Search

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

Dogs diagnosed with multicentric lymphoma often relapse following induction therapy within the first year of treatment. The primary aim of this study was to evaluate the tolerability of a novel drug combination using melphalan, vincristine, and cytarabine (MOC) for the treatment of relapsed lymphoma. On day 1, dogs were treated with vincristine (0.5–0.6 mg/m2 IV) and cytarabine (300 mg/m2 IV over 4–6 hr or subcutaneously over 2 days). On day 7, dogs were treated with melphalan (20 mg/m2per os). This 2 wk protocol was repeated for at least three cycles or until treatment failure. Twenty-six dogs were treated with MOC and met the inclusion criteria. Twenty-three dogs had toxicity data, and all experienced adverse events with the majority graded as mild. The overall response rate was 38%, which included 19% of dogs who achieved a complete response. The median progression-free survival was 29 days (range 1–280 days). The overall clinical benefit was 65% for a median of 37 days (range 33–280 days). MOC is a safe treatment option for relapsed lymphoma in dogs. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) appears capable of detecting diabetic retinopathy (DR) with a high degree of accuracy in adults; however, there are few studies in children and young adults. Methods: Children and young adults (3-26 years) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were screened at the Dhaka BIRDEM-2 hospital, Bangladesh. All gradable fundus images were uploaded to Cybersight AI for interpretation. Two main outcomes were considered at a patient level: 1) Any DR, defined as mild non-proliferative diabetic retinopathy (NPDR or more severe; and 2) Referable DR, defined as moderate NPDR or more severe. Diagnostic test performance comparing Orbis International's Cybersight AI with the reference standard, a fully qualified optometrist certified in DR grading, was assessed using the Matthews correlation coefficient (MCC), area under the receiver operating characteristic curve (AUC-ROC), area under the precision-recall curve (AUC-PR), sensitivity, specificity, positive and negative predictive values. Results: Among 1274 participants (53.1% female, mean age 16.7 years), 19.4% (n = 247) had any DR according to AI. For referable DR, 2.35% (n = 30) were detected by AI. The sensitivity and specificity of AI for any DR were 75.5% (CI 69.7-81.3%) and 91.8% (CI 90.2-93.5%) respectively, and for referable DR, these values were 84.2% (CI 67.8-100%) and 98.9% (CI 98.3%-99.5%). The MCC, AUC-ROC and the AUC-PR for referable DR were 63.4, 91.2 and 76.2% respectively. AI was most successful in accurately classifying younger children with shorter duration of diabetes. Conclusions: Cybersight AI accurately detected any DR and referable DR among children and young adults, despite its algorithms having been trained on adults. The observed high specificity is particularly important to avoid over-referral in low-resource settings. AI may be an effective tool to reduce demands on scarce physician resources for the care of children with diabetes in low-resource settings. [ABSTRACT FROM AUTHOR]

Aims: To characterise continuous glucose monitor and flash glucose monitor use and related issues (both positive and negative) in the population of children and young people living with type 1 diabetes in the Southern Health and Social Care Trust (SHSCT), Northern Ireland. Methods: Four focus groups were conducted in the SHSCT with people with type 1 diabetes and their families, to assess opinions of diabetes technology. In addition, questionnaires were distributed to diabetes specialist nurses (DSNs), young people and their families about use and access to diabetes technology. Results: Questionnaires were completed by 68 children, young people (0–18 years) and their parents/guardians. Nearly all (98.5%) had access to their own diabetes related data, and 70.6% used diabetes data systems, for example, Libreview. Most of those using these systems found them beneficial and easy for daily use and clinical review. Most DSNs (83.9%) agreed that the systems were easy to use, and 82.3% were confident in interpreting the data accurately. DSNs felt virtual review was beneficial in over half of young people with 62.9% advising changes to diabetes management based on the data. Focus groups participants deemed diabetes technology a 'gamechanger' and 'lifechanging'. Some drawbacks included 'disruptive' alarms, self‐confidence issues, visible diabetes technology and problems in school. Conclusions: Most young people, their families and healthcare professionals reported they were confident in interpreting diabetes data and technology was easy to use. Diabetes technology could improve access to care through virtual clinics, improve clinical outcomes and enhance quality of life. [ABSTRACT FROM AUTHOR]

