RESUMO
The most effective anticancer drugs currently entail substantial and formidable side effects, and resistance of tumors to chemotherapeutic agents is a further challenge. Thus, the search for new anticancer drugs as well as novel therapeutic methods is still extremely important. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit COX (cyclooxygenase), overexpressed in some tumors. Carboranes are emerging as promising pharmacophores. We have therefore combined both moieties in a single molecule to design drugs with a dual mode of action and enhanced effectiveness. The NSAIDs ibuprofen, flurbiprofen, and fenoprofen were connected with 1,2-dicarba-closo-dodecaborane(12) via methylene, ethylene or propylene spacers. Three sets of carborane-NSAID conjugates were synthesized and analyzed through multinuclear (1H, 11B, and 13C) NMR spectroscopy. Conjugates with methylene spacers exhibited the most potent COX inhibition potential, particularly conjugates with flurbiprofen and fenoprofen, displaying higher selectivity towards COX-1. Furthermore, conjugates with methylene and ethylene spacers were more efficient in suppressing the growth of human cancer cell lines than their propylene counterparts. The carborane-flurbiprofen conjugate with an ethylene spacer was the most efficient and selective toward the COX-2-negative cell line HCT116. Its mode of action was basically cytostatic with minor contribution of apoptotic cell death and dominance of cells trapped in the division process.
RESUMO
Background and Aims: The shortage of beds at the maternity ward is ever increasing with an increasing trend in total birth and cesarean section deliveries thereby increasing the daily number of obstetric patients awaiting admission. This quality improvement (QI) project was conducted to mitigate the problem of bed shortage by implementing modified enhanced recovery after surgery in low-risk cesarean section mothers. We aimed to increase the process measure of second day postoperative discharge in low-risk cesarean section mothers admitted in the maternity ward from 0% to 25% over 2 months period. Simultaneously, the outcome measure of daily number of obstetric patients awaiting admission was assessed. Methods: The study was conducted at the maternity ward, Jigme Dorji Wangchuck National Referral Hospital, Thimphu Bhutan. Fishbone analysis was used to analyze problems leading to delayed discharge. Interventions were discussed, implemented, and reviewed using Plan, Do, Study, and Act (PDSA) cycle over 8 week period from June 1 to July 31, 2021. Data were collected using the EXCEL sheet and analyzed using STATA 13. Process and outcome measures during the pre and postintervention period were analyzed. Descriptive statistics were used to express the results. Wilcoxon Signed-Rank test was used to determine the statistical significance at p < 0.05. Results: The postintervention second day postoperative discharge increased to a median value of 65.5% (interquartile range [IQR]: 45-80) compared to the preintervention value of zero. The number of daily waiting obstetric patients decreased from the preintervention median value of 6.0 (IQR: 0-7) to the postintervention median value of 1.0 (IQR: 0-2) which was statistically significant at p = 0.0001. Conclusion: QI initiative can address bed shortages by increasing the early postoperative discharge, thereby reducing the number of obstetric patients awaiting admissions. The outcome of this QI initiative can be used to provide evidence to modify the existing Standard Operating Procedures in our setup.
