Chemopreventive Activity of 80% Methanol Leaf Extract of Vernonia auriculifera Hiern (Asteraceae) Against Dimethylhydrazine-Induced Colorectal Carcinogenesis in Rats.

Background: Vernonia auriculifera Hiern (Asteraceae) is among Ethiopian herbal medicines that are traditionally used to treat skin and gastrointestinal cancers. In this study, the chemopreventive potential of Vernonia auriculifera leaf extract in dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats was investigated. Methods: Rats were assigned to nine groups (normal, positive, and negative control groups, and three pre- and three post-initiation groups). Except for the normal control group (administered with 1 mL/100 g distilled water), the remaining eight groups were given DMH (20 mg/kg) intraperitoneally (ip) for 15 consecutive weeks to induce colorectal tumours. The extract was given orally to the pre-initiation and post-initiation groups at doses of 100, 200, and 400 mg/kg before and after the induction of cancer, respectively. The positive control group was treated with aspirin (60 mg/kg/day) orally for the whole experimental period. Parameters including body weight, average tumour number, size, progression, incidence, total cholesterol, serum total protein, and triglyceride levels were determined. The cytotoxic activity of the extract in Caco-2 cells was evaluated using the MTT assay, and the antioxidant activity of the extract was also assessed using 2.2-diphenyl-1-picrylhydrazine (DPPH) and reducing power methods. Moreover, total phenol and flavonoid contents were determined using appropriate methods. Results: Rats treated with the extract showed a lower incidence of up to 50% in the pre-initiation higher dose, average number (p<0.05),and size (p<0.05) of tumours compared to untreated rats. It also inhibited colorectal cancer-associated increases in serum total cholesterol and triglycerides. The extract's IC50 value in the MTT assay was found to be higher than 200 µg/mL. The extract had an IC50 of 74.88 ± 0.86 µg/mL and 84.69 ± 2.02 µg/mL in the reducing power and DPPH assays, respectively. Total flavonoid and phenol contents were 14.51 ± 0.41 mg quercetin acid equivalent/gm and 47.37 ± 0.72 mg gallic acid equivalent/gm of the crude extract, respectively. Conclusion: The findings collectively indicated that the leaves of V. auriculifera possess chemopreventive activity, probably mediated through antioxidant mechanisms, which supports the traditional claim.

Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia.

Introduction: Genetic variation in the thiopurine S-methyltransferase (TPMT) gene by and large predicts variability in 6-mercaptopurine (6-MP) related toxicities. However, some individuals without genetic variants in TPMT still develop toxicity that necessitates 6-MP dose reduction or interruption. Genetic variants of other genes in the thiopurine pathway have been linked to 6-MP related toxicities previously. Objective: The aim of this study was to evaluate the effect of genetic variants in ITPA, TPMT, NUDT15, XDH, and ABCB1 on 6-MP related toxicities in patients with acute lymphoblastic leukemia (ALL) from Ethiopia. Methods: Genotyping of ITPA, and XDH was performed using KASP genotyping assay, while that of TPMT, NUDT15, and ABCB1 with TaqMan® SNP genotyping assays. Clinical profile of the patients was collected for the first 6 months of the maintenance phase treatment. The primary outcome was the incidence of grade 4 neutropenia. Bivariable followed by multivariable cox regression analysis was performed to identify genetic variants associated with the development of grade 4 neutropenia within the first 6 months of maintenance treatment. Results: In this study, genetic variants in XDH and ITPA were associated with 6-MP related grade 4 neutropenia and neutropenic fever, respectively. Multivariable analysis revealed that patients who are homozygous (CC) for XDH rs2281547 were 2.956 times (AHR 2.956, 95% CI = 1.494-5.849, p = 0.002) more likely to develop grade 4 neutropenia than those with the TT genotype. Conclusion: In conclusion, in this cohort, XDH rs2281547 was identified as a genetic risk factor for grade 4 hematologic toxicities in ALL patients treated with 6-MP. Genetic polymorphisms in enzymes other than TPMT involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.

Dyslipidemia and associated cardiovascular risk factors in HIV-positive and HIV-negative patients visiting ambulatory clinics: A hospital-based study.

