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Nanosponges, crosslinker, nanocarrier, cyclodextrin, analgesics, drug efficacy, Therapeutics. Pharmacology, and RM1-950

AbstractCyclodextrin nanosponges are solid nanoparticles, designed by cross-linking of cyclodextrin polymer; it has been used widely as a good delivery system for water insoluble drugs. The aim of this study is to enhance the solubility of Piroxicam (PXM) using β-Cyclodextrin based nanosponges formulations. PXM nanosponge (PXM-NS) formulations were prepared using β-cyclodextrin and carbonyldiimidazole as a cross linker, three ratios of β-cyclodextrin to crosslinker in addition to three drug to nanosponges ratios were tested. Piroxicam nanosponge formulations were characterized for its particle size, zeta potential, physical compatibility and in vitro release. Stability studies at three temperatures (4 °C, 25 °C and 40 °C) were done for optimal formula. Finally, the in vivo analgesic activity and pharmacokinetic parameters of the optimal formula were conducted. The optimized PXM-NS formula (PXM-NS10) showed particle size (362 ± 14.06 nm), polydispersity index (0.0518), zeta potential (17 ± 1.05 mV), and %EE (79.13 ± 4.33). The dissolution study showed a significant increase in the amount of PXM dissolved compared with the unformulated drug. Stability studies confirmed that nanosponge showed accepted stability for 90 days at 4 °C and 25 °C. In vivo analgesic studies verified that there was a significant enhancement in the analgesic response to PXM in mice, and 1.42 fold enhancement in the relative bioavailability of PXM-NS10 as compared to commercial tablets. Nanosponge prepared under optimal conditions is an encouraging formula for increasing the solubility and therefore the bioavailability of Piroxicam.

Background: Epilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice.
Methods: Pharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice.
Results: PK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T 1/2 . In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks.
Conclusion: Keppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)

Anti-Epileptic drugs, Levetiracetam, Pharmacokinetics, Liver enzymes, High-performance liquid chromatography, Saudi Arabia, Therapeutics. Pharmacology, and RM1-950

Background: Epilepsy is a common global neurological disorder. About 30% of epileptic patients are managed with anti-epileptic Drugs (AEDs). Since 2000, Levetiracetam (LEV) has been marketed around the world as an AED under the brand name Keppra, and recently more generics are found in the Saudi market as cheaper alternatives. The objective of this study is to evaluate the bioequivalence of LEV brand and generics available in the Saudi market in mice. Methods: Pharmacokinetics (PK), liver function test, and behavioral studies were conducted for LEV brand and generic in different groups of Blab/c mice. Results: PK results show a significance difference in PK parameters mostly evidenced with generic 3, then generic 2. The only significant different between Keppra and generic 1 was in T1/2. In addition, Keppra did not significantly increase liver enzymes in comparison to other generics. On the other hand, other generics showed less favorable results in increasing liver enzymes. Keppra reduced the number and intensity of epileptic attacks, had no mortality rate due to epilepsy, and was associated with less sever seizures attacks. Conclusion: Keppra, the brand form of LEV, has better safety and efficacy profiles in mice compared to 3 generics found in the Saudi market. Therefore, we recommend evaluating the same parameters tested in this study in patients utilizing similar generics and brand to establish the existence of bioequivalence between LEV brand and generics.

The development of competency frameworks serves as the foundation for the development of competency-based education. It is vital to develop a country-specific framework to address the specific needs of the local population for pharmacy services. This study aimed to describe the development process of a competency framework for undergraduate pharmacy education in Kuwait with a unique matrix structure. The process started with the development of guiding principles for curriculum revision and implementation, as well as the identification of global educational outcomes. This process was followed by: (A) a needs assessment with key stakeholders; (B) development of the initial competency framework; and (C) refinement of the framework. Qualitative data were thematically analyzed to identify the main competency domains that students need to perform the identified entrustable professional activities (EPAs). Five population needs were identified by the needs assessment, with 17 EPAs suggested to fulfill those needs. In addition, 11 competency domains were identified. The initial competency framework was created as a 3 × 8 matrix, with 3 professional and 8 transversal competency domains. Refinement of the framework resulted in the removal of redundancies and the development of a global behavior competency profile. The development of a matrix competency framework and associated EPAs for Kuwait serves as a foundation for preparing pharmacists to fulfill local population needs and expanding the scope of practice in the country.

