RESULTS: We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studies and drug sensitivity studies in physiological models are necessary to unleash the prospect of this combination for cervical cancer therapy.
Methods: PubMed and EMBASE databases (until May 2, 2017) were searched to identify studies reporting drug induced long QT syndrome and followed the PRISMA guidelines. The main outcomes measured in these studies were QTc prolongation, ventricular arrhythmias, torsade de pointes (TdP) and death.
Results: Out of 176 non-duplicate reports, 36 studies satisfied inclusion criteria and provided data on patients exposed to drugs that can potentially cause long QT. Totally, 14,756 patients were exposed and 930 patients (6.3%) were found to have QTc prolongation. The number of males was 6,400 and females were 5,723 patients. The mean age of the patients was 43.8 ± 9.36 years. Ventricular arrhythmias were found in 379 patients (2.6%), 26 patients were found to have premature atrial contractions (PACs) and premature ventricular contractions (PVCs). TdP was found in 49 patients (0.33 %), sudden cardiac death (SCD) was found in five patients and 586 patients were found to have all-cause mortality.
Conclusions: Around 6% of patients have risk of QT prolongation when exposed but only 0.3% developed TdP and 2.6% developed ventricular arrhythmias. Risk of developing arrhythmias is higher with concomitant use of multiple QT prolonging drugs.
METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).
RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.
CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.