Getnet Mengistu

The RANK/RANKL/OPG system in tumorigenesis and metastasis of cancer stem cell: potential targets for anticancer therapy

The molecular triad involving receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL)/osteoprotegerin cytokine system has been well implicated in several physiological and pathological processes including bone metabolism, mammary gland development, regulation of the immune function, tumorigenesis and metastasis of cancer stem cell, thermoregulation, and vascular calcification. However, this review aimed to summarize several original and up-to-date articles focusing on the role of this signaling system in cancer cell development and metastasis as well as potential therapeutic agents targeting any of the three tumor necrotic factor super family proteins and/or their downstream signaling pathways. The RANK/RANKL axis has direct effects on tumor cell development. The system is well involved in the development of several primary and secondary tumors including breast cancer, prostate cancer, bone tumors, and leukemia. The signaling of this triad system has also been linked to tumor invasiveness in the advanced stage. Bone is by far the most common site of cancer metastasis. Several therapeutic agents targeting this system have been developed. Among them, a monoclonal antibody, denosumab, was clinically approved for the treatment of osteoporosis and cancer-related diseases.

Investigation of prescribing behavior at outpatient settings of governmental hospitals in eastern Ethiopia: an overall evaluation beyond World Health Organization core prescribing indicators

BackgroundRational prescribing remains an important component of rational drug use. The World Health Organization (WHO) standardized and validated core prescribing indicators for evaluating prescribing pattern of drugs. The prescribing practice has been shown to deviate from national and WHO guidelines in Ethiopia. The aim of this study was; therefore, to investigate the overall prescribing behavior of four governmental hospitals: Hiwot Fana Specialized University Hospital (HFSUH), Federal Harar Police Hospital (FHPH), Jugel Hospital (JH) and Southeast Command III Hospital (SECIIIH), Harar, eastern Ethiopia.MethodsHospital based retrospective cross-sectional study was employed to evaluate outpatient prescriptions dispensed from January 1 – December 31, 2016. A total of 2400 prescriptions (600 from each hospital) were assessed. A combination of prescription completeness and prescribing indicator forms were used to collect the data.ResultFrom a total of 2400 prescriptions reviewed, only HFSUH and FHPH were using standard prescription at prevalence of 92.5 and 99.8%, respectively. Name and weight of the patient were the most and the least commonly recorded information, respectively. A total of 5217 drugs were prescribed with an average number of drugs per encounter to be 2.17 (±0.39) and the highest value (2.60) was observed at FHPH. The frequency of administration was the most commonly written component (85.0%) with an average of 1.85 per prescription. Among all prescriptions analyzed, the percentage of encounters with antimicrobials and injectables prescribed were 66.9 and 26.5%, respectively. The prevalence of drugs prescribed with generic name and from essential drug list were 4644 (89.01%) and 4613 (88.42%), respectively. Among health professional related information, dispenser name was the least documented in all hospitals with the prevalence being 3.9%.ConclusionJH and SECIIIH were not using standard prescriptions at all during the review period. Besides, some important components of the prescription such as age, sex and diagnosis were not properly recorded or missed at all in the selected hospitals. The tendency of prescribing drugs with dose and dosage form was very poor. Overall, none of the core prescribing indicators was in line with the WHO standards. These and other related problems should be investigated in-depth to find out the underlying problems for which interventional strategies can be designed to reverse this worrying practice.

Antimicrobial Utilization Pattern in Pediatric Patients in Tertiary Care Hospital, Eastern Ethiopia: The Need for Antimicrobial Stewardship:

Background: Antimicrobials are among the most frequently prescribed medications for pediatric patients. However, inappropriate use of them can increase morbidity, mortality, healthcare costs, and largely antimicrobial resistance. This study aims to assess the antimicrobial utilization pattern in the pediatric ward of Hiwot Fana Specialized University Hospital. Methods: Retrospective cross-sectional study was conducted to assess the antimicrobial utilization. In this study, 403 pediatric medical records selected by systematic random sampling were reviewed. Data were collected using structured data abstraction format. Results: Ceftriaxone (n = 176, 26.5%), gentamicin (n = 125, 18.82%), and ampicillin (n = 119, 17.9%) were the most frequently prescribed antimicrobials, whereas ampicillin and gentamicin combination took the largest percentage share (n = 91, 43.3%). The most common reasons for which antimicrobials prescribed were severe pneumonia (n = 93, 18.82%), severe acute malnutrition (n = 69, 13.97%), and meningitis (n = 67, 13.56%). On average, the highest number of antimicrobials per card was observed in neonates. The percentage of antimicrobials administered by parenteral route was found to be 84.33%. Less than half of antimicrobials (46.98%) were prescribed with dosage form. Besides, strength and duration were recorded in 20.03% and 4.21% of antimicrobial agents, respectively. Conclusion: Generally, there was an overuse of injectables despite the fact that oral formulations are safer alternatives. This result is too far from World Health Organization (WHO) standard (13.4%-21.1%). The degree of polypharmacy of antimicrobials falls within the WHO cutoff point (<2). There are no antibiogram tests conducted in the hospital. By and large, this study provides an impetus towards the establishment of antimicrobial stewardship programs.

