Characteristics of recent clinical investigations into systemic therapy against cervical cancer: systematic analysis of trial details from Clinicaltrials.gov.

A review that systematically assessed the current state of clinical research into systematic therapy-based interventions against invasive cervical cancer. It analysed registry details of 59 systemic therapy-based cervical cancer trials on ClinicalTrials.gov with study start dates between January 2010 and June 2018. The review characterised the present cervical cancer trial landscape in terms of trial design features, systemic therapy (chemotherapy, targeted therapy, immunotherapy, and repurposed therapy), and disease stages of interest. It also made an attempt to qualitatively synthesise the trial landscape in terms of the nature and trend of research focus, alignment with existing clinical needs, novelty of treatments or concepts pursued, and promise of new treatments.

Efficacy and safety of artemisinin-based combination therapies for the treatment of uncomplicated malaria in pediatrics: a systematic review and meta-analysis.

BACKGROUND: Malaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas. Artemisinin-based combination therapies (ACTs) are the drugs of choice for malaria management particularly across malaria-endemic countries. This systematic review and meta-analysis was performed to assess efficacy and safety of ACTs for uncomplicated malaria in pediatric populations. METHODS: A body of evidence was searched for published ACT trials until March 06, 2020. The search was focused on efficacy and safety studies of ACTs for uncomplicated malaria in pediatrics. PubMed library was searched using best adapted search terms after multiple trials. References were exported to the endnote library and then to Covidence for screening. Data was extracted using the Covidence platform. The per-protocol analysis report for the efficacy and the intention-to-treat analysis for the safety were synthesized. Met-analysis was carried using Open Meta-Analyst software. Random effects model was applied and the heterogeneity of studies was evaluated using I2 statistic. RESULTS: Nineteen studies were included in the final analysis. Overall, crude, PCR-corrected P. falciparum malaria treatment success rate was 96.3 and 93.9% for day 28 and 42, respectively. In the subgroup analysis, PCR-corrected adequate clinical and parasitological response (ACPR) of dihydroartemisinin-piperaquine (DP) was 99.6% (95% CI: 99.1 to 100%, I2 = 0%; 4 studies) at day 28 and 99.6% (95% CI of 99 to 100%, I2 = 0%; 3 studies) at day 42. Nine studies reported ACT related adverse drug reactions (ADR) (8.3%, 356/4304). The reported drug related adverse reactions ranged from 1.8% in DP (two studies) to 23.3% in artesunate-pyronaridine (AP). Gastrointestinal symptoms were the most common ACT related adverse effects, and all ADRs were reported to resolve spontaneously. CONCLUSION: ACTs demonstrated a high crude efficacy and tolerability against P. falciparum. The high treatment success and tolerability with low heterogeneity conferred by DP has implication for policy makers who plan the use of ACTs for uncomplicated falciparum malaria treatment in pediatrics.

Reproducibility of malaria sporozoite challenge model in humans for evaluating efficacy of vaccines and drugs: a systematic review.