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD), accounting for more than half of all instances of coronary artery disease globally (CAD). Purpose: The purpose of this study was to determine lipid-related cardiovascular risks in HIV-positive and HIV-negative individuals by evaluating lipid profiles, ratios, and other related parameters. Methods: A hospital-based study was carried out from January 2019 to February 2021 in both HIV + and HIV- ambulatory patients. Results: High TG (p = .003), high TC (p = .025), and low HDL (p < .001) were all associated with a two-fold increased risk of CVD in people aged 45 and up. Due to higher TG (p < .001) and lower HDL (p < .001), males were found to have a higher risk of atherogenic dyslipidemia. A twofold increase in the likelihood of higher TG levels has been associated with smoking (p = .032) and alcohol intake (p = .022). A twofold increase in a high TC/HDL ratio and an elevated TG/HDL ratio was observed with an increase in waist-to-height ratio (p = .030) and a high level of FBS (126 mg/dl) and/or validated diabetes (p = .017), respectively. In HIV + participants, central obesity (p < .001), diabetes (p < .001), and high blood pressure (p < .001) were all less common than in HIV- participants. Conclusions: Dyslipidemia is linked to advanced age, male gender, diabetes, smoking, alcohol consumption, and increased waist circumference, all of which could lead to an increased risk of CVD, according to the study. The study also revealed that the risks are less common in HIV + people than in HIV-negative ambulatory patients.

Prevalence and predictors of glucose metabolism disorders among People Living with HIV on combination antiretroviral therapy.

OBJECTIVE: We investigated prevalence and predictors of glucose metabolism disorders (GMDs) among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART). METHODS: This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to determine predictors. RESULTS: The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0-32.6%] s, with 31.1% (75/240) [95% CI 25.4-37.5%] for efavirenz-based and 19.8% (22/111) [95% CI 12.9-28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240); 95%CI (11.1-20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2-13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age ≥46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in both groups. Whereas the male gender and BMI category were predictors of GMDs among EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were predictors in the ATV/r-based group. CONCLUSIONS: GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age ≥46 years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for early diagnosis of type-2 diabetes and management.

Predicting the risk of atherosclerotic cardiovascular disease among adults living with HIV/AIDS in Addis Ababa, Ethiopia: A hospital-based study.

BACKGROUND: Atherosclerotic Cardiovascular Disease (ASCVD) is an emerging problem among People living with HIV/AIDS (PLWHA). The current study aimed at determining the risk of ASCVD among PLWHA using the Pooled Cohort Equation (PCE) and the Framingham Risk score (FRS). METHODS: A hospital-based study was carried out from January 2019 to February 2020 in PLWHA. The prevalence of ASCVD risk was determined in individuals aged between 20 to 79 and 40 to 79 years using the FRS and PCE as appropriate. Chi-square, univariate and multivariate logistic regressions were employed for analysis. RESULTS: The prevalence of high-risk ASCVD for subjects aged 20 and above using both tools was 11.5 %. For those aged 40 to 79 years, PCE yielded an increased risk (28%) than FRS (17.7%). Using both tools; advanced age, male gender, smoking, and increased systolic blood pressure were associated with an increased risk of ASCVD. Younger age (adjusted odds ratio, AOR) 0.20, 95%CI: 0.004, 0.091; P< 0.001), lower systolic blood pressure (AOR 0.221, 95%CI: 0.074, 0.605 P< 0.004), and lower total cholesterol (AOR 0.270, 95%CI: 0.073, 0.997; p<0.049) were found to be independent predictors of reduced risk of ASCVD. Likewise, younger age (40 to 64 years), female gender, and lower systolic blood pressure were significantly associated with lower risk of ASCVD among patients aged 40 to 79 years using both PCE and FRS. CONCLUSIONS: A considerable number of PLWHA have been identified to be at risk for ASCVD. ASCVD risk was significantly associated with advanced age, male gender, higher blood pressure, and smoking using both FRS and PCE. These factors should therefore be taken into account for designing management strategies.

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer; Part 3: Selective Cytotoxic Activity of 22 Plants against Human Cancer Cell Lines.

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC50 values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC50 values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.

Ethnobotanical Study of Medicinal Plants Used by Traditional Healers to Treat Cancer-Like Symptoms in Eleven Districts, Ethiopia.