Self-Medication and Contributing Factors Among Pregnant Women Attending Antenatal Care at Public Hospitals of Harar Town, Ethiopia

Background: Self-medication has been increasing in many developing and developed countries. Its use during pregnancy presents a major challenge due to potential undesirable effects on mother and the fetus. So the aim of this study was to assess the prevalence of self-medication and contributing factors, among pregnant women. Methodology: Institution based cross sectional study was conducted among 244 pregnant women attending antenatal care at Hiwot Fana Specialized University Hospital and Jugal Hospital from February to March, 2017. A structured questionnaire based interview was used to collect data from each study subject. Then, data were categorized and analyzed using SPSS version 20 software. Logistic regression analysis was used to determine the significance of the association between the outcome and independent variables. P-value <0.05 was considered as a statistically significant in multivariate analysis. Results: The prevalence of self-medication during current pregnancy was 69.4%; out of which, 40.6% uses only herbal medicines to self-medicate. Time saving (50.7%) and prior experience of the drug (25.35%) were the main reasons for self-medication using conventional medicines while fewer side effects (59.86%) and effectiveness (35.92%) were the common reasons for self-medication using herbal medicines. Common cold and headache were among the common indications for self-medication. Friends (28.17%) and the pharmacist/druggist (23.94%) were the commonest source of information for conventional medicines while family/friends (69.72%) and neighbors (26.76%) were the common source of information for herbal medicines. Community drug retail outlets and neighbors were the commonly used sources of conventional medicines; while market place and self-preparation were the common sources of herbal medicines. Previous history of self-medication was significantly associated (P < 0.05) with current self-medication with conventional drugs and being a farmer by occupation and poor monthly income were significantly associated with herbal medicine use during pregnancy (P < 0.05). Conclusion: The prevalence of self-medication during pregnancy was very high in this study which showed a need for public trainings for all women of reproductive age about the risks of inappropriate self-medication.

Appropriateness of Cotrimoxazole Prophylactic Therapy Among HIV/AIDS Patients in Public Hospitals in Eastern Ethiopia: A Retrospective Evaluation of Clinical Practice

Background: Cotrimoxazole prophylactic therapy (CPT) is a feasible, cost-effective, and safe way of using cotrimoxazole intervention to reduce HIV/AIDS related morbidities and mortalities associated with opportunistic infections. Despite its effectiveness in reducing the incidence of opportunistic infections, the actual drug utilization process has been shown to deviate from World Health Organization (WHO) guideline in Ethiopia. This study, therefore, aims to evaluate CPT among HIV/AIDS patients in Jugel Hospital (JH), Harar and Dilchora Referral Hospital (DRH), Dire Dawa, Eastern Ethiopia. Methods: A cross sectional study was conducted to evaluate the use of cotrimoxazole as prophylactic therapy. In this study, 556 medical records (305 in JH and 251 in DRH) of HIV/AIDS patients who had been taking CPT within September 2015–August 2016 were reviewed. Systematic random sampling was employed to obtain medical records from the sampling frame. Data were abstracted from the patient medical records using structured checklist customized from the WHO guideline. The data were entered into Epi-data 3.1 and exported to and analyzed with statistical Package for Social Sciences (SPSS) version 20. The finding was evaluated against the WHO guideline on the use of cotrimoxazole prophylaxis in HIV/AIDS patients. Descriptive statistics was used to present the data in tables, figures and pie chart. Results: Majority of the HIV/AIDS patients who had been taking CPT were adults (95.9%), female (61.2%), married (43.7%), Orthodox Christian (54.3%), and attended primary school (40.1%). At the initiation of CPT, most of the patients were at WHO clinical stage III (40.8%). The major comorbid illnesses identified were tuberculosis and pneumocystis-jiroveci pneumonia. Initially, majority of the patients were at CD4 count of less than 350 cells/mm3 (n = 504, 90.6%). Greater proportion of patients started CPT prior to initiating antiretroviral therapy (ART). Most of the patients took CPT for greater than 6 months. The primary reasons for premature discontinuation of CPT were CD4 greater than 350 cells/mm3, severe sulfa allergy and first trimester of pregnancy. Generally, the use of cotrimoxazole prophylaxis was consistent with the WHO guideline for indication to start (n = 519, 93.3%) and dose (n = 552, 99.28%), despite the presence of contraindication in 6.65% patients. Conclusion: In reference to the WHO guideline, the use of CPT was found to be fully appropriate in nearly two-thirds of HIV/AIDS patients. For the rest patients, inappropriate use of cotrimoxazole was observed based on the WHO criteria for initiation, discontinuation, continuation and dose with rate of discontinuation being the dominant one. Such practice may lead to adverse health outcomes including adverse drug reactions and negative treatment outcome.