Detection of Visual Field Loss in Pituitary Disease: Peripheral Kinetic Versus Central Static.

Visual field assessment is an important clinical evaluation for eye disease and neurological injury. We evaluated Octopus semi-automated kinetic peripheral perimetry (SKP) and Humphrey static automated central perimetry for detection of neurological visual field loss in patients with pituitary disease. We carried out a prospective cross-sectional diagnostic accuracy study comparing Humphrey central 30-2 SITA threshold programme with a screening protocol for SKP on Octopus perimetry. Humphrey 24-2 data were extracted from 30-2 results. Results were independently graded for presence/absence of field defect plus severity of defect. Fifty patients (100 eyes) were recruited (25 males and 25 females), with mean age of 52.4 years (SD = 15.7). Order of perimeter assessment (Humphrey/Octopus first) and order of eye tested (right/left first) were randomised. The 30-2 programme detected visual field loss in 85%, the 24-2 programme in 80%, and the Octopus combined kinetic/static strategy in 100% of eyes. Peripheral visual field loss was missed by central threshold assessment. Qualitative comparison of type of visual field defect demonstrated a match between Humphrey and Octopus results in 58%, with a match for severity of defect in 50%. Tests duration was 9.34 minutes (SD = 2.02) for Humphrey 30-2 versus 10.79 minutes (SD = 4.06) for Octopus perimetry. Octopus semi-automated kinetic perimetry was found to be superior to central static testing for detection of pituitary disease-related visual field loss. Where reliant on Humphrey central static perimetry, the 30-2 programme is recommended over the 24-2 programme. Where kinetic perimetry is available, this is preferable to central static programmes for increased detection of peripheral visual field loss

First Prospective Cohort Study of Diabetic Retinopathy from Sub-Saharan Africa High Incidence and Progression of Retinopathy and Relationship to Human Immunodeficiency Virus Infection

PurposeTo describe the prevalence, incidence, and progression of retinopathy and to report associations with demographic, clinical, and biochemical variables in people with diabetes in Southern Malawi.DesignProspective cohort study.ParticipantsSubjects were systematically sampled from 2 primary care diabetes clinics.MethodsWe performed the first prospective cohort study of diabetic retinopathy from Sub-Saharan Africa over 24 months. Visual acuity, glycemic control, blood pressure, human immunodeficiency virus (HIV) status, urine albumin-to-creatinine ratio, hemoglobin, and lipids were assessed. Retinopathy was graded at an accredited reading center using modified Wisconsin grading of 4-field mydriatic photographs.Main Outcome MeasuresIncidence of sight-threatening retinopathy and progression of retinopathy by 2 steps on the Liverpool Diabetic Eye Study Scale.ResultsA total of 357 subjects were recruited to the 24-month cohort study. At baseline, 13.4% of subjects were HIV positive and 15.1% were anemic. The 2-year incidence of sight-threatening diabetic retinopathy (STDR) for subjects with level 10 (no retinopathy), level 20 (background), and level 30 (preproliferative) retinopathy at baseline was 2.7% (95% confidence interval [CI], 0.1–5.3), 27.3% (95% CI, 16.4–38.2), and 25.0% (95% CI, 0–67.4), respectively. In a multivariate logistic analysis, 2-step progression of diabetic retinopathy was associated with glycosylated hemoglobin (odds ratio [OR], 1.27; 95% CI, 1.12–1.45), baseline grade of retinopathy (OR, 1.39; 95% CI, 1.02–1.91), and HIV infection (OR, 0.16; 95% CI, 0.03–0.78). At 2 years, 17 subjects (5.8%) lost ≥15 letters.ConclusionsIncidence of STDR was approximately 3 times that reported in recent European studies. The negative association of HIV infection with retinopathy progression is a new finding

Evaluating the impacts of tiered restrictions introduced in England in December 2020 on covid-19 hospitalisations: a synthetic control study

ABSTRACTObjectivesTo assess the impact of Tier 3 covid-19 restrictions implemented in December 2020 in England on covid-19 hospital admissions compared to Tier 2 restrictions, and its potential variations by neighbourhood deprivation levels and the prevalence of the Alpha variant (B.1.1.7).DesignObservational study utilising a synthetic control approach. Comparison of changes in weekly hospitalisation rates in Tier 3 areas to a synthetic control group derived from Tier 2 areas.SettingEngland between 4thOctober 2020 and 21stFebruary 2021.Participants23 million people under Tier 3 restrictions, compared to a synthetic control group derived from 29 million people under Tier 2 restrictions.InterventionsImplementation of Tier 3 covid-19 restrictions in designated areas on 7thDecember 2020, with additional constraints on indoor and outdoor meetings and the hospitality sector compared to less stringent Tier 2 restrictions.Main Outcome MeasuresWeekly covid-19 related hospital admissions for neighbourhoods in England over a 12-week period following the interventions.ResultsThe introduction of Tier 3 restrictions was associated with a 17% average reduction in hospital admissions compared to Tier 2 areas (95% CI 13% to 21%; 8158 (6286 to 9981) in total)). The effects were similar across different levels of neighbourhood deprivation and prevalence of the Alpha variant (B.1.1.7).ConclusionsRegionally targeted Tier 3 restrictions in England had a moderate but significant effect on reducing hospitalisations. The impact did not exacerbate socioeconomic inequalities during the pandemic. Our findings suggest that regionally targeted restrictions can be effective in managing infectious diseases.SUMMARY BOXESWhat is already known on this topic— Previous studies of localised non-pharmaceutical interventions (NPIs) found that they could be effective in reducing covid-19 transmissions.— covid-19 hospitalisation was a key indicator of healthcare resource dynamics, encompassing supply, demand, burden, and allocation, during the pandemic.— There is a need for a detailed examination of the impact of specific localised restrictions in the UK, such as Tier 3 measures, on hospital admissions to inform targeted public health strategies.What this study adds— This study found that additional localised restrictions on outdoor gatherings and in the hospitality sector were effective in mitigating hospital admissions during the pandemic.How this study might affect research, practice or policy— This study provides evidence for future public health policies and preparedness strategies supporting the use of differential regional restrictions during pandemics.</jats:sec

