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.

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.

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.

Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multidrug-Resistant Tuberculosis.

Objective: This study aimed to explore the population pharmacokinetic modeling (PopPK) of levofloxacin (LFX) and moxifloxacin (MXF), as well as the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24 h and the in vitro minimum inhibitory concentration (AUC0-24/MIC) in Ethiopian multidrug resistant tuberculosis (MDR-TB) patients. Methods: Steady state-plasma concentration of the drugs in MDR-TB patients were determined using optimized liquid chromatography-tandem mass spectrometry. PopPK and simulations were run at various doses, and pharmacokinetic parameters were estimated. The effect of covariates on the PK parameters and PTA for maximum mycobacterial kill and resistance prevention was also investigated. Results: LFX and MXF both fit in a one-compartment model with adjustments. Serum-creatinine (Cr) influenced (p = 0.01) the clearance of LFX, whereas body mass index (BMI) influenced (p = 0.01) the apparent volume of distribution (V) of MXF. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L with the simulated 750 mg, 1000 mg, and 1500 mg doses were 29%, 62%, and 95%, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no change in the PTA for maximum bacterial kill when the MXF dose was increased (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention was improved. Conclusion: The standard doses of LFX and MXF may not provide adequate drug exposure. PopPK of LFX is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Cr and BMI are likely important covariates for dose optimization in Ethiopian patients.

CYP3A and CYP2B6 Genotype Predicts Glucose Metabolism Disorder among HIV Patients on Long-Term Efavirenz-Based ART: A Case-Control Study.

Long-term antiretroviral treatment (cART) increases the risk of glucose metabolism disorders (GMDs). Genetic variation in drug-metabolizing enzymes and transporters may influence susceptibility to cART-associated GMDs. We conducted a case-control study to investigate the association of pharmacogenetic variations with cART-induced GMDs. A total of 240 HIV patients on long-term efavirenz-based cART (75 GMD cases and 165 controls without GMDs) were genotyped for CYP3A4*1B, CYP3A5 (*3,*6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). GMD cases were defined as the presence of impaired fasting glucose, insulin resistance, or diabetes mellitus (DM). Case-control genotype/haplotype association and logistic regression analysis were performed by adjusting for age, sex, and BMI. The major CYP3A haplotype were CYP3A5*3 (53.8%), CYP3A4*1B (17.3%), combinations of CYP3A4*1B, and CYP3A5*6 (10.9%), and CYP3A wild type (7%). CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Multivariate analysis indicated CYP3A haplotype as a significant predictor of GMD (p = 0.02) and IFG (p = 0.004). CYP2B6*6 significantly predicted DM (p = 0.03). CYP3A haplotype and CYP2B6*6 genotype are independent significant predictors of GMD and DM, respectively, among HIV patients on long-term EFV-based cART.

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.

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.

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.

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.

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.

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.

Evaluation of Anticonvulsant Activity of 80% Methanolic Root Bark Extract and Solvent Fractions of Pentas schimperiana (A. Rich.) Vatke (Rubiaceae) in Swiss Albino Mice.

BACKGROUND: Epilepsy is one of the most common serious neurological disorders, responsible for substantial morbidity and mortality due to limited efficacy and negative properties of antiepileptic drugs. Medicinal plants are believed to be an important source of new chemical substances with potential therapeutic effects. Pentas schimperiana (A. Rich.) Vatke is a medicinal plant used in Ethiopian traditional medicine for the treatment of epilepsy. However, it lacks scientific investigation on its anticonvulsant activity. Therefore, this study was conducted to evaluate the anticonvulsant activity of 80% methanol root bark extract and solvent fractions of Pentas schimperiana (A. Rich.) Vatke in mice. METHODS: Anticonvulsant activity was evaluated by using the pentylenetetrazole and maximal electroshock-induced seizure test. The 80% methanolic root bark extract was subjected to successive fractionation with solvents differing polarity, i.e., chloroform, butanol, and water. The test groups received 100, 200, and 400 mg/kg bodyweight of extract and its solvent fractions. RESULT: The ME400 and BF400 at the higher dose exhibited a significant (p < 0.001) anticonvulsant effect in both the pentylenetetrazole and maximal electroshock-induced seizure test compared with control. However, chloroform fraction only showed a significant (p < 0.001) anticonvulsant effect in the PTZ-induced seizure test, while aqueous fraction had least anticonvulsant activity in both seizure-induced tests. Phytochemical screening of Pentas schimperiana (A. Rich.) Vatke root bark extract revealed the presence of alkaloids, saponins, flavonoids, phenols, steroids, terpenoids, and tannins. CONCLUSION: This study indicated that the plant has anticonvulsant activity and is considered as a potential source to develop a new antiepileptic drug.

