An exploration of factors influencing the selection of generic and innovator medicines in Saudi Arabia using an observational cross-sectional study.

Background and objectives: Generic medications are cost-effective without compromising therapeutic outcomes. Therefore, the goal of this study was to investigate, using a cross-sectional study design, the factors influencing Saudi Arabian consumers' preferences between innovator and generic medications. Methods: This cross-sectional study was carried out in Saudi Arabia using a Google survey form. For data collection, a simple random sampling strategy was used. The recruited participants were surveyed using a validated questionnaire that focused on six influencing domains: physician, pharmacist, perceived effectiveness, price, information availability, and confidence based on prior experience. The obtained data was used to analyze factors that have an association with any of the six domains using multinomial regression analysis. A correlation analysis was performed to examine the relationship between domains. Results: The 317 participants included 64.4 % females, 52 % aged ≥ 26, and a large proportion of Saudi nationals (82.6 %) and university graduates (78.9 %). Being employed (OR:3.029; P = 0.006; CI: 6.715-1.366), a healthcare providers (OR:2.298; P = 0.043; CI: 5.151-1.025), and having insurance coverage (OR:1.908; P = 0.017; CI: 3.245-1.122) had a greater influence on medication selection. Participants with linguistic and business educational backgrounds (OR:3.443; P = 0.022; CI: 9.950-1.191), those living in the northern region of Saudi Arabia (OR:3.174; P = 0.009; CI: 7.585-1.328), having chronic ailments (OR:3.863; P = 0.013; CI: 11.274-1.324), and possess insurance (OR:1.748; P = 0.039; CI: 2.971-1.028) get readily influenced by pharmacist. People who were married and lived in Saudi Arabia's southern region were influenced by perceived effectiveness when choosing medicine. Participants from the northern region were found to be influenced by the price of the medicines, information about the medicines, and confidence based on previous experience. The price of medicines has a significant impact on those suffering from chronic diseases. At a significant level of P = 0.01, all six influencing domains were found to be positively correlated with each other. Conclusion: The study shows that healthcare providers, drug prices, perceived efficacy, and information availability all have a big influence on the Saudi Arabian population's choice of medications. Educational background, location, and chronic disease status are associated with several influencing domains. Aside from public awareness campaigns, healthcare professionals should be involved in the implementation of the generic medication policy.

Vaccine hesitancy in the Gulf Cooperation Council countries.

Background: Vaccination has a tremendous impact on health at the regional and global levels, however, the tendency for people to hesitate on vaccination has been increasing in the past few decades. Aims: We assessed vaccine hesitancy and its determinants in the Gulf Cooperation Council countries. Methods: We conducted a literature review to assess peer-reviewed articles published up to March 2021 on vaccine hesitancy in the Gulf Cooperation Council countries using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach. A search was conducted via PubMed and 29 articles were identified. After the removal of duplicates and irrelevant articles, 14 studies remained relevant and were used for the review. Results: Vaccine hesitancy in the Gulf Cooperation Council countries ranged from 11% to 71%. Differences in rates were noted for vaccine type, with COVID-19 vaccine having the highest reported hesitancy (70.6%). The likelihood of accepting vaccination was associated with previous individual acceptance of vaccine, specifically the seasonal influenza vaccine. The most common determinants of vaccine hesitancy were distrust in vaccine safety and concerns about side-effects. Healthcare workers were among the main sources of information and recommendations about vaccination, but 17-68% of them were vaccine-hesitant. The majority of the healthcare workers had never received any training on addressing vaccine hesitancy among patients. Conclusions: Vaccine hesitancy is prevalent among the publics and healthcare workers in the Gulf Cooperation Council countries. There is a need to continually monitor perceptions and knowledge about vaccines and vaccination in these countries to better inform interventions to improve vaccine uptake in the sub-region.

Risk of Prostate Cancer in Chronic Kidney Disease Patient: A Meta-Analysis using Observational Studies.

Background: Both clinical and experimental findings demonstrated a rise in prostate cancer in chronic renal illness. However, the clinical data associated with CKD was not looked at the context of prostate cancer. The study aims to investigate prostate cancer risk in CKD patients using clinical data via systemic review and meta-analysis. Materials and Methods: Using pertinent pairing keywords, I carried out a thorough exploration of PubMed/MEDLINE and Web of Science. The pooled HR with 95% CI of the considered clinical findings was estimated involving the general inverse variance outcome type. With RevMan 5.3, the total pooled estimate meta-analysis was evaluated utilizing the random effects model. Results: Total of six findings were considered for this analysis, with a total of 2,430,246 participants. The age and mean follow-up of the included patients and studies ranged from 55 to 67.4 years and 10.1 to 12 years, respectively. The meta-analysis showed no significant risk of prostate cancer among CKD patients (HR: 0.92; 95% CI: 0.60-1.41; P = 0.70). The results from subgroup analysis based on eGFR levels ranged ≥30-59 ml/min per 1.73 m2 and also found no significant risk of prostate cancer among CKD patients (HR: 1.04; 95% CI: 0.92-1.18; P = 0.52). Here I did not report statistical heterogeneity found (Q = 0.56, I2 = 0%, P = 0.87). As per the Newcastle-Ottawa scale, the included studies suggested good quality. Conclusion: The results suggest no significant risk of developing prostate cancer among CKD patients. Therefore, well-designed prospective cohort studies with stages of CKD and clear predefined prior history and causative factors are needed to support the present evidence strongly.