Evaluating Social and Spatial Inequalities of Large Scale Rapid Lateral Flow SARS-CoV-2 Antigen Testing in COVID-19 Management: An Observational Study of Liverpool, UK (November 2020 to January 2021)

Background: The aim of the study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19.Methods: Linked pseudonymised records for asymptomatic residents in Liverpool (UK) who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action (CIPHA) data resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing.Findings: 214 525 residents (43%) received a LFT identifying 5557 individuals as positive cases of COVID-19 (1.3%). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake and repeat testing were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for ‘Mixed’ ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas.Interpretation: Large-scale voluntary asymptomatic community testing saw social, ethnic, and spatial inequalities in an ‘inverse care’ pattern, but with an added digital exclusion factor. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access.Funding: Department of Health and Social Care (UK), National Institute for Health Research and Economic and Social Research Council).Conflict of Interest: None declared.Ethical Approval: The University of Liverpool has provided secondary data analysis as part of a national service evaluation with data collected by Department of Health and Social Care (Sponsor) for quality assurance of Innova lateral flow tests in a public health service intervention. There was no research commissioned by Department of Health and Social Care on this aspect of the Liverpool pilot of asymptomatic, community testing. As such, research ethics approval was not sought by the Department of Health and Social Care. Some aspects of the evaluation requiring fieldwork and primary data collection by the University of Liverpool were subject to ethical approval, which was confirmed prior to the commencement of activities by the University of Liverpool’s Research Ethics Committee. The provision of secondary data analysis and interpretation did not require further ethical approval. Cheshire & Merseyside Health & Care Partnership Combined Intelligence for Population HealthAction (CIPHA) Data Access Committee approved access to the data and analysis contained in the study. MAST/SMART was defined as ‘an emergency public health intervention during an extraordinary event’ which were subject to the legal and ethical provisions of a health protection activity and COVID-19 specifically. The secondary analysis of data provided in a health protection activity is not classified as research, and so does not require research ethics committee review (see http://www.hradecisiontools.org.uk/research/docs/DefiningResearchTable_Oct2017-1.pdf)

Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy

Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection

Background & Aims Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30–50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection. Methods A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application. Results Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort – low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'. Conclusions Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials. Lay summary The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence

Safety, Efficacy and Cost Effectiveness of Individualised Screening for Diabetic Retinopathy: The ISDR Randomised Controlled Trial

Background: varying diabetic retinopathy (DR) screening intervals, informed by personal risk-levels, empowers people with diabetes (PWD), and offers reallocation of resources to high risk groups, while addressing the increasing prevalence of diabetes. Safety data on extending intervals is minimal. We evaluated the safety, efficacy and cost effectiveness of individualised risk-based variable-interval population screening compared to usual care, with design input from PWD.Methods: two-arm, parallel assignment, equivalence randomised controlled trial (minimum 2 year follow-up) in PWD aged ≥12 years registered with one English screening programme. Randomisation was 1:1 to individualised screening (6, 12 or 24 months for high, medium and low risk) determined by a risk calculation engine, using local demographic, screening and clinical data, or to annual screening (control). Primary outcome was attendance (safety). A secondary safety outcome was the development of sight threatening DR (STDR). Cost effectiveness was evaluated within a 2 year time horizon from NHS and societal perspectives.Findings: 4534 participants were randomised, 2265 to the individualised and 2269 to the control arm. Attendance rates at first follow-up were equivalent between individualised (1754/2097, 83·6%) and control (1883/2224, 84·7%) arms (difference -1·0, 95% CI -3·2 to 1·2). STDR detection rates were non-inferior: individualised 1·4%, control 1·7% (- 0·3, -1·1 to 0·5). Sensitivity analyses confirmed findings. Incremental QALYs/person were non-significant: EQ-5D-5L 0·035 (CI -0·04, 0·13), HUI3 0·009 (CI -0·09, 0·10). Incremental cost savings were £21·31 (CI 15·24, 26·79)/person for the NHS and £28·87 (CI 21·08, 35·78) including societal costs. 43·2% fewer screening appointments were required in the individualised arm.Interpretation: stakeholders involved in diabetes care can be reassured by this largest ophthalmic RCT in DR screening to date that extended and individualised risk-based intervals can be safely and cost effectively introduced in established screening programmes