Sustained release local anesthetics for pain management: relevance and formulation approaches.

This review attempted to ascertain the rationale for the formulation of sustained-release local anesthetics and summarize the various formulation approaches designed to date to achieve sustained and localized local analgesic effects. The incidence of pain, which is the concern of patients as well as health care professionals, is increasing due to accidents, surgical procedures, and other diseases. Local anesthetics can be used for the management of moderate to severe acute and chronic pain. They also allow regional analgesia, in situations where the cause and source of the pain are limited to a particular site or region, without the need for loss of consciousness or systemic administration of other analgesics thereby decreasing the risk of potential toxicities. Though they have an interesting antipain efficacy, the short duration of action of local anesthetics makes the need for their multiple injections or opioid adjuvants mandatory. To overcome this problem, different formulations are being designed that help achieve prolonged analgesia with a single dose of administration. Combination with adjuvants, liposomal formulations, lipid-based nanoparticles, thermo-responsive nanogels, microspheres, microcapsules, complexation with multivalent counterions and HP-ß-CD, lipid-based nanoparticles, and bio-adhesive films, and polymeric matrices are among the approaches. Further safety studies are required to ensure the safe and effective utilization of sustained-release local anesthetics. Moreover, the release kinetics of the various formulations should be adequately established.

Validation of Blood Glucose and Lipid-Lowering Effect of Solvent Fractions of the Crinum Abyssinicum Shoot Tips in Streptozotocin-Induced Diabetic Mice.

Background: Diabetes mellitus prevalence has reached epidemic levels despite the existence of contemporary treatments. People thus started looking at the possible therapeutic value of natural therapies. Crushed shoot tips of Crinum abyssinicum (Amaryllidaceae) are mixed with water in Ethiopia to treat diabetes, yet this practice is not well supported by science. Objective: In this experiment, mice models were used to verify the blood sugar and lipid-lowering benefits of solvent fractions of C. abyssinicum shoot tips. Materials and Methods: In a single-dose treated Streptozotocin (STZ)-induced diabetic model, mice were randomly grouped into eleven categories which include diabetic negative control, diabetic positive control, and 9 diabetic treatment groups. In repeated daily doses treated STZ-induced model, Mice were divided into 6 groups which included normal and diabetic negative control (TW80), diabetic positive control (5 mg/kg glibenclamide), and three diabetic treatment groups 100, 200, and 400 mg/kg). Finally, blood glucose, lipid level, and body weight were examined. Results: In the single-dose treated diabetic model, there was a significant blood glucose reduction at 200 and 400 mg/kg doses of aqueous fraction and glibenclamide starting from the sixth-hour post-administration unlike ethyl acetate and chloroform fraction compared to baseline and negative control. In repeated daily dose-treated diabetic mice, all three doses (100, 200, and 400 mg/kg of aqueous fraction) resulted in a substantial reduction (P < .001) in blood glucose compared to baseline and negative control on the seventh day and 14th day. Besides the AQF shows improvement in lipid levels and body weight parameters. Conclusion: The results of the study demonstrated that C. abyssinicum shoot tip fractions have the greatest potential to lower blood sugar and lipid levels, supporting conventional claims for the treatment of diabetes.

Acute coronary syndrome and its treatment outcomes in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and burden of in-hospital mortality in Ethiopia. This study, therefore, aimed to assess the magnitude of risk factors, management, and in-hospital mortality of ACS in Ethiopia. METHODS: Electronic searching of articles was conducted using PubMed, Science Direct, EMBASE, Scopus, Hinari, and Google Scholar to access articles conducted in Ethiopia. The Preferred Reporting Items for Systematic Reviews checklist was used for identification, eligibility screening, and selection of articles. Data were extracted with an abstraction form prepared with Microsoft Excel and exported to STATA for analysis. Funnel plot, Begg's test, and Egger's test were used to determine publication bias. Heterogeneity between the studies was checked by I2 statistic. The pooled prevalence of risk factors and in-hospital mortality of ACS were estimated using a random-effects meta-analysis model. RESULTS: Most (59.367%) of the patients had ST-segment elevation myocardial infarction (STEMI). Hypertension (54.814%) was the leading risk factor for ACS followed by diabetes mellitus (38.549%). Aspirin (56.903%) and clopidogrel (55.266%) were most frequently used in patients with STEMI ACS, respectively. The pooled proportion of in-hospital mortality of ACS was 14.82% which was higher in patients with STEMI (16.116%). CONCLUSION: The rate of in-hospital mortality is still high which was higher in patients with STEMI. Initiation of treatment must consider the heterogeneity of each patient's risk factor and reperfusion therapy should be implemented in our setting.