Impact of medication therapy management service on selected clinical and humanistic outcomes in the ambulatory diabetes patients of Tikur Anbessa Specialist Hospital, Addis Ababa, Ethiopia.

BACKGROUND: Diabetes mellitus (DM) patients are at increased risk of developing drug therapy problems (DTPs). The patients had a variety of comorbidities and complications, and they were given multiple medications. Medication therapy management (MTM) is a distinct service or group of services that optimize therapeutic outcomes for individual patients. The study assessed the impact of provision of MTM service on selected clinical and humanistic outcomes of diabetes patients at the diabetes mellitus clinic of Tikur Anbessa Specialized Hospital (TASH). METHODS: A pre-post interventional study design was carried out at DM clinic from July 2018 to April 2019. The intervention package included identifying and resolving drug therapy problems, counseling patients in person at the clinic or through telephone calls, and providing educational materials for six months. This was followed by four months of post-intervention assessment of clinical outcomes, DTPs, and treatment satisfaction. The interventions were provided by pharmacist in collaboration with physician and nurse. The study included all adult patients who had been diagnosed for diabetes (both type I & II) and had been taking anti-diabetes medications for at least three months. Patients with gestational diabetes, those who decided to change their follow-up clinic, and those who refused to participate in the study were excluded. Data were analyzed using Statistical Package for the Social Sciences (SPSS). Descriptive statistics, t-test, and logistic regressions were performed for data analyses. RESULTS: Of the 423 enrolled patients, 409 fulfilled the criteria and included in the final data analysis. The intervention showed a decrease in average hemoglobin A1c (HbA1c), fasting blood sugar (FBS), and systolic blood pressure (SBP) by 0.92%, 25.04 mg/dl, and 6.62 mmHg, respectively (p<0.05). The prevalence of DTPs in the pre- and post-intervention of MTM services was found to be 72.9% and 26.2%, respectively (p<0.001). The overall mean score of treatment satisfaction was 90.1(SD, 11.04). Diabetes patients of age below 40 years (92.84 (SD, 9.54)), type-I DM (93.04 (SD, 9.75)) & being on one medication regimen (93.13(SD, 9.17)) had higher satisfaction score (p<0.05). CONCLUSION: Provision of MTM service had a potential to reduce DTPs, improve the clinical parameters, and treatment satisfaction in the post-intervention compared to the pre-intervention phase.

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.

Efficacy and Safety of Artemisinin-Based Combination Therapy for the Treatment of Uncomplicated Malaria in Pregnant Women: A Systematic Review and Meta-Analysis.

INTRODUCTION: Malaria is one of the infectious diseases with substantial risks for pregnant women, the fetus and the newborn child. Thus, prevention and treatment of malaria with safe and effective drugs is of paramount importance. Pregnant women are mostly excluded from clinical trials, and systematic approaches of pharmacovigilance in pregnancy are limited. This means the safety and efficacy of antimalarial agents during pregnancy are unclear. PURPOSE: This study was designed to carry out a systematic review and aggregate data meta-analysis of literature published on efficacy and safety of artemisinin-based combination therapy (ACT) for uncomplicated malaria in pregnant women. METHODS: A search of literature published between 1998 to 2020 on efficacy and safety of artemisinin-based combination therapy (ACT) in pregnant women was made using Cochrane Library, Medline and the Malaria in Pregnancy Consortium Library. Data were extracted independently by two reviewers, and any discrepancies were resolved by consensus. Meta-analysis was carried out using Open Meta-Analyst software. Random effects model was applied, and the heterogeneity of studies was evaluated using Higgins I2. RESULTS: Twenty-four studies that fulfilled the inclusion criteria were included in the final assessment. Overall, days 28 to 63 malaria treatment success rate was 96.1%. Overall days 28 to 63 cure rates for AL, AS+AQ, AS+MQ, DHA+PQ, AS+ATQ+PG and AS+SP were 95.1%, 92.2%, 97.0%,94.3%, 96.5% and 97.4%, respectively. Comparison of ACTs with non-ACTs revealed that the risk of treatment failure was substantially lower in patients treated with ACTs than with non-ACTs (risk ratio 0.20, 95% C.I. 0.09-0.43). The overall prevalences of miscarriage, stillbirth and congenital anomalies were 0.3%, 2.1% and 1.0%, respectively, and found to be comparable among various ACTs. There was comparable tolerability across ACTs during pregnancy. CONCLUSION: ACTs demonstrated a high cure rate, safety and tolerability against Plasmodium falciparum infection in pregnant women. The higher treatment success and comparable tolerability could be used as an input for decision makers to support the continued usage of ACTs for treatment of uncomplicated falciparum malaria in pregnant women.