BACKGROUND: The development of novel malaria vaccines and antimalarial drugs is limited partly by emerging challenges to conduct field trials in malaria endemic areas, including unknown effects of existing immunity and a reported fall in malaria incidence. As a result, Controlled Human Malaria Infection (CHMI) has become an important approach for accelerated development of malarial vaccines and drugs. We conducted a systematic review of the literature to establish aggregate evidence on the reproducibility of a malaria sporozoite challenge model. METHODS: A systematic review of research articles published between 1990 and 2018 on efficacy testing of malaria vaccines and drugs using sporozoite challenge and sporozoite infectivity studies was conducted using Pubmed, Scopus, Embase and Cochrane Library, ClinicalTrials.gov and Trialtrove. The inclusion criteria were randomized and non-randomized, controlled or open-label trials using P. falciparum or P. vivax sporozoite challenges. The data were extracted from articles using standardized data extraction forms and descriptive analysis was performed for evidence synthesis. The endpoints considered were infectivity, prepatent period, parasitemia and safety of sporozoite challenge. RESULTS: Seventy CHMI trials conducted with a total of 2329 adult healthy volunteers were used for analysis. CHMI was induced by bites of mosquitoes infected with P. falciparum or P. vivax in 52 trials and by direct venous inoculation of P. falciparum sporozoites (PfSPZ challenge) in 18 trials. Inoculation with P. falciparum-infected mosquitoes produced 100% infectivity in 40 studies and the mean/median prepatent period assessed by thick blood smear (TBS) microscopy was ≤ 12 days in 24 studies. On the other hand, out of 12 infectivity studies conducted using PfSPZ challenge, 100% infection rate was reproduced in 9 studies with a mean or median prepatent period of 11 to 15.3 days as assessed by TBS and 6.8 to 12.6 days by PCR. The safety profile of P. falciparum and P.vivax CHMI was characterized by consistent features of malaria infection. CONCLUSION: There is ample evidence on consistency of P. falciparum CHMI models in terms of infectivity and safety endpoints, which supports applicability of CHMI in vaccine and drug development. PfSPZ challenge appears more feasible for African trials based on current evidence of safety and efficacy.

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.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models.

BACKGROUND: Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. METHODS: Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). RESULTS: In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. CONCLUSION: This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

Level of adherence to ocular hypotensive agents and its determinant factors among glaucoma patients in Menelik II Referral Hospital, Ethiopia.

BACKGROUND: Good adherence to ocular hypotensive agents is important to control intraocular pressure and hence to prevent progressive glaucomatous optic nerve head damage. Periodic investigation of adherence is crucial in glaucoma treatment. The purpose of this study was to assess level of adherence to ocular hypotensive agents and to identify factors affecting adherence among glaucoma patients at a tertiary public eye care center. METHODS: The study was a hospital-based cross-sectional study that was conducted in Menelik II Referral Hospital from June 1, 2015 to July 31, 2015. A systematic random sampling technique was used to select 359 study participants from the source population. The study patients were interviewed and their medical charts were reviewed using a pretested structured questionnaire. Adherence was assessed using Morisky Medication Adherence Scale - 8 and adherence determinant factors were identified using multivariate binary logistic regression analysis. The association was declared statistically significant at p < 0.05. RESULTS: Among the 359 study glaucoma patients, 42.6 % were adherent to their prescribed hypotensive agents. Higher educational level (AOR = 4.60, 95 % CI: 1.01-21.03, p < 0.049), being self - employed (AOR = 6.14, 95 % CI: 1.37-27.50, p < 0.018) and taking lesser frequency of drops (AOR = 2.89, 95 % CI: 1.25-6.66, p < 0.013) were significantly associated with adherence, whereas being a farmer (AOR = 0.07, 95 % CI: 0.01-0.75, p < 0.028), having very low monthly family income (AOR = 0.22, 95 % CI: 0.06-0.77, p < 0.019) and self - purchasing of medications (AOR = 0.30, 95 % CI: 0.10-0.93, p < 0.036) were significantly associated with non-adherence. CONCLUSIONS: The study has identified the adherence level to the prescribed ocular hypotensive agents to be sub-optimal and is influenced by different factors among glaucoma patients of the public tertiary center. We recommend glaucoma care providers to pay due attention on the importance of adherence.

Antidiarrheal activity of 80 % methanol extract of the aerial part of Ajuga remota Benth (Lamiaceae) in mice.