Systematic Review of Safety of RTS,S with AS01 and AS02 Adjuvant Systems Using Data from Randomized Controlled Trials in Infants, Children, and Adults.

Background: Emergence of antimalarial drugs and insecticides resistance alarms scientists to develop a safe and effective malaria vaccine. A pre-erythrocytic malaria vaccine called RTS,S has made great strides. Aim: The review was aimed to assess the safety of the candidate malaria vaccine RTS,S with AS01 and AS02 adjuvants using data from Phase I-III randomized controlled clinical trials (RCTs). Methods: This systematic review was conducted based on PRISMA 2020. Regardless of time of publication year, all articles related with safety of RTS,S, RCTs published in the English language were included in the study. The last search of databases, and registry was conducted on 30 May, 2022. Pubmed, Google Scholar, Cochrane Library, Wiley Online Library, and Clinical trials.gov were thoroughly searched for accessible RCTs on the safety of RTS,S malaria vaccine. The studies were screened in three steps: duplicate removal, title and abstract screening, and full-text review. The included studies' bias risk was assessed using the Cochrane risk of bias tool for RCTs. This systematic review is registered at Prospero (registration number: CRD42021285888). The qualitative descriptive findings from the included published studies were reported stratified by clinical trial phases. Findings: A total of thirty-five eligible safety studies were identified. Injection site pain and swelling, febrile convulsion, fever, headache, meningitis, fatigue, gastroenteritis, myalgia, pneumonia, reactogenicity, and anemia were the most commonly reported adverse events. Despite few clinical trials reported serious adverse events, none of them were related to vaccination. Conclusion: Most of the adverse events observed from RTS,S/AS01 and RTS,S/AS02 malaria vaccines were reported in the control group and shared by other vaccines. Hence, the authors concluded that both RTS,S/AS01 and RTS,S/AS02 malaria vaccines are safe.

Magnitude of anemia and associated factors among adult patients at Baso Liben District: a cross-sectional study.

BACKGROUND: Despite the fact that anemia is a common health problem with many consequences, its magnitude among adults and the different contributing factors have not been documented in the study setting. Hence, this study aimed to determine the magnitude of anemia and associated factors among adult patients of Baso Liben District. METHODS: A facility-based cross-sectional study was conducted from 1 December 2019, to February 30, 2020. A total of 347 adult patients attending Yejubie Hospital were enrolled in the study. Socio-demographic data were collected through face-to-face interview. Patients' hemoglobin level was determined by a Mindray BC-5800 CBC hematology analyzer. The presence of intestinal parasites and malaria infection were assessed. RESULTS: The overall magnitude of anemia was 25.94% with moderate severity according to the WHO anemia classification. The prevalence of mild, moderate, and severe anemia was 13.54%, 8.36%, and 4.03%, respectively. Anemia was associated with age range ≥55 years (AOR = 31.66), large family size (AOR = 6.62), being married (AOR = 0.24), intestinal parasite infections (AOR = 4.05), malaria infection (AOR = 4.61), and pregnancy (AOR = 4.09). CONCLUSION: The prevalence of anemia was moderate. Intestinal parasitic infection, age, malaria, family size, and pregnancy were associated factors with anemia.

Survival and predictors of mortality among HIV-positive children on antiretroviral therapy in public hospitals.