Explorative Analysis of Treatment Outcomes of Levofloxacin- and Moxifloxacin-Based Regimens and Outcome Predictors in Ethiopian MDR-TB Patients: A Prospective Observational Cohort Study.

PURPOSE/BACKGROUND: Although Ethiopia is among the thirty high multi-drug resistant tuberculosis (MDR-TB) burden countries in the world, comparative therapeutic efficacy of moxifloxacin and levofloxacin has not been explored, particularly in MDR-TB patients. We therefore aimed to prospectively compare clinical outcomes and determine potential predictors of the outcomes among patients on moxifloxacin or levofloxacin-based MDR-TB drug regimens. METHODS: We analyzed clinical parameters and laboratory data of eighty MDR-TB patients on moxifloxacin- or levofloxacin-based regimens. The clinical outcomes were compared using the Kaplan-Meier survival functions and the outcome definitions of the 2013 World Health Organization. Monthly sputum culture conversions and a molecular line probe assay results were also assessed. Observed outcomes and patient-related variables between the two groups were compared using chi-square, Wilcoxon Rank and Fisher exact tests. We also determined the potential predictors influencing treatment outcomes of moxifloxacin and levofloxacin using Cox proportional hazard model. RESULTS: The levofloxacin-based treatment group had a lower failure rate and adverse drug events as well as better treatment success than the moxifloxacin-based group. Overall treatment success was 65%. Disaggregating the data revealed that 53.8% were cured, 11.2% completed treatment, 10.0% died, 11.2% failed, and 13.8% were lost-to-follow-up. The line probe assay result showed that 11.3% of the clinical isolates were resistant to fluoroquinolones and 3.8% were resistant to both fluoroquinolones and injectable anti-TB agents. Treatment regimen type, culture conversion rate, alcohol use, cavity lesion, serum levels of creatinine and alanine aminotransferase were independent predictors of treatment outcome. CONCLUSION: The levofloxacin-based regimen group has a better overall treatment success than the moxifloxacin-based group among MDR-TB patients. Clinical parameters and substance use history of the patients influenced treatment outcomes. We recommend further broader clinical studies to substantiate our findings as an input to review MDR-TB treatment guidelines.

Management of hospital-acquired infections among patients hospitalized at Zewditu memorial hospital, Addis Ababa, Ethiopia: A prospective cross-sectional study.

BACKGROUND: Hospital-Acquired Infections (HAIs) are acquired when the patient is hospitalized for more than 48 hours. In Ethiopia data are scarce in management appropriateness of HAIs. Hence, this study was aimed to assess the prevalence and management of HAIs among patients admitted at Zewditu Memorial Hospital. METHOD: A facility based prospective cross sectional study was conducted from March 1, 2017 to August 30, 2017. The sample was proportionally allocated among (medical, pediatrics, gynecology and obstetrics and surgical) wards, based on patient flow. Data were collected using data abstraction format and supplemented by key informant interview. Interview was made on eight physicians and four microbiologists who have been working in the wards during study period. Management appropriateness was assessed using Infectious Disease Society of America guideline and experts opinion (Infectious disease specialist). A multivariate logistic regression was used to identify factors associated with HAIs. RESULT: The prevalence of HAIs was 19.8%. Surgical Site Infection (SSI) and pneumonia accounted for 20 (24.7%) of the infections. Culture and sensitivity was done for 24 (29.6%) patients. Of the 81 patients who developed HAIs, 54 (66.67%) of them were treated inappropriately. Physicians' response for this variation was information gap, forgetfulness, affordability and availability issue of first line medications. Younger age (AOR (Adjusted odds ratio) = 8.53, 95% CI: 2.67-27.30); male gender (AOR = 2.06, 95% CI: 1.01-4.22); longer hospital stay (AOR = 0.17, 95% CI: 0.06-0.51); and previous hospital admission (AOR = 3.22, 95% CI: 1.76-5.89); were independent predictors of HAIs. CONCLUSION: Prevalence of HAIs and inappropriate management were substantially high in this study. Pneumonia and SSI were the common types of HAIs. Locally conformable guidelines could help to correct such problems.

