Medical interventions for non‐arteritic anterior ischaemic optic neuropathy

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness and safety of different medical interventions in the treatment of non‐arteritic anterior ischaemic optic neuropathy (NA‐AION) in adults

Topographical Response of Retinal Neovascularization to Aflibercept or Panretinal Photocoagulation in Proliferative Diabetic Retinopathy Post Hoc Analysis of the CLARITY Randomized Clinical Trial

Importance Eyes with proliferative diabetic retinopathy have a variable response to treatment with panretinal photocoagulation (PRP) or anti–vascular endothelial growth factor agents. The location of neovascularization (NV) is associated with outcomes (eg, patients with disc NV [NVD] have poorer visual prognosis than those with NV elsewhere [NVE]). Objective To investigate the distribution of NV in patients with proliferative diabetic retinopathy and the topographical response of NV to treatment with aflibercept or PRP. Design, Setting, and Participants This post hoc analysis of the phase 2b randomized clinical single-masked multicenter noninferiority Clinical Efficacy and Mechanistic Evaluation of Aflibercept for Proliferative Diabetic Retinopathy (CLARITY) trial was conducted from November 1, 2019, to September 1, 2020, among 120 treatment-naive patients with proliferative diabetic retinopathy to evaluate the topography of NVD and NVE in 4 quadrants of the retina on color fundus photography at baseline and at 12 and 52 weeks after treatment. Exposures In the CLARITY trial, patients were randomized to receive intravitreal aflibercept (2 mg/0.05 mL at baseline, 4 weeks, and 8 weeks, and as needed from 12 weeks onward) or PRP (completed in initial fractionated sessions and then on an as-needed basis when reviewed every 8 weeks). Main Outcomes and Measures Main outcomes were per-retinal quadrant frequencies of NV at baseline and frequencies of patterns of regression, recurrence, and new occurrence at 12-week and 52-week unmasked follow-up. Results The study included 120 treatment-naive patients (75 men; mean [SD] age, 54.8 [14.6] years) with proliferative diabetic retinopathy (there was a 1:1 ratio of eyes to patients). At baseline, NVD with or without NVE was observed in 42 eyes (35.0%), and NVE only was found in 78 eyes (65.0%); NVE had a predilection for the nasal quadrant (64 [53.3%]). Rates of regression with treatment were higher among eyes with NVE (89 of 102 [87.3%]) compared with eyes with NVD (23 of 43 [53.5%]) by 52 weeks, with NVD being more resistant to either treatment with higher rates of persistence than NVE (20 of 39 [51.3%] vs 29 of 100 [29.0%]). Considering NVE, the regression rate in the temporal quadrant was lowest (32 of 42 [76.2%]). Eyes treated with aflibercept showed higher rates of regression of NVE compared with those treated with PRP (50 of 52 [96.2%] vs 39 of 50 [78.0%]; difference, 18.2% [95% CI, 5.5%-30.8%]; P = .01), but no difference was found for NVD (11 of 17 [64.7%] vs 12 of 26 [46.2%]; difference, 18.6% [95% CI, −11.2% to 48.3%]; P = .23). Conclusions and Relevance This post hoc analysis found that NVD is less frequent but is associated with more resistance to currently available treatments than NVE. Aflibercept was superior to PRP for treating NVE, but neither treatment was particularly effective against NVD by 52 weeks. Future treatments are needed to better target NVD, which has poorer visual prognosis. Trial Registration isrctn.org Identifier: ISRCTN3220758

Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study

Background The associations between England’s incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. Methods A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0–3, 4–6, or 7–9), in 2010–2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. Results 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89–0.99) and 0.87 (0.83–0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97–1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62–0.87) for HbA1c, 0.78 (0.67–0.91) for BP, and 0.82 (0.67–0.99) for cholesterol). Completion of 7–9 vs. 0–3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55–0.94)). Conclusions Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England

Data Resource Profile: the Children and Young People with Long COVID (CLoCk) Study

Key Features: The Children and Young People with Long COVID (CLoCk) study is a national matched prospective study which was set up with the aims of (i) describing the clinical phenotype of post-COVID symptomology in children and young people (CYP), (ii) producing a research definition for long COVID in CYP and (iii) establishing the prevalence of long COVID in CYP. In total, 219 175 CYP aged 11–17 years, who were tested for SARS-CoV-2 via polymerase chain reaction (PCR) testing between September 2020 and March 2021 in England, were invited to participate. Test-positive and test-negative CYP were matched at study invitation on month of test, age, sex and geographical region. CYP were enrolled into the study at 3, 6 or 12 months after their index PCR test (n = 31 012). Depending on when they enrolled, they were also invited to fill in follow-up questionnaires at 6, 12 and 24 months after their index test. The overall response rate was 14.1%, with retention across sweeps varying from 36.6% to 54.1%. The dataset includes information on physical and mental health using validated scales over time, allowing for examination of within-individual change. CYP report symptoms themselves rather than relying on parental report or administrative records. Requests for access to the participant-level data from this study can be submitted via email to: [[email protected]]

Predicting post-COVID-19 condition in children and young people up to 24 months after a positive SARS-CoV-2 PCR-test: the CLoCk study