BACKGROUND: In the Ethiopian traditional medicine, the aerial part of Ajuga remota Benth is used in the treatment of diarrhea. There are different mechanisms by which Ajuga remota may have antidiarrheal effect. Some of the possible mechanisms are through its anthelmintic and antibacterial activity. The present study aimed to evaluate whether the antidiarrheal effect of the plant also include antimotility and antisecretory effect using 80 % methanol extract of A. remota (MEAR). METHODS: The MEAR was administered at doses of 200, 400, 600 and 800 mg/kg to four groups of mice (six animals per group) orally in castor oil diarrhea model. The effect of the extract on enteropooling and gastrointestinal transit model was also evaluated using the same grouping and dosing. Two other groups, one as control and the other as standard (loperamide 5 mg/kg) were used for comparison with the treatment groups. RESULTS: The extract at the doses of 400, 600, and 800 mg/kg produced a dose-dependent and significant inhibition both on the frequency and onset of diarrhea. The percentage purging frequency was 53.4, 66.7, 79.6, and 66.7 % (p < 0.001) at three doses of MEAR (400, 600, and 800 mg/kg) and with loperamide (5 mg/kg), respectively. The percentage inhibition in intestinal fluid accumulation was 42.5, 62.1, and 74.2 % (p < 0.001) at the doses of 400, 600 and 800 mg/kg of MEAR, respectively. The MEAR also inhibited the intestinal transit of charcoal meal in a dose dependent manner both in the normal and castor oil induced intestinal transit. CONCLUSION: This study has shown that the 80 % methanol extract of A. remota contains pharmacologically active substances with significant antimotility and antisecretory effect contributing for its antidiarrheal activity.

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.

Evaluation of the in vitro antibacterial activity of the solvent fractions of the leaves of Rhamnus prinoides L'Herit (Rhamnaceae) against pathogenic bacteria.

BACKGROUND: Medicinal plants play great roles in the treatment of various infectious diseases. Rhamnus prinoides is one of the medicinal plants used traditionally for treatment of bacterial diseases. The antibacterial activity of the crude extract of the plant had been shown by a previous study, but this study was undertaken to further the claimed medicinal use of the plant by screening its solvent fractions for the said activity so that it could serve as a basis for subsequent studies. METHODS: The solvent fractions of the plant were obtained by successive soxhlet extraction with solvents of increasing polarity, with chloroform and methanol, followed by maceration of the marc of methanol fraction with water. The antibacterial activity of the solvent fractions was evaluated on seven bacterial species using agar well diffusion method at different concentrations (78 mg/well, 39 mg/well and 19.5 mg/well) in the presence of positive and negative controls. The minimum inhibitory concentration of the solvent fractions was determined by micro-broth dilution method using resazurin as indicator. RESULT: Methanol and chloroform fractions revealed antibacterial activities against the growth of test bacterial strains with varying antibacterial spectrum and the susceptible bacterial species were Staphylococcus aureus, Streptococcus pyogen, Streptococcus pneumoniae and Salmonella typhi. The average minimum inhibitory concentration value of the methanol and chloroform fractions ranged from 8.13 mg/ml to 32.5 mg/ml and from 8.13 mg/ml to 16.25 mg/ml, respectively. CONCLUSION: The methanol and chloroform fractions demonstrated significant antibacterial activities against the growth of pathogenic bacteria but the aqueous fraction did not reveal antibacterial activity against any of the test bacteria.

Antitrypanosomal activity of Verbascum sinaiticum Benth. (Scrophulariaceae) against Trypanosoma congolense isolates.

BACKGROUND: African Trypanosomiasis is a neglected tropical disease with a large impact on the livelihood of the rural poor in Sub-Saharan Africa. The available drugs for managing this disease are old, expensive and are facing the problem of drug resistance. Thus, the aim of this study was to evaluate in vivo antitrypanosomal efficacy of aqueous and absolute methanol leaf extracts of Verbascum sinaiticum Benth. against Trypanosoma congolense field isolate. METHODS: Verbascum sinaiticum (Local name 'qetetina') is a biennial plant, and 60-150 cm tall. It is traditionally used to treat wound, stomachache, viral infection, cancer, sunstroke, fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The efficacy of aqueous and absolute methanol leaf extracts of V. sinaiticum was evaluated in a randomized experiment with Swiss albino mice infected with T. congolense field isolate. The extracts were administered at doses of 100, 200 and 400 mg/kg by intraperitoneal injection for seven days at 12 Days Post-Infection (DPI) when the peak parasitaemia level was approximately 10(8) trypanosomes/ml. Parasitaemia, Packed Cell Volume (PCV), mean survival time and change in body weight were used as indices for monitoring the efficacy of the extracts. Diminazene (28 mg/kg) was used as a positive control while 2 % Tween was used as the negative control. Phytochemicals screening were conducted following standard methods. RESULTS: The extracts showed no toxicity effect in Swiss albino mice and had LD50 above 2000 mg/kg. The phytochemicals screened in V. sinaiticum were alkaloids, flavonoids, glycoside, saponins, steroids, phenolic compounds, and tannins. The mice treated with absolute methanol leaf extract of V. sinaiticum at 400 mg/kg dose had significantly lower mean parasitaemia (7.20 ± 0.16) (p < 0.001) as compared to the negative control group (8.82 ± 0.12) on day 14 of treatment. Animals treated with the same dose had significant (p < 0.001) higher PCV value and body weight and as well as the highest mean survival time of 40.20 ± 0.31 days as compared to the negative control at the end of the observation period. CONCLUSION: This study established that Verbascum sinaiticum had trypanocidal activity. The crude extracts have partially eliminated trypanosomes in a dose-dependent manner. The study can be a basis for future in-depth analysis of the biologically active chemicals.

