Aflibercept or ranibizumab for diabetic macular edema.

Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

International consensus on fasting terminology.

Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys. Consensus was achieved for the following terms: "fasting" (voluntary abstinence from some or all foods or foods and beverages), "modified fasting" (restriction of energy intake to max. 25% of energy needs), "fluid-only fasting," "alternate-day fasting," "short-term fasting" (lasting 2-3 days), "prolonged fasting" (≥4 consecutive days), and "religious fasting." "Intermittent fasting" (repetitive fasting periods lasting ≤48 h), "time-restricted eating," and "fasting-mimicking diet" were discussed most. This study provides expert recommendations on fasting terminology for future research and clinical applications, facilitating communication and cross-referencing in the field.

Recommendations for Development and Validation of a Fit-For-Purpose Biomarker Assays Using Western Blotting; An-AAPS Sponsored Initiative to Harmonize Industry Practices.

Western blot (WB) assays are routinely used for detection and quantification of biomarkers. Although assay validation to measure biomarkers in complex matrices has become a mainstay process for ligand binding assays (LBA) and mass spectrometry (MS), no guidelines exist yet validate biomarker methods using WB techniques. In this cross-industry white paper, we outlined in detail the key steps for development and for validation of WB assays for protein biomarkers under different contexts of use (COU). In addition, we described how to determine the level of assay validation needed for biomarker assays using Western blotting. For simplicity, we described two paths of WB assay validation. The first path (Path 1) is for biomarkers being analyzed for exploratory research or for internal go- or no/go- decision making. The second path (Path 2) is for clinical decision making such as dose determination or drug response that need to be run in a regulated environment. This work is supported through AAPS Biomarkers and Precision Medicine subteam and represents AAPS members opinion.

An update on the current characteristics and status of care for Muslims with type 2 diabetes fasting during Ramadan: the DAR global survey 2022.

BACKGROUND: Managing diabetes during Ramadan fasting is a challenge due lifestyle changes. We described the characteristics and patterns of care for type 2 diabetes mellitus (T2DM) during Ramadan 2020 and 2022. METHODS: Our study included multinational Muslims with T2DM who were during routine consultation. We collected data on demographics, fasting characteristics, and complications. Descriptive statistics, chi-square test, and multiple testing were performed. RESULTS: 12,529 patients participated. Mean age was 55.2 ± 11.8 years; 52.4% were females. Mean diabetes duration was 9.9 ± 7.4 years; 27.7% were with HbA1c >9% (75 mmol/mol) and 70% had complications. Metformin was the most used medication followed by insulin. 85.1% fasted ≥1 day; fasting mean duration was 27.6 ± 5.6 days. Hypoglycemia occurred in 15.5% of whom 11.7% attended emergency department or were hospitalized; this was significantly associated with age and/or duration of diabetes. Hyperglycemia occurred in 14.9% of whom 6.1% attended emergency department or were hospitalized and was also associated with age or duration of diabetes. 74.2% performed SMBG during fasting. 59.2% were educated on Ramadan fasting, with 89.7% receiving it during routine consultation. CONCLUSIONS: Ramadan fasting in T2DM is high. Multidisciplinary approach is required to mitigate complications. Our findings support current recommendations for safe fasting.

The goal of this survey was to describe the characteristics and current ways of care for Muslim patients with type 2 diabetes mellitus fasting during and after Ramadan 2020 and 2022. Most of the participants fasted a minimum of one day during Ramadan (85.1%). Overall, 15.5 and 14.9% reported low blood sugar levels or high blood sugar levels during fasting, respectively. Low blood sugar level was more reported in patients with older age, patients with longer diabetes duration, and women. High blood sugar level was more reported in patients with longer diabetes duration. Educational programs focusing on the risks occurring with fasting and practices that improve control of the disease will raise knowledge and awareness among patients with diabetes. Improving blood sugar control during Ramadan fasting remains a major need for both patients and healthcare providers who should collaborate to reduce the risk of diabetes-related problems.

Anterior Distal Femoral Hemiepiphysiodesis Using Coronally Oriented 8-plates for the Correction of Fixed Knee Flexion Deformities in Children-Preliminary Results.