There is no ethnobotanical study conducted specifically on medicinal plants traditionally used to treat cancer in Ethiopia. Yet, traditional herbalists in different parts of the country claim that they have been treating cancer-like symptoms using herbal remedies. The objective of this study was to document medicinal plants traditionally used to treat cancer-like symptoms in eleven districts, Ethiopia. Traditional herbalists were interviewed using semistructured questionnaires, and field visits were also carried out to collect claimed plants for identification purpose. Seventy-four traditional herbalists, who claimed that they knew about and/or had used medicinal plants to treat cancer-like symptoms, were selected using the snowball method and interviewed. Herbalists used their intuition and relied on the chronicity, growth of external mass, and spreading of the disease to other parts of the body, as a means to characterize cancer symptoms. Furthermore, in some of the study districts, herbalists reported that they treat patients who had already been diagnosed in modern healthcare institutions prior to seeking help from them. The inventory of medicinal plants is summarized in a synoptic table, which contains the scientific and vernacular names of the plants, their geographical location, the parts of the plants, and the methods used to prepare the remedies. A total of 53 traditionally used anticancer plants, belonging to 30 families, were identified during the survey. The most frequently reported anticancer plants were Acmella caulirhiza Del (Asteraceae), Clematis simensis Fresen. (Ranunculaceae), Croton macrostachyus Del. (Euphorbiaceae), and Dorstenia barnimiana Schweinf. (Moraceae). Organizing traditional healers, documenting their indigenous knowledge, and scientifically validating it for the development of better cancer therapeutic agents constitute an urgent and important task for policymakers and scientists.

Identification and Resolution of Drug-Related Problems among Childhood Cancer Patients in Ethiopia.

BACKGROUND: Even though medications play a major role in the cure, palliation, and inhibition of disease, they also expose patients to drug-related problems. Drug-related problems are frequent and may result in reduced quality of life, morbidity, and mortality. OBJECTIVES: The study was aimed to identify, characterize, and resolve drug-related problems in the Pediatric Hematology/Oncology ward of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. METHODS: A prospective observational study was conducted from 25 June to 25 October 2018 to assess DRPs on patients admitted at the pediatric hematology/oncology ward of Tikur Anbessa Specialized Hospital, which is the highest level governmental tertiary care hospital in Ethiopia. Data were obtained from patients' medical charts, physicians, patients/caregivers, pharmacists, and nurses. All the collected data were entered and analyzed using the Statistical Package for the Social Sciences version 25e. Descriptive statistics were used to represent the data. RESULTS: Among the total 156 participants, DRPs were identified in 68.6% of the study subjects. Dosing problems which include dosage too low and high were the top ranking (39.3%) of all DRPs followed by needs additional therapy (27.2%) and nonadherence (14.0%). Systemic anti-infectives were the most common class of drugs involved in DRPs. Trimethoprim-sulfamethoxazole, methotrexate, vincristine, ondansetron, and metoclopramide were frequently involved in DRPs. The addition of drugs and change in drug dose were the two most proposed intervention types. Among the proposed interventions, 223 (92.15%) were fully accepted, 9 (3.72%) partially accepted, and 10 (4.13%) not accepted. CONCLUSION: DRPs are common among Pediatric Hematology/Oncology ward patients. The hospital should develop a pediatric dosing chart for the commonly prescribed medications to prevent drug-related morbidity and mortality. The integration of clinical pharmacists can mitigate risks associated with DRPs.

Evaluation of current practice of antimicrobial use and clinical outcome of patients with pneumonia at a tertiary care hospital in Ethiopia: A prospective observational study.

