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Bekalu Amare Tesfaye, Abera Hadgu Berhe, Dawit Zewdu Wondafrash, Derbew Fikadu Berhe Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Derbew Fikadu Berhe Email derakorem@gmail.comBackground: Globally, cardiovascular diseases (CVDs) are becoming the major cause of death. Urtica simensis is one of endogenous plant which treats a wide range of disease conditions including heart diseases. However, there is limited information on safety and efficacy of the plant.Objective: To evaluate the in vitro antioxidant, the in vivo cardioprotective activity of crude extract and solvent fractions of Urtica simensis leaves on cyclophosphamide-induced myocardial injury.Methods: The cardioprotective activity of the crude extract, aqueous and hexane fraction of Urtica simensis leaves was evaluated based on anatomical, biochemical and histopathological methods. The in vitro antioxidant activity of the plant was also assayed in terms of free radical scavenging activity (RSA).Results: Crude extract and solvent fractions of Urtica simensis significantly prevented the deleterious effect of cyclophosphamide on body weight (P< 0.001), heart weight to body ratio (P< 0.01), cardiac biomarkers including troponin I (P< 0.01), alanine transaminase (ALT) (P< 0.001), aspartate aminotransferase (AST) (P< 0.01) and lipid profiles including triglycerides (P< 0.001) and total cholesterol (P< 0.01). The histopathological study confirmed presence of necrosis, oedema and haemorrhage on cyclophosphamide alone-treated groups while the 200mg/kg and 400mg/kg of the crude extract and aqueous fraction showed normal cardiocytes. The antioxidant assay of Urtica simensis plant exhibited free radical scavenging activity of inhibitory concentration of 50% (IC50) for the crude extract with the values of 63.27μg/mL, aqueous fraction with the values of 136.38μg/mL and hexane fraction with the values of 258.70μg/mL.Conclusion: Crude extract and solvent fractions of Urtica simensis leaves have cardioprotective activities. The cardioprotective effect could be attributed to the antioxidant activity of the plant extracts. However, this requires further in-depth understanding.Keywords: cardioprotective, cardiac biomarkers crude extract, cyclophosphamide, solvent fractions, Urtica simensis

Bekalu Amare Tesfaye, Haftom Gebregergs Hailu, Kaleab Alemayehu Zewdie, Muluken Altaye Ayza, Derbew Fikadu Berhe Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Haftom Gebregergs Hailu Tel +251912085606Fax +251344416681Email haftomphar@gmail.comAbstract: Currently, there is no definitive cure for epilepsy. The available medications relieve symptoms and reduce seizure attacks. The major challenge with the available antiepileptic medication is safety and affordability. The repurposing of montelukast for epilepsy can be an alternative medication with a better safety profile. Montelukast is a leukotriene receptor antagonist that binds to the cysteinyl leukotrienes (CysLT) receptors used in the treatment of bronchial asthma and seasonal allergies. Emerging evidence suggests that montelukast’s anti-inflammatory effect can help to maintain BBB integrity. The drug has also neuroprotective and anti-oxidative activities to reduce seizure incidence and epilepsy. The present review summarizes the neuropharmacological actions of montelukast in epilepsy with an emphasis on the recent findings associated with CysLT and cell-specific effects.Keywords: repurposing, seizure, inflammation, cysteinyl leukotriene receptors

Muluken Altaye Ayza, Kaleab Alemayehu Zewdie, Bekalu Amare Tesfaye, Selamawit Tesfamariam Gebrekirstos, Derbew Fikadu Berhe Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Muluken Altaye Ayza Tel +251-916707913 Email Mulealto1@gmail.comAbstract: Telmisartan is an angiotensin II receptor antagonist, which selectively inhibits the angiotensin II type 1 receptor. Thus, it is widely used for hypertension management. Nowadays, telmisartan’s effect on peroxisome proliferator-activated receptors (PPARs) is gaining wider attention. PPARs are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Telmisartan is reported to have a partial PPARγ-agonistic effect while avoiding the safety concerns found with full PPARγ agonists (thiazolidinediones). Telmisartan could be an alternative treatment option, with dual benefit for diabetes mellitus (DM) and hypertension. This review summarizes the anti-diabetic activity of telmisartan via its partial PPARγ-agonistic activity.Keywords: diabetes mellitus, hypertension, peroxisome proliferator-activated receptors, telmisartan

Kaleab Alemayehu Zewdie, Muluken Altaye Ayza, Bekalu Amare Tesfaye, Dawit Zewdu Wondafrash, Derbew Fikadu Berhe Department of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, Mekelle, EthiopiaCorrespondence: Kaleab Alemayehu ZewdieDepartment of Pharmacology and Toxicology, School of Pharmacy, Mekelle University, P.O. Box: 1871, Mekelle, EthiopiaTel +251921546562Email kalxy2919@gmail.comBackground: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED.Methods: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics.Results: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failure-induced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and age-related ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase.Conclusion: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.Keywords: ROCK, Rho-kinase inhibitors, novel, therapeutic target, erectile dysfunction