Surgical Antimicrobial Prophylaxis and Incidence of Surgical Site Infections at Ethiopian Tertiary-Care Teaching Hospital.

BACKGROUND: Surgical site infections (SSIs) are infections that develop within 30 days after an operation or surveillance of surgical wound infection implementation within 90 days after surgery when an implant is placed. The objective of this study was to assess preoperative and postoperative antimicrobial use in St. Paul's Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia. METHODS: A hospital-based cross-sectional study was undertaken in surgery wards of SPHMMC for 4 months by reviewing 413 patients' charts. All patients 13 years and older who were admitted and underwent different types of surgical procedures were included in the study. Epi info 7 was used for data entry, and then data were exported to Statistical Package for Social Sciences (SPSS) version 20.0 software for analysis. Descriptive analyses were computed and rate of SSI was calculated in this study. Moreover, bivariate analysis was done to examine the relationship between the outcome variable and predictor variables with a value of P < .2 retained for subsequent multivariate analyses using multiple logistic regressions. P value of <.05 was considered as statistically significant. RESULTS: Out of 413 patients, 152 (36.8%) were operated for general surgery, and the remaining were for other types of surgeries. Most of the patients, 196 (79.7%), were managed by a single surgical antibiotic agent, followed by 2 agents (20.3%) for surgical prophylaxis indication. Surgical site infections occurred in 46 (11.1%) patients before discharge from the hospital. In those patients who need treatment for SSIs, almost half of them (49.5%) received combination therapy of ceftriaxone and metronidazole. Emergency surgical cases were 2.647 times more likely to develop SSIs than the elective surgical cases (adjusted odds ratio [AOR] = 2.647; 95% confidence interval [CI] = 1.406-4.983; P = .003). Patients who did not receive antibiotic prophylaxis were 2.572 times more likely to develop SSIs compared to those who received antibiotic prophylaxis (AOR = 2.572; 95% CI = 1.02-6.485; P = .045). Clean-contaminated and contaminated types of wound were a protective factor against SSI in our study. CONCLUSIONS: This study indicated that most of the patients (72.1%) received surgical antimicrobial prophylaxis. The overall incidence rate of SSIs was 11.1% in the studied hospital. Ceftriaxone was the most commonly used drug. Being not receiving prophylaxis, wound class, and surgery types were significantly associated with the development of SSI.

Drug therapy problems, medication adherence and treatment satisfaction among diabetic patients on follow-up care at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

BACKGROUND: Patients with diabetes are at high risk of drug therapy problems (DTPs), as they are receiving multiple medications. To date, studies regarding DTPs in patients with diabetes in Ethiopia are limited. The aim of this study was to assess prevalence of DTPs, medication adherence and treatment satisfaction of patients with diabetes at Tikur Anbessa Specialized Hospital (TASH). METHOD: A cross-sectional study was conducted on randomly selected 418 participants who fulfilled the inclusion criteria. Data were collected using structured questionnaire and patients' chart review. Cipolle's classification system was used to determine DTPs. Modified Morisky's Adherence Scale (MMAS-8) was used to measure patients' adherence to their medication. Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) patient satisfaction assessment questionnaire was used to assess patients' treatment satisfaction. RESULTS: A total of 207 DTPs in 177 (42.3%) of participants were identified. Commonly identified DTPs were dosage too low (58, 28.0%), ineffective drug therapy (54, 26.1%), and need additional drug therapy (52, 25.1%). Factors associated with DTPs were female gender (Adjusted Odds Ratio [AOR] = 2.31,95% CI:1.30-4.12); ≥3comorbidities (AOR = 3.61, 95% CI:1.19-10.96); ever married (AOR = 2.58,95% CI:1.23-5.48); type 2 diabetes (AOR = 5.62, 95% CI:1.21-26.04); non-adherence (AOR = 5.26,95% CI:2.51-11.04) and residence out of Addis Ababa (AOR = 0.30, 95% CI:0.12-0.73). Twenty four percent of participants were non-adherent to their drug therapies. Factors associated with non-adherence were diabetes complications (AOR = 2.00, 95% CI: 1.2-3.32), the female gender (AOR = 1.67, 95%CI: 1.01-2.8) and level of education (AOR = 0.42, 95%CI: 0.18-0.96). Eighty one percent of participants were satisfied with the current treatment. CONCLUSION: A significant proportion of patients were satisfied with their treatment and a quarter of the study participants were non-adherent to their medications at TASH diabetic clinic. However, DTPs were considerably higher among the study participants. Hence, future interventions targeting prevention and resolution of DTPs deemed to be necessary.