BACKGROUND: Antimicrobial resistance, which is commonly observed in the management of pneumonia, is a major threat to public health and is driven by inappropriate antimicrobial use. The aim of this study was therefore to assess the current practice of antimicrobial utilization and clinical outcomes in the management of adult pneumonia at Tikur Anbessa Specialized Hospital. METHOD: A prospective observational study was conducted in the internal medicine wards of Tikur Anbessa Specialized Hospital. The study was conducted from 1 September 2016 to 30 June 2017 and patients aged ≥ 14 years and diagnosed with pneumonia were included. Chart review and self-administered questionnaire were used to collect data regarding pneumonia diagnosis and management as well as clinical outcomes (stable, complications, and in-hospital mortality). Descriptive statistics and binary logistic regressions were performed for data analyses. RESULTS: Out of 200 enrolled patients, clinical diagnosis was supported by microbiologic testing and imaging in 75 (37.5%) and 122 (61.0%) cases, respectively. The treatment approach in almost all patients (99.5%) was empirical and no de-escalation therapy was made even after acquiring culture results. The total duration of antimicrobial therapy was 12.05±5.09 days and vancomycin was the most commonly prescribed antimicrobial agent (25%), with 70% of the patients receiving this drug empirically. Nearly, 30% of the patients missed their antimicrobial doses during the course of treatment and stock-out (36.7%) was the major reason. Close to 113 (66%) of the treating physicians used reference books to prescribe antimicrobial agents. Patients' outcomes were found to be stable (66%), in-hospital mortality (18.5%), and ending up in complications (17%). Poor clinical outcome (death and complicated cases) was found to be associated with recent antimicrobial use history (p = 0.007, AOR 2.86(1.33-6.13)), cancer (p = 0.023, AOR 3.46(1.18-10.13)), recent recurrent upper respiratory tract infection (p = 0.046, AOR 3.70(1.02-13.40)), respiratory rate >24 breaths/min or <12 breaths/min (p = 0.013, AOR 2.45(1.21-4.95)) and high level of serum creatinine after initiation of antimicrobial therapy (>1.4mg/dl) (p = 0.032, AOR 2.37(1.07-5.20)). CONCLUSION: Antimicrobials are empirically prescribed without sufficient evidence of indication and microbiological or radiological findings. The practice also is not based on local guidelines and no multidisciplinary approach is apparent. [How about: "It is likely that these factors contributed to higher rates of mortality (18.5%) when compared with similar studies in other countries" instead of this "As a result, there were higher rates of mortality (18.5%) when compared with other similar studies"]. Hence, the hospital requires a coordinated intervention to improve rational use of antimicrobials and clinical outcomes through establishing an antimicrobial stewardship program.

Prevalence of cardiometabolic syndrome in HIV-infected persons: a systematic review.

INTRODUCTION: HIV infected persons are twofold likely to experience a heart attack, stroke, and other forms of Cardiometabolic Syndrome (CMetS). METHODS: Electronic searches of databases (MEDLINE and Google Scholar) were queried for articles written in English from 2000 to 2019. RESULTS: In this review (16 publications), a total of 14,002 participants from 8 countries were included. Two continents contributed to 62.5% of the CMetS studies while 38.1% from Latin America and 24.4% from North America. The studies were conducted in 113 different centers, with an average study length of 2.8 years. The majority of the study designs were cross-sectional (62%) followed by a cohort study (25%) and clinical trials (12.5%). The mean age of the population enrolled was 41.9 years and 54.6% of the participants were males. The overall prevalence of CMetS using the National Cholesterol Education Adult Treatment Panel definition was 20.6%. Only 31.3% of the studies were reported using the International Diabetes Federation definition. Smoking and high blood pressure were reported as a risk factor in 62.5% of the studies, while diabetes (31.3%), family history of CMetS (25%), and cardiac vascular and cancer diseases were reported in 12.5% of the studies. The average duration of stay with HIV after confirmation was 5.23 + 1.4 (years + SD) and the median duration on HAART was 4.5 + 2.3 (years + SD). CONCLUSIONS: CMetS was a common problem among HIV infected persons. Several RFs can contribute to the development of CMetS with smoking and hypertension highly interrelated. PROSPERO-NUMBER: CRD42018107187.

Prevalence and determinants of non-adherence to Imatinib in the first 3-months treatment among newly diagnosed Ethiopian's with chronic myeloid leukemia.

OBJECTIVES: Imatinib has shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML) but continuous dosing and patient adherence is essential treatment success. The study aimed to assess prevalence and reasons for non-adherence to Imatinib in newly diagnosed patients with CML in the first 3-months of treatment. METHODS: The study was conducted from October 1, 2016 to November 30, 2017 at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A total of 147 newly diagnosed patients were followed and their adherence status was determined using the 8-items Morisky Medication Adherence Scale and reasons for their non-adherence were evaluated using semi-structured questionnaire. Descriptive statistics were used to summarize the data while multivariable logistic regression was employed to explore associations among variables of interest. RESULTS: Participants' median age at time of confirmed diagnosis was 36 years; with most of them in the age group of <40 years (64.6%). Males comprised 59.2%. Adherence rate was found to be 55.1%. Those who lived in rural area, had low income, adverse drug events and comorbidity were significantly associated with treatment non-adherence. Most (68.4%) patients missed their medication due to adverse drug events. Three patients were lost-to-follow-up. Among 144 patients who finished the 3-month follow-up, 91.7% of them achieved complete hematologic remission. Morisky high adherent (AOR = 8.6, 95%CI:4.32-11.1) was positively associated with complete hematologic remission. CONCLUSIONS: Overall treatment adherence is suboptimal. Thus, efforts should be made to improve adherence and further study is required to explore impact adherence on the cytogenetic and molecular responses of Ethiopian patients with CML.