INTRODUCTION: The original technique for guided growth of the distal femur for correction of pediatric fixed knee flexion deformities (FKFDs) involves the utilization of two 8-plates inserted on either side of the trochlear groove, a technique that has been frequently linked to the development of persistent postoperative knee pain and crepitus. The present study aimed to assess the preliminary results of a novel technique where the two 8-plates are fixed in the coronal plane, one on each of the medial and lateral surfaces, so that they occupy the anterior part of the distal femur. METHODS: Our study was a prospective case series that included cases with FKFD of >10 degrees in children with at least 12 months of predicted growth remaining. The preoperative knee flexion contracture angle was documented. The surgical procedure entailed the insertion of 2 coronally oriented 8-plates on the medial and lateral surfaces of the distal femur as anterior as possible to the axis of the femur without encroachment on the trochlear groove. The duration of time required to attain full knee extension and any complications encountered were recorded. Wilcoxon signed-rank was used to compare the preoperative and final contracture angles. The level of statistical significance was set at P<0.05. RESULTS: Thirteen knees in 8 patients (6 boys and 2 girls) were included. The median age was 11 years (6 to 14). There was a significant improvement in the FKFD for the whole cohort from 25 degrees (14 to 42) to 0 degrees (-9 to 8), P<0.05. The median rate of correction was 2.0 degrees/month (0.9 to 5.8). The time till full correction was 14 months (4 to 25). Postoperative knee pain and metalware-related complications were not reported by any patient during follow-up. CONCLUSIONS: Guided growth of the distal femur using coronally oriented 8-plates is an effective procedure for the treatment of FKFDs in children. This modified technique may achieve faster correction while minimizing the risk of postoperative knee pain compared with the conventional technique. LEVEL OF EVIDENCE: Level IV-case series.

Etiologies underlying subtypes of long-standing type 2 diabetes.

BACKGROUND: Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants. METHODS: The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results. RESULTS: Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions. CONCLUSIONS: Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone.

Consensus recommendations on fasting during Ramadan for patients with kidney disease: review of available evidence and a call for action (RaK Initiative).

Ramadan fasting (RF) involves abstaining from food and drink during daylight hours; it is obligatory for all healthy Muslims from the age of puberty. Although sick individuals are exempt from fasting, many will fast anyway. This article explores the impact of RF on individuals with kidney diseases through a comprehensive review of existing literature and consensus recommendations. This study was conducted by a multidisciplinary panel of experts.The recommendations aim to provide a structured approach to assess and manage fasting during Ramadan for patients with kidney diseases, empowering both healthcare providers and patients to make informed decisions while considering their unique circumstances.

Digitising diabetes education for a safer Ramadan: Design, delivery, and evaluation of massive open online courses in Ramadan-focused diabetes education.

AIMS: Ramadan-focused diabetes education is critical to facilitate safer Ramadan fasting amongst Muslim people living with diabetes. We present the design, delivery, and evaluation of two parallel massive open online courses (MOOCs) in Ramadan-focused diabetes education for people with diabetes and HCPs. METHODS: Two Ramadan-focused diabetes education MOOCs were developed and delivered for Ramadan 2023: one for HCPs in English, and another for people with diabetes in English, Arabic and Malay. A user-centred iterative design process was adopted, informed by user feedback from a 2022 pilot MOOC. Evaluation comprised a mixed-methods evaluation of pre- and post-course user surveys. RESULTS: The platform was utilised by people with diabetes and their family, friends and healthcare professionals. Overall, a total of 1531 users registered for the platform from 50 countries, 809 started a course with a 48% subsequent completion rate among course starters. Qualitative analysis showed users found the course a user-friendly and authoritative information source. In the HCP MOOC, users reported improved post-MOOC Ramadan awareness, associated diabetes knowledge and ability to assess and advise patients in relation to their diabetes during Ramadan (p<0.01). CONCLUSIONS: We demonstrate the potential of MOOCs to deliver culturally tailored, high-quality, scalable, multilingual Ramadan-focused diabetes education to HCPs and people with diabetes.

Safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus from Gulf countries during Ramadan holy month: A subgroup analysis of the SoliRam observational study.

AIM: To investigate safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus (T2DM) observing fast during Ramadan from Gulf countries. METHODS: This planned subgroup analysis of the SoliRam - a multinational, prospective, non-interventional, real-world, observational study - focused on participants from Gulf countries. Primary endpoint was proportion of participants experiencing ≥1 episode of severe and/or symptomatic documented (<70 mg/dL [<3.9 mmol/L]) hypoglycemia. RESULTS: A total of 241 individuals with T2DM (mean age: 58.1 years; male: 54.4%; mean duration of diabetes: 13.3 years) were included. All 234 eligible participants followed during Ramadan were able to fast for ≥25 days and no participants broke fast due to hypoglycemia. Primary endpoint was reported in one participant (0.5%) during fasting hours during Ramadan. Improvements (mean ± SD change) in HbA1c (-1.0 ± 1.0% [-11 ± 10 mmol/mol]), FPG (-22.5 ± 29.7 mg/dL), and body weight (-1.5 ± 2.0 kg) were observed from pre-Ramadan to post-Ramadan. Three participants (1.2 %) reported an adverse event (AE) of any cause and one (0.4%) reported a gastrointestinal AE. CONCLUSIONS: iGlarLixi is an effective and well-tolerated treatment in people with T2DM from Gulf countries, including during Ramadan fasting, and is associated with low risk of hypoglycemia.

Western blotting: evolution of an old analytical method to a new quantitative tool for biomarker measurements.