Mulugeta Mihrete Tefera,1,2 Birhanetensay Masresha Altaye,2,3 Ebrahim M Yimer,2,4 Derbew Fikadu Berhe,2 Senait Tadesse Bekele5 1Department of Pharmacy, Bahirdar Health Science College, Bahirdar, Ethiopa; 2Department of Pharmacology and Toxicology, College of Health Sciences, Mekelle University, Mekelle, Ethiopia; 3College of Medicine, Debre Berhan University, Debre Berhan, Ethiopia; 4Department of Pharmacy, College of Medical and Health Sciences,Wollo University, Dessie, Ethiopa; 5Medical Laboratory Department, Health Science College, Bahir Dar University, Bahir Dar, EthiopiaCorrespondence: Mulugeta Mihrete TeferaDepartment of Pharmacy, Bahirdar Health Science College Tel +251 92 835 1786 Email mihretetefera12@gmail.comBackground: Lens culinaris Medik seed has been used in traditional practices to treat various ailments, including diabetes mellitus, in Ethiopia. Previous phytochemical screening studies indicated that germination of the seed of L. culinaris contains more bioactive constituents compared to raw seeds. The aim of this study was to investigate the antidiabetic activity of an aqueous methanol extract of germinated L. culinaris seed extract in streptozotocin (Stz)-induced diabetic mice.Methods: The antidiabetic effect of germinated L. culinaris seed extract was determined using Stz-induced diabetic mice. An 80% aqueous methanol extract of germinated L. culinaris seed at doses of 100, 200, and 400 mg/kg was used in the treatment group. Glibenclamid (5 mg/kg) and dimethyl sulfoxide 2% were used as positive and negative controls, respectively. The test extract and controls were given daily for 3 weeks. Blood-glucose levels and body-weight changes were measured weekly. Lipid-profile levels were measured at the end of each experiment. Oral glucose-tolerance tests were performed to evaluate the postprandial effect of the extract.Results: The aqueous methanol extract of germinated L. culinaris significantly reduced blood-glucose levels and increased body weight (p< 0.05). The extract also improved serum-lipid profiles in diabetic mice after 21 days (p< 0.05). The seed extract also resulted in significant reductions in blood-glucose levels after an oral glucose load in normal mice (p< 0.05).Conclusion: An aqueous methanol extract of germinated L. culinaris seed has both antidiabetic and antihyperlipidemic effects.Keywords: Lens culinaris Medik, diabetes mellitus, mice

Desalegn Getnet Demsie,1,2 Ebrahim M Yimer,1 Abera Hadgu Berhe,1 Birhanetensay Masresha Altaye,3 Derbew Fikadu Berhe11Department of Pharmacology and Toxicology, College of Health Sciences, Mekelle University, Mekelle, Ethiopia; 2Department of Pharmacy, College of Medicine and Health Sciences, Adigrat University, Adigrat, Ethiopia; 3Department of Pharmacy, College of Medicine, Debre Berhan University, Debre Berhan, EthiopiaBackground: Societies in developing countries use traditional medicine as alternatives for management of pain and inflammation. The plant Cucumis ficifolius has been used in Ethiopia to treat many ailments including inflammation and pain. The objective of this study was to evaluate the antinociceptive and anti-inflammatory activities of the crude root extract and solvent fractions of C. ficifolius.Methods: The analgesic activity of crude extract and solvent fractions of C. ficifolius was evaluated with acetic acid-induced writhing, hot plate, and formalin-induced paw licking tests. The anti-inflammatory effect of crude methanolic root extract and solvent fractions of C. ficifolius was evaluated using carrageenan-induced paw edema. The crude extract was given at 200, 400 and 800 mg/kg. Butanol and aqueous fractions were given at 100 and 200 mg/kg doses. The negative control groups were treated with distilled water (10 mL/kg). Standard drugs used wereacetylsalicylic acid(ASA) in acetic acid, formalin tests and carrageenan-induced paw edema and morphine (20 mg/kg) in hot plate test.Results: The crude extract, at its maximum dose, produced comparable analgesic activity (72.5%) to ASA in acetic acid writhing test. In the hot plate test, both the crude extract and solvent fractions exhibited a significant prolongation of nociception reaction time. Formalin test result indicated a significant reduction of mean lick time with maximal protection of 64% (early phase) and 83% (late phase). Aqueous and butanol fractions showed good analgesic activity in the three models. Inflammation was decreased by 69% with butanol (200 mg/kg); 71% (800 mg/kg) of crude extract and by 41% and 56% with the use of aqueous fraction at 100 and 200 mg/kg, respectively (p