Validation of the Amharic Version of the Brief Fatigue Inventory for Assessment of Cancer-Related Fatigue in Ethiopian Cancer Patients.

BACKGROUND: Although cancer-related fatigue (CRF) is a highly prevalent and distressing symptom associated with cancer and its treatment, it is mostly underscreened, underassessed, and undertreated. The Brief Fatigue Inventory (BFI) is a reliable and valid instrument to assess CRF. OBJECTIVE: To validate the Amharic version of the BFI (BFI-Am) for assessment of CRF in Ethiopian cancer patients. METHODS: The BFI-Am was developed from its original English version through standard forward-backward translation approach. Two hundred eight consented cancer patients filled the questionnaires, along with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, version 3. In addition, sociodemographic and clinical information were collected. Psychometric properties of the BFI-Am were evaluated in terms of acceptability, internal consistency, construct validity, concurrent validity, and known group validity. Linear regression analysis was performed to identify possible predictors of fatigue severity. RESULTS: Two hundred two cancer patients completed the questionnaires and included in the data analysis. The BFI-Am had an overall Cronbach's alpha of 0.97. The results of the principal axis factor analysis suggested a one-factor solution explaining 78.4% of the variance, supporting the hypothesis of unidimensionality of the BFI-Am. The global BFI-Am interference items score was highly correlated with fatigue subscale score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 than single items, showing an inverse correlation between the BFI-Am and the global health status/quality of life (r = -0.324; P = 0.000). The BFI-Am significantly detected the differences in fatigue severity in patients with poor performance status (P < 0.001), indicating known group validity. CONCLUSION: The BFI-Am is an excellent assessment tool with adequate psychometric properties for use in both clinical management and symptom research of CRF in Ethiopian cancer patients.

Multiple challenges of antibiotic use in a large hospital in Ethiopia - a ward-specific study showing high rates of hospital-acquired infections and ineffective prophylaxis.

BACKGROUND: This project aims to study the use of antibiotics in three clinical wards in the largest tertiary teaching hospital in Ethiopia for a period of 1 year. The specific aims were to assess the prevalence of patients on antibiotics, quantify the antibiotic consumption and identify the main indications of use. METHOD: The material was all the medical charts (n = 2231) retrieved from three clinical wards (internal medicine, gynecology/obstetrics and surgery) in Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa between September 2013 and September 2014. Data collection was performed manually by four pharmacists. RESULTS: Each medical chart represented one patient. About 60% of the patients were admitted to internal medicine, 20% to each of the other two wards. The number of bed days (BD) was on average 16.5. Antibiotics for systemic use were prescribed to 73.7% of the patients (on average: 2.1 antibiotics/patient) of whom 86.6% got a third or fourth generation cephalosporin (mainly ceftriaxone). The average consumption of antibiotics was 81.6 DDD/100BD, varying from 91.8 in internal medicine and 71.6 in surgery to 47.6 in gynecology/obstetrics. The five most frequently occurring infections were pneumonia (26.6%), surgical site infections (21.5%), neutropenic fever (6.9%), sepsis (6.4%) and urinary tract infections (4.7%). About one fourth of the prescriptions were for prophylactic purposes. Hospital acquired infections occurred in 23.5% of the patients (353 cases of surgical site infection). The prescribing was based on empirical treatment and sensitivity testing was reported in only 3.8% of the cases. CONCLUSIONS: In the present study from three wards in the largest tertiary teaching hospital in Ethiopia, three out of four patients were prescribed antibiotics, primarily empirically. The mean antibiotic consumption was 81.6 DDD/100BD. Surgical site infections constituted a large burden of the infections treated in the hospital, despite extensive prescribing of prophylaxis. The findings show the need to implement antibiotic stewardship programs in Ethiopian hospitals with focus on rational prescribing, increased sensitivity testing and better procedures to prevent hospital acquired infections.

Genotoxicity study of Ethiopian medicinal plant extracts on HepG2 cells.

