported as positive for sarcoidosis. At presentation to our clinic, the patient had band keratopathy, vascularization of the inferonasal cornea, and active anterior uveitis of the right eye. When the patient returned for a follow-up of 15 months after the initial presentation, the cornea of the right eye exhibited widespread stromal scarring and vascularization. Because of the corneal scarring, the patient underwent an implantation of a Boston type 1 keratoprosthesis in the right eye. Histopathological examination of the host corneal tissue removed at the time of the keratoprosthesis procedure revealed extensive noncaseating granulomas in the deep corneal stroma. The patient underwent penetrating keratoplasty 8 months later, and histopathological examination again demonstrated noncaseating granulomas, this time at the edges of the donor corneal graft used during the keratoprosthesis implantation.We present the histopathological evidence of sarcoidosis involving the corneal stroma. Interestingly, the stromal keratitis also subsequently involved the donor cornea tissue after the patient underwent a keratoprosthesis implantation. It seems that sarcoidosis is a rare cause of stromal keratitis.

Purpose To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). Methods Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. Results Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. Conclusions A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

OBJECTIVE To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada. DESIGN HIV clinical cohort consortium. METHODS We followed PWH at least 18 years old in care 2005-2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load. RESULTS Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32-1.61] and Indigenous (1.99, 1.44-2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68-3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P

To quantitate the risk of relapse of ocular and extraocular disease among patients with mucous membrane pemphigoid (MMP) who had undergone drug-free remission.Retrospective, comparative, interventional case series.There were 167 patients with biopsy-proven MMP who were seen at the Wilmer Eye Institute between November 1984 and December 2019. Among the 167 patients, 119 patients had ocular involvement and 103 of those patients received systemic treatment for MMP. The main outcome measures were the incidence of ocular remission, incidence rate of disease relapse after remission, and risk factors for disease relapse.Over a median follow-up time of 7 years, 74 of 103 treated patients (71.8%) experienced drug-free remission (incidence rate = 0.28/person-year [PY], 95% confidence interval [CI] 0.22-0.35/PY). Most patients (80/103, 77.7%) received cyclophosphamide therapy. Thirteen of the 74 patients (17.6%) had disease relapse after remission: 4 with ocular disease only, 4 with extraocular disease only, and 5 with both. The rate relapse of ocular MMP was 0.020/PY (95% CI 0.009-0.038/PY), and the rate of relapse of MMP at any site (ocular or extraocular site) was 0.029/PY (95% CI 0.015-0.050/PY). The use of cyclophosphamide was associated with a greater chance of remission (hazard ratio [HR] = 3.84, P.0001) and a lower risk of relapse (HR = 0.32, P = .05) compared with other immunosuppressive drugs except for rituximab. Five patients experienced drug-free remission after rituximab therapy and none of them had relapse (median follow-up after remission = 3.6 years). When use of cyclophosphamide or rituximab was compared with all other treatments, the risk of MMP relapse at any site (HR = 0.17, P = .02) and of ocular MMP (HR = 0.11, P = .007) were significantly lower.Rates of relapse of MMP after drug-free remission are low but not zero; therefore, monitoring of patients remains necessary. Relapses were not observed among those patients treated with rituximab who had remission; however, follow-up duration in those patients was shorter than the whole MMP cohort and the sample size was small.

We evaluated the associations of clinical and demographic characteristics with visual acuity (VA) with over 5 years in a subspecialty noninfectious uveitis population.Retrospective data from 5,530 ...

Topic An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical relevance The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Topic The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Purpose To evaluate dexamethasone intravitreal implant effectiveness in lieu of high-dose oral prednisone for short-term treatment of noninfectious intermediate and posterior uveitis in patients requiring immunosuppression. Methods This is a proof-of-concept, open-label, non-comparative clinical trial with 12-month follow-up. The primary outcome was uveitis control without additional prednisone at 6 and 12 months. Secondary outcomes were need for multiple implants or additional prednisone, and safety data. Results 20 patients (28 eyes) were enrolled- 16 eyes had control by 6 months; 20 by 12 months. No patients required high-dose prednisone. 6 patients enrolled on prednisone: 2 stopped; 4 tapered to 7.5 mg daily or less by 12 months. 16 eyes required multiple implants; five required cataract surgery; 12 required drops to control IOP; 2 underwent glaucoma surgery. Conclusions The dexamethasone implant was effective in lieu of high-dose prednisone although the majority required multiple implants. All patients decreased or discontinued prednisone during follow-up.

