Study of Optimal Perimetric Testing In Children (OPTIC): Feasibility, reliability and repeatability of perimetry in children

Purpose: To investigate feasibility, reliability and repeatability of perimetry in children. Methods: A prospective, observational study recruiting 154 children aged 5-15 years, without an ophthalmic condition that affects the visual field (controls), identified consecutively between May 2012 and November 2013 from hospital eye clinics. Perimetry was undertaken in a single sitting, with standardised protocols, in a randomised order using the Humphrey static (SITA 24-2 FAST), Goldmann and Octopus kinetic perimeters. Data collected included test duration, subjective experience and test quality (incorporating examiner ratings on comprehension of instructions, fatigue, response to visual and auditory stimuli, concentration and co-operation) to assess feasibility and reliability. Testing was repeated within 6 months to assess repeatability. Results: Overall feasibility was very high (Goldmann=96.1%, Octopus=89% and Humphrey=100% completed the tests). Examiner rated reliability was ‘good’ in 125 (81.2%) children for Goldmann, 100 (64.9%) for Octopus and 98 (63.6%) for Humphrey perimetry. Goldmann perimetry was the most reliable method in children under 9 years of age. Reliability improved with increasing age (multinomial logistic regression (Goldmann, Octopus and Humphrey), p<0.001). No significant differences were found for any of the three test strategies when examining initial and follow-up data outputs (Bland-Altman plots, n=43), suggesting good test repeatability, although the sample size may preclude detection of a small learning effect. Conclusions: Feasibility and reliability of formal perimetry in children improves with age. By the age of 9 years, all the strategies used here were highly feasible and reliable. Clinical assessment of the visual field is achievable in children as young as 5 years, and should be considered where visual field loss is suspected. Since Goldmann perimetry is the most effective strategy in children aged 5-8 years and this perimeter is no longer available, further research is required on a suitable alternative for this age group

Identification of subgroup effect with an individual participant data meta-analysis of randomised controlled trials of three different types of therapist-delivered care in low back pain

Background: Proven treatments for low back pain, at best, only provide modest overall benefits. Matching people to treatments that are likely to be most effective for them may improve clinical outcomes and makes better use of health care resources. Methods: We conducted an individual participant data meta-analysis of randomised controlled trials of three types of therapist delivered interventions for low back pain (active physical, passive physical and psychological treatments). We applied two statistical methods (recursive partitioning and adaptive risk group refinement) to identify potential subgroups who might gain greater benefits from different treatments from our individual participant data meta-analysis. Results: We pooled data from 19 randomised controlled trials, totalling 9328 participants. There were 5349 (57%) females with similar ratios of females in control and intervention arms. The average age was 49 years (standard deviation, SD, 14). Participants: with greater psychological distress and physical disability gained most benefit in improving on the mental component scale (MCS) of SF-12/36 from passive physical treatment than non-active usual care (treatment effects, 4.3; 95% confidence interval, CI, 3.39 to 5.15). Recursive partitioning method found that participants with worse disability at baseline gained most benefit in improving the disability (Roland Morris Disability Questionnaire) outcome from psychological treatment than non-active usual care (treatment effects, 1.7; 95% CI, 1.1 to 2.31). Adaptive risk group refinement did not find any subgroup that would gain much treatment effect between psychological and non-active usual care. Neither statistical method identified any subgroups who would gain an additional benefit from active physical treatment compared to non-active usual care. Conclusions: Our methodological approaches worked well and may have applicability in other clinical areas. Passive physical treatments were most likely to help people who were younger with higher levels of disability and low levels of psychological distress. Psychological treatments were more likely to help those with severe disability. Despite this, the clinical importance of identifying these subgroups is limited. The sizes of sub-groups more likely to benefit and the additional effect sizes observed are small. Our analyses provide no evidence to support the use of sub-grouping for people with low back pain

Type 2 Diabetes Is Associated with Reduced ATP-Binding Cassette Transporter A1 Gene Expression, Protein and Function

