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Thyroid eye disease (TED) affects 25% of patients with Graves' hyperthyroidism, where 1 in 20 patients has active, moderate-to-severe disease that will require medical treatment for reducing TED activity and severity. Intravenous corticosteroid has been the mainstay of treatment for active moderate-to-severe TED. With improved understanding of the pathophysiology of TED, immunotherapy targeting different molecular pathways including T cells, B cells, cytokines and cell surface receptors have been investigated in randomised clinical trials. This review provides an overview of the current advances in medical treatment including teprotumumab, tocilizumab, rituximab and mycophenolate and the indications for their use in the management of active, moderate-to-severe TED.Purpose We examined the longitudinal association of baseline alcohol intake and frequency with the 6-year incidence and progression of diabetic retinopathy (DR) in a population-based cohort of Singaporean Indians. Methods We included 656 participants with diabetes mellitus, gradable retinal photographs from baseline (2007-2009) and follow-up (2013-2015) examinations, information on alcohol intake and other relevant data from the Singapore Indian Eye Study were included. Incident DR was defined using the Modified Airlie House Classification as no DR at baseline and at least minimal non-proliferative DR at follow-up; and DR progression as at least a one-step worsening in DR at follow-up from minimal or worse status at baseline, excluding those with proliferative DR. Results The mean age (SD) of our participants (n=656) was 58.8 (9.2) years, and 54.4% were male. At follow-up, 82 of 510 (16%) participants developed DR, and 45 of 146 (30.8%) had DR progression. 65 (12.7%) and 28 (19.1%) participants consumed alcohol in incident DR and progression categories, respectively. ABBV-075 In multivariable analyses, those who consumed alcohol had nearly two-thirds reduced odds of incident DR (OR (95% CI) 0.36 (0.13 to 0.98)) compared with those who did not. Participants with infrequent consumption of alcohol also had a reduction in odds of incident DR (0.17 (0.04 to 0.69)), compared with non-drinkers. No association was found between alcohol consumption and DR progression. Conclusions and relevance In our longitudinal population of Singapore Indians, baseline alcohol intake, particularly infrequent consumption, was associated with lower risk of developing DR, compared with non-drinkers, in line with previous cross-sectional findings.Purpose To investigate the characteristics, risk factors and visual impact of myopic traction maculopathy (MTM) among adults with myopia in Singapore. Methods We analysed 3316 myopic eyes of adults aged over 40 years who participated in the Singapore Epidemiology of Eye Diseases-2 study. Detailed questionnaires and ophthalmic examinations were conducted. A total of 2913 myopic eyes of 1639 subjects were graded for MTM by spectral-domain optical coherence tomography. MTM is defined as the presence of retinoschisis, lamellar or full-thickness macula hole and foveal retinal detachment. Fundus photographs were graded for myopic macular degeneration (MMD). Results Of these 2913 myopic eyes, the mean and SD of age was 60.1±8.0 years; the spherical equivalent (SE) was -2.5±2.3 D; and the axial length (AL) was 24.6±1.3 mm. MTM was found in 0.9% of myopic eyes and 7.3% of highly myopic eyes. In the multivariate analysis, myopic SE (p less then 0.001), longer AL (p less then 0.001), MMD (p=0.01) and epiretinal traction (p less then 0.001) were independent risk factors for MTM. MTM was not associated with age (p=0.38). MTM was significantly associated with poorer best-corrected visual acuity (BCVA) (p less then 0.01). Conclusions Our population-based study revealed that MTM was present in 0.9% of myopic eyes and 7.3% of highly myopic eyes. While greater myopic SE, longer AL, MMD and epiretinal traction are risk factors of MTM, age was not related to MTM. MTM has a negative effect on BCVA.Objectives Test of cure (TOC) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infection is an important tool in the public health management of STIs. However, there are limited data about the optimal time to perform TOC using nucleic acid amplification tests (NAATs) for NG and CT infections. A study was performed to assess the feasibility of a larger study to determine the optimal time to TOC using NAATS. Methods The Sexually Transmitted Bacteria Reference Unit at Public Health England undertook testing of gonococcal and chlamydial nucleic acids within neat urine stored in different conditions over 25 days to provide evidence of the stability of the nucleic acid prior to recruitment. Individuals diagnosed with uncomplicated NG or CT infection were recruited from three sexual health clinics. Individuals were asked to return nine self-taken samples from the site of infection over a course of 35 days. Survival analyses of time to first negative NAAT result for NG and CT infection and univariate regression analysis of factors that affect time to clearance were undertaken. Results At room temperature, chlamydial DNA in urine is stable for up to 3 weeks and gonococcal DNA for up to 11 days. We analysed data for 147 infections (81 NG and 66 CT). The median time to clearance of infection was 4 days (IQR 2-10 days) for NG infection and 10 days (IQR 7-14 days) for CT infection. Vaginal CT infections took longer to clear (p=0.031). NG infection in men who have sex with men took longer to clear (p=0.052). Conclusion Chlamydial and gonococcal nucleic acids are stable in urine before addition of preservatives, longer than recommended by the manufacturer. The TOC results suggest that it may be possible to undertake TOC for NG and CT infections earlier than current guidelines suggest and that anatomical site of infection may affect time to clearance of infection.Background The chromosomal region 11p15.5 harbours two imprinting centres (H19/IGF2IG-DMR/IC1, KCNQ1OT1TSS-DMR/IC2). Molecular alterations of the IC2 are associated with Beckwith-Wiedemann syndrome (BWS), whereas only single patients with growth retardation and Silver-Russell syndrome (SRS) features have been reported. CNVs in 11p15.5 account for less than 1% of patients with BWS and SRS, and they mainly consist of duplications of both ICs either affecting the maternal (SRS) or the paternal (BWS) allele. However, this correlation does not apply to smaller CNVs, which are associated with diverse clinical outcomes. Methods and results We identified a family with a 132 bp deletion within the KCNQ1OT1 gene, associated with growth retardation in case of paternal transmission but a normal phenotype when maternally inherited. Comparison of molecular and clinical data with cases from the literature helped to delineate its functional relevance. Conclusion Microdeletions within the paternal IC2 affecting the KCNQ1OT1 gene have been described in only five families, and they all include the differentially methylated region KCNQ1OT1TSS-DMR/IC2 and parts of the KCNQ1 gene.
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