Enhancement of apixaban's solubility and dissolution rate by inclusion complex (β-cyclodextrin and hydroxypropyl β-cyclo¬dextrin) and computational calculation of their inclusion complexes

Background and Purpose: Apixaban (AP) is a factor X inhibitor, an orally active drug that inhibits blood coagulation for better prevention of venous thromboembolism. It has poor solubility, dissolution rate and low bioavailability. The aim of this study was to improve the aqueous solubility and dissolution rate of oral AP as a step to enhance its bioavailability by preparing it as an inclusion complex with beta- and hydroxy propyl beta-cyclodextrin. Experimental Approach: A simple, rapid method of analysis of AP was developed using ultraviolet spectrophotometry (UV) and partially validated in terms of linearity, precision and accuracy, recovery, and robustness. AP was prepared as a complex with beta cyclodextrin (βCD) and hydroxy propyl beta cyclodextrin (HPβCD) in weight ratios 1:1, 1:2, and 1:3 by kneading, solvent evaporation and spray drying methods and characterized by Fourier transfer infra-red (FTIR), differential scanning calorimetry (DSC), and percent drug content in each of the prepared complex. Using the computer simulation, the interactions of AP with βCD and HPβCD were investigated. Key Results: The phase solubility study showed that the solubility of AP was greatly enhanced from 54×10-3 mmol /L to 66 mmol/L using HPβCD with acceptable stability constant. Computer docking supports the formation of a stable 1:1 complex between AP and CD’s. The dissolution test results showed that the complex gave a significantly higher percentage of drug release (95%) over one hour compared to the free AP (60%) (p<0.05). Conclusion: AP- HPβCD complex in the ratio of 1:2 (w/w) can significantly improve the solubility and in vitro dissolution rate of AP

Perceived attitudes and barriers towards medical research: a survey of Jordanian interns, residents, and other postgraduates

Purpose We investigated research barriers among Jordanian medical postgraduates to understand the current context of the local health research landscape and improve scholarly output. Methods Using a validated questionnaire, Jordanian interns, residents, specialists, and consultants were examined for their perceived attitudes and barriers towards research. Participants were conveniently sampled from public, university, military, and private institutions. Differences in responses were examined using the Student t-test and analysis of variance. Binary logistic regression was utilized to examine predictors of being able to publish. Results A total of 1,141 Jordanian medical postgraduates were recruited, of which 61.3% were junior postgraduates (i.e., interns and residents in their first 2 years of residency) while 38.7% were senior postgraduates (i.e., senior residents, specialists, and consultants). Around 76.0% of participants had no peer-reviewed publications. Of those with least one publication (n=273), only 31.1% had first authorships. Participants portrayed dominantly positive attitudes towards the importance of research. There were no significant differences between junior and senior postgraduates for overall attitudes (p=0.486) and knowledge barriers scores (p=0.0261). Conversely, senior postgraduates demonstrated higher mean organizational barriers (p<0.001). Seniority (odds ratio [OR], 5.268; 95% confidence interval [CI], 3.341–8.307), age (OR, 1.087; 95% CI, 1.019–1.159), academic standing (OR, 1.730; 95% CI, 1.103–2.715), and confidence (OR, 1.086; 95% CI, 1.009–1.169) were positive predictors of publication in peer reviewed journals. Conclusion The Jordanian medical research landscape is riddled with all forms of different barriers. The reworking of current and integration of new research training programs are of utmost importance

Intravesical Therapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease Recurrence

Context Patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. Objective To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. Evidence acquisition The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. Evidence synthesis Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26–1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39–2.11 vs OR 0.93, 95% CI 0.40–2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). Conclusions Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. Patient summary A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence

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

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- A nd 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

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

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. © 2020 American Medical Association. All rights reserved

Knowledge, Attitudes, and Perceptions of Jordanians Toward Adopting and Using Telemedicine: National Cross-sectional Study

BackgroundDue to the upsurge of COVID-19, nations are increasingly adopting telemedicine programs in anticipation of similar crises. Similar to all nations worldwide, Jordan is implementing efforts to adopt such technologies, yet it is far from complete. ObjectiveThis study aims to assess the knowledge, attitudes, and perceptions of Jordanians toward telemedicine, to identify key factors predisposing individuals to its use or acting as barriers to its implementation. MethodsWe implemented a cross-sectional design using an online, self-administered questionnaire executed in Google Forms and distributed through social media. Differences in knowledge and attitude scores were examined using independent sample t tests and ANOVA. A multivariate linear regression model was computed to assess predictors of awareness toward telemedicine. ResultsA total of 1201 participants fully completed the questionnaire. Participants were characterized by a mean age of 36.3 (SD 14.4) years and a male-to-female ratio of nearly 1:1. About 50% (619/1201, 51.5%) of our studied population were aware of telemedicine, while nearly 25% (299/1201, 24.9%) declared they had observed it in action. Approximatively 68% (814/1201, 67.8%) of respondents were willing to use telemedicine. The majority of the sample portrayed favorable and positive views toward telemedicine. Higher educational degrees, living in urban districts, and having a higher perception of electronic usage ability were associated with higher knowledge and better attitudes toward telemedicine (all P<.05). The multivariate linear regression analysis demonstrated that perceived ability to use electronics was associated with positive attitudes (β=0.394; 95% CI 0.224 to 0.563), while living in Southern Jordan predicted poor attitudes toward telemedicine (β=–2.896; 95% CI –4.873 to –0.919). ConclusionsJordanians portray favorable perceptions of telemedicine. Nonetheless, concerns with regards to privacy, medical errors, and capacity for accurate diagnoses are prevalent. Furthermore, Jordanians believe that integrating telemedicine within the health care system is not applicable due to limited resources

Midline Gliomas: A Retrospective Study from a Cancer Center in the Middle East

Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) is a diffuse glioma that occurs in the classical midline structures, characterized by a specific genetic alteration, and associated with grim outcome. This study was conducted at King Hussein Cancer Center and reviewed the medical records of 104 patients with circumscribed and diffuse gliomas involving midline structures that underwent biopsy between 2005 and 2022. We included a final cohort of 104 patients characterized by a median age of 23 years and a male-to-female ratio of 1.59-to-1. Diffuse high-grade glioma (DHGG) was the most common pathological variant (41.4%), followed by DMG (28.9%). GFAP was positive in most cases (71.2%). Common positive mutations/alterations detected by surrogate immunostains included H3 K27me3 (28.9%), p53 (25.0%), and H3 K27M (20.2%). Age group, type of treatment, and immunohistochemistry were significantly associated with both the location of the tumor and tumor variant (all; p < 0.05). DMGs were predominantly found in the thalamus, whereas circumscribed gliomas were most commonly observed in the spinal cord. None of the diffuse gliomas outside the classical location, or circumscribed gliomas harbored the defining DMG mutations. The median overall survival (OS) for the entire cohort was 10.6 months. Only the tumor variant (i.e., circumscribed gliomas) and radiotherapy were independent prognosticators on multivariate analysis