Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Potential Utility of Sodium Selenate as an Adjunct to Metformin in Treating Type II Diabetes Mellitus in Rats: A Perspective on Protein Tyrosine Phosphatase

Metformin is widely regarded as the standard first-line antidiabetic agent, in terms of efficacy and safety profiles. However, in most patients with type II diabetes mellitus (T2DM), it was found that metformin alone is not enough to adequately control hyperglycemia. Thus, we designed this study with the aim to investigate the effect of sodium selenate, a protein tyrosine phosphatase (PTP) inhibitor, individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. T2DM model was achieved by feeding the rats with high-fat, high-fructose diet (HFFD) for 8 weeks followed by a low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.). Changes in serum glucose, insulin, adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and the lipid profile were assessed. In addition, the level of reduced glutathione (GSH) and the activity of PTP were determined in the liver. Results showed that the addition of sodium selenate to metformin was able to restore hepatic GSH back to normal levels. Also, this combination therapy corrected the altered serum total cholesterol (TC), triglycerides (TG), and adiponectin levels. In conclusion, additive therapeutic effect was recorded when sodium selenate was used as an adjunct to metformin

Applicability of American College of Clinical Pharmacy (ACCP) competencies to clinical pharmacy practice in Egypt

Background: The American College of Clinical Pharmacy (ACCP) prepared clinical pharmacist competencies that have specific recommendations. Recently, many efforts to advance clinical pharmacy services in Egypt exist. The literature revealed that no country has assessed the extent of applicability of ACCP competencies in its current pharmacy practice setting. Egyptian pharmacists can provide feedback about applicability of such competencies in clinical pharmacy settings in Egypt. Objective: The objective of this study was to investigate the extent to which ACCP competencies were implemented by Egyptian clinical pharmacists and therefore evaluate development of clinical pharmacy practice in Egypt. The study also investigated factors affecting the applicability of such competencies in the current clinical pharmacy practice setting in Egypt. Methods: Four hundred and ninety-five randomly selected clinical pharmacists from several hospitals were invited to participate in a cross sectional survey using a self-administered validated questionnaire composed of 31 questions classified into six domains. This questionnaire was designed to determine the pharmacists’ perception about applicability of ACCP competencies to clinical pharmacy practice in Egypt. Results: The response rate was 64% as 317 out of 495 pharmacists completed the questionnaire. These pharmacists were categorized according to age; gender; qualifications; years of previous work experience, years since BSc. and type of hospitals they are currently working at. Analysis of data revealed the professionalism domain to have the highest percentage of acceptance among pharmacists, while the system-based care & population health domain had the lowest percentage of acceptance. Results also showed that qualifications of participants did not affect their response in three domains; “Direct Patient Care”, “Systems-based Care & Population Health” and “Continuing Professional Development” (p=0.082, 0.081, 0.060), respectively. Nevertheless, qualifications of participants did affect their response in the other three domains; “Pharmacotherapy Knowledge”, “Communication” and “Professionalism” (p<0.05). The age of pharmacists, gender, years of previous work experience, and graduation year did not affect their responses in all six domains. The type of hospital they are currently working at, though, affected their responses where, there was a highly statistically significant increase of the mean score of all domains among participants working at the NGOs/private hospitals compared to governmental hospitals (p<0.001). Conclusions: Egyptian pharmacists generally apply high percentage of ACCP competencies but the provided clinical pharmacy services need to be improved through applying the standards of best practice

Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties.

Huntington's disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities

Effects of 3-NPA and/or genistein on striatal, cortical and hippocampal AChE activity of ovariectomized rats.

<p>3-NPA was administered i.p. (20 mg/kg) for 4 consecutive days. 17β-estradiol (2.5 mg/kg body weight, s.c) and genistein (10 and 20 mg/kg body weight, i.p) were administered for 8 days, beginning 4 days before and continued for 4 days one hour before 3-NPA injections. Data are presented as means ±S.E.M. (n = 6). ^x statistically significant compared to sham group at P< 0.05, * statistically significant compared to control group at P< 0.05, ^# statistically significant compared to 3-NPA-treated group at P< 0.05 (one-way ANOVA followed by Tukey test).</p

Effects of 3-NPA and/or genistein on striatal, cortical and hippocampal AChE activity of ovariectomized rats.

<p>3-NPA was administered i.p. (20 mg/kg) for 4 consecutive days. 17β-estradiol (2.5 mg/kg body weight, s.c) and genistein (10 and 20 mg/kg body weight, i.p) were administered for 8 days, beginning 4 days before and continued for 4 days one hour before 3-NPA injections. Data are presented as means ±S.E.M. (n = 6). ^x statistically significant compared to sham group at P< 0.05, * statistically significant compared to control group at P< 0.05, ^# statistically significant compared to 3-NPA-treated group at P< 0.05 (one-way ANOVA followed by Tukey test).</p

Effects of 3-NPA and/or genistein on step through passive avoidance in ovariectomized rats.

<p>3-NPA was administered i.p. (20 mg/kg) for 4 consecutive days. 17β-estradiol (2.5 mg/kg body weight, s.c) and genistein (5, 10 and 20 mg/kg body weight, i.p) were administered for 8 days, beginning 4 days before and continued for 4 days one hour before 3-NPA injections. Training was performed on day 5. First and second retention latencies were assessed at days 6 (A) and 8 (B). Data are presented as medians and quartiles (n = 8). ^x statistically significant compared to sham group at P< 0.05, * statistically significant compared to control group at P< 0.05, ^# statistically significant compared to 3-NPA-treated group at P< 0.05 (Kruskal-Wallis nonparameteric test followed by Dunn’s test).</p

H & E staining of the cortices of rats belonging to the sham group (A), control group (B), 3-NPA-treated group (C), 17β-estradiol- and 3-NPA-treated group (D), genistein (5 mg/kg)- and 3-NPA-treated group (E), genistein (10 mg/kg)- and 3-NPA-treated group (F), genistein (20 mg/kg)- and 3-NPA-treated group (G) and genistein alone-treated group (H): A, B, D and H showed no histological alterations, C showed severe hemorrhage (h), E showed focal gliosis (g) F showed focal gliosis (g) and G showed congested blood vessel (C).

<p>H & E staining of the cortices of rats belonging to the sham group (A), control group (B), 3-NPA-treated group (C), 17β-estradiol- and 3-NPA-treated group (D), genistein (5 mg/kg)- and 3-NPA-treated group (E), genistein (10 mg/kg)- and 3-NPA-treated group (F), genistein (20 mg/kg)- and 3-NPA-treated group (G) and genistein alone-treated group (H): A, B, D and H showed no histological alterations, C showed severe hemorrhage (h), E showed focal gliosis (g) F showed focal gliosis (g) and G showed congested blood vessel (C).</p