Visuopathy of prematurity: is retinopathy just the tip of the iceberg?

Background: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. Methods: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. Results: Patients’ (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3)

Patient satisfaction following a switch from treat-and- extend to observe-and-plan regimen in age-related macular degeneration

Objective Standard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each individual’s relapse interval lead to fewer clinical visits and has so far shown to be safe in treatment-naïve patients. In this study, we explore patient satisfaction and safety in nAMD when switching from TnE to OnP. Methods and analysis 38 participants treated according to TnE for ≥12 months were included and switched from TnE to OnP with their last stable interval. Main outcome was patient satisfaction (Leeds Satisfaction Questionnaire). Secondary outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT) before and 12 months after switch and number of monitoring visits and injections of anti-VEGF 12 months prior to and following switch. Results Mean patient satisfaction was higher (3.7±0.5 SD) at 12 months after switch from TnE to OnP than before (3.6±0.5 SD, p=0.009, response rate 76%). BCVA and CRT were unchanged. Number of monitoring visits and injections were lower in the 12 months following than prior to switch (p<0.001). Conclusion A switch from TnE to OnP in a non-treatment- naïve population resulted in higher patient satisfaction, while maintaining stable BCVA. This indicates that OnP may be applicable in the large group of nAMD patients that have received IVI for several years. OnP may alleviate the treatment burden on both individual and society of frequent clinical visits while increasing patient satisfaction

Nurse-administered intravitreal injections of anti-VEGF: study protocol for noninferiority randomized controlled trial of safety, cost and patient satisfaction

Background: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) now improve or stabilize visual acuity in a number of previously untreatable eye diseases, of which the main are age-related macular degeneration, retinal vein occlusion and diabetic macular edema. Most patients require multiple injections over lengthy periods of time and the prevalence of treatable conditions is increasing. Anti-VEGF IVI normally administered by physicians, therefore represent a considerable workload on ophthalmologic clinics and will continue to do so in the near future. Nurse-administered IVI may relieve this workload, but the safety, cost and patient satisfaction of such an extended role for nurses in ophthalmologic clinics has not earlier been investigated. To investigate these outcomes following independent anti-VEGF IVI by trained nurses, a noninferiority randomized controlled trial is being conducted. Methods/Design: Patients eligible for anti-VEGF treatment, minimum 304, are recruited and randomized to IVI administration by either trained nurses or physicians. The primary outcome is safety, measured by difference in mean change in visual acuity between the two groups during an observation period of 12 months. Secondary outcomes are incidence of ocular adverse events, cost per patient and patient satisfaction. Discussion: This study protocol describes the design of the first randomized controlled trial of nurse-administered IVI of anti-VEGF. The study is designed to examine safety, cost and patient satisfaction during 12 months follow-up

Transient effect of melatonin treatment after neonatal hypoxic-ischemic brain injury in rats

Melatonin has potential neuroprotective capabilities after neonatal hypoxia-ischemia (HI), but long-term effects have not been investigated. We hypothesized that melatonin treatment directly after HI could protect against early and delayed brain injury. Unilateral HI brain injury was induced in postnatal day 7 rats. An intraperitoneal injection of either melatonin or vehicle was given at 0, 6 and 25 hours after hypoxia. In-vivo MRI was performed 1, 7, 20 and 43 days after HI, followed by histological analysis. Forelimb asymmetry and memory were assessed at 12–15 and at 36–43 days after HI. More melatonin treated than vehicle treated animals (54.5% vs 15.8%) developed a mild injury characterized by diffusion tensor values, brain volumes, histological scores and behavioral parameters closer to sham. However, on average, melatonin treatment resulted only in a tendency towards milder injury on T2-weighted MRI and apparent diffusion coefficient maps day 1 after HI, and not improved long-term outcome. These results indicate that the melatonin treatment regimen of 3 injections of 10 mg/kg within the first 25 hours only gave a transient and subtle neuroprotective effect, and may not have been sufficient to mitigate long-term brain injury development following HI

Task shifting of intraocular injections from physicians to nurses: a randomized single-masked noninferiority study

Purpose To test if task shifting of intraocular injections to nurses in a real‐world setting can result in similar visual function outcome with equal safety profile. Method All patients with either age‐related macular degeneration, retinal vein occlusion or diabetic macular oedema remitted to intraocular injections at a tertiary ophthalmology department in Norway between March 2015 and May 2017, were asked to participate. The participants were randomized to either nurse‐ or physician‐administered intraocular injections of anti‐vascular endothelial growth factor. The primary outcome measure was change in best‐corrected visual acuity from baseline to 1‐year follow‐up. The mean difference in the primary outcome between the groups was analysed by a noninferiority test with a margin of three letters in disfavour of the nurse group. Adverse events were recorded. Results Three hundred and forty‐two patients entered the study. Two hundred and fifty‐nine completed the 1‐year follow‐up and were included in the study sample for the analysis of the primary outcome. Nurse‐administered intraocular injections were noninferior to physician‐administered injections with 0.7 and 1.6 letters gained, respectively (95% CI of the mean difference, −2.9 to 1.0; p = 0.019, one‐sided t‐test). Two thousand and seventy‐seven injections and three ocular adverse events were recorded. Conclusion Task shifting of intraocular injections to nurses can be performed without increased risk to visual function. Such a task shift can alleviate the burden of performing intraocular injections in ophthalmology departments. To our knowledge, this is the first RCT on task shifting of a surgical procedure from physicians to nurses in a high‐income country

Neuron-astrocyte interactions, pyruvate carboxylation and the pentose phosphate pathway in the neonatal rat brain

Glucose and acetate metabolism and the synthesis of amino acid neurotransmitters, anaplerosis, glutamate-glutamine cycling and the pentose phosphate pathway (PPP) have been extensively investigated in the adult, but not the neonatal rat brain. To do this, 7 day postnatal (P7) rats were injected with [1-(13)C]glucose and [1,2-(13)C]acetate and sacrificed 5, 10, 15, 30 and 45 min later. Adult rats were injected and sacrificed after 15 min. To analyse pyruvate carboxylation and PPP activity during development, P7 rats received [1,2-(13)C]glucose and were sacrificed 30 min later. Brain extracts were analysed using (1)H- and (13)C-NMR spectroscopy. Numerous differences in metabolism were found between the neonatal and adult brain. The neonatal brain contained lower levels of glutamate, aspartate and N-acetylaspartate but similar levels of GABA and glutamine per mg tissue. Metabolism of [1-(13)C]glucose at the acetyl CoA stage was reduced much more than that of [1,2-(13)C]acetate. The transfer of glutamate from neurons to astrocytes was much lower while transfer of glutamine from astrocytes to glutamatergic neurons was relatively higher. However, transport of glutamine from astrocytes to GABAergic neurons was lower. Using [1,2-(13)C]glucose it could be shown that despite much lower pyruvate carboxylation, relatively more pyruvate from glycolysis was directed towards anaplerosis than pyruvate dehydrogenation in astrocytes. Moreover, the ratio of PPP/glucose-metabolism was higher. These findings indicate that only the part of the glutamate-glutamine cycle that transfers glutamine from astrocytes to neurons is operating in the neonatal brain and that compared to adults, relatively more glucose is prioritised to PPP and pyruvate carboxylation. Our results may have implications for the capacity to protect the neonatal brain against excitotoxicity and oxidative stress