Objective: The objective of this scoping review was to explore and synthesize the available literature on health research mentorship in low- and middle-income countries (LMICs)., Introduction: Research mentorship is broadly considered a useful strategy to improve research capacities and research outputs. Existing literature and guidance on research mentorship have focused on high-income countries and assumed resource-rich environments. Despite the successful endeavors to improve health research capacity in LMICs, the strategies that work best under different circumstances are poorly understood. There is a need to map and understand the evidence on health research mentorship in the context of LMICs., Inclusion Criteria: Sources that reported existing practices, barriers, and mitigation strategies related to health research mentorship in LMICs were included., Methods: We searched for published and unpublished studies and reports written in English, Spanish, or Portuguese. The search strategy was not limited by search dates and the last search was conducted on January 28, 2022. The databases searched included MEDLINE (PubMed), Embase, Web of Science Core Collection, CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, and JBI Evidence Synthesis . We also searched for gray literature in a selection of websites and digital repositories. The JBI scoping review methodology was used., Results: A total of 77 studies and reports were included in the review. The majority of the papers were from Africa (n=28). Others were from the Americas (n=7), South East Asia (n=4), East Mediterranean (n=2), and Western Pacific (n=2). The remaining studies were from LMICs that included at least 2 regional offices. Most of the mentorship projects (n=55) were initiated and funded by institutions from high-income countries. The first authors of 41 papers were primarily affiliated with LMICs. The findings were categorized under a description of research mentorship practices, barriers related to research mentorship, and suggested mitigation strategies. Deliverable-driven training using intensive hands-on mentorship and ongoing peer mentorship programs were some of the non-regular, non-institutionalized approaches used to improve research capacity for junior researchers in LMICs. None of the included papers focused on institutional components of research mentorship in LMICs. The barriers to research mentorship activities in LMICs included lack of clarity on mentorship, cultural variations, unbalanced power dynamics, socio-political influences, language barriers, lack of experienced mentors, and limited local funding. Institutionalizing research mentorship, adapting mentoring methodologies relying on local resources, and addressing and respecting diversity in mentorship programs were among the main strategies identified to effectively implement research mentorship in LMICs., Conclusions: Research mentorship initiatives and practices are limited in LMICs. Few available practices have been introduced by researchers and research institutions from high-income countries and those that have are not yet institutionalized. The identified existing practices, barriers, and facilitators on health research mentorship could help the design, implementation, and evaluation of programs to institutionalize health research mentorship in LMICs., Review Registration: Open Science Framework osf.io/jqa9z/., Supplemental Digital Content: A Spanish-language version of the abstract of this review is available as supplemental digital content: http://links.lww.com/SRX/A32., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Background: Statin-induced myopathy is reported to be associated with the solute carrier organic anion transporter family member 1B1 gene single nucleotide polymorphism, c.521 T > C. There is no epidemiologic data on this gene polymorphism in several countries. Therefore, this study aimed at assessing the genotype and allele frequencies of the gene variant in three countries., Methods: This study involved healthy individuals from Colombia, Mozambique, and Portugal. Genomic DNA was isolated from blood samples using the Qiamp DNA Extraction Kit (Qiagen). The isolated DNA was genotyped using novel Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. Microstat and GraphPad QuickCal software were used for the Chi-square test and the evaluation of Hardy-Weinberg equilibrium respectively., Results: A total of 181 individuals' blood samples were analyzed. Overall, the TT (74.0%) genotype was the highest and the CC (7.8%) was the lowest. Country wise genotypic frequencies were Colombia 47(70.2%) TT, 12(17.9%) TC and 8(11.9%) CC; Mozambique 47(88.7%) TT, 5(9.4%) TC, and 1(1.9%) CC; and Portugal 40(65.6%) TT, 16(26.2%) TC, and 5(8.2%) CC. The reference (T) allele was highest among Mozambicans (93.4%) compared to Colombians (79.1%) and Portuguese (78.7%). Mozambicans showed statistically significant genotypic and allelic frequency differences compared to Colombians (p < 0.01) and Portuguese (p < 0.01)., Conclusions: Overall and country-wise, CC genotype was less frequent and it is relatively high for Colombians and Portuguese populations. This finding may imply statins risk-benefit variability associated with CC genotype among these populations that needs further understanding., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In developing nations with fragile healthcare systems, the effect of war is likely to be much worse than it would be in more developed countries. The presence of COVID-19 will also likely exacerbate the war's impact. This study set out to determine the effect of armed conflict and the COVID-19 pandemic on health service utilization at Ayder Comprehensive Specialized Hospital, in the Tigray region of Ethiopia., Methods: An interrupted time-series study design was used to analyze patient visits over forty-eight consecutive months (from July 2017 to June 2021) at inpatient, outpatient, and emergency departments. Data were analyzed using segmented regression analysis with a defined outcome of level and trend changes in the number of patient visits. In addition, negative binomial regression analysis was also used to estimate the impact of both COVID-19 and the war on patient flow., Results: There were 59,935 admissions, 876,533 outpatient visits, and 127,872 emergency room visits. The effect of COVID-19 was seen as soon as the Tigray regional government imposed comprehensive restrictions. Immediately after COVID-19 appeared, all the service areas exhibited a significant monthly drop in visits; [-35.6% (95% CI: -48.2%, -23.1%)] for inpatient, [-60.6% (95% CI: -71.6%, -49.5%)] for outpatient, and [-44.1% (95% CI: -59.5%, -28.7%)] for emergency department visits. The impact of the war became apparent after a lag time of one month. Controlling the effects of time and COVID-19, the war led to a significant fall in inpatient visits [-44.3% (95% CI: -67.2%, -21.5%)], outpatients [-52.1% (95% CI: -82.7%, -21.5%)], and emergency-room attendances [-45.0% (95% CI: -74.8%, -15.2%)]. An upward trend in outpatient flow was observed after the war [1,219.4 (95% CI: 326.1, 2,112.8)]., Conclusions: The present study has clearly indicated that the war and COVID-19 have led to a large reduction in admissions, outpatient attendance, and emergency department visits. The evidence from this study suggests that due to this double catastrophe, thousands of patients could not gain access to healthcare, with probable negative consequences. Governments and organizations should implement measures to buttress the healthcare system to maintain pre-war status of service., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: World Health Organization/Tropical Disease Research (WHO/TDR) has enduring investment in transfers of skills critical to sustaining resilient health research systems through postgraduate training, clinical research and development fellowship (CRDF), bioethics, and grants to neglected tropical disease research. TDR has a long history of partnership with Armauer Hansen Research Institute (AHRI) in Ethiopia. The collaboration started with individuals and lead to institution survival and success. Therefore, the purpose of this study was to explore the impact and lessons learned of TDR initiatives in Ethiopia., Method: This study was guided by the 'TDR Impact Pathways'. A total of thirteen in-depth, and five key informant interviews were conducted with individuals who are currently working in Addis Ababa, Gondar, Jimma Universities and AHRI. In addition to the interviews, reports, written communications and publications were reviewed. Interviews were audio recorded, transcribed verbatim, inductively coded, and analyzed thematically. The results were presented following the themes with supportive verbatim quotes., Conclusion: TDR's seed grants, training opportunities and technical support catalyzed individual, institutional and national research capacity in Ethiopia. This is a useful indication of how long-term collaboration between individuals could have broader institutional implication as evidenced from the TDR-AHRI complementary partnership., (© 2023. The Author(s).)