Background: Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP. Methods: CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting. Results: While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064–1.142; C-statistic: 0.724–0.755). Conclusions: To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support

Children and Young People with Long COVID:comparing those seen in Post-COVID services with a non-hospitalised national cohort: a descriptive study

Background: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described.Purpose: (1) To describe the characteristics of children aged 11-17 referred to the Pan London Post-COVID service and (2) To compare characteristics of these children with those taking part in the UK’s largest research study of Long COVID in children (CLoCk).Design: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk.Results: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pan-demic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk.Conclusions: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short and long-term outcomes of interventions by clinical services can help direct future therapy for this group.<br/

Children and Young People with Long COVID—Comparing Those Seen in Post-COVID Services with a Non-Hospitalised National Cohort: A Descriptive Study

Background: Post-COVID services have been set up in England to treat children with ongoing symptoms of Long COVID. To date, the characteristics of children seeking treatment from these services has not been described. / Purpose: (1) to describe the characteristics of children aged 11–17 referred to the Pan-London Post-COVID service and (2) to compare characteristics of these children with those taking part in the United Kingdom’s largest research study of Long COVID in children (CLoCk). / Design: Data from 95 children seeking treatment from the Post-COVID service between May 2021 and August 2022 were included in the study. Their demographic characteristics, symptom burden and the impact of infection are described and compared to children from CLoCk. / Results: A high proportion of children from the Post-COVID service and CLoCk reported experiencing health problems prior to the pandemic. Almost all Post-COVID service children met the research Delphi definition of Long COVID (94.6%), having multiple symptoms that impacted their lives. Symptoms were notably more severe than the participants in CLoCk. / Conclusions: This study describes the characteristics of children seeking treatment for Long COVID compared to those identified in the largest longitudinal observational study to date. Post-COVID service children have more symptoms and are more severely affected by their symptoms following infection with COVID-19 than children in the CLoCk study. Research to understand predisposing factors for severity and prognostic indicators is essential to prevent this debilitating condition. Evaluation of short- and long-term outcomes of interventions by clinical services can help direct future therapy for this group

Mental health in the COVID-19 pandemic:A longitudinal analysis of the CLoCk cohort study

BACKGROUND: Little is known about the long-term mental health consequences of the pandemic in children and young people (CYP), despite extremely high levels of exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus and the disruption to schooling and leisure activities due to the resultant restrictions. There are mixed findings from systematic reviews of how the pandemic affected CYP's mental health, which may be due to heterogeneous methods and poor quality studies. Most, but not all, suggest deterioration in mental health but population level studies may obscure the differing experiences of subgroups. The study questions are: (i) are there subgroups of CYP with distinct mental health profiles over the course of the second year of the Coronavirus Disease 2019 (COVID-19) pandemic (between April 2021 and May 2022); and (ii) do vulnerability factors influence CYP's mental health trajectories.METHODS AND FINDINGS: A matched longitudinal cohort study of non-hospitalised test-positive and test-negative 11- to 17-year-old CYP in England were recruited from the UK Health Security Agency having undergone PCR testing for COVID-19. They completed the Strengths and Difficulties Questionnaire (SDQ) at least twice over a 12-month follow-up period. Overall, 8,518 of 17,918 (47.5%) CYP who returned their first SDQ at 3 or 6 months post-testing were included in the analytical sample. Associations between age, sex, ethnicity, socioeconomic status (SES), and an educational health and care plan (EHCP, indicating special educational needs) on SDQ score trajectories were examined separately, after adjusting for PCR test result. Findings from multilevel mixed-effects linear regression model showed that on average mental health symptoms as measured by the total SDQ score increased over time (B = 0.11 (per month), 95% CI = 0.09 to 0.12, p &lt; 0.001) although this increase was small and not clinically significant. However, associations with time varied by age, such that older participants reported greater deterioration in mental health over time (B = 0.12 (per month), 95% CI = 0.10 to 0.14 for 15 to 17y; 0.08 (95% CI = 0.06 to 0.10) for 11 to 14y; pinteraction = 0.002) and by sex, with greater deterioration in girls. Children with an EHCP experienced less deterioration in their mental health compared to those without an EHCP. There was no evidence of differences in rate of change in total SDQ by ethnicity, SES, or physical health. Those with worse prior mental health did not appear to be disproportionately negatively affected over time. There are several limitations of the methodology including relatively low response rates in CLoCk and potential for recall bias.CONCLUSIONS: Overall, there was a statistically but not clinically significant decline in mental health during the pandemic. Sex, age, and EHCP status were important vulnerability factors that were associated with the rate of mental health decline, whereas ethnicity, SES, and prior poor physical health were not. The research highlights individual factors that could identify groups of CYP vulnerable to worsening mental health.</p

The CLoCk study: A retrospective exploration of loneliness in children and young people during the COVID-19 pandemic, in England

BACKGROUND: During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness. METHODS AND FINDINGS: Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas. CONCLUSIONS: We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time

Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study

To describe the prevalence of long COVID in children infected for the first time (n=332) or reinfected (n=243) with Omicron variant SARS-CoV-2, compared with test-negative children (n=311). 12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection (pchi-square=0.17)