Investigating the Effect of Cigarette Smoking on Serum Uric Acid Levels in Multiple Sclerosis Patients: A Cross Sectional Study.

OBJECTIVES: The present study is aimed at determining the effect of cigarette smoking (CS) on serum uric acid (UA) levels quantitatively before and after smoking cessation among people with MS (pwMS). Additionally, a possible correlation between UA levels and both disability progression and disease severity was also investigated. A retrospective cross-sectional study was conducted using the Nottingham University Hospitals MS Clinics database. It involves 127 people with definite MS recorded when reporting the latest smoking status and the clinical diagnosis. All necessary demographics and clinical characteristics were collected. We found that smoker pwMS had significantly lower serum UA levels than non-smoker pwMS (p-value = 0.0475), and this reduction was recovered after smoking cessation (p-value = 0.0216). However, the levels of disability or disease severity were not correlated with the levels of serum UA in current smoker pwMS, measured by the expanded disability status scale (EDSS; r = -0.24; p-value = 0.38), multiple sclerosis impact scale 29 (MSIS-29; r = 0.01; p-value = 0.97) and MS severity score (MSSS; r = -0.16; p-value = 0.58), respectively. Our result suggests that the reduction in UA levels is more likely a consequence of oxidative stress triggered by many risk factors, including CS, and could be considered a potential indicator of smoking cessation. In addition, the absence of a correlation between UA levels and disease severity and disability suggests that UA is not an optimal biomarker for disease severity and disability prediction among current smoker, ex-smoker or non-smoker pwMS.

Secondary Metabolite Profiling, Antioxidant, Antidiabetic and Neuroprotective Activity of Cestrum nocturnum (Night Scented-Jasmine): Use of In Vitro and In Silico Approach in Determining the Potential Bioactive Compound.

This study aims to describe the therapeutic potential of C. nocturnum leaf extracts against diabetes and neurological disorders via the targeting of α-amylase and acetylcholinesterase (AChE) activities, followed by computational molecular docking studies to establish a strong rationale behind the α-amylase and AChE inhibitory potential of C. nocturnum leaves-derived secondary metabolites. In our study, the antioxidant activity of the sequentially extracted C. nocturnum leaves extract was also investigated, in which the methanolic fraction exhibited the strongest antioxidant potential against DPPH (IC50 39.12 ± 0.53 µg/mL) and ABTS (IC50 20.94 ± 0.82 µg/mL) radicals. This extract strongly inhibited the α-amylase (IC50188.77 ± 1.67 µg/mL) and AChE (IC50 239.44 ± 0.93 µg/mL) in a non-competitive and competitive manner, respectively. Furthermore, in silico analysis of compounds identified in the methanolic extract of the leaves of C. nocturnum using GC-MS revealed high-affinity binding of these compounds with the catalytic sites of α-amylase and AChE, with binding energy ranging from -3.10 to -6.23 kcal/mol and from -3.32 to -8.76 kcal/mol, respectively. Conclusively, the antioxidant, antidiabetic, and anti-Alzheimer activity of this extract might be driven by the synergistic effect of these bioactive phytoconstituents.

Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug.

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

Hobson's choice or a horned dilemma: a grounded theory on adherence to adjuvant endocrine therapy verified with breast cancer survivors.

PURPOSE: A literature review and meta-synthesis of qualitative research had enabled us to develop a grounded theory explaining the difficulties breast cancer survivors face with the initial decision to accept long-term endocrine therapy, and the everyday challenges of continuing or deciding to stop treatment early. Our objective was to interview a cohort of women in a UK setting to corroborate and complete the grounded theory with the end users' primary involvement. METHODS: A semi-structured interview schedule was written based on the existing grounded theory. Fourteen women with a history of hormone-positive breast cancer were recruited and interviewed. The audio-recorded interviews were transcribed and analysed against the existing grounded theory. RESULTS: The findings were compatible with the core theory 'Hobson's choice or a horned dilemma' and its constituent categories previously developed, with additional concepts identified and added to our paradigm models. Importantly, we found that some women who started with a strong sense of commitment to their treatment changed their mind as they experienced the medication side effects over time, impacting on their persistence with long-term endocrine therapy. CONCLUSION: The findings indicate an opportunity for health providers to intervene and influence women's waning perceptions of the necessity of their treatment, for example upon experiencing the side effects. Interventions could involve the provision of side effect management strategies via accessible resources.

Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol.

Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of -19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH.

Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: A possible mechanism for a protective effect against ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory life-threatening and premalignant disorder with no cure that even might end up with surgical removal of a large section or even all of the colon. It is characterized by relapsing-remitting courses of intestinal inflammation and mucosal damage in which oxidative stress and exaggerated inflammatory response play a significant role. Most of the current medications to maintain remission are symptomatic and have many adverse reactions. Therefore, the potential for improved management of patients with UC continues to increase. Yet, the benefits of using the antiarthritic agent diacetylrhein to counteract inflammation in UC are still obscure. Hence, our study was designed to explore its potential role in UC using a model of dextran sodium sulfate-induced acute colitis in rats. Our results revealed that diacetylrhein targeted the NLRP3 and inhibited the inflammasome assembly. Consequently, caspase-1 activity and the inflammatory cytokines IL-1ß and IL-18 were inhibited leading to a curbed pyroptosis process. Additionally, diacetylrhein revealed a significant antiapoptotic potential as revealed by the levels of pro-apoptotic and anti-apoptotic proteins. Concomitant to these effects, diacetylrhein also interrupted NFκB signals leading to improved microscopic features of inflamed colon and decreased colon weight to length ratio, indices of disease activity, and macroscopic damage. Additionally, a reduction in the myeloperoxidase activity, IL-6, and TGF-ß alongside an increase in the gene expression of Ocln and ZO-1 were detected. To conclude diacetylrhein showed a significant antioxidant and anti-inflammatory potential and therefore might represent a promising agent in the management of acute UC.

Pimitespib, an HSP90 inhibitor, augments nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop in rats with bleomycin-challenged lungs: Evolutionary perspective in managing pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a fatal lung disorder in which the etiology and pathogenesis are still unobvious. Effective treatments are urgently needed considering that lung transplantation is the only treatment that could improve outcomes. This study aimed to investigate the therapeutic significance of the dual administration of pimitespib, an HSP90 inhibitor, and nifuroxazide, a STAT3 inhibitor, against bleomycin-induced pulmonary fibrosis in rats. Our results revealed that pimitespib/nifuroxazide inhibited bleomycin-induced alterations in the structure and the function of the lungs. They demonstrated significant decreases in the BALF total and differential cell counts, LDH activity, and total protein. Concurrently, there was a reduction in the accumulation of collagen as proved by decreased hydroxyproline and the gene expression of COL1A1 accompanied by lower levels of PDGF-BB, TIMP-1, and TGF-ß. The levels of IL-6 were also downregulated. Pimitespib-induced inhibition of HSP90 led to subsequent inhibition of HIF-1α and STAT3 client proteins since the closed HSP90 would not enclose its client proteins. Therefore, pimitespib resulted in the repression of HIF-1α/CREB-p300 HAT as well as the STAT3/CREB-p300 HAT nuclear interactions. On the other hand, nifuroxazide resulted in a notable decline in pSTAT3 and HIF-1α levels. Subsequently, the combined effects of both drugs led to a substantial reduction in ECM deposition. Herein, pimitespib augmented nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop. Our findings also disclose that this novel loop is a promising therapeutic attack site for possible pulmonary fibrosis repression studies. Therefore, the use of pimitespib/nifuroxazide embodies an evolutionary perspective in managing pulmonary fibrosis.

The Development of Schematics to Illustrate Women's Experiences with Adjuvant Hormone Therapy in the Treatment of Breast Cancer.

Objective: Non-adherence to adjuvant hormone therapy prescribed orally in the treatment of breast cancer is complex as the literature has shown. Many women find it hard to adhere to the hormonal medicines they are prescribed and expected to take for at least 5 years following the initial management of their breast cancer. Arguably, communicating other women's 'trials, tribulations, and triumphs' with medication-taking could help newly-diagnosed patients to better prepare for the journey ahead. Our objective was to visually represent women's experiences with these medicines using data synthesized in the literature. Methods: Three schematics were drawn for each phase of medication-taking, namely, starting out, adherence, and cessation. The schematics were validated by interviewing a panel of healthcare professionals (n=10) and calculating a Content Validity Index (CVI). The edited drawings were discussed with a separate panel of breast cancer survivors (n=14) whose responses were elicited qualitatively in one-to-one interviews. Results: A total of 76 individual pictograms were drawn across the three schematics. The 13 pictograms that had an item-level CVI<0.8 were modified according to feedback resulting in three final schematics with an overall CVI of 87%, 87% and 80%, respectively. Conclusion: Synthesised summaries of women's experiences with oral hormone therapy for breast cancer were visualised via three validated schematics. The schematics could aid patient-professional communication to help anticipate and tackle negative experiences and support decisions to take hormone medication in breast cancer.

