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.

Overview of child sexual and substance abuse among children in Ethiopia.

BACKGROUND: Child sexual abuse is common typically concealed while substance abuse is unhidden in their nature of practice globally. OBJECTIVE: The study aims to express the overview of child sexual and substance abuse among children in Ethiopia. METHOD: A facility-based cross-sectional study design with simple random sampling method was used to recruit study participants, after the allocation of sample size to the study institutions. Both descriptive and inferential statistics were used to describe the variables and to show the association of factors. RESULTS: A total of 450 children participated in the study. The mean age of the study participants was 13.67. More than 38% of the study participants were of age below the mean age. The majority of 61.3% of the study population were living with their parents. Factors associated with child sexual abuse were sex (AOR = 2.92; 95% CI; 1.84,4.63), alcohol intake (AOR = 2.53; 95% CI; 1.461, 4.36), chewing chat (AOR = 3.84; 95% CI; 1.68, 8.75), cigarette smoking (AOR = 3.83; 95% CI; 1.67-8.81), age (AOR = 4.38 (95% CI: 2.90, 6.62), educational level (AOR = 0.64 (95% CI: 0.44, 0.93), living conditions (AOR = 4.44; 95%CI: 0.73, 26.87), and conflict between parents AOR = 2.50 (95% CI: 1.43, 4.35). Moreover, the age and educational level of the study participants were statistically significant at P < 0.05. CONCLUSION: The study concluded that a significant proportion of children who participated in the study experienced sexual abuse and/or substance abuse. Therefore, there should be an intrusion to reverse the prevalent children's sexual and/or substance abuse in the country.

Transmission dynamics of foot and mouth disease in selected outbreak areas of northwest Ethiopia.

Foot and mouth disease (FMD) is a highly contagious and economically important disease of cloven-hoofed animals, which is endemic in Ethiopia. An outbreak follow-up study was undertaken to quantify the transmission parameters of FMD in the crop-livestock mixed (CLM) system and commercial dairy farms in selected areas of northwest Ethiopia. The transmission parameters were quantified using a generalised linear model (GLM) based on a susceptible-infectious-recovered (SIR) epidemic model. The per day average transmission rate between animals was 0.26 (95% CI 0.22-0.32) and 0.33 (95% CI 0.21-0.57) in the CLM system and in the commercial dairy farms, respectively. The average basic reproduction ratio of FMD was 1.68 (95% CI 1.42-2.07) in the CLM system and 1.98 (95% CI 1.26-3.42) in the commercial dairy farms. The medium per day transmission rate and moderate basic reproduction ratio observed in this study indicated that a vaccination coverage needed to stop transmission of the disease in these populations might not be very high.

Hepatic and renal toxicity and associated factors among HIV-infected children on antiretroviral therapy: a prospective cohort study.

OBJECTIVES: The aim of the study was to investigate the prevalence of renal function and liver enzyme abnormalities among HIV-infected children, changes in prevalence with time on combination antiretroviral therapy (cART), and the factors associated with these abnormalities. METHODS: A prospective cohort study was conducted among HIV-infected children < 18 years old (n = 705) who were on first-line cART. Liver enzymes, renal function, haematology, immunology and virological response were assessed at enrolment and followed bi-annually for 18 months. Liver fibrosis and cirrhosis were assessed using noninvasive markers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis score (FIB-4). RESULTS: The median age was 12 [interquartile range (IQR) 8-14] years; 53.3% of patients were male. At enrolment, the median cART duration was 3.3 (IQR 1.1-6.1) years; 177 (25.1%) and 83 (11.8%) patients had elevated AST and alanine aminotransferase (ALT), respectively. A tenth of the children had an APRI score > 0.5, suggesting liver fibrosis. Being on a zidovudine (ZDV)- or nevirapine (NVP)-based regimen and having a viral load > 1000 HIV-1 RNA copies/mL were significantly associated with elevated ALT. Twenty-four (3.4%) and 84 (12.1%) patients had elevated creatinine and blood urea nitrogen (BUN), respectively. As cART duration increased by 6 months, median BUN increased by 1.6 [95% confidence interval (CI) 0.4-2.7] mg/dL (P = 0.01); the glomerular filtration rate (GFR) decreased by 35.6 (95% CI 17.7-53.4) mL/min/1.73 m2 (P < 0.0001); and AST and ALT decreased by 1.4 (95% CI 0.4-2.5) IU/L (P = 0.01) and 1.4 (95% CI 0.2-2.6) IU/L (P = 0.01), respectively. CONCLUSIONS: A high prevalence of liver enzyme and renal function abnormalities was observed at enrolment. Decreasing liver enzyme levels during follow-up are possibly reassuring, while the progressive reduction in GFR and the increase in BUN are worrisome and require further study.