Objective Increasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ). Methods and Results Leukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, p<0.001; rho = −0.34, p = 0.006 respectively) and was reduced in Type 2 diabetes (T2DM) (p = 0.03). Leukocyte ABCA1 protein was lower in T2DM (p = 0.03) and positively associated with plasma HDL cholesterol (HDL-C) (rho = 0.34, p = 0.02). Apolipoprotein-A1-mediated cholesterol efflux correlated negatively with fasting glucose (rho = −0.50, p = 0.01) and positively with HDL-C (rho = 0.41, p = 0.02). It was reduced in T2DM compared with controls (p = 0.04). These relationships were independent of LXRα and PPARγ expression. Conclusions ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT

A África, o Sul e as ciências sociais brasileiras : descolonização e abertura

O texto introduz questões recentes sobre a relação entre as ciências sociais na África e no Brasil, inserindo-as no debate sobre as sociologias do Sul e a geopolítica do conhecimento na produção de teoria social. A partir da noção de sociologia não exemplar são apresentados alguns dos possíveis caminhos teórico-metodológicos que possibilitariam um posicionamento mais simétrico para a produção de conhecimento localizada fora da Euro-América.The paper introduces the contemporary debates on the relation of social sciences in Africa and Brazil by framing them both under the current discussion about the "sociologies of the south" and the ones on "the geopolitics of knowledge". Deploying the notion of a "non-exemplary sociology", I seek to present some possible theoretical and methodological ways that would enable a more symmetric positioning of the knowledge produced outside the Euro-America

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Evaluating the Quantity and Quality of Health Economic Literature in Blinding Childhood Disorders: A Systematic Literature Review

BACKGROUND: Evidence on the socioeconomic burden associated with childhood visual impairment, severe visual impairment and blindness (VI/SVI/BL) is needed to inform economic evaluations of existing and emerging interventions aimed at protecting or improving vision. This study aimed to evaluate the quantity and quality of literature on resource use and/or costs associated with childhood VI/SVI/BL disorders. METHODS: PubMed, Web of Science (Ovid), the National Health Service (NHS) Economic Evaluation Database and grey literature were searched in November 2020. The PubMed search was rerun in February 2022. Original articles reporting unique estimates of resource use or cost data on conditions resulting in bilateral VI/SVI/BL were eligible for data extraction. Quality assessment (QA) was undertaken using the Drummond checklist adapted for cost-of-illness (COI) studies. RESULTS: We identified 31 eligible articles, 27 from the peer-reviewed literature and four from the grey literature. Two reported on resource use, and 29 reported on costs. Cerebral visual impairment and optic nerve disorders were not examined in any included studies, whereas retinopathy of prematurity was the most frequently examined condition. The quality of studies varied, with economic evaluations having higher mean QA scores (82%) compared to COI studies (77%). Deficiencies in reporting were seen, particularly in the clinical definitions of conditions in economic evaluations and a lack of discounting and sensitivity analyses in COI studies. CONCLUSIONS: There is sparse literature on resource use or costs associated with childhood visual impairment disorders. The first step in addressing this important evidence gap is to ensure core visual impairment outcomes are measured in future randomised control trials of interventions as well as cohort studies and are reported as a discrete health outcome

Neonatal Fc receptor blockade by Fc engineering ameliorates arthritis in a murine model

Multiple autoimmune diseases are characterized by the involvement of autoreactive Abs in pathogenesis. Problems associated with existing therapeutics such as the delivery of intravenous immunoglobulin have led to interest in developing alternative approaches using recombinant or synthetic methods. Toward this aim, in the current study, we demonstrate that the use of Fc-engineered Abs (Abs that enhance IgG degradation [Abdegs]) to block neonatal FcR (FcRn) through high-affinity, Fc region binding is an effective strategy for the treatment of Ab-mediated disease. Specifically, Abdegs can be used at low, single doses to treat disease in the K/BxN serum transfer model of arthritis using BALB/c mice as recipients. Similar therapeutic effects are induced by 25- to 50-fold higher doses of i.v. Ig. Importantly, we show that FcRn blockade is a primary contributing factor toward the observed reduction in disease severity. The levels of albumin, which is also recycled by FcRn, are not affected by Abdeg delivery. Consequently, Abdegs do not alter FcRn expression levels or subcellular trafficking behavior. The engineering of Ab Fc regions to generate potent FcRn blockers therefore holds promise for the therapy of Ab-mediated autoimmunity.</p