BACKGROUND: Most of herbal medicines are used without any standard safety and toxicological trials although common assumption is that these products are nontoxic. However, this assumption is incorrect and dangerous, so toxicological studies should be done for herbal drugs. Although Pterolobium stellatum, Otostegia integrifolia and Vernonia amygdalina root extracts are frequently used in Ethiopian traditional medicine, there are no evidences of their active toxic compounds. Therefore, we made an effort to assess probable genotoxic effect of these plant extracts on DNA of human hematoma (HepG2) cells using alkaline comet assay. METHODS: Genotoxic effects of extracts were evaluated using single cell gel electrophoresis (SCGE) method on HepG2 cell. Regarding comet data, the average mean tail intensities (TI) from each individual experiment and treatment (usually at least 3 cultures/treatment) were pooled and the average mean TI was used as an indicator of DNA damage and the standard error of mean (SEM) as the measure of variance. RESULTS: DNA damage in the form of comet tail has been observed for 1 and 0.5 mg/ml P. stellatum chloroform and 80% methanol extracts on HepG2 cells, respectively. The chloroform extract of P. stellatum showed increased tail DNA percentage in a concentration dependent manner. Comet tail length in the chloroform P. stellatum extract treated cells (1 mg/ml) was significantly higher by 89% (p < 0.05) compared to vehicle treated controls. The rest of test extracts seemed to be without genotoxic effect up to a concentration of 0.5 mg/ml. CONCLUSIONS: Our findings show that two extracts from one plant evaluated have a genotoxic potential in vitro which calls for a more thorough safety evaluation. Such evaluation should include other end-points of genotoxicity apart from DNA damage, and possibly also pure compounds.

Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice.

BACKGROUND: Diarrheal disease remains a public health problem in developing countries, including Ethiopia. In order to alleviate this disease, Ethiopian traditional healers use a wide range of medicinal plants from which Lantana camara is one of them. The stem of this plant is traditionally used for the treatment of diarrhoea. In addition, this plant is scientifically evaluated to have an antispasmodic effect on in vitro study. The aim of this study was to evaluate the antidiarrheal activity of the aqueous stem extract of L. camara Linn in mice. METHODS: The antidiarrheal activity of the extract was investigated using castor oil induced diarrhoea, enteropooling and small intestine transit models. The test groups received various doses (100, 200, and 400 mg/kg) of the extract, whereas positive controls received Loperamide (3 mg/kg) and negative controls received distilled water (10 ml/kg). RESULTS: In castor oil induced diarrhoea model, the extract, at all test doses, significantly (p < 0.001) prolonged diarrhoea onset, decreased the frequency of defecation, and weight of faeces. Similarly, the extract produced a significant (p < 0.001) decline in the weight and volume of intestinal contents at all tested doses. In addition, a significant (P < 0.001) reduction in the gastrointestinal motility in charcoal meal test was also observed in all doses of the extract. Phytochemical screening of the extract revealed the presence of flavonoids, alkaloids, tannins, and phytosterols that may play a key role in its antidiarrheal activity. CONCLUSION: The obtained results of the present study confirm antidiarrheal activity of the stem of L. camara, thus provide the scientific basis for the traditional uses of this plant as a treatment for diarrhoea.

Evaluation of the antidiarrheal activity of the leaf extracts of Myrtus communis Linn (Myrtaceae) in mice model.

