Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified

Giant Merkel cell carcinoma of the eyelid: a case report and review of the literature

Merkel cell carcinoma (MCC) is a rare cutaneous tumor and cases located in the eyelid have been described, but still its rarity may lead to difficulty in diagnosis and delay in treatment. A 51-year-old female patient that presented with large lesions in the eyelid underwent surgery after the diagnosis of acute chalazion. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and was not fit for complete excision treatment. Histopathological investigation of the biopsies, taken from the tumor, revealed that it was undifferentiated small cell carcinoma. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm

Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

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

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

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 who discontinued the study 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. Main Outcome Measures: 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. Results: 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. Conclusions: 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

Preterm infants have significantly longer telomeres than their term born counterparts

There are well-established morbidities associated with preterm birth including respiratory, neurocognitive and developmental disorders. However several others have recently emerged that characterise an `aged' phenotype in the preterm infant by term-equivalent age. These include hypertension, insulin resistance and altered body fat distribution. Evidence shows that these morbidities persist into adult life, posing a significant public health concern. In this study, we measured relative telomere length in leukocytes as an indicator of biological ageing in 25 preterm infants at term equivalent age. Comparing our measurements with those from 22 preterm infants sampled at birth and from 31 term-born infants, we tested the hypothesis that by term equivalent age, preterm infants have significantly shorter telomeres (thus suggesting that they are prematurely aged). Our results demonstrate that relative telomere length is highly variable in newborn infants and is significantly negatively correlated with gestational age and birth weight in preterm infants. Further, longitudinal assessment in preterm infants who had telomere length measurements available at both birth and term age (n = 5) suggests that telomere attrition rate is negatively correlated with increasing gestational age. Contrary to our initial hypothesis however, relative telomere length was significantly shortest in the term born control group compared to both preterm groups and longest in the preterm at birth group. In addition, telomere lengths were not significantly different between preterm infants sampled at birth and those sampled at term equivalent age. These results indicate that other, as yet undetermined, factors may influence telomere length in the preterm born infant and raise the intriguing hypothesis that as preterm gestation declines, telomere attrition rate increases

Corneal confocal microscopy detects a reduction in corneal endothelial cells and nerve fibres in patients with acute ischemic stroke

YesEndothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P<0.001) and endothelial cell area (P<0.001) and perimeter (P<0.001) were higher, whilst corneal nerve fbre density (P<0.001), corneal nerve branch density (P<0.001) and corneal nerve fbre length (P=0.001) were lower in patients with acute ischemic stroke compared to controls. Corneal endothelial cell density, cell area and cell perimeter correlated with corneal nerve fber density (P=0.033, P=0.014, P=0.011) and length (P=0.017, P=0.013, P=0.008), respectively. Multiple linear regression analysis showed a signifcant independent association between corneal endothelial cell density, area and perimeter with acute ischemic stroke and triglycerides. CCM is a rapid non-invasive ophthalmic imaging technique, which could be used to identify patients at risk of acute ischemic stroke.Qatar National Research Fund Grant BMRP2003865

Health-related quality of life dynamics of HIV-positive South African women up to ART initiation : evidence from the CAPRISA 002 acute infection cohort study.

CAPRISA, 2014.Few studies have investigated the long-term dynamics in health-related quality of life (HRQoL) among HIV-positive persons from acute infection. From 2004, 160 women were enrolled into the CAPRISA 002 Acute Infection study at two sites in the province of KwaZulu-Natal and underwent 3–6 monthly HRQoL assessments using the functional assessment of HIV infection (FAHI) instrument. Overall and 5 sub-scale FAHI scores [physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB) and cognitive functioning (CF)] were calculated up to antiretroviral therapy (ART) initiation and scores at enrollment were compared to the acute, early and established infection phases. Mixed-effects regression models adjusting for behavioral and clinical factors were applied to assess HRQoL trends and the proportion of women meeting minimally important differences was calculated. Our analyses revealed that overall/sub-scale scores improved over time, except from PWB and CF. A higher educational status, contraceptive use and a higher BMI were the strongest predictors of higher overall/sub-scale FAHI scores. CD4 count and HIV viral load were strongly associated with PWB and CF, but not overall FAHI and other sub-scales. Women newly diagnosed with acute HIV infection face profound HRQoL challenges. While early ART delivery may be important for PWB and CF, factors such as education, contraception provision and good nutritional status should be promoted to maximize HRQoL in HIV positive individuals