Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.

Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes' genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient's age, diagnosis, concomitant medications, and clinical status should also be considered.

Hand hygiene knowledge, attitude, and practice before, during and post COVID-19: a cross-sectional study among university students in the United Arab Emirates.

Aims: Hand hygiene (HH) is an essential practice to evade the transmission of germs and minimize community-acquired infections. This study assesses the knowledge, attitude and practice (KAP) of HH and other health and safety measures before, during, and after the COVID-19 pandemic. in university students in the United Arab Emirates (UAE). Methods: A cross-sectional questionnaire study was conducted between December 2022 and March 2023, targeting university students from all disciplines and study levels. A 44-item questionnaire was used which included student demographics, knowledge, attitude, and practice of HH, as well as the anticipated risk of COVID-19 morbidity and mortality. Participants consented before commencing the questionnaire, and the collected data were analysed using the student's t-test and ANOVA test, as required. Results: A total of 378 responses were received nationwide, with a valid response rate of 98%. The HH knowledge revealed an average score of 62%, which was significantly higher in students with moderate family income. Additionally, the average attitude score was 74.7%, as measured on the Likert scale, and the score lacked any correlation with the other variables. HH practice showed an average score of 86.8%, which was correlated with the students' gender and field of study. Conclusions: This study showed a moderate level of knowledge, a good attitude, and good practice around HH and other safety measures among the UAE's university students. Socioeconomic status, gender, and field of study influenced the study outcomes. This study highlights the need for effective awareness campaigns to reinforce students' health and safety, especially for male and non-health science students, in order to protect against communicable diseases.

Medical school origins of award-winning psychiatrists; analysis of a complete national dataset.

BACKGROUND: Britain attracts doctors from all over the world to work in the National Health Service. Elucidating the educational backgrounds of award-winning doctors working in the country is potentially an important medical education issue and a merit award audit. Using the British clinical merit award schemes as outcome measures, we identify medical school origins of award-winning doctors who have been identified as having achieved national or international prominence. METHODS: The Clinical Excellence Awards/Distinction Awards schemes select doctors in Britain who are classified as high achievers, with categories for national prominence and above. We used this outcome measure in a quantitative observational analysis of the 2019-20 dataset of all 901 award-winning doctors. Pearson's Chi-Square test was used where appropriate. RESULTS: Five university medical schools (London university medical schools, Glasgow, Edinburgh, Aberdeen and Cambridge) accounted for 59.1% of the psychiatrist award-winning doctors in the 2019 round, despite the dataset representing 85 medical schools. 84.1% of the psychiatrist award-winners were from European medical schools, compared to 92.1% of the non-psychiatrist award-winners. International medical graduates accounted for 22.7% of the award-winning psychiatrists. Psychiatrists with the lower grade national awards came from a more diverse educational background of 17 medical schools. IMGs represented diverse medical schools from five continents and were most represented in the lowest grade of national merit awards at 24.2%. CONCLUSIONS: The majority of the award-winning psychiatrists originated from only five medical schools. A greater diversity of medical school origin existed for the lowest grade national psychiatrist award-winners. International medical graduates contributed substantially to these award-winners; psychiatrist award-winners were more likely to be international medical graduates (22.7%) than non-psychiatrist award-winners (10.8%). This study not only indicates educational centres associated with the production of award-winners but also provides students with a roadmap for rational decision making when selecting medical schools.

Medical school origins of award-winning physicians; analysis of a complete national dataset.

BACKGROUND: Educators and medical students share the same objective of achieving success in medical practice. Both groups consider doctors' successes to include optimum patient care outcomes and positive career progressions. Accordingly, identifying common educational features of such high-achieving doctors facilitates the generation of excellence amongst future medical trainees. In this study we use data from the British clinical merit award schemes as outcome measures in order to identify medical school origins of doctors who have achieved national or international prominence. METHODS: Britain has Clinical Excellence Awards/Distinction Awards schemes that financially reward all National Health Service doctors in England, Scotland and Wales who are classified as high achievers. We used these outcome measures in a quantitative observational analysis of the 2019-20 dataset of all 901 national award-winning doctors. Where appropriate, Pearson's Chi-Square test was applied. RESULTS: The top five medical schools (London university medical schools, Glasgow, Edinburgh, Oxford and Cambridge) were responsible for 51.2% of the physician merit award-winners in the 2019-20 round, despite the dataset representing 85 medical schools. 91.4% of the physician merit award-winners were from European medical schools. The lowest national award-winners (tier 3) originated from 61 medical schools representing six continents. International medical graduates comprised 11.4% of all award-winners. CONCLUSIONS: The majority of physicians who were national merit award-winners originated from only five, apparently overrepresented, UK university medical schools. In contrast, there was a greater diversity in medical school origin among the lower grade national merit awards; the largest number of international medical graduates were in these tier 3 awards (13.3%). As well as ranking educationally successful university medical schools, this study assists UK and international students, by providing a roadmap for rational decision making when selecting physician and non-physician medical education pathways that are more likely to fulfil their career ambitions.