Western blotting (WB) is a widely used laboratory technique for detecting specific proteins in biological matrices. Recent advances in antibody production, automation, gel and membrane manufacturing and highly sensitive detection platforms have transformed WB from a labor-intensive and qualitative method into a highly reproducible and quantitative assay suitable for biomarker detection. Despite these significant improvements in the capabilities and efficiency of WB, there remain challenges that hinder its widespread application as a research, diagnostic (in two-tiered assays like Lyme disease testing) and drug development tool. This article describes recent innovations introduced to WB methodology and the remaining challenges that prevent its wider adoption for biomarker measurements throughout the drug development process.

Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-κB signals.

Cardiotoxicity is a significant adverse effect of cisplatin (CIS) that necessitates extensive medical care. The current study examines the cardioprotective effects of edaravone (EDV), obeticholic acid (OCA), and their combinations on CIS-induced cardiac damage. Rats were allocated into five groups: the normal control group, the remaining four groups received CIS (7.5 mg/kg, i.p.) as a single dose on the fifth day and were assigned to CIS, OCA (10 mg/kg/day) + CIS, EDV (20 mg/kg/day) + CIS, and the (EDV + OCA) + CIS group. Compared to the CIS-treated group, co-treating rats with EDV, OCA, or their combinations significantly decreased ALP, AST, LDH, CK-MB, and troponin-I serum levels and alleviated histopathological heart abnormalities. Biochemically, EDV, OCA, and EDV plus OCA administration mitigated cardiac oxidative stress as indicated by a marked decrease in heart MDA content with a rise in cardiac antioxidants SOD and GSH associated with upregulating Nrf2, PPARγ, and SIRT1 expression. Besides, it dampened inflammation by decreasing cardiac levels of TNF-α, IL-1ß, and IL-6, mediated by suppressing NF-κB, JAK1/STAT3, and TLR4/p38MAPK signal activation. Notably, rats co-administered with EDV plus OCA showed noticeable protection that exceeded that of EDV and OCA alone. In conclusion, our study provided that EDV, OCA, and their combinations effectively attenuated CIS-induced cardiac intoxication by activating Nrf2, PPARγ, and SIRT1 signals and downregulating NF-κB, JAK1/STAT3, and TLR4/p38MAPK signals.

The Usage Pattern of Patients’ Drug Information Leaflet for Oral Non-Prescription Drugs Among University Students in the United Arab Emirates: Cross-Sectional Study

Background: Very few extensive studies have measured the prevalence and usage pattern of drug information leaflet (DIL) for oral non-prescription drugs (ONPDs) or identified the associated risk factors for not reading DIL among university students in the UAE. Objective: The current study aimed to estimate the prevalence of the usage pattern of DIL for ONPDs, and delineate the associated risk factors for not reading the DIL among university students. Methods: A cross-sectional survey-based multistage sampling technique conducted among 2875 students at three major universities in UAE. The self-administered validated questionnaire was constructed and developed based on Andersen’s behavioral model. Binomial logistic regression performed to ascertain the effects of 25 potential predictors on the likelihood that participants not reading (discarded) the DIL after reading them. The primary outcome measure was reading (discarding without reading) the DIL, and the associated behaviours. (AU)

Non-penetrating deep sclerectomy versus combined trabeculotomy-trabeculectomy in primary congenital glaucoma.

Background: The primary mode of therapy in children with primary congenital glaucoma (PCG) and mild or no corneal edema is goniotomy, which has a high success rate. However, in developing countries, the diagnosis of PCG is usually delayed, and corneal cloudiness interferes with goniotomy. Therefore, trabeculotomy may be the best choice in such eyes. We compared the short-term efficacy and safety of primary combined trabeculotomy-trabeculectomy (primary CTT) with that of non-penetrating deep sclerectomy (NPDS) in managing PCG. Methods: This prospective, randomized, comparative study included patients with PCG referred to Al-Azhar University Hospitals within a 1-year period. Eyes were randomly allocated to one of two groups: eyes in NPDS group underwent NPDS, and those in primary CTT group underwent primary CTT. Baseline and frequent postoperative assessments of intraocular pressure (IOP), cup-to-disc ratio (C/D ratio), corneal diameter, and axial length were performed for up to 6 months. The success rates were recorded in both groups. Results: Forty eyes of 26 patients were included, with 20 eyes allocated to each group. The mean (standard deviation) age of all patients was 12.9 (9.5) months, with comparable ages and sex ratios between groups (both P > 0.05). Both groups demonstrated a significant reduction in IOP and C/D ratio at each postoperative visit compared to the baseline visit (all P < 0.001), with no significant difference detected between the groups (all P > 0.05), except for a significantly lower IOP in NPDS group at 1 month (P < 0.05). The corneal diameter and axial length were comparable between groups at baseline and remained unchanged at all postoperative visits (all P > 0.05). The groups had comparable success rates (P > 0.05). No serious complications were detected. Conclusions: CTT and NPDS both yielded reasonable IOP control and reversal of cupping in eyes with PCG. We observed equal effectiveness of the surgical procedures without major safety concerns. Further large-scale clinical trials with longer follow-up periods are needed to verify our preliminary findings.