Drug dosage adjustment in hospitalized patients with renal impairment at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia.

BACKGROUND: Dose adjustment for certain drugs is required in patients with reduced renal function to avoid toxicity as many drugs are eliminated by the kidneys. The aim of this study was to assess whether appropriate dosage adjustments were made in hospitalized patients with renal impairment. METHODS: A prospective cross-sectional study was carried out in the internal medicine wards of Tikur Anbessa Specialized Hospital. All patients with creatinine clearance ≤ 59 ml/min admitted to hospital between April and July, 2013 were included in the analysis. Data regarding serum creatinine level, age, sex and prescribed drugs and their dosage was collected from the patients' medical records. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The estimated creatinine clearance was calculated using the Cockcroft- Gault (CG) equation. Guideline for Drug prescribing in renal failure provided by the American College of Physicians was used as the standard for dose adjustment. RESULTS: Nine percent (73/810) of medical admissions were found to have renal impairment (CrCl ≤ 59 ml/min). There were 372 prescription entries for 73 patients with renal impairment. Dose adjustment was required in 31 % (115/372) of prescription entries and fifty eight (51 %) prescription entries requiring dose adjustment were found to be inappropriate. Of 73 patients, 54 patient received ≥ 1 drug that required dose adjustment (median 2; range 1-6). Fifteen (28 %) patients had all of their drugs appropriately adjusted while twenty two (41 %) patients had some drugs appropriately adjusted, and seventeen (31 %) of patients had no drugs appropriately adjusted. No patients were documented to have received dialysis. CONCLUSION: The findings indicate that dosing errors were common among hospitalized patients with renal impairment. Improving the quality of drug prescription in patients with renal impairment could be of importance for improving the quality of care.

In Vivo anti-trypanosomal activity of dichloromethane and methanol crude leaf extracts of Dovyalis abyssinica (Salicaceae) against Trypanosoma congolense.

BACKGROUND: African trypanosomiasis affects both humans and livestock in sub-Saharan countries including Ethiopia. Due to limitations to current chemotherapy, there is an urgent need for the development of new, safe, cheap and effective drugs. In the present study, the leaf of Dovyalis abyssinica was tested for its in vivo antitrypanosomal activity against Trypanosoma congolense field isolate on mice. METHODS: The leaf of D. abyssinica was macerated using dichloromethane and methanol. The extracts at doses of 250, 200, 150 and 100 mg/kg body weight were administered intraperitonealy daily for 7 days to mice infected with T. congolense. Following administration, parasitemia, packed cell volume, rectal temperature, body weight and survival time were monitored. RESULTS: Administration of dichloromethane and methanol extracts at 250 and 200 mg/kg reduced (p<0.05) parasitemia and rectal temperature, and improved (p<0.05) PCV, mean body weight, and mean survival time compared to dimethylsulfoxide treatment. CONCLUSION: Crude dichloromethane and methanol leaf extracts of D. abyssinica displayed anti-trypanosomal activity that may serve as lead for the development of effective alternative antitrypanosomal drugs.