AimsTo establish expert recommendations for the management of ocular sarcoidosis (OS).MethodsA question-based survey on the management of OS was circulated to international uveitis experts (members of the International Uveitis Study Group and the International Ocular Inflammation Society) electronically. Subsequently, a consensus workshop was conducted at the 7th International Workshop on Ocular Sarcoidosis (IWOS) in June 2019 in Sapporo, Japan as part of the Global Ocular Inflammation Workshops. Statements on the management of OS that were supported by a two-thirds majority of 10 international panel members of the workshop, after discussion and voting, were taken as consensus agreement.ResultsA total of 98 participants from 29 countries responded to the questionnaire survey. The subsequent consensus workshop established recommendations for the management of OS in five sections. The first section concerned evaluation and monitoring of inflammation. The second, third and fourth sections described ocular manifestations that were indications for treatment, and the management of anterior uveitis, intermediate uveitis and posterior uveitis. In the fifth section, the use of systemic corticosteroids and systemic immunosuppressive drugs were detailed.ConclusionsRecommendations for management of OS were formulated through an IWOS consensus workshop.

To evaluate if there is a difference in the clinical course of primary vitreoretinal lymphoma (PVRL) in vitrectomized versus non-vitrectomized eyes. Observational multicenter retrospective case series of patients diagnosed with PVRL between 2007 and 2019, at three tertiary centers. The main outcomes were relapse rates, inflammatory parameters, and best-corrected visual acuities (BCVA). Statistical methods used were an adjusted generalized estimating equation model, and a proportional Cox model. Eighty patients (150 eyes) were followed for a median of 1.7 years. At presentation, there were no clinical differences between the groups. The relapse rate was 0.091/eye-year (EY) for vitrectomized eyes and 0.087/EY for non-vitrectomized eyes (p = .35). Vitrectomized eyes had better BCVA than non-vitrectomized eyes (p < .001). Vitrectomy had no effect on the relapse rate in eyes with PVRL. However, the decrease in vitreous cell and debris led to vitrectomized eyes having better visual acuity than non-vitrectomized eyes.

BackgroundOcular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.Methods192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.ResultsFor 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.ConclusionOur report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

Purpose To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases. Design Retrospective analysis of cohort study data. Methods Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days. Results The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups. Conclusions Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.

BackgroundMortality among adults with human immunodeficiency virus (HIV) remains elevated over those in the US general population, even in the years after entry into HIV care. We explore whether the elevation in 5-year mortality would have persisted if all adults with HIV had initiated antiretroviral therapy within 3 months of entering care.MethodsAmong 82 766 adults entering HIV care at North American AIDS Cohort Collaboration clinical sites in the United States, we computed mortality over 5 years since entry into HIV care under observed treatment patterns. We then used inverse probability weights to estimate mortality under universal early treatment. To compare mortality with those for similar individuals in the general population, we used National Center for Health Statistics data to construct a cohort representing the subset of the US population matched to study participants on key characteristics.ResultsFor the entire study period (1999–2017), the 5-year mortality among adults with HIV was 7.9% (95% confidence interval [CI]: 7.6%–8.2%) higher than expected based on the US general population. Under universal early treatment, the elevation in mortality for people with HIV would have been 7.2% (95% CI: 5.8%–8.6%). In the most recent calendar period examined (2011–2017), the elevation in mortality for people with HIV was 2.6% (95% CI: 2.0%–3.3%) under observed treatment patterns and 2.1% (.0%–4.2%) under universal early treatment.ConclusionsExpanding early treatment may modestly reduce, but not eliminate, the elevation in mortality for people with HIV.

PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of corneal endothelial transplantation (CET), including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet Membrane Endothelial Keratoplasty procedures. The incidence of CET was calculated; potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis with a median follow-up 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%–1.53%). Risk factors for CET included age >60 years vs.

To describe treatment-related outcomes among patients with birdshot chorioretinitis (BSCR).Retrospective cohort study.Patients diagnosed with BSCR at 2 tertiary care academic medical centers.Clinical and treatment-related data were collected for all patients with BSCR diagnosed between 2003 and 2017 at the 2 centers and for each eye at each clinical visit.Four outcomes were considered: (1) corticosteroid-sparing success, defined as inactive disease and prednisone dose of ≤7.5 mg/day; (2) corticosteroid-discontinuation success, defined as inactive disease and discontinuation of prednisone; (3) sustained drug-free remission, defined as inactive disease off all medications for ≥3 months; and (4) relapse of BSCR after remission.A total of 107 patients with BSCR were identified, of whom 94 had follow-up data. Corticosteroid-sparing success was achieved in 95.4% of the oral corticosteroid-treated patients at a rate of 0.60 successes per person-year (PY) (95% CI: 0.50/PY, 0.70/PY). The median time to corticosteroid-sparing success was 12 months. Corticosteroids were discontinued successfully in 76.5% of oral corticosteroid-treated patients (rate = 0.28/PY; 95% CI: 0.21/PY, 0.35/PY). The median time to successful corticosteroid discontinuation was 2.0 years. A sustained drug-free remission was achieved in 24 patients (rate = 0.06/PY; 95% CI: 0.04/PY, 0.09/PY), with approximately 25% of patients achieving remission by 4 years of follow-up. Relapse of inflammation in patients after achieving a sustained, drug-free remission occurred at a rate of 0.24/PY (95% CI: 0.14/PY, 0.37/PY).Successful corticosteroid sparing and discontinuation was achieved in the majority of patients with BSCR. Remission occurred less often, but data were limited by the time needed to induce a remission (4 years) and the amount of follow-up (median, 4.6 years). The relapse rate after a remission was 0.24/PY.

BackgroundIndependent of CD4 cell count, low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the USA and Canada.MethodsWe examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines.Models were adjusted for age, sex, race/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all pConclusionsLow CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Purpose To estimate ophthalmologist-level variation in cataract surgery billing and evaluate patient and ophthalmologist characteristics associated with complex cataract surgery coding. Setting Cross-sectional study. Design Retrospective case series. Methods Medicare beneficiaries aged 65 years or older who had cataract surgery between January 1, 2016, and December 31, 2017, were included. Billing of cataract surgery as complex versus routine and patient and physician characteristics associated with billing of cataract surgery as complex were evaluated. Results An estimated 3.5 million cataract procedures were performed on Medicare beneficiaries in 2016 and 2017. Men (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.75-1.82), patients 75 years or older (versus those aged 65 to 74 years: OR, 1.35; 95% CI, 1.33-1.36), and racial minorities (blacks versus whites: OR, 1.80; 95% CI, 1.75-1.85) had increased odds of having cataract surgery coded as complex. The mean rate of coding for complex cataract surgery by individual surgeons (n = 10 075) in the United States was 11.2%, with significant variation. A high-risk clinical diagnosis code was associated with 40.0% of complex cataract surgeries. Adjusted for patient characteristics, ophthalmologists who graduated from medical school within the past 10 years (OR, 1.35; 95% CI, 1.22-1.49) were more likely to code for complex cataract surgery. Higher volume ophthalmologists were less likely to code for complex cataract surgery than low-volume ophthalmologists. Conclusions There was marked variation among ophthalmologists in the use of complex cataract surgery. Some variability might represent inaccurate coding and was not entirely based on differences in referral patterns for more complex patients.

Background: Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought. Patients and Methods: Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team’s recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed. Results: The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought. Conclusions: A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.