Purpose To estimate the incidences of ocular complications and vision loss in patients with juvenile idiopathic arthritis (JIA)-associated uveitis, to describe risk factors for vision loss, and to ...describe the association between therapy and complications and vision loss. Design Retrospective cohort study. Methods setting: Single-center, academic practice. study population: A total of 75 patients with JIA-associated uveitis evaluated between July 1984 and August 2005. procedures: Clinical data on these patients were analyzed. outcome measures: Occurrence of ocular complications and visions of 20/50 or worse and 20/200 or worse. Results Over a median follow-up of three years, the incidence of any ocular complication was 0.33/eye-year (EY). Rates of vision loss to 20/50 or worse and 20/200 or worse were 0.10/EY and 0.08/EY, respectively. Risk factors at presentation for incident vision loss included presence of posterior synechiae, anterior chamber flare ≥ 1+, and abnormal intraocular pressure (IOP). During follow-up, ocular inflammation ≥ 0.5+ cells was associated with an increased risk of visual impairment (relative risk RR = 2.02, P = .006) and of blindness (RR = 2.99, P = .03). Immunosuppressive drug therapy reduced the risk of hypotony by 74% ( P = .002), epiretinal membrane formation by 86% ( P = .05), and blindness in the better eye by 60% ( P = .04). Conclusions Incident vision loss and complications were common. Presence of posterior synechiae, anterior chamber flare ≥ 1+, and abnormal IOP at presentation were associated with vision loss during follow-up. Use of immunosuppressive drugs reduced the risk of some ocular complications and of blindness in the better-seeing eye.
Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related ...to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged.
A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine.
Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups.
Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.
Classification Criteria for Fuchs Uveitis Syndrome Working Group, The Standardization Of Uveitis Nomenclature Sun; Jabs, Douglas A; Acharya, Nisha R ...
American journal of ophthalmology,
08/2021, Letnik:
228
Journal Article
Recenzirano
Odprti dostop
To determine classification criteria for Fuchs’ uveitis syndrome.
Machine learning of cases with Fuchs’ uveitis syndrome and 8 other anterior uveitides.
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.
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 misclassification rates for Fuchs’ uveitis syndrome were 4.7% in the training set and 5.5% in the validation set, respectively.
The criteria for Fuchs’ uveitis syndrome had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.
To evaluate the responsiveness of quality of life (QoL) metrics to ocular and systemic events in patients with noninfectious uveitis.
Cohort study using randomized controlled trial data.
Patients ...with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study.
Data on the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), EuroQol Questionnaire (EQ-5D), and Short Form Survey Instrument (SF-36) were evaluated semiannually during the first 3 years after randomization. The impact of ocular (e.g., changes in visual acuity VA, activity status, cataract surgery) and systemic events (e.g., infections requiring treatment) on the 6-month changes in QoL was assessed for each metric using generalized estimating equations.
The primary outcomes were the 6-month changes in vision-related (NEI-VFQ-25) and general health-related (EQ-5D index, SF-36 physical component summary PCS) QoL.
Changes in VA (adjusted change aΔ: 2.70 units per 5 letter change, P < 0.001), implant placement in at least 1 eye (aΔ: 5.50, P < 0.001), cataract surgery (aΔ: 3.01, P = 0.017), and quieting of all eyes active at the beginning of the interval (aΔ: 2.20, P < 0.010) were associated with improvements in the NEI-VFQ-25. Reductions in VA (aΔ: -0.014 per 5 letter decline, P = 0.003), infections requiring a prescription (aΔ: -0.024, P = 0.021), and incident uveitis activity in at least 1 eye (aΔ: -0.023, P = 0.031) were associated with declines in the EQ-5D index. Hospitalization (aΔ: -2.24, P = 0.019), infections requiring a prescription (aΔ: -1.00, P = 0.024), and vitreous hemorrhage in at least 1 eye (aΔ: -1.92, P = 0.021) were associated with declines in the SF-36 PCS. Declines in VA, initiation in IOP medication, and age were associated with changes in SF-36 PCS; however, the magnitude of the change was less than a single point.
