METHODS: Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.
KEY FINDINGS: Correlation between Ke and age was favourable (r = -0.453; P = 0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P
AIM: To determine the survival outcomes of New Zealand patients with unresectable or metastatic melanoma treated with pembrolizumab or nivolumab.
METHODS: This is a national retrospective cohort study. Patients with advanced unresectable or metastatic melanoma who received publicly funded immune-checkpoint inhibitors (ICIs) from 2017 to 2019 were included. Individual patient data were extracted from national administrative databases. The primary endpoint was OS, and secondary endpoints included OS by age, duration of treatment, posttreatment survival, and 30-day mortality from last pharmaceutical claim.
RESULTS: Five hundred ninety-seven patients were included, with a median follow-up of 25 months. One-year OS was 72%, the 2-year OS estimate was 60%, and median OS not reached. Survival did not differ by dichotomized age (≥70 vs. <70 year old), hazard ratio (HR) .94 (95% confidence interval (CI): .72-1.22; p = .62). Median duration of treatment was 9.0 months (95% CI: 7.9-10.1). Median post-treatment survival for the subgroup who had ceased treatment was 12.0 months (95% CI: 9.0-14.0). For the sample as a whole, the estimated 30-day mortality from last pharmaceutical claim was 15.7%.
CONCLUSION: OS in our New Zealand real-world population is comparable to pivotal clinical trials and real-world data (RWD) from other countries. These findings support the achievement of health gains from use of ICI in advanced unresectable and metastatic melanoma.
METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period.
RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21).
CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.
METHODS: This study was designed to investigate the effect of SynacinnTM and its individual biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography- tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron).
RESULTS: Result showed that SynacinnTM at maximum concentration (5000 µg/ml) 100% inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively. Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and CYP2C19 (72%) at 10µM.
CONCLUSION: Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.
PARTICIPANTS: The study included 16 patients with UVFP who underwent either LR (9 patients) or thyroplasty (7 patients) between 2015 and 2018 who fulfilled the inclusion criteria.
MAIN OUTCOME MEASURES: The outcomes were measured subjectively and objectively with: (1) voice handicap index-10 (VHI-10- Malay version); (2) auditory perceptual evaluation using the breathiness component of Grade, Roughness, Breathiness, Asthenia, Strain scale; (3) maximum phonation time (MPT); and (4) acoustic analysis (jitter%, shimmer%, and NHR) using OperaVOXTM. The outcomes were measured at baseline, 6 and 12-months postoperative. The comparison of outcomes between pre and postoperative of each group was evaluated using one-way ANOVA test. Mann-Whitney test was used to compare the outcomes between the two groups.
RESULTS: Comparison of each group at different time points showed significant improvement of VHI-10 and MPT of LR group between baseline and 12 months (P ≤ 0.05) whereas, the improvement in thyroplasty group was observed at all time points (P ≤ 0.05). When comparing between the two groups at 12 months, the VHI-10 and MPT was significantly better in the LR group than thyroplasty group with P = 0.004 and P = 0.001 respectively. Other outcome measures did not reveal significant difference between the two groups.
CONCLUSION: This observational study showed that LR may be better than thyroplasty in improving VHI-10 and MPT in selected patients with UVFP.
METHODS: We conducted a randomised, double blinded, two-armed parallel study comparing 20 g/day of Tualang Honey versus 20 g/day Honey Cocktail among postmenopausal women aged 45-65 years. The cardiovascular parameters and anthropometrics measurements were assessed at baseline, 6 months, and 12 months of the intervention.
RESULTS: 100 subjects were successfully randomised into the groups. There was a significant decrease in the diastolic blood pressure from 77.92 mmHg at baseline to 73.45 mmHg at 12 months (F-statistic = 2.55, p-value = 0.047) in the Tualang Honey group compared to Honey Cocktail. There was also a significant decrease in the fasting blood sugar from 6.11 mmol/L at baseline to 5.71 mmol/L at 12 months (F-statistic = 4.03, p-value = 0.021) in the Tualang Honey group compared to the Honey Cocktail group. The body mass index remained unchanged at 27 kg/m2 (F-statistic = 1.60, p-value = 0.010) throughout 12 months of the intervention in the Honey Cocktail group.
CONCLUSION: Subjects who received Honey Cocktail showed remarkable effects on body mass index. However, Tualang Honey supplementation showed superior effect in lowering diastolic blood pressure and fasting blood sugar compared to Honey Cocktail. Further studies are required to ascertain the underlying mechanism(s) of Tualang Honey and Honey Cocktail on each observed parameter.