Spatial and spatio-temporal statistical analyses of retinal images: a review of methods and applications.

Background: Clinical research and management of retinal diseases greatly depend on the interpretation of retinal images and often longitudinally collected images. Retinal images provide context for spatial data, namely the location of specific pathologies within the retina. Longitudinally collected images can show how clinical events at one point can affect the retina over time. In this review, we aimed to assess statistical approaches to spatial and spatio-temporal data in retinal images. We also review the spatio-temporal modelling approaches used in other medical image types. Methods: We conducted a comprehensive literature review of both spatial or spatio-temporal approaches and non-spatial approaches to the statistical analysis of retinal images. The key methodological and clinical characteristics of published papers were extracted. We also investigated whether clinical variables and spatial correlation were accounted for in the analysis. Results: Thirty-four papers that included retinal imaging data were identified for full-text information extraction. Only 11 (32.4%) papers used spatial or spatio-temporal statistical methods to analyse images, others (23 papers, 67.6%) used non-spatial methods. Twenty-eight (82.4%) papers reported images collected cross-sectionally, while 6 (17.6%) papers reported analyses on images collected longitudinally. In imaging areas outside of ophthalmology, 19 papers were identified with spatio-temporal analysis, and multiple statistical methods were recorded. Conclusions: In future statistical analyses of retinal images, it will be beneficial to clearly define and report the spatial distributions studied, report the spatial correlations, combine imaging data with clinical variables into analysis if available, and clearly state the software or packages used

Laparoscopy-assisted gastrectomy in the elderly: experience from a UK centre

BACKGROUND Gastric cancer has a high incidence in the elderly in the UK, with a significant number of patients aged 75 years or more. While surgery forms the mainstay of treatment, evidence pertaining to the management of gastric cancer in the Western population in this age group is scarce. METHODS We retrospectively reviewed the outcomes of laparoscopy-assisted total and distal gastrectomies at our centre from 2005 to 2015. Patients aged 70 years or above were included in the elderly group. RESULTS A total of 60 patients underwent laparoscopy-assisted gastrectomy over a 10-year period, with a predominance of male patients. There was no significant difference in the rate of overall surgical and non-surgical complications, in-hospital mortality, operation time and length of hospital stay, between the elderly and non-elderly groups. Univariate analysis, performed for risk factors relating to anastomotic leak and surgical complications, showed that age over 70 years and higher American Association of Anesthesiologists grades are associated with a higher, though not statistically significant, number of anastomotic leaks (P = 1.000 and P = 0.442, respectively) and surgical complications (P = 0.469 and P = 0.162, respectively). The recurrence rate within the first 3 years of surgery was significantly higher in the non-elderly group compared with the elderly group (Log Rank test, P = 0.002). There was no significant difference in survival between the two groups (Log Rank test, P = 0.619). CONCLUSIONS Laparoscopy-assisted gastrectomy is safe and feasible in an elderly population. There is a need for well-designed, prospective, randomised studies with quality of life data to inform our practice in future

A Randomized Controlled Trial of Extended Brief Intervention for Alcohol-Dependent Patients in an Acute Hospital Setting

To determine whether alcohol-dependent patients in a hospital setting benefit from extended brief interventions (EBI) delivered by an Alcohol Specialist Nurse. Methods Alcohol-dependent patients recruited via screening at the emergency department (ED) (n = 267), whether or not admitted to hospital, were randomized to EBI (up to six counselling sessions offered) or control. At 6 months, 84.2% of patients were assessed by a researcher blinded to the intervention. The primary outcome was a fall in Severity of Alcohol Dependence Questionnaire. Results There was no difference between groups in the primary outcome [odds ratio (OR) 1.02; 95% confidence interval (CI): 0.38, 2.75, P = 0.97]. Secondary outcomes including alcohol consumption and readiness to change did not show a significant difference between groups. However, all secondary outcome measures improved, on average, in both arms. Conclusions Although EBI can be delivered in an ED or inpatient setting, it was not shown to be an advantage over screening and usual management (which included advice on alternative services), with patients in both groups showing an average improvement

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified

Flomoxef and fosfomycin in combination for the treatment of neonatal sepsis in the setting of highly prevalent antimicrobial resistance.

BACKGROUND: Neonatal sepsis is a serious bacterial infection of neonates, globally killing up to 680 000 babies annually. It is frequently complicated by antimicrobial resistance, particularly in low- and middle-income country (LMIC) settings with widespread resistance to the WHO's recommended empirical regimen of ampicillin and gentamicin. OBJECTIVES: We assessed the utility of flomoxef and fosfomycin as a potential alternative empirical regimen for neonatal sepsis in these settings. METHODS: We studied the combination in a 16-arm dose-ranged hollow-fibre infection model (HFIM) experiment and chequerboard assays. We further assessed the combination using clinically relevant regimens in the HFIM with six Enterobacterales strains with a range of flomoxef/fosfomycin MICs. RESULTS: Pharmacokinetic/pharmacodynamic modelling of the HFIM experimental output, along with data from chequerboard assays, indicated synergy of this regimen in terms of bacterial killing and prevention of emergence of fosfomycin resistance. Flomoxef monotherapy was sufficient to kill 3/3 strains with flomoxef MICs ≤0.5 mg/L to sterility. Three of three strains with flomoxef MICs ≥8 mg/L were not killed by fosfomycin or flomoxef monotherapy; 2/3 of these were killed with the combination of the two agents. CONCLUSIONS: These data suggest that flomoxef/fosfomycin could be an efficacious and synergistic regimen for the empirical treatment of neonatal sepsis in LMIC settings with prevalent antimicrobial resistance. Our HFIM results warrant further assessment of the flomoxef/fosfomycin combination in clinical trials

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study.

INTRODUCTION: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. METHODS AND ANALYSIS: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. ETHICS AND DISSEMINATION: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media