Background: Toxic alcohol poisoning is regularly encountered in emergency departments and intensive care units (ICUs). Most patients present with an altered level of consciousness, but the subsequent course and spectrum of neurologic complications and outcomes is highly variable.
Methods: We performed a population-based, multicenter retrospective cohort study of critically ill patients with toxic alcohol poisoning admitted to ICUs in Alberta, Canada, between 2007 and 2019 to describe neurologic sequelae, including seizures, coma, neuroimaging abnormalities, persistent cognitive or visual impairment, and mortality. Multivariate analysis was performed to identify predictors of poor outcome.
Results: We identified 104 patients, including 55 (53%) with methanol ingestion, 36 (35%) with ethylene glycol ingestion, and 13 (13%) with isopropanol ingestion. In patients who underwent neuroimaging, abnormalities were detected in 9 of 24 (38%) with methanol toxicity, 5 of 20 (25%) with ethylene glycol toxicity, and 0 of 10 with isopropanol toxicity (p = 0.07). Basal ganglia were commonly involved with both methanol and ethylene glycol poisoning, but prominent subcortical involvement and restricted diffusion were observed only with methanol poisoning. The composite of death, persistent cognitive impairment, or visual loss occurred in 13 (24%) patients with methanol poisoning, compared with one (3%) with ethylene glycol poisoning and none with isopropanol poisoning (p = 0.006). Among patients with methanol toxicity, greater elevation of the anion gap and lower Glasgow Coma Scale score were independent predictors of poor outcome. No patient with an anion gap ≥ 28 at presentation had a favorable recovery. Progression to death by neurologic criteria occurred in 3 of 55 (5%) patients with methanol poisoning and in none with other toxic alcohols.
Conclusions: Methanol overdose is the most common form of toxic alcohol poisoning to result in ICU admission. Poor neurologic outcomes may occur especially with methanol poisoning, with more than one in five patients dying or having persistent cognitive or visual impairment. A wide anion gap independently predicts poor outcome, emphasizing the importance of expeditious recognition and treatment.
(© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: To analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan.
Methods: We reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death.
Results: Twenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4-38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms ( n  = 3) or metastases ( n  = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage ( p  < 0.0001), the presence of high-risk pathological features in the enucleated eyes ( p  = 0.013), parental refusal of the recommended primary treatment plan ( p  < 0.0001), and extraocular extension ( p  < 0.0001).
Conclusion: The 5-year survival rates of Rb patients in Jordan are as high as those in high-income countries. However, 5% are still dying from metastatic disease, prompting the need for awareness campaigns to educate the public about the high cure rates and to prevent treatment abandonment.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Bilbeisi, Almasry, Obeidat, Mohammad, Jaradat, Halalsheh, Alni’mat, Ahmad, Alsaket, Mehyar, Al-Nawaiseh and Yousef.)

Humans, Child, Memory, Short-Term, Diffusion Magnetic Resonance Imaging, Cognition, Memory Disorders, White Matter pathology, and Attention Deficit Disorder with Hyperactivity diagnostic imaging

Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with many functional impairments thought to be underpinned by difficulties in executive function domains such as working memory. The superior longitudinal fasciculus (SLF) plays an integral role in the development of working memory in neurotypical children. Neuroimaging research suggests reduced white matter organization of the SLF may contribute to working memory difficulties commonly seen in ADHD. This study aimed to examine the relationship between white matter organization of the SLF and working memory in children with ADHD.
Methods: We examined the association of tract volume and apparent fibre density (AFD) of the SLF with working memory in children with ADHD (n = 64) and controls (n = 58) aged 9-11years. Children completed a computerized spatial n-back task and underwent diffusion magnetic resonance imaging (dMRI). Constrained spherical deconvolution-based tractography was used to construct the three branches of the SLF bilaterally and examine volume and AFD of the SLF.
Results: Regression analyses revealed children with ADHD exhibited poorer working memory, and lower volume and AFD of the left SLF-II compared to healthy controls. There was also an association between reaction time and variability (RT and RT-V) and the left SLF-II. Further analyses revealed volume of the left SLF-II mediated the relationship between ADHD and working memory performance (RT and RT-V).
Discussion: These findings add to the current body of ADHD literature, revealing the potential role of frontoparietal white matter in working memory difficulties in ADHD.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile  infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.
Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.
Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.
Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI . Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)

Humans, Middle Aged, Treatment Outcome, Retrospective Studies, Prospective Studies, Saudi Arabia epidemiology, Hospitals, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage therapy, and Hematoma complications