BACKGROUND: Human immunodeficiency virus and acquired immunodeficiency syndrome had created enormous challenges worldwide, and continues to be the world's serious health and development challenges. Globally, at the end 2017, there were 1.8 million children (< 15 years) living with HIV. The survival of HIV-positive children treated with ART depends on a variety of factors, which might vary greatly with economic, socio-demographic, behavioral risk, and health factors. This study aimed to assess survival status and predictors of mortality among HIV-positive children on antiretroviral therapy at East Gojjam Zone Public hospitals, Northwest Ethiopia. METHODS: An institution-based retrospective cohort study was conducted in selected hospitals of the East Gojjam zone, Northwest Ethiopia, among < 15-year-old children who were newly enrolled in HIV care clinic from January 1st, 2014 to December 31, 2018. Data were collected from patient charts from March 1 to 22, 2019 using a standardized checklist. Data were analyzed by SPSS version 24. A Kaplan-Meier curve and log-rank test were used to estimate the survival time and compare survival curves between variables. Multivariable Cox proportional-hazards model was fitted to identify predictors of survival status taking p-value < 0.05 as statistically significant. RESULT: In this study, a total of 251 HIV-positive children on ART were followed up for a total of 60 months, with a mean survival time of 55.54 (± 0.83) (95% CI: 53.90-57.17) months. The overall mortality incidence rate in the cohort during the 626 Child-Year-Observation (CYO) was 2.56/100 CYO. The overall estimated survival probability after starting ART was 0.90 at 60 months of follow-up. In this study age < 5 years, Hgb < 10 gm/dl, CD4 count below threshold, cotrimoxazole preventive therapy, and subnormal weight for height were statistically significant predictors of survival status (P < 0.05). CONCLUSION AND RECOMMENDATION: Age, hemoglobin level, CD4 count, weight for height, and not taking cotrimoxazole preventive therapy were independent predictors of mortality. Therefore, concerned stakeholders should focus on the above-mentioned predictors of mortality and nutritional interventions to enhance the survival of HIV-infected children on antiretroviral therapy.

Medicinal plants used for management of hemorrhoids in Ethiopia: A systematic review.

Background: Hemorrhoids have been reported to beset human beings since the earliest history of mankind. Utilization of herbal medicines is ever increasing as the demand for natural remedies is growing. In Ethiopia, many patients commonly use herbal medicines for hemorrhoids management despite lack of organized information at country level. This systematic review was aimed to document reports about utilization of medicinal plants for hemorrhoids management in Ethiopia. Method: A web-based systematic literature search was carried out through electronic databases like PubMed, Google Scholar, Web of Sciences, Science Direct, and websites of different organizations. All studies with complete ethnobotanical information were included in this review without regard to methodology and publication year. Results: A total of 23 articles were included in this systematic review. Majority (41.7%) of studies were reported from Oromia region followed by Amhara (33.3%) regional state. A total of 50 medicinal plants have been reported where Fabaceae and Solanaceae represent the most commonly used families. Herbs were the most (38%) commonly used medicinal plants followed by shrubs (34%) and trees (26%). Leaf (44%) and root (24%) were the first and second most commonly used plant parts, respectively. Most of the medicinal remedies (36%) were prepared by pounding the fresh part of the plant. Besides, 56.1% of the herbal preparations were administered through topical route. Conclusion and recommendations: Numerous medicinal plants from various families have been documented in this review as anti-hemorrhoidal remedies. Further studies could be anticipated in the search for new, effective, and safe plant-based medications from medicinal plants discussed in this review.

Prevalence of Medication Non-Adherence and Associated Factors among Diabetic Patients in A Tertiary Hospital at Debre Markos, Northwest Ethiopia.

