Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

Perceptions of primary health care physicians about the prescription of antibiotics in Saudi Arabia: Based on the model of Theory of planned behaviour.

INTRODUCTION: Knowledge of different factors that influence physician decision-making in general practice for prescribing antibiotics is vital for successfully implementing antimicrobial stewardship interventions. The Theory of planned behaviour (TPB) is an established model that describes how cognitions drive human behaviour. OBJECTIVES: The present study was performed to identify the socio-cultural and behavioural determinants that affect antibiotics prescription behaviour among primary care physicians and estimate the awareness about antibiotic resistance of public health importance. METHODOLOGY: The questionnaire was divided into three sections: Section-I, which contained demographic content. Section-II contained 21 question items measuring attitudes, subjective norms, perceived behavioural control, and behavioural intentions of the prescribers. Section III had 12 questions related to knowledge about antibiotic resistance. As determined by Cronbach's α for each set of measured constructs of questionnaire scale, the internal consistency was good (α ≥ 0.7). The participants' socio-cultural and behavioural determinants were graded in 3 categories depending upon the mean score, while frequencies were used to estimate antibiotic resistance awareness. The data was analyzed by calculating the one-way ANOVA and by post-hoc Tukey-Kramer HSD multiple comparison test. RESULTS: Four hundred thirty-four primary health care physicians responded to the questionnaire, and data was statistically investigated. Participants' knowledge of antibiotic-resistant bacteria was poor with greater behavioural intentions to prescribe antibiotics, but a positive attitude and acceptable perceived social pressure towards antibiotics. CONCLUSION: Our study showed that awareness towards antibiotic-resistant bacteria among primary care physicians of Saudi Arabia stands insufficient but favourable attitude and satisfactory social pressure towards antibiotics with greater behavioural intentions to prescribe antibiotics. The continued medical education (CME) and frequent training interventions can increase these parameters of rational prescribing practice for antibiotics.

Safety of Linagliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs. OBJECTIVES: We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus. METHODS: We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel-Haenszel test. RESULTS: A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms. The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.62, 95% CI: 0.45-0.85, and I2 = 0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.35, 95% CI: 0.16-0.77, and I2 = 0%). CONCLUSION: Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.

Exploring the interaction of curcumin with ß-cyclodextrin and its binding with DNA: A combined spectroscopic and molecular docking study.

At present, a major effort in biophysical studies has been paid towards exploring the interactions and release of therapeutic payloads to the specific site leaving behind healthy cells unaffected and hence, lower the drug-induced toxicity. For the purpose, interaction of ß-bound CUR with calf thymus DNA (ctDNA) has been examined intensely using a series of biophysical methods like absorption, steady state fluorescence emission, and circular dichroism together with molecular docking study. The experimental analysis divulge that CUR interacts with both ß-CD (although with different molar ratio) and DNA. However, the binding affinity of CUR with the target (DNA) is higher than it does with the ß-CD. When ß-CD-carried (10 mM) CUR (µM) (inclusion complex) comes near DNA (15-372 µM), CUR gets out from ß-CD's void and approaches to binds with the DNA. The relocation of the probe occurred due to competitive binding of the CUR between ß-CD and the DNA. The present investigation may provide a simple yet probable route for the transfer of encapsulated therapeutic payload of ß-CD to the most relevant biomolecular target DNA.

Exploring Entrepreneurship in Pharmacy: Attitudes and Perceptions Among Saudi Pharmacists and Students.

Introduction: Entrepreneurship has recently become a focus in community development, innovation, and economic growth, including within pharmaceutical organizations. However, it remains a relatively new aspect of pharmacy education. For the effective incorporation of entrepreneurship in this field, a robust educational foundation is critical, one that emphasizes risk-taking, strategic planning, competitive spirit, and a sense of social responsibility. This study aims to evaluate Saudi pharmacists' attitudes towards entrepreneurship in their practice. Methods: A cross-sectional survey design to assess the attitudes of pharmacists and pharmacy students in Saudi Arabia towards entrepreneurship. The study sample consisted of 302 individuals, selected through convenience sampling, all of whom were either licensed pharmacists or pharmacy students in Saudi Arabia. The survey was conducted electronically and disseminated online throughout the duration of January 2023, spanning a one-month period. The research sought to provide a deeper understanding of how entrepreneurship is perceived within the pharmacy field. Results: The study involved 302 pharmacists in Saudi Arabia, with the majority being pharmacy students and Doctor of Pharmacy holders. Over 60% of the participants worked for the government sector. Results showed a strong interest in entrepreneurship, with nearly 80% expressing interest and believing in the entrepreneurial potential of pharmacists. However, there was a knowledge gap, as only 52% were familiar with entrepreneurship concepts, and most had not taken entrepreneurship courses. More than half of the participants reported insufficient institutional support for entrepreneurship. Remarkably, only 1% had started a pharmaceutical business. Conclusion: In conclusion, this study emphasizes the interest in entrepreneurship among pharmacists, highlighting the need for raising familiarity and formal education in the field. Factors such as working in the government sector were associated with higher willingness to become entrepreneurs, while the lack of awareness and institutional support hindered the entrepreneurial mindset.