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.

Compliance with Surgical Safety Checklist completion in the operating room of University of Gondar Hospital, Northwest Ethiopia.

BACKGROUND: Appropriate utilization and compliance of Surgical Safety Checklist reduces occurrence of perioperative surgical complications and improve patient outcomes. However, data on compliance of surgical checklists are scarce in the study area. Therefore, the aim of this study was to evaluate compliance of checklist completion and its barrier for utilization at University of Gondar Hospital, Northwest Ethiopia. METHODS: A prospective observational study was conducted among 282 patients undergoing elective and emergency surgery from January to March 2013. Compliance and completeness rate with implementation of Sign-in, Time-out, and Sign-out domains was computed with SPSS 20 package. RESULTS: A total of 282 operations were performed and checklists were utilized in 39.7% (112/282) of cases. Among these, most checklists were employed during emergency procedures (61.6%) that need general anesthesia (75.9%) in department of surgery (58.9%). The overall compliance and completeness rate were 39.7 and 63.4% respectively. The sign-in, time-out and sign-out were missed in 30.5% (273/896), 35.4 % (436/1,232) and 45.7% (307/672) respectively. The main reasons cited for non-user were lack of previous training (45.1%) and lack of cooperation among surgical team members (21.6%). CONCLUSIONS AND RECOMMENDATIONS: The completeness rate was satisfactory but the overall compliance rate was suboptimal. An instrument that is used 40% of the time has been a fairly basic introduction without significant reinforcement training. Moreover, frequent use of the checklist during emergency cases has been deemed to be of value by clinicians. Supplementary training and attention to actual checklist use would be indicated to ensure that this valuable tool could be used more routinely and improve communication. Conducting regular audit of checklist utilization is also recommended.

Childhood behavioural disorders in Ambo district, western Ethiopia. I. Prevalence estimates.

The study was conducted between September 1994 and May 1995 in Ambo district, western Ethiopia. The prevalence of childhood behavioural disorder in children was found to be 17.7%. Behavioural disorder was found to be more common in boys than in girls. The prevalence increased with age. The most frequent symptoms reported were headache and nervousness. The least prevalent symptom was stealing things from home. As age increased, the risk of behavioural disorder increased. The increase in risk was statistically significant in the 15-year-old group when compared to the age group 5-7 years (adjusted Odds Ratio, OR = 1.89, 95% confidence interval, CI: 1.08-2.85). Childhood mental disorder was statistically significantly associated with parental age and with parental marital status. Children whose parents were < or = 24 years old had a higher risk of having mental disorders (OR: 2.03, 95% CI: 1.30-3.16) compared to those children whose parents were in the 45+ age group. Children whose parents were categorized as unmarried, divorced, separated, or widowed had a higher risk of having behavioural disorders (OR: 2.22, 95% CI: 1.70-2.91) than children whose parents were married. There was a statistically significant association between parental psychoneurosis and children's behavioural disorders; children whose mothers had psychoneuroses were at a higher risk of having behavioural disorders as compared to those whose mothers had no psychoneurosis (OR: 1.78, 95% CI: 1.34-2.35).

Childhood behavioural disorders in Ambo district, western Ethiopia. II. Validation of the RQC.

We report here on a study conducted to measure the validity of an Amharic version of the Reporting Questionnaire for Children (RQC), that was used in a survey of childhood behavioural disorders in a predominantly rural district in western Ethiopia. Mothers of 196 children aged 5-15 years, who were initially interviewed by the RQC were re-interviewed by a psychiatrist who was unaware of the RQC status of these children. The re-interview was conducted using a DSM IV checklist. The study showed that a cut-off point of one or more positive responses to any of the 10 questions on the RQC maximized sensitivity (87.5%) and specificity (65%). The discriminatory power of each item was also computed, and the item dealing with wetting/soiling oneself was found to have the highest ability to identify cases from non-cases. The item on abnormal speech was found to have the least discriminating power.