Background: Non-adherence to prescribed medications is possibly the most common reason for poor treatment outcomes among people with diabetes although its rate is highly variable. Data on the magnitude of medication non-adherence and associated factors are scarce in the study area. This study aimed to assess the rate of non-adherence and associated factors among diabetic patients at Debre Markos Comprehensive Specialized Hospital. Methods: A cross-sectional study was conducted from June 17 to July 17, 2021. Study participants were selected using a simple random sampling technique. Data were collected with a pre-tested structured questionnaire and entered into SPSS version 25. Logistic regression was utilized to determine predictors of medication non-adherence at a significance level of ≤ 0.05. Results: A total of 176 study participants were enrolled in the study. About 59% of the study participants had type-2 diabetes mellitus. The prevalence of non-adherence to anti-diabetic medications was found to be 41.5%. Male sex, rural residence, being divorced, being merchant, self- or family-borne medical cost, and presence of comorbidities were significantly associated with increased rate of non-adherence to anti-diabetic medications. Conclusion: The prevalence of non-adherence to medications among diabetic patients is significantly high in the study area. Public health measures should be strengthened to decrease nonadherence among diabetic patients.

Off-label medication use in pediatrics and associated factors at public hospitals in east Gojjam zone, Ethiopia.

Objective: Due to a lack of appropriate pediatric preparations, health providers frequently use adult formulations in an off-label manner. This study aimed to assess pediatric off-label medication use patterns and associated factors in East Gojjam, Ethiopia. Methods: Institutional-based cross-sectional study was conducted from December 2020 to June 2021 at three randomly selected hospitals. Data were collected by using self-structured questionnaires and a data abstraction checklist from health care workers and prescriptions, respectively. The collected data were analyzed using SPSS version 25. Logistic regression analysis was used to assess the association between independent and dependent variables. Results: A total of 285 eligible health professionals from the pediatric unit and pharmacies, and 1,800 eligible prescriptions were involved in the study. The response rate of healthcare workers was 94.37%. Around 74.4% of professionals had good knowledge about off-label medication. Only 8% of participants had taken training on pediatric off-label medications. Of all prescriptions, 27.6% of them have contained at least one off-label medication. Phenobarbitone (16.1%) and phenytoin (12.7%) were the most frequently prescribed off-label medication. In all, 496 (27.6%) prescriptions contained off-label drugs in the form of overdose, cutting adult tablets into small portions, and formulating tablets/capsules into solution. Lack of information on off-label prescribing, shortage of pediatric drugs, and suitable dosage forms showed significant association with off-label prescribing with p-value < 0.001. Conclusion: Almost one-third of pediatric prescriptions contained off-label medication. Only a small number of healthcare workers had taken training on pediatric off-label medications. Lack of sufficient information on risks of off-label medication, shortage of pediatric medication, and suitable pediatric dosage forms were associated with the use of off-label medication compared to non-use. Further research should be done on the long-term effects associated with off-label prescribing in pediatrics to assess whether the potential risks are balanced with the therapeutical benefit.

Mothers' health care-seeking behavior and associated factors for common childhood illnesses in Ethiopia: A systematic review and meta-analysis.

Objective: This review is aimed to estimate the pooled prevalence of mothers' health care-seeking behavior and associated factors in Ethiopia. Methods: International databases were systematically searched for studies that were published between 2008 and 2019. Data were extracted in Microsoft Excel 2019 and then exported to STATA version 14 for further analysis. Publication bias was determined by funnel plot, Begg's test, and Egger's test. Heterogeneity between the studies was checked by I2 statistic. The pooled proportion was estimated using random-effects meta-analysis model. Results: This review and meta-analysis included 14 studies from a total of 581 papers that were screened. The pooled proportion of mothers' health care-seeking behavior in Ethiopia was 50.24% (95% CI: 37.13%, 63.35%). Health facility distance (OR = 2.07), awareness about common childhood illnesses (OR = 2.06), educational levels (OR = 1.82), and income (OR = 2.07) were significantly associated variables. Conclusion: The overall health care-seeking behavior of mothers for common childhood illnesses in Ethiopia is low. Accordingly, educating mothers/caregivers about the importance of health care-seeking behavior and increasing the proximity of health facilities were recommended to improve health care-seeking behavior.

