Mekonnen Sisay

Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016

Introduction Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care. Objective To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016. Design and Setting We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study. Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates. We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region. We collected data on approval of lenalidomide and bortezomib worldwide. Main Outcomes and Measures Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year. Results Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles. The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe. Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016. Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East. In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively. Conclusions and Relevance Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries. Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa. Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient. Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence.

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.

Ethnobotanical, Ethnopharmacological, and Phytochemical Studies of Myrtus communis Linn: A Popular Herb in Unani System of Medicine

Myrtus communis L (Myrtaceae) is one of the popular drugs being used in the Unani system of phytomedicine since ancient Greece period. From time immemorial, different parts of this plant and essential oil have been used for a variety of purposes such as cosmetics (hair fall control), flavoring of food and drinks as well as extensive therapeutic purposes. Ethnobotanical information revealed that M communis L has been a folkloric repute for the treatment of several diseases like gastric ulcer, diarrhea, dysentery, cancer, rheumatism, hemorrhage, deep sinuses, leucorrhoea, hemorrhoid, inflammation, dyspepsia, anxiety, insomnia, diabetes, hypertension, pulmonary disorders, and skin diseases. Moreover, ethnopharmacological studies revealed that the plant is endowed with extensive pharmacological activities, including antimicrobial, antidiarrheal, antidiabetic, antispasmodic, vasodilator, antiulcer, antioxidant, anticancer, anxiolytic, sedative-hypnotic, and anti-inflammatory activities, among others. The plant has been known to contain phenolic acids, tannins, flavonoids, glycosides, and terpenes. The myrtle oil was also found to be rich in a variety of bioactive monoterpenes and sesquiterpenes with their derivatives. Most of these studies validate the aforementioned traditional claims of this medicinal plant. Further studies are needed to unravel other pharmacological activities of this plant in the long run.

Evaluation of the diuretic activity of the aqueous and 80% methanol extracts of the root of Euclea divinorum Hiern (Ebenaceae) in Sprague Dawley rats

BACKGROUND Diuretics are drugs that increase the formation of urine and are important for the treatment of various diseases including hypertension and edema. The root decoction of Euclea divinorum has been used as a diuretic agent in the traditional medicine. Therefore, this study was aimed to evaluate the diuretic activity of the crude extracts of the roots of Euclea divinorum in Sprague Dawley rats. METHODS The aqueous extract (AE) and 80% methanol extract (80ME) of the plant were prepared using decoction and maceration, respectively. Vehicle (distilled water, 10ml/kg), standard drug (hydrochlorothiazide, 10mg/kg) and three doses (100mg/kg, 200mg/kg and 400mg/kg) of the AE and 80ME were given to male rats by oral gavage. Parameters like urine volume (for 5h), electrolyte concentration and pH were measured (at 5th h) and analyzed. Data were analyzed using one way analysis of variance (ANOVA) followed by Tukey post hoc test. Linear regression was also applied to show the dose dependency nature of the diuretic effect. RESULTS The result indicated that the 80ME of the plant significantly (p<0.05) produced diuresis at 200mg/kg and 400mg/kg. Furthermore, the AE produced significant diuresis (p<0.05) at all doses. With regard to the electrolyte excretion, the AE produced significant natriuresis and kaliuresis at all tested doses (p<0.001), while the 80ME showed significant natriuresis and kaliuresis at 200mg/kg (p<0.01) and 400mg/kg (p<0.001). Preliminary phytochemical screening revealed the presence of secondary metabolites, including saponins, flavonoids, glycosides, steroids, tannins and terpinoids in both extracts. These constituents might be responsible for the diuretic activity of Euclea divinorum. Both extracts were also found to be safe at 2000mg/kg on the acute toxicity study. CONCLUSION This finding provides a scientific support for the acclaimed traditional use of the roots of Euclea divinorum as a diuretic agent.

Drug Prescribing and Dispensing Practices in Tertiary Care Hospital of Eastern Ethiopia: Evaluation with World Health Organization Core Prescribing and Patient Care Indicators