The NEI-VFQ-25 was more sensitive to ocular changes than the general QoL metrics but less sensitive to acute systemic events. When performing QoL or cost-effectiveness analyses, it is important to consider the expected outcomes (e.g., ocular vs. systemic) to ensure that the selected measurement is sensitive enough to detect clinically important changes in disease status or effects of treatment.
•Eighty-three percent of eyes with anterior scleritis treated with difluprednate achieved disease resolution.•Twenty-six percent of eyes treated with difluprednate had elevated intraocular pressure.
...To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis.
Retrospective, interventional case series.
Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from January 1, 2018, to January 1, 2020, including 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.
Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were White. Forty percent had bilateral disease, and 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 = .02). Nine eyes had IOP elevation. Four eyes lost ≥2 lines of BCVA, and 1 due to cataract progression. One eye underwent cataract surgery.
Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.
Electronic health record (EHR) systems based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding of disease entities are increasingly ...being used to generate large data sets for analysis. However, the reproducibility of ICD-10 coding in uveitis has not been assessed across EHR platforms, and imprecision in coding may lead to improper conclusions in big-data analyses.
To compare ICD-10 coding of uveitis using 2 EHR systems.
This study compares ICD-10 codes for 27 uveitic diseases generated by the Epic and MDIntelleSys EHR systems to the ICD-10 descriptions associated with the codes. No patient data were assessed in this study.
The number of diseases for which ICD-10 coding differed between the 2 systems.
Thirteen of 27 uveitic diseases were coded differently by the 2 EHR systems. Coding imprecision was notable in that the Epic system returned 16 ICD-10 codes and the MDIntelleSys returned 12 ICD-10 codes to describe 13 diseases; 4 diseases had multiple codes returned, and 6 codes were used to describe more than 1 disease. For example, MDIntelleSys uses ICD-10 code H30.13 for both birdshot choroiditis and acute retinal necrosis, while Epic uses H30.9 for both birdshot choroiditis and multiple evanescent white dot syndrome; MDIntelleSys uses this code for multifocal choroiditis. Furthermore, the ICD-10 descriptions for certain codes lack specificity, allowing variable interpretation by the coder.
This study suggests there is substantial disparity in the ICD-10 codes that are generated for specific uveitides by the 2 EHR systems studied. This result implies that analysis of large databases generated from the pooling of EHR data could produce results with substantial bias because of misclassification resulting from conflicting and imprecise coding of uveitides. Therefore, research into outcomes, costs, health care utilization, and epidemiology in uveitis might be improved if a more uniform coding system to describe ocular inflammatory disease is implemented.
Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.
Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ...ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.
Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.
Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.
To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation.
Retrospective cohort study.
A total of 373 patients with noninfectious ocular inflammation managed ...at 4 tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007 inclusive.
Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.
Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity.
Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of inflammation over at least 2 visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone < or = 10 mg/day) was achieved by 22.1% by 6 months and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year by 10.7% of the population. Patients aged more than 55 years were more than 3-fold more likely to discontinue therapy because of toxicity than patients aged 18 to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower doses and were not associated with a higher discontinuation for toxicity rate; higher doses did not seem to offer a therapeutic advantage.
Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation. Our data support a preference for cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was tolerated by the majority of patients, toxicity was more frequent with increasing age; alternative agents may be preferred for patients aged more than 55 years.
To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.
Open-label, multicenter, phase 3 extension study ...(VISUAL III).
Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis).
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.
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 systemic corticosteroids.
At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing 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. Mean daily dose of systemic 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 were infections (n = 275; 79 events/100 patient-years PY); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively.
Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.
CD4/CD8 Ratio and Cancer Risk Among Adults With HIV Castilho, Jessica L; Bian, Aihua; Jenkins, Cathy A ...
JNCI : Journal of the National Cancer Institute,
06/2022, Letnik:
114, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract
Background
Independent of CD4 cell count, a 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 United States and Canada.
Methods
We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 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 and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.
Results
Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 95% confidence interval = 1.14 to 1.35). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values.
Conclusions
A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
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