BACKGROUND: Myrtus communis L. has a folkloric repute for the management of diarrhea and dysentery in different parts of the world. However, the safety and efficacy of the leaf extract have not been scientifically validated in animal model. This study was, therefore, aimed to investigate the antidiarrheal effect of 80% methanol extract (80ME) and solvent fractions of the leaves of Myrtus communis L. in mice. METHODS: The antidiarrheal activity of the 80ME and solvent fractions was evaluated against castor oil induced diarrheal model, charcoal meal and enteropooling tests. For the 80%ME, the test groups received 100, 200 and 400 mg/kg of the extract. In case of fractions, the test groups received various doses of fractions (200, 300, 400 mg/kg and an additional dose of 800 mg/kg for the aqueous fraction (AF)), where as negative controls received the vehicle (10 ml/kg) and positive controls received loperamide (3 mg/kg). RESULTS: The 80ME at 200 mg/kg (p < 0.05) & 400 mg/kg (p < 0.01) as well as the chloroform fraction (CF) and methanol fraction (MF) at 400 mg/kg (p < 0.05) significantly delayed the onset of diarrhea. Besides, the 80ME (at all tested doses) and both of these fractions (at 300 & 400 mg/kg) significantly decreased the frequency and weight of fecal outputs. Results from the charcoal meal test revealed that the 80ME, at all doses, (p < 0.001) as well as the CF and MF at 300 mg/kg (p < 0.05) & 400 mg/kg (p < 0.001) produced a significant anti-motility effect. Similarly, in the entero-pooling test, the 80ME (at all tested doses) (p < 0.01) as well as the CF and MF (at 300 & 400 mg/kg, p < 0.05) produced a significant decline in the weight and volume of intestinal contents, whereas the AF revealed significant effect (p < 0.05) at dose of 800 mg/kg only. CONCLUSION: The study demonstrated that the 80ME and solvent fractions contain bioactive constituents that have antidiarrheal activity. Therefore, this study provides a scientific support for the acclaimed traditional use of Myrtus communis L for the treatment of diarrheal diseases.

Validation of the Amharic Version of the Brief Pain Inventory for Utility in Ethiopian Cancer Patients.

BACKGROUND: Pain is a highly prevalent and distressing symptom in patients with cancer but at the same time inadequately treated in many of these patients. The major reason for such imbalance is inappropriate pain assessment. To overcome such a barrier, the use of a valid and reliable pain assessment tool in the language the patient understands is invaluable. Unfortunately, until now, no such standardized tool has been utilized in Ethiopian patients with cancer for both clinical and research purposes. OBJECTIVES: This study tried to validate the Amharic language version of the Brief Pain Inventory (BPI-Am) and evaluate the adequacy of cancer pain management using the Pain Management Index (PMI). METHODS: A standard forward/backward translation technique was used for translating the BPI from its original English version into Amharic (BPI-Am). The BPI-Am was administered to 291 Ethiopian patients with cancer who fulfilled the inclusion criteria. Factor analysis was used to identify the underlying constructs of the tool. Mean comparison was used to confirm the sensitivity of the BPI-Am to known patient groups that differed based on their performance status. Cronbach's α and intraclass correlation coefficients, respectively, were used to assure internal consistency and test-retest reliability of the BPI-Am. The PMI was calculated to identify the level of inadequate pain management in the current sample. Stepwise logistic regression was used to identify potential predictors of inadequate pain management. RESULTS: Factor analysis yielded 3 factors-pain severity, physical activity interference, and psychosocial interference-with Cronbach's α coefficients of 0.85, 0.87, and 0.77, respectively. The BPI-Am showed the capacity to detect higher mean pain severity and mean pain interference scores in patients with poor performance status as compared with those having a good performance status (P < 0.001). Intraclass correlation coefficients for test-retest reliability were 0.75 and 0.78 for the pain severity and pain interference composite scores, respectively. Sixty-seven percent of patients in the current sample were inadequately treated for their pain according to the PMI. Good performance status (odds ratio [OR] = 2.9, P < 0.01), absence of cancer-related complications (OR = 2.1, P < 0.05), and being unemployed (OR = 2.6, P < 0.01) were identified as predictors of inadequate pain management. CONCLUSION: The BPI-Am is a valid and reliable tool for use in Ethiopian patients with cancer. The inadequacy of cancer pain management in these groups of patients is high, which calls for needed attention.

Evaluation of the anti-diarrheal activity of the leaf extract of Croton macrostachyus Hocsht. ex Del. (Euphorbiaceae) in mice model.