Background: Antimicrobial resistance is one of the major public health challenges in Ethiopia. However, there is no comprehensive summary of existing AMR data in the country., Aim: To determine the prevalence of antimicrobial resistance and its clinical implications in Ethiopia., Methods: A systematic literature search was performed on the PubMed/Medline database. Original studies on antimicrobial resistance conducted in Ethiopia between 1st January 2009 and 31st July 2019 were included. The outcome measure was the number of isolates resistant to antimicrobial agents in terms of specific pathogens, and disease condition. Data was calculated as total number of resistant isolates relative to the total number of isolates per specific pathogen and medication., Results: A total of 48,021 study participants enrolled from 131 original studies were included resulting in 15,845 isolates tested for antimicrobial resistance. The most common clinical sample sources were urine (28%), ear, nose, and throat discharge collectively (27%), and blood (21%). All the studies were cross-sectional and 83% were conducted in hospital settings. Among Gram-positive bacteria, the reported level of resistance to vancomycin ranged from 8% (Enterococcus species) to 20% (S. aureus). E. coli, K. pneumoniae and P. aeruginosa were the most common Gram-negative pathogens resistant to key antimicrobial agents described in the national standard treatment guideline and were associated with diverse clinical conditions: urinary tract infections, diarrhea, surgical site infections, pneumonia, ocular infections, and middle ear infections., Conclusion: Overall, there is a high prevalence of antimicrobial resistance in Ethiopia. Empirical treatment of bacterial infections needs to be guided by up-to-date national guidelines considering local antimicrobial susceptibility patterns. Equipping diagnostic laboratories with culture and drug susceptibility testing facilities, and establishing a strong antimicrobial stewardship program should be high priorities., (© 2021. The Author(s).)

