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OBJECTIVE In vivo glycolysis-related glucose metabolism and electron transport chain-related mitochondrial activity may be different regionally in the brains of patients with Alzheimer disease (AD). To test this hypothesis regarding AD pathophysiology, we measured the availability of mitochondrial complex-I (MC-I) with the novel PET probe [18F]2-tert- butyl-4-chloro-5-2H- pyridazin-3-one ([18F]BCPP-EF), which binds to MC-I, and compared [18F]BCPP-EF uptake with 18F-fluorodeoxyglucose ([18F]FDG) uptake in the living AD brain. METHODS First, the total distribution volume (VT) of [18F]BCPP-EF from 10 normal controls (NCs) was quantified using arterial blood samples and then tested to observe whether VT could substitute for the standard uptake value relative to the global count (SUVRg). Eighteen NCs and 14 different NCs underwent PET with [18F]BCPP-EF or [18F]FDG, respectively. Second, 32 patients with AD were scanned semiquantitatively with double PET tracers. Interparticipant and intraparticipant comparisons of the levels of MC-I activity ([18F]BCPP-EF) and glucose metabolism ([18F]FDG) were performed. RESULTS The [18F]BCPP-EF VT was positively correlated with the [18F]BCPP-EF SUVRg, indicating that the use of the SUVRg was sufficient for semiquantitative evaluation. The [18F]BCPP-EF SUVRg, but not the [18F]FDG SUVRg, was significantly lower in the parahippocampus in patients with AD, highlighting the prominence of oxidative metabolic failure in the medial temporal cortex. Robust positive correlations between the [18F]BCPP-EF SUVRg and [18F]FDG SUVRg were observed in several brain regions, except the parahippocampus, in early-stage AD. CONCLUSIONS Mitochondrial dysfunction in the parahippocampus was shown in early-stage AD. Estrogen agonist Mitochondria-related energy failure may precede glycolysis-related hypometabolism in regions with pathologically confirmed early neurodegeneration in AD. © 2020 American Academy of Neurology.BACKGROUND/AIMS This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. METHODS This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). RESULTS 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. CONCLUSION In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To conduct a review and meta-analysis for investigating the relative reduction of central corneal basal cell density (BCD) and nerve parameters in ocular surface disease (OSD) and limbal stem cell deficiency (LSCD). METHODS A systematic literature search using the terms ((1) "ocular surface disease" or "ocular surface disorder"; (2) "in vivo confocal microscopy"; (3) "limbal stem cell deficiency"; (4) "basal cell density" or "corneal basal cell density" or "central corneal basal cell density"; (5) "corneal nerves" or "corneal nerve parameters" or "central corneal nerve parameters") was performed. The results are presented as weighted mean difference (WMD) with corresponding 95% CI. RESULTS 16 studies that reported the central corneal BCD and 21 studies that reported the central corneal nerve parameters in OSD (including LSCD) were included. A significant reduction in central corneal BCD was observed in patients with various OSDs (WMD=-9.50, 95% CI -14.04 to -4.97, p less then 0.01) as well as in patients with LSCD (WMD=-22.14, 95% CI -37.91 to -6.37, p less then 0.01) compared with healthy controls, however, no significant difference in BCD was observed between the two groups (WMD=-11.61, 95% CI -15.96 to -7.26, p=0.13). There was no conclusive difference in various central corneal nerve parameters between OSDs and LSCD. CONCLUSION Central corneal BCD and nerve parameters are reduced in LSCD, there is a similar reduction in other OSDs. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND/AIMS Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops. METHODS A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways. link2 RESULTS Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation. CONCLUSIONS The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. link3 Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption. TRIAL REGISTRATION NUMBER ISRCTNIDISRCTN75888393. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Screening of diabetic retinopathy (DR) reduces blindness by early identification of retinopathy. This study compares DR grades derived from a two-field imaging protocol from two imaging platforms, one providing a single 60-degree horizontal field of view (FOV) and the other, a standard 45-degree FOV. METHODS Cross-sectional study which included 1257 diabetic patients aged ≥18 years attending their DR screening visit in the English National Diabetic Eye Screening Programme (NDESP). Patients with maculopathy (M1), preproliferative (R2) or proliferative DR (R3) were referred to an ophthalmologist. Patients with ungradable images (U) are examined in a slit-lamp biomicroscopy clinic. Image acquisition under mydriasis of two images per eye was carried out with the EIDON and with standard fundus cameras. Evaluation was performed by masked graders. RESULTS Agreement after consensus with kappa statistic was 0.89 (quadratic weights (95% CI 0.87 to 0.92)) for NDESP severity grade, 0.88 (quadratic weights (95% CI 0.82 to 0.94)) for referable disease and 0.92 (linear weights (95% CI 0.88 to 0.95)) for maculopathy. The EIDON detected clinically relevant DR features outside the 45-degree fields in two patients (0.16%) one with intraretinal microvascular abnormalities (IRMAs) and one with neovascularisation. In eight patients (0.64%), the EIDON allowed DR feature visualisation inside the 45-degree fields that were not identified in the NDESP images three patients (0.24%) with IRMA and five patients (0.40%) with maculopathy. The rates of ungradable encounters were 12 (0.95%) and 13 (1.03%) with the EIDON and NDESP images, respectively. CONCLUSION The EIDON identifies a small number of additional patients with referable disease which are not detected with standard imaging. This is due to the EIDON finding disease outside the standard FOV and greater clarity finding disease within the standard FOV. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Chemsex, the use of select psychoactive drugs to enhance sexual experience, typically among men who have sex with men (MSM), is associated with sexual behaviours with higher STI risk. Understanding patterns of chemsex among MSM as well as the characteristics and sexual health service engagement of chemsex participants is important for developing interventions. METHODS Between 5/2016 to 5/2017, 3933 MSM completed an online survey, recruited in sexual health clinics (SHCs) in England (n=421) and via four social networking/dating apps (n=3512). We described patterns of chemsex in the past year and used multivariable logistic regression to investigate differences in demographics and sexual behaviours by chemsex history. We described history of SHC attendance and STI test in the past year among app-recruited chemsex participants. RESULTS Chemsex in the past year was reported by 10% of respondents; 19% of SHC-recruited and 9% of app-recruited. Among chemsex participants, 74% had used ≥2 chemsex drugs. In the multivariable model, MSM engaging in chemsex had a raised odds of being HIV-positive (adjusted OR (aOR) 3.6; 95% CI 2.1 to 6.1), aged 30-44 (aOR 1.5 vs less then 30 years; 95% CI 1.0 to 2.1), being born outside the UK and having engaged in higher risk sexual behaviours in the past 3 months. Chemsex participants also had higher odds of condomless anal sex with partners of different or unknown HIV status, but only among HIV-negative/untested. In the past year, 66% of app-recruited chemsex participants had attended a SHC and 81% had had an STI test. CONCLUSION One in 10 MSM recruited through community and clinical settings across England had engaged in chemsex in the past year. Those that did appear to be at greater STI risk but engaged more actively with sexual health services. This highlights the need and opportunity for chemsex-related services in SHCs and robust referral pathways to drug treatment services. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
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