Qualitative Interviews with Stakeholders in Herbal Pharmacovigilance and Recommendations for Best Practices to be Applied Worldwide.

BACKGROUND AND OBJECTIVE: The use of herbal products globally is substantial, but varying definitions and regulatory frameworks have led to differences in their status as medicinal products and in approaches to monitoring their safety. This article explores the current landscape of herbal pharmacovigilance, drawing insights from interviews with global experts in the field, and offers recommendations for best practices to enhance the safety and benefit-to-harm balance of herbal products. METHODS: This study comprised semi-structured interviews with members of the International Society of Pharmacovigilance-Herbal and Traditional Medicines Special Interest Group and the Nutrivigilance Information Exchange Network, recruited using purposive sampling. Data were stored and coded using NVIVO® and analysed thematically using a qualitative inductive approach. RESULTS: Sixteen participants from 11 countries were interviewed, revealing diverse regulatory approaches and challenges in herbal pharmacovigilance. Key themes included legal status, awareness, identification and coding of herbal products, pre-/post-marketing product control, reporting of adverse drug reactions, causality assessment and signals of herbal products. This study yielded five general recommendations to further improve herbal pharmacovigilance worldwide. CONCLUSIONS: This study offers an overview of the global landscape of herbal pharmacovigilance, highlighting challenges in monitoring herbal products and presenting universal recommendations. These recommendations encompass increasing awareness, enhancing education and improving legislative frameworks. Given the growing use of herbal products, the implementation of strong pharmacovigilance practices is crucial to ensure consumer safety.

Signal Detection and Assessment of Herb-Drug Interactions: Saudi Food and Drug Authority Experience.

INTRODUCTION: Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb-Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence. METHODS: First, SFDA-registered herbal products (n = 30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event. RESULTS: The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric-tacrolimus, etoposide-Echinacea, Ginkgo biloba-ibuprofen, green tea-warfarin, and licorice-thiazides interactions. CONCLUSION: The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions.

The Potential Association Between Periodontal Diseases and Adverse Pregnancy Outcomes in Pregnant Women: A Systematic Review of Randomized Clinical Trials.

Preceding studies have demonstrated that periodontitis might increase the liability of adverse pregnancy outcomes such as preterm birth, preeclampsia, low birth weight, and perinatal fatality in pregnant women. Nonetheless, there is no convincing testimony that periodontitis is related directly to adverse pregnancy outcomes in pregnant women. This systematic review intended to assess and review all the available randomized clinical trials that concentrated on the association between periodontal diseases and adverse pregnancy outcomes, and the impact of periodontal disease therapy on adverse pregnancy outcomes. The databases like Scopus, PubMed, Google Scholar, and Web of Science were consumed to explore relevant and suitable studies after adopting the inclusion and exclusion criteria. The search included articles with no time restrictions and certain keywords were utilized in the databases. The investigation was done through four independent reviewers employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-three studies fulfilled the exclusion and inclusion criteria and were used and included in this systematic review. The above-mentioned studies assessed the association between periodontal diseases and adverse pregnancy outcomes and the effect of periodontal disease treatment in reducing the influence of adverse pregnancy outcomes. This systematic review revealed that there is a relationship between periodontitis and adverse pregnancy outcomes, and periodontal treatment has a reducing impact on adverse pregnancy outcomes in pregnant women with periodontitis. Prospect studies are warranted to investigate the relationship between periodontitis and different adverse pregnancy outcomes and to decide the best type and the most effective therapy to treat periodontitis in pregnant women.

The Right to Refuse: Understanding Healthcare Providers' Perspectives on Patient Autonomy in Emergency Care.

Healthcare providers in prehospital care and emergency departments are often at the frontline of medical crises, facing a range of ethical dilemmas, particularly when it comes to patients refusing treatment. This study aimed to delve into the attitudes of these providers toward treatment refusal, unearthing the strategies they employ in navigating such challenging situations while actively working in prehospital emergency health services. Our findings showed that, as the participants' age and experience increased, so did their inclination to respect patient autonomy and avoid persuading them to change their decision about treatment. It was noted that doctors, paramedics, and emergency medical technicians demonstrated a deeper understanding of patients' rights than other medical specialists. However, even with this understanding, the prioritization of patients' rights tended to diminish in life-threatening situations, giving rise to ethical dilemmas. This underlines the complexity of balancing the healthcare professionals' responsibilities and the patients' autonomy, which can generate ethically challenging scenarios for those working in emergency healthcare. By investigating these attitudes and experiences, this study seeks to foster a more profound understanding of the ethical quandaries faced by emergency healthcare providers. Our ultimate aim is to contribute to the development of effective strategies that support both patients and professionals in managing these tough circumstances.