While current lymphoma therapies induce remission in most dogs, drug‐resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9‐(2‐phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty‐three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T‐cell immunophenotype and corticosteroid pre‐treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG‐CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic test accuracy (DTA) of trained nurses, mid‐level and senior ophthalmologists in Vietnam against a reference standard from the UK, and assess the impact of further training on graders. Methods: Fundus photographs were taken and graded at two different time points by trained nurses, mid‐level ophthalmologists and senior ophthalmologists in Vietnam using the UK National Screening Committee classification system. A reference standard from the UK regraded all images in masked fashion and DTA was calculated using sensitivity and specificity (with 95% CIs), and positive and negative predictive values. Results: Between September and November 2018, 431 people with diabetes attended diabetic retinopathy (DR) screening in Southern Vietnam. The sensitivity for detecting any DR for all grader groups in Vietnam was low (<43%) against the reference standard in the UK. The sensitivity for detecting referable DR and referrable diabetic macular oedema was particularly low (<20%) for all grader groups. Subsequently, an additional subset of images from 138 consecutive patients screened from March to April 2021 was regraded in the UK to evaluate graders' performance after additional training was delivered. A significant improvement in DTA among all grader groups in Vietnam was identified, with sensitivity for detecting any DR exceeding 85%. Nurses achieved the highest sensitivity for grading referable DR (76.9%, 60.3–88.3%) and mid‐level ophthalmologists attained the highest sensitivity for detecting referable maculopathy (77.5%, 61.2–88.6). Conclusions: Grading accuracy was low in Vietnam in the first six months of implementing a training programme. Many factors may have contributed to poor grader performance, including inadequate training and feedback, insufficient time to participate in quality assurance testing and competing work responsibilities. After further training was delivered, DTA among all graders in Vietnam increased. Findings from this study are particularly important for DR programme planners in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Cancer patients commonly develop infectious complications over the course of the disease. One thousand patients receiving treatment for an oncologic disease at a single veterinary teaching hospital were retrospectively reviewed for concurrent infections. A total of 153 confirmed bacterial infections were identified, 82 of which were abscesses or wounds, 13 of which were respiratory infections, 3 of which were ear infections, and 55 of which were urinary tract infections. It was observed that the majority of the infections were caused by bacteria that are normally associated with that specific site location. Escherichia coli was the most common pathogen linked to infections in general, but Staphylococcus pseudintermedius was a frequently identified pathogen associated with wound infections. The susceptibility to diverse antimicrobials varied with the site of infection. Eleven cases (7.1%) were caused by opportunistic infections of the site, and E. coli and Pseudomonas aeruginosa were the pathogens isolated. Those bacteria were resistant to many antibiotics but showed susceptibility to aminoglycosides, imipenem, quinolones, and polymyxin B. In conclusion, veterinary patients with cancer or those under treatment for tumors develop infections by commonly encountered bacteria in the different sites of the body, with a susceptibility to antibiotics that is not out of line from what is expected. A small subset of cases developed opportunistic infections, with microbes that were more resistant to many classes of antibiotics. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the reproducibility of SIMPLE (Single field Image Multi Parameters defined Lesions Extent), a new Diabetic Retinopathy (DR) classification for screening of 45° single field fundus pictures of patients with diabetes (PwDM), assessing DR, Diabetic Maculopathy (DMac) and referral rate agreement and comparing it to current Italian Guidelines (IG)., Materials and Methods: We conducted a retrospective, observational, multicentre study, collecting 1000 retinal 45° single field images of PwDM obtained during routine visits in two diabetes clinics. Three ophthalmologists evaluated each image, determining the presence and number of specific DR lesions and then assigning a stage according to the current IG for screening. SIMPLE staging was performed automatically via Excel software, based on the pre-specified DR characteristics observed by the graders. We analysed intra-centre, inter-centre and total inter-grader agreement for DR and DMac stage and referral rate of the two classifications., Results: Agreement amongst the three graders was consistently higher when using SIMPLE classification than when using current IG classification. For DR, kappa (k) was 0.86 with IG and 0.95 with SIMPLE classification; for DMac, k-IG was 0.78, while k-SIMPLE was 0.96; concordance on the referral rate was 0.91 with IG and 0.99 with SIMPLE. Similar results were obtained in sub-analyses for the evaluation of intra-centre and inter-centre concordance., Conclusions: Our results suggest that the new SIMPLE classification has an excellent reproducibility amongst graders, comparable or superior to the current IG for DR screening proposed in 2015, improving the standardisation of the decision on referability., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line)., Objectives: The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months)., Search Methods: We searched various electronic databases on 8 July 2022., Selection Criteria: We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO., Data Collection and Analysis: We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence., Main Results: We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs., Authors' Conclusions: There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants., Competing Interests: GV: none known KC: none known EL: none known TP: received honoraria for advisory board and lecture fees from Bayer, Allergan, B-I, Sandoz, Roche, Novartis, Heidelberg, Zeiss, and Optos MP: received payment for participating on the Advisory Board for