A systematic review on traditional medicinal Animal's parts and products used for the treatment of respiratory tract disorders in Ethiopia.

BACKGROUND: Respiratory diseases affect more than one billion people worldwide. Although medicinal animals have huge importance in primary health care, limited effort applied so far been in Ethiopia to properly identify, document, and conserve these animals and the related knowledge. This systematic review was aimed to identify the medicinal animals and document reports on the use of medicinal animals for the management of respiratory disorders. METHODS: Both published and unpublished articles on the ethnozoological use of medicinal animals were searched using electronic database (Science Direct, Pub Med, Google Scholar, Scopus, hinari, and research gate) and institutional repositories. Different keywords were used separately and in combination using Boolean operators "OR" or "AND" as well as medical subject heading [MeSH] terms. Studies that did not address respiratory disorders were excluded. Data were extracted using Microsoft excel spread sheet. RESULTS: Among 211 articles obtained from database searches, nine articles were eligible and included in the review. Thirty two medicinal animals were reported for treatment of respiratory disorders. Mammals were the most commonly (43.8%) used medicinal animals. Meat was reported as the most commonly (22.6%) used medicinal remedy. CONCLUSIONS: Most of the medicinal remedies were obtained from mammals and administered orally. As the majority of the medicinal animals were obtained from wild sources, due attention should be given to conserve them. Besides, this traditional medicinal knowledge should be integrated to modern medicine to investigate the acute and chronic toxicity profile and efficacy of these remedies to identify potential lead compounds to modern drugs.

Ethnozoological study of medicinal animals and animals' products used by traditional medicinal practitioners and indigenous people in Motta city administration and Hulet Eju Enessie District, East Gojjam, Northwest Ethiopia.

BACKGROUND: In Ethiopia, many ethnic communities use traditional/indigenous medicine for primary health care. However, this indigenous medicinal practice is being neglected and continued to be lost due to poor documentation as they are transferred from generation to generation through oral tradition. Therefore, this ethnozoological study aimed to assess and document the medicinal use of animals and animals' products used by traditional medicinal practitioners and indigenous people in Motta city administration and Hulet Eju Enessie Districts, East Gojjam Zone, Ethiopia. METHODS: Cross-sectional ethnozoological survey was conducted using a Semi-structured questionnaire among purposively selected respondents in Motta city administration and Hulet Eju Enessie District, East Gojjam Zone, Ethiopia from September 2020 to June 2021 GC. The ethnozoological data were analyzed using SPSS version 26 and Microsoft Excell Spreadsheet. Fidelity level, use-value, and informant consensus factor were determined. RESULTS: A total of 25 animal species were reported to be used for the treatment of different ailments by 33 informants. The majority of animals (64%) were mammals followed by birds (16%). The fidelity level ranged from 18.2 (Hyena for bad spirit) to 100% (stingless be for asthma, Tiger for rabies virus, Whisper for nightmare). CONCLUSION: This study showed the wide use of medicinal animals and their parts/products for meeting the primary healthcare needs of the community in the study area. Therefore, this ethnozoological medicinal knowledge needs to be integrated with modern medicine to use animals/animals' products as a potential source of effective drugs for different ailments.

Management, survival, and predictors of mortality among hospitalized heart failure patients at Debre Markos comprehensive specialized hospital, Northwest Ethiopia: Prospective cohort study.

