METHODS: Articles were retrieved from EMBASE, Medline and Cochrane Library from inception to January 2016. Treatment outcomes were analysed based on responder, seizure-free, withdrawal and adverse event rates. Quality of each study was also assessed.
RESULTS: Twelve articles fulfilled the inclusion criteria. Heterogeneity and quality of the included studies were considered acceptable. Overall, newer AEDs as adjunct therapy in children with inadequate control of focal seizure showed a trend of better seizure outcomes. The pooled ORs for responder, seizure-free and withdrawal rates were 2.15 (95%CI:1.72, 2.69), 1.99 (95%CI:0.72, 5.48) and 0.69 (95%CI:1.13, 2.39) respectively. Adverse events of newer AEDs were comparatively higher than placebo (OR:1.64, 95%CI:1.13, 2.39).
CONCLUSION: In our updated review, newer AEDs as adjunct therapy for focal epilepsy in children have trends of better effectiveness compared to placebo. Newer AEDs are associated with statistically more children with >50% seizure reduction, and a trend of better seizure freedom. Their tolerability would also be considered acceptable with the observed low withdrawal rate. However, the relative lack of well-conducted RCTs evaluating their effectiveness against other active AED treatment in children would not facilitate evidence-based practice. This highlights the knowledge gap and the need for more well-conducted RCTs against active treatments to ascertain the long term effectiveness and the role of newer AEDs in managing epilepsy in children.
METHODS: A Markov model of a Malaysian hypothetical cohort aged ≥30 years (N = 14,589,900) was used to estimate the total and per-member-per-month (PMPM) costs of RAS uptake. This involved an incidence and prevalence rate of 9.0% and 10.53% of patients with diabetes and hypertension respectively. Transition probabilities of health stages and costs were adapted from published data.
RESULTS: An increasing uptake of RAS drugs would incur a projected total treatment cost ranged from MYR 4.89 billion (PMPM of MYR 27.95) at Year 1 to MYR 16.26 billion (PMPM of MYR 92.89) at Year 5. This would represent a range of incremental costs between PMPM of MYR 0.20 at Year 1 and PMPM of MYR 1.62 at Year 5. Over the same period, the care costs showed a downward trend but drug acquisition costs were increasing. Sensitivity analyses showed the model was minimally affected by the changes in the input parameters.
CONCLUSION: Mild impact to the overall healthcare budget has been reported with an increased utilization of RAS. The long-term positive health consequences of RAS treatment would reduce the cost of care in preventing deterioration of kidney function, thus offsetting the rising costs of purchasing RAS drugs. Optimizing and increasing use of RAS drugs would be considered an affordable and rational strategy to reduce the overall healthcare costs in Malaysia.
RESULTS: In this study, we propose the Context Based Dependency Network (CBDN), a method that is able to infer gene regulatory networks with the regulatory directions from gene expression data only. To determine the regulatory direction, CBDN computes the influence of source to target by evaluating the magnitude changes of expression dependencies between the target gene and the others with conditioning on the source gene. CBDN extends the data processing inequality by involving the dependency direction to distinguish between direct and transitive relationship between genes. We also define two types of important regulators which can influence a majority of the genes in the network directly or indirectly. CBDN can detect both of these two types of important regulators by averaging the influence functions of candidate regulator to the other genes. In our experiments with simulated and real data, even with the regulatory direction taken into account, CBDN outperforms the state-of-the-art approaches for inferring gene regulatory network. CBDN identifies the important regulators in the predicted network: 1. TYROBP influences a batch of genes that are related to Alzheimer's disease; 2. ZNF329 and RB1 significantly regulate those 'mesenchymal' gene expression signature genes for brain tumors.
CONCLUSION: By merely leveraging gene expression data, CBDN can efficiently infer the existence of gene-gene interactions as well as their regulatory directions. The constructed networks are helpful in the identification of important regulators for complex diseases.
MATERIALS AND METHODS: 12 adult patients with focal supraspinatus tendinosis recruited after they had less than 30% improvement in functional (DASH) scores after one month of physiotherapy following initial presentation. Seven patients had 0.5-1.0 ml of prolotherapy injection (12.5% dextrose, 0.5% lignocaine) injected into the area of focal tendinosis under ultrasound guidance. Meanwhile, five patients continued standard physiotherapy with no intervention performed. Regional area of echogenicity in decibels, DASH, range of movements of the shoulder, pain, and sleep scores were measured at baseline and at 12 weeks.
RESULTS: The prolotherapy group showed significant improvement in shoulder abduction (p=0.030) and an improvement in sleep score (p=0.027). The echogenicity of area of tendinosis significantly increases at the end of treatment (p=0.009). However, there was a nonsignificant reduction in pain score in the injection group (43.5%) and in the control group (25%) at 12 weeks (p > 0.005).
CONCLUSION: Ultrasound-guided intratendinous prolotherapy injection significantly improves patient's range of abduction and improves sleep within 12 weeks of treatment compared to conventional physiotherapy management.
TRIAL REGISTRATION: This study was registered under Current Controlled Trials (UK) and given International Standard Randomised Controlled Trial Number (ISRCTN) of 43520960.
PURPOSE: The study aimed to evaluate the budget impact of increasing the uptake of denosumab for the management of postmenopausal osteoporosis in Malaysia.
METHODS: A Markov budget impact model was developed to estimate the financial impact of osteoporosis treatment. We modelled a scenario in which the uptake of denosumab would increase each year compared with a static scenario. A 5-year time horizon from the perspective of a Malaysian MOH healthcare provider was used. Model inputs were based on Malaysian sources where available. Sensitivity analyses were performed to examine the robustness of the modelled results.
RESULTS: An increase in denosumab uptake of 8% per year over a 5-year time horizon would result in an additional budget impact, from MYR 0.26 million (USD 0.06 million) in the first year to MYR 3.25 million (USD 0.78 million) in the fifth year. When expressed as cost per-member-per-month (PMPM), these were less than MYR 0.01 across all five years of treatment. In sensitivity analyses, the acquisition cost of denosumab and medication persistence had the largest impact on the budget.
CONCLUSION: From the perspective of a Malaysian MOH healthcare provider, moderately increasing uptake of denosumab would have a minimal additional budget impact, partially offset by savings in fracture treatment costs. Increasing the use of denosumab appears affordable to reduce the economic burden of osteoporosis in Malaysia.