Evaluation of anxiolytic activity of the essential oil of the aerial part of Foeniculum vulgare Miller in mice.

BACKGROUND: Foeniculum vulgare locally known as ensilal, is an aromatic plant widely cultivated in temperate and tropical regions. The anti-anxiety activity of the crude extract of F. vulgare has been reported. However, the fraction responsible for anxiolytic activity is not known and there is no any report on the anti-anxiety activity of the essential oil of F. vulgare. The objective of study was to evaluate the anxiolytic activity of the essential oil of Foeniculum vulgare Miller. METHODS: Adult Swiss albino male mice were randomly divided into six groups (n = 6). Groups I and II received Tween 80 (5%, v/v) and diazepam (0.5 mg/kg, ip), respectively, while groups III to V received orally 50, 100, and 200 and 400 mg/kg doses of the essential oil of F. vulgare, respectively. The mice were then individually placed in animal anxiety models: elevated plus maze (EPM), staircase test (SCT) and open field test (OFT) and evaluated for various parameters. RESULTS: In EPM test, 100 and 200 mg/kg doses of the essential oil significantly increased percent number of entries and time spent in open arms compared to control. In SCT these doses also reduced rearing significantly compared to controls, while only the 200 mg/kg dose significantly increased number of squares crossed at the center in the OFT test. CONCLUSION: The essential oil of F. vulgare was found to exhibit a promising anxiolytic activity.

Evaluation of in vivo antitrypanosomal activity of crude extracts of Artemisia abyssinica against aTrypanosoma congolense isolate.

BACKGROUND: African trypanosomiasis is a major disease of economic and public health importance affecting agricultural and human development. The search for alternative compounds against African trypanosomiasis is justified by various limitations of existing chemotherapeutic agents. This study was aimed at screening the hydromethanolic and dichloromethane (DCM) crude extracts of aerial parts of Artemisia abyssinica for in vivo antitrypanosomal activity against Trypanosoma congolense isolate in mice. METHODS: The aerial parts of the plant were extracted by maceration technique using dichloromethane and 80% methanol to obtain the corresponding crude extracts. The plant extracts at doses of 100, 200 and 400 mg/kg body weight were administered intraperitoneally daily for 7 days to mice infected with Trypanosoma congolense. Diminazene aceturate and distilled water were used as positive and as negative controls respectively. The level of parasitaemia, body weight, packed cell volume, differential leukocyte counts and mean survival period were monitored. RESULTS: The study showed that the DCM extract at 200 and 400 mg/kg, and the hydromethanolic extract at 400 mg/kg reduced parasitaemia (p < 0.05), ameliorated anaemia (p < 0.05), prevented body weight loss (p < 0.05) and resulted in significant increase in neutrophil levels (p < 0.05) and marked decrease in lymphocyte levels (p < 0.05) compared to the negative control. CONCLUSIONS: This study established that aerial parts of A. abyssinica have antitrypanosomal potential and can be considered a potential source of new drugs for the treatment of tropical diseases caused by trypanosomes.

Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus.

Background: Despite its widespread use and favored profile, there are extensive variations in the treatment outcome of metformin therapy. Furthermore, studies reported that the inter-individual variability in the occurrence of metformin treatment associated side effects were related to the differences in individual genetic profiles. Thus, this study aimed to evaluate whether the reduced function methionine deletion at codon 420 (Met420del) variant of SLC22A1 (rs72552763) is associated with metformin induced gastrointestinal intolerance in Ethiopian patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A retrospective observational study was conducted on 47 T2DM patients on metformin treatment for <3 years to assess the association of SLC22A1 (rs72552763) polymorphism with metformin induced gastrointestinal intolerance. Accordingly, 24 metformin tolerant and 23 metformin intolerant individuals with T2DM were recruited. Genotyping of rs72552763 was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association to metformin induced gastrointestinal intolerance was assessed based on switching to a new class of glucose lowering agents or failure to up titrate dose due to metformin induced gastrointestinal intolerance. Chi-square, logistic regression and Mann-Whitney statistical tests were used as appropriate. Statistical significance was set at p < 0.05. Results: In our study, no significant association was observed between rs72552763 and metformin induced gastrointestinal intolerance. We found that the female gender and physical inactivity were risk factors for metformin gastrointestinal intolerance. Conclusion: Our study found that the Met420del variant of SLC22A1 (rs72552763) was not associated with metformin induced gastrointestinal intolerance in Ethiopian patients with T2DM. This is the study first to investigate the association of rs72552763 with metformin intolerance in the Ethiopian population with T2DM. However, the findings need to be cautiously interpreted given the relatively small sample size. In addition, a more complete investigation of SLC22A1 variants would be required to fully assess the effect of the gene on metformin induced gastrointestinal intolerance as several variants with a more severe loss of function have been described.