Background: Intracerebral hemorrhage (ICH) has worse clinical outcomes than other stroke types. The risk factors contributing to ICH outcomes are not entirely understood, and published literature from Saudi Arabia on ICH outcomes is limited. Our goal was to study the specific clinical and imaging determinants of ICH outcomes.
Methods: We retrospectively retrieved all patients with spontaneous ICH (SICH) from a prospective King Fahd Hospital University registry between 2017 and 2019. The clinical characteristics of ICH events and data on clinical outcomes (6 to 12 mo) were recorded. Groups of patients with a favorable modified Rankin Scale of 0 to 2 and nonfavorable outcomes of a modified Rankin Scale of 3 to 6 were investigated. The relationship between the clinical characteristics of the SICH event and its outcomes was assessed using linear and logistic regression analyses.
Results: A total of 148 patients with a mean age of 60.3 years (±15.2) and a median follow-up of 9 months were included. Unfavorable outcomes were reported in 98 patients (66.2%). The ICH event variables associated with unfavorable outcomes were impaired renal function, Glasgow Coma Score <8, hematoma volume, hematoma expansion, and intraventricular extension (IVE).
Conclusions: Our study demonstrated important clinical and radiologic features in patients with ICH that may affect their clinical long-term functional outcomes. A larger multicenter study is required to validate our results and evaluate the methods to improve health care in patients with SICH.
Competing Interests: The authors declare no conflict of interest.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Female, Humans, Adult, Middle Aged, Male, Risk, Food Handling, Inflammatory Bowel Diseases epidemiology, Crohn Disease, and Colitis, Ulcerative

Background & Aims: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association.
Methods: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors.
Results: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I 2  = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I 2  = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I 2  = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I 2  = 0%).
Conclusions: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.
(Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

death, Jordan, metastasis, retinoblastoma, survival, Medicine (General), and R5-920

PurposeTo analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan.MethodsWe reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death.ResultsTwenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4–38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p

glycated hemoglobin, HbA1c level, acute ischemic stroke, intracranial large artery atherosclerotic disease, functional outcomes, predictor, Neurology. Diseases of the nervous system, and RC346-429

ObjectiveThis study aimed to investigate the effect of the glycated hemoglobin A1c (HbA1c) level on the functional outcome (FOC) in patients with intracranial large artery atherosclerotic disease (ICLAD)-related acute ischemic stroke (AIS).MethodsThis retrospective study enrolled patients with ICLAD-related AIS who were admitted to King Fahd University Hospital between January 2017 and September 2021. Patients were divided into two groups based on the optimal cutoff HbA1c level determined using receiver operating characteristic curve analysis—those with HbA1c ≤6.9% and those with HbA1c >6.9%. Demographic and other clinical characteristics were compared between the two groups using chi-square tests. The association between HbA1c and 90-day FOC was assessed using the chi-square test and odds ratios (ORs). Multivariate analysis was performed to adjust for confounding factors.ResultsA total of 140 patients were included in the analysis. A significant association was observed between the HbA1c level and FOC. Compared to patients with HbA1c ≤6.9%, patients with HbA1c >6.9% were more likely to have an unfavorable FOC [p = 6.9% and unfavorable FOC was sustained even after adjusting for confounding factors (p = 0.008) and atherosclerosis risk factors (p = 0.01). HbA1c >6.9% was also associated with higher ORs for in-hospital complications (p = 0.06, OR = 1.34, 95% CI = 1.02–1.77) and mortality (p = 0.07, OR = 1.42, 95% CI = 1.06–1.92) although these associations did not attain significant p-values.ConclusionHbA1c >6.9% was significantly associated with unfavorable FOC in ICLAD-related AIS. However, further studies with larger sample sizes are required to verify whether HbA1c is an independent predictor of poor FOC. Nevertheless, targeting HbA1c

Surgery and RD1-811

Summary:. Silicone liquid (polydimethylsiloxane) is an inert material commonly used for cosmetic purposes. A combination of both systematic and local devastating complications can cause end-organ toxicity and multi-organ dysfunction. In this article, we examine the literature and present a case of a patient who presented with lower extremity filler migration and granuloma formation 11 years post gluteal silicone injection. A 31-year-old woman who had received a gluteal silicone injection 11 years ago was experiencing painful erythema, progressive fibrosis, and swelling as the result of the injection. The patient was diagnosed with postfiller autoimmune syndrome. Multiple surgical interventions were conducted to remove the permanent filler from her left knee. As a result of multiple surgical sessions, the patient has been managed successfully with no relapses. This case demonstrated complications of an unusual silicone injection technique for gluteal augmentation. Despite silicone being considered inert, complications can arise years after injection, necessitating extensive medical intervention. This case also raises questions regarding the systemic effects of silicone fillers, warranting further research. Through this report, we aimed to enhance awareness and management of similar future cases.

Clostridium difficile infection (CDI), Vedolizumab, Crohn’s disease, Ulcerative colitis, Inflammatory bowel disease, 5- Aminosalicylates acid, Therapeutics. Pharmacology, and RM1-950

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.