INTRODUCTION: Heart failure is a major public health problem worldwide. Since heart failure with reduced ejection fraction and preserved ejection fraction are different clinical entities, in-hospital mortality may occur at different rates. This study aimed to assess the management, survival, and predictors of mortality among hospitalized heart failure patients at Debre Markos comprehensive specialized medical ward. METHODS: A prospective cohort study was conducted on 228 heart failure patients at Debre Markos Comprehensive Specialized Hospital medical wards. A structured data collection tool was used to collect data. Data were analyzed using SPSS version 21.0. The Kaplan-Meier survival curve was used to investigate if there was a difference in the in-hospital survival between heart failure with a reduced ejection fraction and heart failure with a preserved ejection fraction. Those variables having p-value < 0.05 were considered statistically significant. RESULTS: From the 228 participants, 126 (55.3%) were females with a mean age of 53.32 ± 15.68 years. One hundred thirty-three (58.3%) patients were presented with preserved (⩾50%) level of ejection fraction. The all-cause in-hospital death rate was 12.7%, and the risk of in-hospital mortality was higher in heart failure patients with reduced ejection fraction (7.4% vs 5.3%; p = 0.005). Current occupation (p = 0.041), elevated serum creatinine (p = 0.010), reduced ejection fraction (p = 0.017), and asthma/chronic obstructive pulmonary disease comorbidity (p = 0.002) were the independent predictors of high hospital mortality. CONCLUSION: The rate of in-hospital mortality among heart failure patients was high. Healthcare providers should provide effective education activities and define disease management strategies for patients with reduced ejection fractions.

Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity.

Responsible for more than 4.9 million deaths so far, COVID-19, caused by SARS-CoV-2, is instigating devastating effects on the global health care system whose impacts could be longer for the years to come. Acquiring a comprehensive knowledge of host-virus interaction is critical for designing effective vaccines and/or drugs. Understanding the evolution of the virus and the impact of genetic variability on host immune evasion and vaccine efficacy is helpful to design novel strategies to minimize the effects of the emerging variants of concern (VOC). Most vaccines under development and/or in current use target the spike protein owning to its unique function of host receptor binding, relatively conserved nature, potent immunogenicity in inducing neutralizing antibodies, and being a good target of T cell responses. However, emerging SARS-CoV-2 strains are exhibiting variability on the spike protein which could affect the efficacy of vaccines and antibody-based therapies in addition to enhancing viral immune evasion mechanisms. Currently, the degree to which mutations on the spike protein affect immunity and vaccination, and the ability of the current vaccines to confer protection against the emerging variants attracts much attention. This review discusses the implications of SARS-CoV-2 spike protein mutations on immune evasion and vaccine-induced immunity and forward directions which could contribute to future studies focusing on designing effective vaccines and/or immunotherapies to consider viral evolution. Combining vaccines derived from different regions of the spike protein that boost both the humoral and cellular wings of adaptive immunity could be the best options to cope with the emerging VOC.

Evaluation of drug prescription pattern using World Health Organization prescribing indicators in public health facilities found in Ethiopia: systematic reviews and meta-analysis.

BACKGROUND: Drug use evaluation is a structured, methodological, and criteria-based drug assessment system that helps to evaluate the actual trend of drug use in a particular setting. If drug prescription practices are inappropriate, need to examine the patterns of drug use is necessary to change prescribing patterns accordingly. Therefore, this review aimed to determine the drug prescription pattern in public health facilities found in Ethiopia using prescribing indicators developed by the World Health Organization. METHODS: This review was conducted as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Extensive searching to identify articles was conducted in PubMed, Medline, Web of Science, Research Gate, Africa Journal of Online, and Google scholar. Finally, 10 eligible articles were selected for analysis based on inclusion and exclusion criteria. The median value, as well as the 25th and 75th percentiles for each WHO prescribing indicator, were computed. RESULT: The pooled median value of WHO prescribing indicators was reported as follows: the average number of drugs prescribed per encounter = 2.14 (IQR 1.79-2.52), the percentage of encounters with antibiotics prescribed = 43.46% (IQR 30.01-58.67), the percentage of encounters with an injection prescribed = 13.20% (6.47-40.7), percentage of drugs prescribed by generic name = 93.49% (89.13-97.96), and the percentage of medicines prescribed from essential medicines list = 92.54% (85.10-97.7). The forest plots determined for each prescribing indicator indicated that there is a high degree of heterogeneity across articles. CONCLUSION: All of the prescribing indicators were not consistent with the standard values recommended by the World Health Organization. Therefore, public health facilities should take appropriate measures for improving the prescription patterns as per the recommendation set by the World Health Organization.