Background: Rational prescribing, dispensing and patient use are the major components of rational drug use; however, the actual drug use pattern is not in line with World Health Organization (WHO) guidelines and is often irrational in many healthcare settings, particularly in developing countries. Therefore, this study aimed to highlight general prescribing and dispensing practices at Hiwot Fana Specialized University Hospital (HFSUH) outpatient settings. Method: Across-sectional study design was employed to determine the medication prescribing and dispensing practices at HFSUH. As per the WHO guideline for prescribing encounters, about 600 prescriptions were included in the study. Systematic random sampling was applied to obtain samples from encounters prescribed and dispensed from Jan 1-June 30, 2016. Moreover, as per the minimum requirement of the WHO guideline, 100 patient encounters were also included in the study with convenient sampling method. The data were evaluated against WHO standards for core drug use indicators. Results: From the total of 600 outpatient prescribing encounters, the prevalence of getting recorded diagnosis was almost negligible (4.67%). Only two thirds (67.60%) of prescription contain the patient name to whom the drug was prescribed. Coming to the drug related information, the prevalence of getting written dosage forms (18.5%), and the total quantity (35.34%) were found suboptimal. Duration of treatment had been documented in less than threefourth of encounters (73.00%). Regarding the WHO core prescribing indicators, the average number of drugs prescribed per encounter was found to be 1.89. The percentage of encounters that contain at least one antibiotic and injection was 304 (50.67%) and 315 (59.16%), respectively. Besides, the percentage of drugs prescribed by generic name and from an Essential Drug List (EDL) of the country was 1055 (93.04%) and 1134 (100.00%), respectively. The most commonly prescribed antibacterial agents were ceftriaxone 110 (36.20%), metronidazole 52 (17.11%), and cloxacillin 27 (8.89%). Besides, the top four prescribed injections were tramadol 214 (34.79%) ceftriaxone 110 (17.89%), furosemide 95 (15.45) and metronidazole 52 (8.46%). Looking at the patient care indicators, the percentage of drugs actually dispensed and labeled were 86% and 11%, respectively. The average dispensing time was 59.9 s and the percentage of patients knowing the entire regimen was 61.88%. Conclusion: As a tertiary care hospital, the overall completeness and rationality of prescription was found suboptimal since some of the key components were missed. The degree of polypharmacy fell within the window of WHO criteria. However, inappropriate use of antibiotics and injections was highly noticeable (significant deviation from the upper limit of the WHO standard). These are two critical but commonly misused classes of drugs given greater emphasis by WHO. Prescribing practice with generic name and from EDL is highly appreciable in this setting. However, labelling practice has been significantly poor in this setting.

Recent advances of cyclin-dependent kinases as potential therapeutic targets in HR+/HER2− metastatic breast cancer: a focus on ribociclib

In normal cell cycle progression, transition of G0/G1 phase to synthesis (S) phase for breast and other cells is regulated by association of cyclin D and cyclin-dependent kinases 4 and 6 (CDK4/6) that leads to phosphorylation of retinoblastoma (Rb) protein. Imbalance of this cyclin D-CDK4/6-inhibitors of CDK4/6-Rb phosphorylation pathway is associated with tumorigenesis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancers. Despite effective first-line endocrine therapy, HR+/HER2− metastatic breast cancers remain still incurable. Currently, advances in understanding of cell cycle checkpoints are evolving as promising strategy to target in treatment of various types of cancers including breast cancer. Therapies that target this cell cycle machinery in HR+/HER2− breast cancers are getting approval by the US Food and Drug administration (FDA) including ribociclib (LEE011). Ribociclib got the first FDA approval in March 13, 2017, as an initial therapy for HR+/HER2− advanced or metastatic breast cancer in combination with an aromatase inhibitor. This review, therefore, addresses the role of selective CDK4/6 inhibitors in advanced or metastatic breast cancer with a specific focus on ribociclib. Some findings of clinical trials involving ribociclib found pivotal benefits of ribociclib in HR+/HER2− metastatic breast cancer in terms of prolonging progression-free survival and objective response rates. Daily dosage range of the drug for such benefits is 50–900 mg with common daily doses of 400 or 600 mg and 600 mg in early and advanced breast cancer therapies, respectively. Along with its therapeutic benefits, however, more incident but manageable dose-limiting grade 3 or 4 toxicities, primarily hematologic adverse events, are common in patients treated with ribociclib. Generally, there are several active clinical trials undergoing to investigate the clinical efficacy and toxicity profile of the drug in various cancerous conditions other than breast cancer and will likely benefit patients with other cancer types.

Evaluation of lipid profiles and hematological parameters in hypertensive patients: Laboratory-based cross-sectional study

Introduction: Hypertension and dyslipidemia are the two coexisting and synergizing major risk factors for cardiovascular diseases. The cellular constituents of blood affect the volume and viscosity of blood, thus playing a key role in regulating blood pressure. Overweight and obesity are key determinants of adverse metabolic changes including an increase in blood pressure. The aim of this study was to evaluate lipid profiles and hematological parameters in hypertensive patients at Debre Markos Referral Hospital, Northwest Ethiopia. Methods: Laboratory-based cross-sectional study was conducted in 100 eligible hypertensive patients at the hospital. The required amount of blood was withdrawn from the patients by healthcare professionals for immediate automated laboratory analyses. Data were collected on socio-demographic factors, anthropometric measurements, blood pressure, lipid profiles, and hematological parameters. Result: The mean serum levels of triglyceride, total cholesterol, and low-density lipoprotein were significantly higher than their respective cut-off values in the hypertensive patients. Besides, 54%, 52%, 35%, and 11% of the hypertensive patients had abnormal low-density lipoprotein, total cholesterol, triglyceride, and high-density lipoprotein levels, respectively. Higher levels of low-density lipoprotein, hemoglobin, and red blood cell count were observed in the hypertensive patients whose blood pressure had been poorly controlled than the controlled ones (p < 0.05). Waist circumference had a significant positive association with the serum levels of total cholesterol and white blood cell count (p < 0.05). Conclusion: Hypertensive patients had a high prevalence of lipid profile abnormalities and poorly controlled blood pressure which synergize in accelerating other cardiovascular diseases. Some hematological parameters such as red blood cell count are also increased as do the severity of hypertension.

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.