Developing Novel Anticancer Drugs for Targeted Populations: An Update.

BACKGROUND: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process, the rate of opportunity to get new, safe and efficacious drugs for the targeted population, including pediatric patients with cancer, becomes sluggish. OBJECTIVES: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of targeted anticancer drug development for the targeted population. METHODS: Information presented in this review was obtained from different databases, including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. RESULTS: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which take 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10- 17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. CONCLUSION: Therefore, to continue with the progress of developing novel anticancer drugs for the targeted population, identification and selection of target to specific disease type is important. Considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we study the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

Magnitude and determinants of complementary feeding practices in Ethiopia: A systematic review and meta-analysis.

BACKGROUND & AIM: Concurrent estimates on the magnitude and evidence on the determinants of complementary feeding (CF) practices in Ethiopia are currently disparate. Hence, this systematic review and meta-analysis assessed the magnitude and determinants of CF among children age 6-23 months in Ethiopia. METHODS: Studies from various databases published until July 2018 were identified, selected, extracted and assessed for risk of bias by two authors independently. A random-effects model was used to pool the prevalence and odds ratios (ORs). RESULTS: 26 studies with 17, 383 children were included. The pooled prevalence estimate of timely initiated CF, minimum dietary diversity (DD), minimum meal frequency and minimum acceptable diet were 61.0%, 18.0%, 56.0%, and 10.0% respectively. The pooled prevalence of timely initiation and minimum DD were higher in Northern Ethiopia. On the other hand, except for the minimum meal frequency, all the three core indicators of CF were better in urban than rural settings. Child age, maternal and/or paternal education, paternal involvement, maternal DD, antenatal and postnatal care, and place of delivery were the main determinants that can increase appropriate CF practices. CONCLUSION: The reported estimates of the prevalence of core CF indicators in Ethiopia remained poor. Therefore, the authors would like to acknowledge the effort that has been done by the minister of health and its partners including Alive & Thrive to improving CF practices in the country, however, these programs should be done more thoroughly, and scaled up by applying and adapting tested, proven approaches and tools in contexts.

If Channel as an Emerging Therapeutic Target for Cardiovascular Diseases: A Review of Current Evidence and Controversies.

In 2015, non-communicable diseases accounted for 39.5 million (70%) of the total 56.4 million deaths that occurred globally, of which 17.7 million (45%) were due to cardiovascular diseases. An elevated heart rate is considered to be one of the independent predictors and markers of future cardiovascular diseases. A variety of experimental and epidemiological studies have found that atherosclerosis, heart failure, coronary artery disease, stroke, and arrhythmia are linked to elevated heart rate. Although there are established drugs to reduce the heart rate, these drugs have undesirable side effects. Hence, the development of new drugs that selectively inhibit the heart rate is considered necessary. In the search for such drugs, almost four decades ago the If channel, also known as the "funny channel," emerged as a novel site for the selective inhibition of heart rate. These If channels, with a mixed sodium and potassium inward current, have been identified in the sinoatrial node of the heart, which mediates the slow diastolic depolarization of the pacemaker of the spontaneous rhythmic cells. The hyperpolarization-activated cyclic nucleotide-gated (HCN) subfamily is primarily articulated in the heart and neurons that are encoded by a family of four genes (HCN1-4) and they identify the funny channel. Of these, HCN-4 is the principal protein in the sinoatrial node. Currently, funny channel inhibition is being targeted for the treatment and prevention of cardiovascular diseases such as atherosclerosis and stroke. A selective If channel inhibitor named ivabradine was discovered for clinical use in treating heart failure and coronary artery disease. However, inconsistencies regarding the clinical effects of ivabradine have been reported in the literature, suggesting the need for a rigorous analysis of the available evidence. The objective of this review is therefore to assess the current advances in targeting the If channel associated with ivabradine and related challenges.