Background: : The safety of COVID vaccines should be continuously followed. This study reports adverse events of the Oxford/AstraZeneca COVID-19 vaccine., Methods: : A prospective single-cohort study design was conducted to assess adverse events following immunization and associated factors of the first dose of Oxford/AstraZeneca's COVID-19 vaccine in Ayder Comprehensive specialized hospital. A structured questionnaire was administered consecutively to 423 participants. Follow-up data were collected 72 hours after vaccination via phone. Bivariate and multivariate logistic regression models were used to find associations between adverse events and independent variables. Statistical significance was declared at P <0.05., Results: : Out of 423 health care workers approached, 395 responded. At least one adverse event (95% CI: 63.58, 72.77) was reported by 270 participants. Local and systemic symptoms occurred in 46.8% (95% CI: 41.94, 51.79) and 58.48% (95% CI: 53.53, 63.26)], respectively. Muscle ache, fatigue, headache and fever were the most common local symptoms. No reports of hospitalization, disability or death. Age (adjusted odds ratio [AOR]=0.97, P =0.048), female sex (AOR=1.84, P =0.028), and comorbidity (AOR=2.28, P =0.040) were independent predictors of adverse events., Conclusion and Recommendation: : Adverse events following immunization are commonly reported after the first dose of the Oxford/AstraZeneca COVID-19 vaccine; age, female sex and comorbidity are independent predictors., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Aim: To investigate the association between initiation of breastfeeding within 1 hour after birth (TIBF) and maternal educational status, paternal educational status, household income, marital status, media exposure and parity in Ethiopia., Methods: We searched PubMed, EMBASE, Web of Science, SCOPUS, CINAHL and WHO Global health library databases. All studies were conducted in Ethiopia and published from 2000 to 2019 were included. To obtain the pooled odds ratio (OR), data were fitted in random-effects meta-analysis model. Statistical heterogeneity was quantified using Cochran's Q test, τ 2 and I 2 statistics. This meta-analytic review was reported in compliance with the PRISMA statement., Results: Out of 553 studies retrieved, 25 fulfilled our inclusion criteria. High maternal educational status (P < .001), paternal educational status (P = .001) and household income (P = .002), being married (P = .001) and multiparity (P = .01) were significantly associated with TIBF. There was no significant publication bias., Conclusions: Our meta-analysis showed that TIBF was associated with high educational and economic status, being married and multiparity. This suggests that the meta-analysis detected small associations that many previous studies in Ethiopia have not been able to show. Our findings can be useful for comparisons with other countries., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Hypertension is the major risk factor for cardiovascular diseases related morbidity and mortality. Blood pressure is often not adequately controlled in clinical practice. Information regarding blood pressure control in primary care settings is limited in Ethiopia., Objectives: This study aimed to assess blood pressure control practice and determinates among hypertensive patients attending primary health care facilities in Addis Ababa., Methods: A cross-sectional study was conducted on 616 hypertension patients in 12 health centers in Addis Ababa city. Data were collected by interviewing patients and reviewing their medical records. Data were collected from 3 August to 30 October 2015., Results: A complete information was obtained from 616 patients' medical records, and patients were then interviewed. The mean age was 58.90 (SD ± 13.04) years, and most of them (n = 321, 52.1%) were 60 years old or above, and more than three-fourth (n = 485) were on monotherapy. Methyldopa was the most monotherapy medication prescribed, 128 (20.8%). Only 31% (n = 191) of the patients had controlled blood pressure. Determinants for poor blood pressure control were age less than 60 years (adjusted odds ratio (AOR) = 3.06, 95% confidence interval (CI): 1.96, 4.78); work status: government employee (AOR = 2.41, 95% CI: 1.18, 4.90), retired (AOR = 1.79, 95% CI: 1.01, 3.18), and private business (AOR = 2.09, 95% CI: 1.17, 3.74); and being hypertensive for 10 or more years (AOR = 1.96, 95% CI: 1.11, 3.43). Significant predictors of achieving controlled blood pressure were weekly blood pressure measurement practice (AOR = 0.57, 95% CI: 0.36, 0.90) and tertiary-level education (AOR = 0.26, 95% CI: 0.13, 0.54)., Conclusions: Only one-third of the patients had controlled blood pressure. Efforts should be made to address identified determinants including age, regular blood pressure monitoring practice, and level of education., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Orexin is a neurotransmitter that mainly regulates sleep/wake cycle. In addition to its sleep cycle regulatory role, it is involved in regulation of attention, energy homeostasis, neurogenesis and cognition. Several evidences has shown the involvement of orexin in narcolepsy, but there are also growing evidences that shows the disturbance in orexin system in neurodegenerative diseases including Alzheimer's, Parkinson's, Epilepsy, Huntington's diseases and Amyotrophic lateral sclerosis. Pathogenesis and clinical symptoms of these disorders can be partly attributed from orexin system imbalance. However, there are controversial reports on the exact relationship between orexin and these neurodegenerative diseases. Therefore, the aim of this review is to summarize the current evidences regarding the role of orexin in these neurodegenerative diseases., Competing Interests: Declaration of competing interest We, the authors, declare that the research was conducted in the absence of any potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Early antiretroviral therapy (ART), isoniazid preventive therapy (IPT), and isoniazid-rifapentine (3HP) are effective strategies for preventing tuberculosis (TB) among people living with HIV (PLHIV). The study aimed to determine the effect of IPT on the TB incidence, follow-up CD4 + T cells, and all-cause mortality rate. Participants . Eligible patients on ART ( n  = 1, 863) were categorized into one-to-two ratios of exposed groups to IPT ( n  = 621) and nonexposed groups to IPT ( n  = 1, 242). Exposed groups entered the cohort at their first prescription of IPT, and unexposed groups entered into the study at the first prescription of ART and then followed until the occurrence of the outcome or date of administrative censoring (June 30, 2017). The outcome endpoints were TB incidence, follow-up CD4 + T cells, and all-cause mortality rate., Results: The follow-up CD4 + T cells for the exposed and nonexposed groups were 405.74 and 366.95 cells/mm (World Health Organization (WHO), 2017), respectively, a statistically significant finding ( t 1861  = -3.770, p < 0.0001; Cohen's d  = 0.186). Nine percent of the exposed patients (620 incidence of TB per 100,000 person-years (PYs)) and 21.9% of the nonexposed patients (3160 incidence of TB per 100,000 PYs) developed TB. Mortality rate (per 100,000 PYs) was 440 for the exposed and 1490 for the unexposed patients. Statistically significant determinants of the all-cause mortality were unscheduled follow-up (AHR = 1.601; 95% CI: 1.154-2.222) and unable to work properly (AHR = 2.324; 95% CI: 1.643-3.288)., Conclusion: This study demonstrates the effect of IPT in reducing incidence of TB and all-cause mortality rate and improving follow-up CD4 + T cells. Promoting IPT use can help to achieve the TB eradicating national agenda in Ethiopia., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Tesfay Mehari Atey et al.)