The prevalence and pattern of complementary and alternative medicine use among cancer patients in a tertiary oncology center: a cross-sectional study.

Background: Complementary and alternative medicine (CAM) is widely used nationally and internationally for multiple medical conditions, including different stages of cancer. It is used by the patients for multiple purposes, including to cure diseases or resolve symptoms, as patients have the misconception that natural remedies are safer than radiotherapy and chemotherapy. Objectives: The aim of this research is to investigate the prevalence, pattern, and purpose of CAM use by cancer patients at Princess Noorah Oncology Center (PNOC), King Abdulaziz Medical City, in Jeddah (KAMC-JD). Methods: This was a cross-sectional study that examined 293 patients (selected through random computerized sampling) who were seen at PNOC during the study period. To be eligible for the study, participants had to be cancer patients over the age of 18 who were seen at PNOC. The authors excluded patients who had privacy requests or did not fit our inclusion criteria. Results: Of the sample, 52.9% [95% confidence interval (CI), 47.0-58.7] used CAM. Only 5.8% of patients delayed their medical treatment to use CAM. A significantly higher proportion of females used CAM than males (61.8% vs. 40.0%, P<0.001). The most common types of CAM were Zamzam water (67.7%), Quran recitation (42.6%), water read upon Quran (41.3%), and black seed (Nigella sativa) (41.3%). The most frequently reported reasons for CAM use were to treat cancer (53.5%), increase immunity (34.2%), and religious beliefs (23.9%). Generally, 57.4% of CAM users felt improvement with CAM modalities. Conclusion: In conclusion, more than 50% of our sample used CAM; 5.8% of patients delayed the medical treatment to use CAM. The most common type of CAM was Zamzam water, and the most frequently reported reason for CAM use was to treat cancer. Of CAM users, 57.4% felt improvement with CAM modalities. Further studies that involve qualitative designs and include a more diverse sample are recommended in the Kingdom of Saudi Arabia to understand CAM utilization patterns.

The Association Between Oral Helicobacter pylori and Gastric Complications: A Comprehensive Review.

Helicobacter pylori (H. pylori) is linked to chronic gastritis, duodenal or gastric ulcers, and gastric cancer (GC). Because the oral cavity is the first component of the gastrointestinal tract (GIT) and the entrance point for H. pylori, it has been proposed as a possible reservoir of H. pylori. As a result, a putative oral-oral transmission pathway of H. pylori poses the possibility of whether personal contact, such as kissing or sharing a meal, might trigger H. pylori transmission. As a result, several investigations have been done on this issue using various approaches for detecting H. pylori in oral and stomach samples. Furthermore, the relationship between H. pylori and gastrointestinal disorders has yet to be studied. The evidence for the association between H. pylori and gastric diseases and their complications is still a controversial subject due to the existing literature in this review. The goal of this comprehensive review was to collect all available published articles and critically evaluate existing investigations looking into the relationship between oral H. pylori contamination and the danger of gastric complications. Few studies indicated an association between H. pylori and gastric diseases. Furthermore, more longitudinal randomized clinical studies to further investigate the association between H. pylori and gastric diseases are warranted.

Risk of Lichen Sclerosus and Lichen Planus in Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen sclerosus (LS) and lichen planus (LP) are two distinct phenotypes of irAEs that occur in a subset of patients treated with ICIs. These adverse effects have a detrimental effect on the patient's quality of life and treatment phases; however, the clinical evaluation and assessment of LS and LP remain uncertain. This study aims to assess and evaluate the risk of LS and LP associated with the use of ICIs via a systematic review of the literature and the USA FDA Adverse Events FAERS database. METHOD: The study searched electronic databases such as PubMed, Medline, Cochrane, and Google Scholar for case reports on immune-checkpoint-inhibitor-associated lichen sclerosus and lichen planus published in English between inception and 31 December 2021. The FDA's adverse event reporting system (FAERS) database was also analyzed. RESULTS: Thirty-eight case reports and two retrospective studies with a total of 101 patients, in addition to the FAERS data, were evaluated. More cases involved lichen planus (78.9%) than lichen sclerosis (21%). Nivolumab and pembrolizumab were most frequently reported with LS and LP, among other ICIs. Thirty-six out of thirty-eight patients with LS or LP experienced complete remission, while two patients experienced partial remission. Most of the cases had an excellent response to corticosteroids (92.1%), while the remainder had moderate (5.2%) and poor (2.6%) responses. Additionally, the reporting odds ratio (ROR) of the FAERS database indicated a favorable association for ICIs, the risk of LP, and LS. A stronger association was uniquely found between nivolumab and pembrolizumab. CONCLUSION: There have been published case reports for these adverse events. Healthcare providers should be aware of the possibility of lichen sclerosis and lichen planus developing in patients receiving ICIs which could necessitate hospitalization or discontinuation. Regulatory agencies are advised to monitor the risks as a potential safety signal.