BACKGROUND: Traditional healers in Ethiopia use a wide range of medicinal plants with antidiarrheal properties. Among these, Croton macrostachyus is one such plant claimed to have an antidiarrheal activity in Ethiopian folklore medicine. Previous studies showed that the crude extract is endowed with the claimed property. The present study was undertaken to further the claim by screening different fractions for the said activity so that it could serve as a basis for subsequent studies. METHODS: The fractions were obtained by successive extraction in soxhlet apparatus with solvents of different polarity (chloroform & methanol) followed by cold maceration of the deposit of the methanol fraction with distilled water. The antidiarrheal activity was evaluated using castor oil induced diarrheal model, charcoal meal test and anti-enteropooling test in mice. The test groups received various doses (300, 400, 500 mg/kg and an additional dose of 1000 mg/kg for the aqueous fraction) of the fractions, whereas positive controls received either Loperamide (3 mg/kg) or Atropine (5 mg/kg) and negative controls received vehicle (10 ml/kg). RESULTS: In the castor oil induced model, the chloroform (at all test doses) and methanol (at 400 & 500 mg/kg) fractions significantly delayed diarrheal onset, decreased stool frequency and weight of feces. The aqueous fraction was however devoid of significant effect at all the tested doses. Chloroform and methanol fractions produced a significant dose dependent decline in the weight and volume of intestinal contents while the aqueous fraction did not have a significant effect. All the fractions produced a significant anti-motility effect either at all doses (chloroform fraction) or at middle and higher doses (methanol and aqueous fractions). CONCLUSION: The present study demonstrated that the chloroform and methanol fractions possessed significant anti-diarrheal activity. Nevertheless, the aqueous fraction showed only significant anti-motility effect at the higher dose (1000 mg/kg) employed in the study.

Validation of the Amharic Version of the M. D. Anderson Symptom Inventory and Assessment of Symptoms in Ethiopian Cancer Patients.

CONTEXT: Cancer patients often face a variety of symptoms that impact their quality of life. The management of these symptoms is highly dependent on the accurate appraisal of their severity through the use of a standardized symptom assessment tool. The M. D. Anderson Symptom Inventory (MDASI), developed in English, is one of such tools that contain 13 core cancer related symptoms that can easily be rated on a scale of 0-10. OBJECTIVES: The present study tried to develop and validate the Amharic language version of the MDASI (MDASI-Am). METHODS: The MDASI-Am was developed by the standard forward/backward translation of the original English version of the MDASI. The MDASI-Am was completed by or administered to 145 randomly selected Ethiopian cancer patients. Factor analysis, Cronbach α coefficient, and mean comparison, respectively, were used to establish construct validity, internal consistency, and known-group validity (Eastern Cooperative Oncology Group Performance Status). RESULTS: Factor analysis identified three symptom constructs interpreted as general, gastrointestinal, and neuropsychiatric symptoms, with Cronbach α coefficients of 0.70, 0.80, and 0.82, respectively. The MDASI-Am significantly detected differences in symptom severity and interference levels in patient groups categorized according to Eastern Cooperative Oncology Group Performance Status (P < 0.01), establishing known-group validity. The most prevalent severe symptoms identified in the current sample were pain, sadness, numbness, distress, and fatigue. CONCLUSION: The MDASI-Am is a valid and reliable tool for measuring symptom severity and symptom interference with daily living in Ethiopian cancer patients.

Drug-related problems and potential contributing factors in the management of deep vein thrombosis.

BACKGROUND: Patients receiving anticoagulant drugs must be carefully screened for drug-related problems, as such medications, including warfarin have narrow therapeutic ranges and a high potential for complications. Thus, this study was designed to assess drug-related problems in the management of patients with deep vein thrombosis at Tikur Anbessa Specialized Hospital. METHODS: A cross-sectional descriptive study involving retrospective chart review of adult patients with deep vein thrombosis was conducted from patients who visited the hospital from July 2012 to June 2013, using structured data collection format and this was complemented by key informant interview. RESULTS: The study included 91 patients with venous thromboembolism. Fifty three (58.2 %) were females. Mean age was 38.6 (±13.76) years and more than 2/3 were below the age of 44 years. About 54 % of them presented with concurrent medical conditions and most commonly with cancer. Adjustment of warfarin dose up or down was done in increments of 16 to 100 % for recent subtherapeutic International Normalized Ratios, 16 to 50 % for therapeutic and 11 to 66 % for overtherapeutic International Normalized Ratios, with the mean of 36.5 (±18.03) based on the cumulative weekly dose of warfarin. There was significant linear relationship between percentage of dose change and consequent International Normalized Ratio values (R(2) = 0.419; p = 0.000). Accordingly, more than 51 % of them presented with nontherapeutic International Normalized Ratio ranges following dose adjustment. CONCLUSIONS: The most prevalent anticoagulation drug-related problems were subtherapeutic doses, overtherapeutic doses and potential drug interactions. Institutional validated decision support tools for dosing decisions during maintenance anticoagulation therapy should be developed and used accordingly in order to prevent recurrent and hemorrhagic complications and to improve clinical outcomes.