Background: Geriatric patients are at high risk of Drug Related Problems (DRPs) due to multi- morbidity associated polypharmacy, age related physiologic changes, pharmacokinetic and pharmacodynamics alterations. These patients often excluded from premarketing trials that can further increase the occurrence of DRPs. This study aimed to identify drug related problems and determinants in geriatric patients admitted to medical and surgical wards, and to evaluate the impact of clinical pharmacist interventions for treatment optimization., Methods: A prospective interventional study was conducted among geriatric patients admitted to medical and surgical wards of Jimma University Medical Center from April to July 2017. Clinical pharmacists reviewed patients drug therapy, identified drug related problems and provided interventions. Data were analyzed by using SPSS statistical software version 20.0. Descriptive statistics were performed to determine the proportion of drug related problems. Logistic regression analyses were performed to identify the determinants of drug related problems., Results: A total of 200 geriatric patients were included in the study. The mean age of the participants was 67.3 years (SD7.3). About 82% of the patients had at least one drug related problems. A total of 380 drug related problems were identified and 670 interventions were provided. For the clinical pharmacist interventions, the prescriber acceptance rate was 91.7%. Significant determinants for drug related problems were polypharmacy (adjusted odds ratio [AOR] = 4.350, 95% C.I: 1.212-9.260, p = 0.020) and number of comorbidities (AOR = 1.588, 95% C.I: 1.029-2.450, p = 0.037)., Conclusions: Drug related problems were substantially high among geriatric inpatients. Patients with polypharmacy and co-morbidities had a much higher chance of developing DRPs. Hence, special attention is needed to prevent the occurrence of DRPs in these patients. Moreover, clinical pharmacists' intervention was found to reduce DRPs in geriatric inpatients. The prescriber acceptance rate of clinical pharmacists' intervention was also substantially high.

Background: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases., Methods: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate., Results: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation., Conclusions: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).

Aims: Understanding how much healthcare professionals (HCPs) know about medication can help in devising strategies to improve rational medication use. This study aimed to synthesize information on the level of medication knowledge of HCPs in Africa., Method: We performed a systematic literature study in Embase and PubMed. We included original studies quantifying HCPs' medication knowledge, published between 2012 and 2016. We extracted disease focus, country, number and type of HCPs included and all medication-related knowledge questions and scored the quality of papers. The outcome measure was the percentage of HCPs who correctly answered medication knowledge questions., Results: We identified 64 studies from 12 African countries, comprising 13 911 HCPs, mostly nurses/midwifes and physicians. We extracted 306 medication-related knowledge questions, and only 52% (SD 28) of HCPs correctly answered them. Knowledge questions were mainly about medication prescribed for communicable diseases (70%), followed by non-communicable diseases (11%), and family planning/gynaecology (10%). Most papers concluded that there was a considerable medication knowledge gap among HCPs., Conclusion: We found a low level of medication knowledge across different disease areas, countries and HCPs. This underlines the continuous need to strengthen the undergraduate and postgraduate education in (clinical) pharmacology and therapeutics in Africa., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Antimicrobial drug resistance is a global threat for treatment of infectious diseases and costs life and money and threatens health delivery system's effectiveness. The resistance of E. coli to frequently utilized antimicrobial drugs is becoming a major challenge in Ethiopia. However, there is no inclusive countrywide study. Therefore, this study intended to assess the prevalence of E. coli resistance and antimicrobial-specific resistance pattern among E. coli clinical isolates in Ethiopia., Methods: Articles were retrieved from PubMed, Embase, and grey literature from 2007 to 2017. The main outcome measures were overall E. coli and drug-specific resistance patterns. A random-effects model was used to determine pooled prevalence with 95% confidence interval (CI), using DerSimonian and Laird method. In addition, subgroup analysis was conducted to improve the outcome. The study bias was assessed by Begg's funnel plot. This study was registered in PROSPERO as follows: PROSPERO 2017: CRD42017070106., Results: Of 164 articles retrieved, 35 articles were included. A total of 19,235 study samples participated in the studies and 2,635 E. coli strains were isolated. Overall, E. coli antibacterial resistance was 45.38% (95% confidence interval (CI): 33.50 to 57.27). The resistance pattern ranges from 62.55% in Addis Ababa to 27.51% in Tigray region. The highest resistance of E. coli reported was to ampicillin (83.81%) and amoxicillin (75.79%), whereas only 13.55% of E. coli isolates showed resistance to nitrofurantoin., Conclusion: E. coli antimicrobial resistance remains high with disparities observed among regions. The bacterium was found to be highly resistant to aminopenicillins. The finding implies the need for effective prevention strategies for the E. coli drug resistance and calls for multifaceted approaches with full involvement of all stakeholders.

Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.

Aims: The aim of the present study was to evaluate the impact of adverse drug events (ADEs) and treatment satisfaction on antihypertensive medication adherence., Methods: A cross-sectional study was conducted in six public hospitals in Ethiopia. We included adult ambulatory patients on antihypertensive medication. Adherence was measured using the eight-point Morisky Medication Adherence Scale, which categorizes as low (0-5), medium (6-7) and high (8) adherence. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4, which included questions about ADEs. Data were analysed using generalized ordered logistic regression with 95% confidence intervals (CIs)., Results: We included 925 out of 968 patients. Overall, 42% of patients scored low, 37% medium and 21% high adherence. Satisfaction with treatment was low, with a mean (standard deviation) TSQM score for global satisfaction of 51 (14). A total of 193 (21%) patients experienced 421 ADEs - mainly dyspeptic symptoms (12%), headache (11%) and cough (11). Experiencing more ADEs reduced the odds of being adherent [low vs. medium/high: odds ratio (OR) OR 1 0.77 (95% CI 0.67, 0.89), and low/medium vs. high: OR 2 0.55 (05% CI 0.41, 0.73)]. Being more satisfied increased the odds of being adherent [low vs. medium/high: OR 1 1.02 (95% CI 1.01, 1.03)]. Taking medication >1 year [OR 1 = 2 , 0.60 (95% CI 0.43, 0.83)] and taking calcium channel blockers [OR 1 = 2 0.71 (95% CI 0.54, 0.92)] decreased the odds for both low vs. medium/high and low/medium vs. high adherence., Conclusions: Only one in five patients reported perfect (high) adherence to their antihypertensive treatment regimen. Experiencing ADEs and being dissatisfied with treatment were associated with lower adherence. In addition to addressing treatment satisfaction and drug safety in first-world countries, these should also be addressed in resource-poor settings, within patient consultations, to enhance adherence., (© 2017 The British Pharmacological Society.)

Objectives: We examined determinants of achieving blood pressure control in patients with hypertension and of treatment intensification in patients with uncontrolled blood pressure (BP)., Design: A retrospective cohort study in six public hospitals, Ethiopia., Participants: Adult ambulatory patients with hypertension and with at least one previously prescribed antihypertensive medication in the study hospital., Outcome: Controlled BP (<140/90 mm Hg) and treatment intensification of patients with uncontrolled BP., Results: The study population comprised 897 patients. Their mean age was 57 (SD 14) years, 63% were females, and 35% had one or more cardiometabolic comorbidities mainly diabetes mellitus. BP was controlled in 37% of patients. Treatment was intensified for 23% patients with uncontrolled BP. In multivariable (logistic regression) analysis, determinants positively associated with controlled BP were treatment at general hospitals (OR 1.89, 95% CI 1.26 to 2.83) compared with specialised hospitals and longer treatment duration (OR 1.04, 95% CI 1.01 to 1.06). Negatively associated determinants were previously uncontrolled BP (OR 0.30, 95% CI 0.21 to 0.43), treatment regimens with diuretics (OR 0.68, 95% CI 0.50 to 0.94) and age (OR 0.99, 95% CI 0.98 to 1.00). The only significant-positive-determinant for treatment intensification was duration of therapy (OR 1.05, 95% CI 1.02 to 1.09)., Conclusions: The level of controlled BP and treatment intensification practice in this study was low. The findings suggest the need for in-depth understanding and interventions of the identified determinants such as uncontrolled BP on consecutive visits, older age and type of hospital., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Non-medicated cosmetics use is very common among the Ethiopian population. However, little is known about these products' related adverse events. The aim of this study was to assess the prevalence and determinants of cosmetics-related adverse events among Jigjiga Town residents, Eastern Ethiopia., Methods: A community-based cross-sectional study design was conducted in May and June 2014. Semi-structured interviews were used to collect cosmetics use pattern and related adverse events. For assessing determinants, logistic regression was used and statistical significance was set at p < 0.05., Results: Overall, 600 participants were approached with a 93% response rate. Ninety-three percent (n = 521) of them reported the use of cosmetics at least once within 2 weeks prior to this study, and of these, 229 (44%) used traditional herbal cosmetics along with modern cosmetics. A total of 342 (61%) reported experiencing adverse events of which the most common reported were: allergic reactions, 149 (36%); the appearance of acne, 66 (16%); and hirsutism, 52 (12.5%). The occurrence of cosmetics-related adverse events were significantly associated with the number of cosmetics used per day, the frequency of use, mixing of different types of cosmetics together, and mixing of cosmetics with water or saliva., Conclusion: A higher proportion of cosmetic users reported experiencing at least one adverse event. The number of cosmetic products and frequency of use were important predictors for experiencing adverse events. This implies the need to consider safety concerns related to cosmetic use. Approaches to address such issues may include awareness creation programs and promoting the concept of cosmetovigilance among cosmetic sellers, users, and other stakeholders.