Assessment Practices of Learning Outcomes of Postgraduate Students in Biomedical and Pharmaceutical Sciences at College of Health Sciences at Addis Ababa University: Student and Faculty Perspectives.

Introduction: Higher education institutions are under increasing pressure to respond to societal needs which has in turn led to changes in the type of knowledge, competencies, and skills required from learners. Assessment of student learning outcomes is the most powerful educational tool for guiding effective learning. In Ethiopia, studies are scarce on assessment practices of learning outcomes of postgraduate students in biomedical and pharmaceutical sciences. Objective: This study investigated the assessment practices of learning outcomes of postgraduate students pursuing studies in biomedical and pharmaceutical sciences at the College of Health Sciences of Addis Ababa University. Methods: A quantitative cross-sectional study was conducted using structured questionnaires administered to postgraduate students and teaching faculty members in 13 MSc programs in biomedical and pharmaceutical sciences at the College of Health Sciences of Addis Ababa University. About 300 postgraduate and teaching faculty members were recruited with purposive sampling. The data collected included assessment methods, types of test items, and student preferences on assessment formats. Data were analyzed using quantitative approaches, descriptive statistics, and parametric tests. Results: The study indicated that several assessment strategies and test items were practiced without a significant difference across fields of study. Regular attendance, oral questioning, quiz, group and individual assignments, seminar presentations, mid-term tests, and final written examination were commonly practiced assessment formats, while short question and long question essays were the most commonly used test items. However, students were not commonly assessed for skills and attitude. The students indicated they mostly preferred short essay questions, followed by practical-based examinations, long essay questions, and oral examination. The study identified several challenges to continuous assessment. Conclusion: Practice of assessing students' learning outcomes involves multiple methods focusing on assessing mainly knowledge; however, the assessment of skills appears inadequate, and several challenges appear to be hindering implementation of continuous assessment.

Cardiometabolic syndrome in HIV-positive and HIV-negative patients at Zewditu Memorial Hospital, Addis Ababa, Ethiopia: a comparative cohort study.

Cardiometabolic syndrome (CMetS) has recently emerged as a serious public health concern, particularly for individuals living with chronic conditions. This study aimed to determine the incidence and prevalence of CMetS, as well as the risk factors linked with it, in HIV-positive and HIV-negative adult patients. Methods: A comparative cohort study was designed. The National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools were used to determine the outcome variables. Association studies were done using logistic regression. Result: CMetS was found to have a greater point and period prevalence, and incidence estimation in HIV-negative than HIV+ patients using both the NCEP and the IDF tools. Using the NCEP tool, the risk of obesity was 44.1% [odds ratio (OR) = 0.559, 95% confidence interval (CI), (0.380-0.824); P = 0.003] lower in HIV+ than in HIV-negative participants. By contrast, no apparent difference was noted using the IDF tool. Similarly, hyperglycemia [OR = 0.651, 95% CI (0.457-0.926); P = 0.017], and hypertension [OR = 0.391, 95% CI (0.271-0.563); P < 0.001] were shown to be lower in HIV+ patients than HIV-negative patients by 34.9% and 60.9%, respectively. The study revealed significant variation in all biomarkers across the follow-up period in both HIV+ and HIV-negative participants, except for SBP. Conclusions: CMetS caused more overall disruption in HIV-negative people with chronic diseases than in HIV-positive people. All of the indicators used to assess the increased risk of CMetS were equally meaningful in HIV+ and HIV-negative subjects.