Breast Tumor Detection Using Robust and Efficient Machine Learning and Convolutional Neural Network Approaches.

Breast cancer develops when cells in the breast expand and divide uncontrollably, resulting in a lump of tissue known as a tumor. This lump of tissue is called a tumor. After skin cancer, breast cancer is the second most common cancer among women. It is more common in women over the age of 50. Men may also acquire breast cancer, albeit it is uncommon. Each year, approximately 2,600 men in the United States are diagnosed with breast cancer, accounting for less than 1% of all cases. Transgender women are more likely than cisgender men to acquire breast cancer. Additionally, transgender males are less likely than cisgender women to acquire breast cancer. Breast cancer is more common in women over the age of 50, although it can affect anyone at any age. Early detection of a breast tumor may significantly lower the risk of developing breast cancer. A public dataset of breast tumor features was used instead to build models for identifying breast tumors through machine learning and deep learning. Prediction models were built using logistic regression (LR), decision tree (DT), random forest (RF), voting classifier (VC), support vector machine (SVM), and a proprietary convolutional neural network (CNN). These models were used to find critical prognostic indicators linked to breast cancer. The proposed network performs far better, with an average accuracy of 99%. This study has six types of models: LR, RF, SVM, VC, DT, and a custom CNN model. They all had 96% to 99% accuracy in this study. CNN, LR, RF, SVM, VC, and DT achieved 99%, 96%, 98%, 97%, 97%, and 96% F1 score, respectively. There were many machine learning algorithms used in this study that were very accurate, which means that these techniques could be used as alternative prognostic tools in breast tumor detection studies in Asia.

Biomedical Applications of polymeric micelles in the treatment of diabetes mellitus: Current success and future approaches.

INTRODUCTION: Diabetes mellitus (DM) is the most common metabolic disease and multifactorial, harming patients worldwide. Extensive research has been carried out in the search for novel drug delivery systems offering reliable control of glucose levels for diabetics, aiming at efficient management of DM. AREAS COVERED: Polymeric micelles (PMs) as smart drug delivery nanocarriers are discussed, focusing on oral drug delivery applications for the management of hyperglycemia. The most recent approaches used for the preparation of smart PMs employ molecular features of amphiphilic block copolymers (ABCs), such as stimulus sensitivity, ligand conjugation, and as a more specific example the ability to inhibit islet amyloidosis. EXPERT OPINION: PMs provide a unique platform for self-regulated or spatiotemporal drug delivery, mimicking the working mode of pancreatic islets to maintain glucose homeostasis for prolonged periods. This unique characteristic is achieved by tailoring the functional chemistry of ABCs considering the physicochemical traits of PMs, including sensing capabilities, hydrophobicity, etc. In addition, the application of ABCs for the inhibition of conformational changes in islet amyloid polypeptide garnered attention as one of the root causes of DM. However, research in this field is limited and further studies at the clinical level are required.

Adherence to adjuvant endocrine therapy among breast cancer survivors: a systematic review and meta-synthesis of the qualitative literature using grounded theory.

PURPOSE: Numerous studies have examined non-adherence to adjuvant endocrine therapy in women recovering from breast cancer, but none provides a comprehensive theory to explain the challenges of long-term medication taking and resilience needed to continue. The aim of this study was to source, appraise, and synthesize data from existing qualitative studies to develop an in-depth explanatory model of non-adherence and discontinuation of hormonal medication among breast cancer survivors. METHODS: A comprehensive search of databases and the literature identified 24 eligible qualitative studies published 2010-2019. Quotations (n = 801) listed within these papers and the original author interpretations were synthesized using NVivo, and grounded theory methodology. RESULTS: At the beginning, knowledge about adjuvant endocrine therapy, trust in doctors, and worries and expectations, mean agreeing to medication is the only viable option, akin to a Hobson's choice. Thereafter, women's ability to deal with medication side-effects, knowledge and support received affect their decision to continue, akin to a horned dilemma where giving up the medication risks cancer recurrence and continuing means reduced contentment. Women stopping medication altogether question treatment necessity, search for normalcy and prioritize quality of life. CONCLUSION: Shared experiences and understandings were uncovered by examining commonalities in existing publications. The core category explained the difficulties women face with the initial decision to accept long-term endocrine therapy and then the everyday challenges of continuing or deciding to stop treatment early. An educational tool to inform survivors and health professionals about these challenges could potentially improve women's experience on treatment and in turn their adherence.