Background: Drug use study in the community enables health authorities to understand pattern of drug utilization and its related aspects. This, in turn, can help to develop rational drug policies to be harmonized in accordance to the need of the community., Objective: The aim of this study was to assess drug use during acute illness by the general population in Tigray region, Northern Ethiopia., Method: A community based cross-sectional study was undertaken in April 2013 in Tigray Region, Ethiopia. A total of 1034 households were interviewed in the study. A multi-stage sampling technique was used to select households. Data were collected using a pre-tested structured questionnaire. Data were analyzed using descriptive statistics and bivariate and multivariate logistic regression model., Results: Out of 1000 households, 210(21%) reported an episode of acute illness. The prevalence of acute illnesses in rural areas 126(25%) (AOR = 1.83, 95% CI: 1.21-2.76) was significantly higher than that of urban areas 84(17%). Cough, runny nose, sore throat, earache, fever and headache added up to 155(52%) of all reported symptoms of acute illnesses. The majority of the patients 162 (77%) took modern medications for the managements of their diseases. Half 105(50%) of the consumed medications were antibiotics. The large proportions 173(83%) of medicines for acute illness were taken orally. The greater proportions 150(93%) of medications were prescribed by health professionals. Thirty-four households (21%) reported treatment discontinuation., Conclusion: The prevalence of acute illnesses in this study was found to be 21%. Acute illnesses were more common in rural areas than urban areas. Antibiotics were the most frequently used drugs for acute illnesses.

Objective: Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW)., Methods: Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI > 0.5., Results: In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44 years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW., Conclusions: 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.', (© 2015 John Wiley & Sons Ltd.)

Background: Post surgical wound infections are global problem in the field of surgery associated with long hospital stay, higher treatment expenditure, morbidity and mortality. Hence to address the limited data in Ethiopia on post surgical wound infections, we conducted this research to determine the prevalence and antimicrobial susceptibility patterns of aerobic bacteria in post-surgical wound infected patients in Ayder teaching and referral hospital, Mekelle, Ethiopia., Methods: Hospital based prospective cross sectional study was carried-out in 128 patients who had undergone surgery in general surgery and orthopaedic wards, and showed symptoms of infection clinically from January to June 2012. Standard bacteriological methods were used for bacterial isolation and antimicrobial susceptibility pattern., Results: A total of 128 patients (98 male and 30 female) with clinical signs of post surgical wound infections were enrolled. The age of the patients ranged from 15-79 years (with mean 35.95 ± 19.01 years). Out of the 128 wound swabs taken, 96/128 (75%) were culture positive aerobically, yielding 123 bacterial isolates. Out of these the predominant bacterial isolates were Staphylococcus aureus 44 (35.77%), Klebsiella species 29 (22.76%) and Coagulase negative Staphylococci (CoNS) 18 (14.63%). No bacterial isolates was found to be sensitive to all antibiotics tested. Isolated bacteria showed 102/123 (82.92%) multi drug resistance to the commonly used antibiotics in the hospital. However, 54/ 65 (83.1%) of Gram negative and 58/58 (100%) of Gram positive isolates were sensitive to Gentamicin and Vancomycin, respectively., Conclusion: Prevalence of was Post-operative wound infections rate in this current study was 75% and multi drug resistance was seen in 102/123(82.92%) of the isolates leaving clinicians with few choices of drugs for the treatment of post surgical wound infected patients. This underscores for periodic surveillance of etiologic agent and antibiotic susceptibility to prevent further emergence and spread of resistant bacteria pathogens.