Allergan, Bayer and Novartis. Jennifer Evans (methods guide, not an author): none known Iris Gordon (search specialist, not an author): none known, (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training., Design: Diagnostic test accuracy study., Setting: Secondary care hospitals in Southern Vietnam., Participants: DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion., Primary and Secondary Outcome Measures: Sensitivity was calculated at the two different time points, and χ 2 was used to test significance., Results: In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8-42.2%) and improved in phase II after additional training was delivered (51.3-87.2%). The greatest improvement was seen among level 1 graders (p<0.001), and the lowest improvement was observed among level 3 graders (p=0.326). There was a statistically significant improvement in sensitivity for detecting referable DR and referable diabetic macular oedema between all grader levels. The post-training values ranged from 40.0 to 61.5% (including ungradable images) and 55.6%-90.0% (excluding ungradable images)., Conclusions: This study demonstrates that targeted training interventions can improve accuracy of DR grading. These findings have important implications for improving service delivery in DR screening programmes in low-resource settings., Competing Interests: Competing interests: NC is employed as a Research Director by Orbis International., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Globally, diabetic retinopathy (DR) is the leading cause of blindness in working-aged adults. Early detection and treatment of DR is essential for preventing sight loss. Services must be available, accessible and acceptable to patients if we are to ensure they seek such care., Objectives: To understand patients' knowledge and attitudes towards laser versus antivascular endothelial growth factor (VEGF) injections to treat DR in Vietnam, and to identify factors Vietnamese ophthalmologists consider when making treatment decisions., Methods: This is a descriptive qualitative study based on semi-structured interviews with 18 patients (12 from Ho Chi Minh City and 6 from Hanoi) plus individual interviews with 24 ophthalmologists working in eye clinics in these cities. Thematic analysis was used to analyse the data., Results: In total, 10/24 (41.7%) ophthalmologists were female, and their median age was 41 years (range 29-69 years). The median age of patients was 56.5 years (range 28-72 years), and 7/18 (38.9%) were female. Briefly, factors that influence DR treatment decisions for ophthalmologists are medical considerations (ie, severity of disease, benefits and risks), availability (ie, treatment and resources) and patient-related factors (ie, costs and adherence). Patient's perceived barriers and facilitators to treatments were based on patient and family related factors (ie, treatment and transportation costs) and previous treatment experiences (ie, positive and negative). Recommendations by all participants included ensuring that both laser and anti-VEGF injections are widely available across the country and controlling costs for patients and the healthcare system., Conclusions: Reducing DR treatment costs, optimising treatments options, and expanding the network of clinics offering treatment outside metropolitan areas were the main issues raised by participants. These findings can help inform policy changes in Vietnam and may be generalisable to other low-resource settings., Competing Interests: Competing interests: NC is employed as a Research Director by Orbis International., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The diabetes mellitus (DM) epidemic is a major public health concern globally, with the highest-burden in low-income and middle-income countries (LMICs). Diabetic retinopathy (DR) is a microvascular complication of diabetes, and if left untreated can lead to visual impairment and blindness. Epidemiological studies suggest that the incidence of sight-threatening DR is decreasing in high-income countries due to improved treatments and management of DM; however, these trends are not replicated in LMICs. In this paper, we outline a scoping review protocol that aims to identify which LMICs have included DR in their national DM, non-communicable disease or prevention of blindness plans. The scoping review also aims to assess gaps when implementing national DR screening programmes in LMICs., Methods and Analysis: This scoping review will follow the Arksey and O'Malley (2005) methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Review guidelines. A comprehensive search of peer-reviewed and grey literature will be conducted from October 1989 (St. Vincent Declaration) to February 2020. Studies will be identified from electronic databases; Medline, Embase and CENTRAL (Cochrane Library). To identify further relevant articles, a hand search will be conducted using the reference lists of included studies. Two reviewers will independently screen records for relevant data and disagreements about eligibility will be resolved through consensus or arbitration by a third reviewer. A quantitative analysis will be performed to highlight key findings and thematic analysis will be used to identify emerging themes and subthemes from included studies. The key themes will highlight countries progress in terms of national-level DR service planning and screening implementation., Ethics and Dissemination: No ethical approval is required because the scoping review methodology aims to synthesise information from publicly available resources. The results will be disseminated through conference presentations and peer-reviewed publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)