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes.

Objective: This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05. Results: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level. Conclusion: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

In vitro antibacterial and antifungal activities of extracts and fractions of leaves of Ricinus communis Linn against selected pathogens.

INTRODUCTION: Infectious disease impacts are reduced due to the development of antimicrobial agents. However, the effectiveness of antimicrobial agents is reduced over time because of the emergence of antimicrobial resistance. To overcome these problems, scholars have been searching for alternative medicines. Ricinus communis is used as a traditional treatment for bovine mastitis, wound infection, and other medicinal purposes. OBJECTIVE: The objective of the present study was to further evaluate the antimicrobial activities of R. communis leaf extracts and fractions. METHODS: R. communis leaves were macerated in methanol and acetone. The methanol extract showed better antimicrobial activity and subjected to further fractionation via increasing polarity of solvents (n-hexane, chloroform, ethyl acetate, and aqueous). Test microorganisms included in the study were six laboratory reference bacteria (Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, Kleibsella pneumoniae, Pseudomonas aeruginosa and Streptococcus pyogenes), two clinical isolate bacteria (E. coli and S. aureus), and Candida albicans. The agar well diffusion method was employed to determine antimicrobial activity. The minimum inhibitory concentrations (MIC) and minimum bactericidal/fungicidal concentrations (MBC/MFC) were determined through broth microdilution. RESULTS: The results indicated that the best antimicrobial activity for ethyl acetate fraction ranged from 14.67 mm (clinical E. coli) to 20.33 mm (S. aureus) at 400 mg/ml, however, n-hexane exhibited the lowest antimicrobial activity. Among the tested fractions, ethyl acetate fraction showed the lowest MIC values ranged from 1.5625 mg/ml (S. aureus) to 16.67 mg/ml (Candida albicans). The ethyl acetate fraction showed bactericidal activity against all tested microorganisms. CONCLUSION: Hence, ethyl acetate fraction of crude methanol extract exhibited the best antimicrobial activity.

Biomarkers and Prevalence of Cardiometabolic Syndrome Among People Living With HIV/AIDS, Addis Ababa, Ethiopia: A Hospital-Based Study.

BACKGROUND: While the fast extension of combination antiretroviral therapy (cART) has resulted in significant increases in life expectancy, disorders such as cardiometabolic syndrome (CMetS), which have received less attention, are becoming a major concern in HIV/AIDS patients (PLWHA). OBJECTIVES: The purpose of this research was to identify biomarkers and determine the prevalence of CMetS in PLWHA using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools. METHODS: Between January 2019 and February 2021, a hospital-based study of HIV-infected patients (n = 288) was conducted. The data were analyzed using binary logistic regression. To control the effect of confounders, independent variables with a P-value of <.20 in the bivariate logistic regression were incorporated into multivariate logistic regression. Statistical significance was defined as a 95% confidence interval and a P-value of less than .05. RESULTS: The risk of CMetS increased twofold as age increased each year (P = .009), 1.2 times as the age at which cART began increased (P = .015), and 6 times with 1 or more co-morbidities (P = .028), according to the NCEP tool. Furthermore, significant NCEP-CMetS correlations were produced by a rise in diastolic blood pressure (P < .001) and cART duration (P = .006). Male gender was 99.9% less likely to be related to CMetS using the IDF tool, and the risk of CMetS increased fourfold with each unit increase in waist circumference (P < .001). Triglycerides and blood type "A" have been found to have substantial relationships with CMetS using both techniques. CONCLUSION: According to the study, CMetS was found to be common in PLWHA. Age, time on cART, age when cART started, gender, co-morbidities, waist circumference, and diastolic blood pressure were all revealed to be significant predictors of CMetS. Triglycerides and blood type "A" were the only biomarkers found to be significant with CMetS using both the NCEP and IDF tools.