Public health and research ethics education: the experience of developing a new cadre of bioethicists at a Ugandan institution.

Research ethics education is critical to developing a culture of responsible conduct of research. Many countries in sub-Saharan Africa (SSA) have a high burden of infectious diseases like HIV and malaria; some, like Uganda, have recurring outbreaks. Coupled with the increase in non-communicable diseases, researchers have access to large populations to test new medications and vaccines. The need to develop multi-level capacity in research ethics in Uganda is still huge, being compounded by the high burden of disease and challenging public health issues. Only a few institutions in the SSA offer graduate training in research ethics, implying that the proposed ideal of each high-volume research ethics committee having at least one member with in-depth training in ethics is far from reality. Finding best practices for comparable situations and training requirements is challenging because there is currently no "gold standard" for teaching research ethics and little published information on curriculum and implementation strategies. The purpose of this paper is to describe a model of research ethics (RE) education as a track in an existing 2-year Master of Public Health (MPH) to provide training for developing specific applied learning skills to address contemporary and emerging needs for biomedical and public health research in a highly disease-burdened country. We describe our five-year experience in successful implementation of the MPH-RE program by the Mbarara University Research Ethics Education Program at Mbarara University of Science and Technology in southwestern Uganda. We used curriculum materials, applications to the program, post-training and external evaluations, and annual reports for this work. This model can be adapted and used elsewhere in developing countries with similar contexts. Establishing an interface between public health and research ethics requires integration of the two early in the delivery of the MPH-RE program to prevent a disconnect in knowledge between research methods provided by the MPH component of the MPH-RE program and for research in ethics that MPH-RE students are expected to perform for their dissertation. Promoting bioethics education, which is multi-disciplinary, in institutions where it is still "foreign" is challenging and necessitates supportive leadership at all institutional levels.

COVID-19 vaccine hesitancy: assessing the prevalence, predictors, and effectiveness of a community pharmacy based counseling intervention.

BACKGROUND: Coronavirus disease (COVID-19) vaccine hesitancy is a global challenge. In low- and middle-income countries (LMICs), the problem has persisted despite vaccine availability and decreasing infections. In Uganda, there is still limited information on the extent and predictors of vaccine hesitancy. This study sought to assess the prevalence and predictors of COVID-19 vaccine hesitancy, and the effectiveness of an intervention that involved community pharmacy counseling in combating COVID-19 vaccine hesitancy. METHODS: A total of 394 participants were enrolled in a 4-week prospective cohort interventional study. The study was conducted across eight community pharmacies in Mbarara City, between 9:00 AM and 5:00 PM daily. The study personnel ascertained the vaccination status of all clients seeking community pharmacy services. All unvaccinated clients were consecutively assessed for eligibility, and eligible clients were systematically enrolled after receiving the community pharmacy services for which they requested. The study intervention involved structured participant counseling (within the pharmacy premise), follow-up short message service (weekly), and telephone calls (bi-weekly). Only participants who did not accept to receive the COVID-19 vaccine despite counseling were followed up for four weeks, or until they accepted to receive a COVID-19 vaccine. The effectiveness of the community pharmacy counseling intervention was determined as an increase in COVID-19 vaccine acceptance, and desirable attitudinal change towards COVID-19 disease, vaccination exercise, and vaccines. Descriptive analysis was used to summarize data, and multivariate analysis was used to determine the predictors of COVID-19 vaccine hesitancy. A p-value < 0.05 was considered statistically significant. RESULTS: Out of 394 participants, 221 (56%) were hesitant to receive a COVID-19 vaccine. Participants expressed several reasons (mean 2±1) for COVID-19 vaccine hesitancy, mostly concerning vaccine safety (N=160, 47.3%). The overall COVID-19 vaccine acceptance rate increased by 25.4 percent points (43.9 - 69.3 percent points) after the study intervention. Age, religion, level of education, distance from the nearest public health facility, having a friend/family diagnosed with COVID-19, and personal suspicion of contracting COVID-19 were significant predictors of COVID-19 vaccine hesitancy. CONCLUSION: COVID-19 vaccine hesitancy is a big challenge in Uganda. A mix of sociodemographic and COVID-19 vaccine perceptions are the key predictors of COVID-19 vaccine hesitancy. Although COVID-19 vaccines were not available at the time of the study, this study found that structured counseling interventions can improve COVID-19 vaccine acceptance rates. Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other healthcare settings.

Postgraduate medical trainees at a Ugandan university perceive their clinical learning environment positively but differentially despite challenging circumstances: a cross-sectional study.

PURPOSE: The clinical learning environment is an essential component in health professions' education. Data are scant on how postgraduate trainees in sub-Saharan Africa perceive their medical school learning environments, and how those perceptions contribute to their engagement during training, their emotional wellbeing, and career aspirations. This study examined perceptions of postgraduate medical trainees (residents) in a resource-limited setting, regarding their learning environment and explored perceptual contributions to their career engagement during training. The data reported contribute to understanding how clinical learning environments can be improved in low-resource settings in Uganda and elsewhere. METHODS: This study was done at the Faculty of Medicine of Mbarara University of Science and Technology in Uganda. We used a descriptive cross-sectional design involving sequential mixed methods. Quantitative data were collected using the Postgraduate Hospital Educational Environment Measure (PHEEM). Qualitative data were collected using focus group discussions. RESULTS: Ninety of the 113 eligible residents responded (79.6%). Of these, 62 (68.9%) were males, 51 (56.7%) were third-year trainees, and the majority (40%) of the residents were aged between 30 and 34 years. Overall PHEEM scored 98.22 ± 38.09; Role Autonomy scored 34.25 ± 13.69, Teaching scored 39.7 ± 13.81, and Social Support scored 24.27 ± 10.59. Gender differences occurred in the perceptions of teaching and social support. Cronbach's alpha coefficient was 0.94 for the overall PHEEM. Five major themes were identified from the qualitative data (trainee support, supervision environment, engagement with overall learning environment, preparation for future practice, and challenges that impede training). CONCLUSIONS: Overall, this study suggests that postgraduate trainees at the institution perceived the clinical learning environment positively amidst challenges of limited resources. Trainees' insights provided data that propose improvements on a number of domains in the learning environment.

Potentially harmful medication use and the associated factors among pregnant women visiting antenatal care clinics in Mbarara Regional Referral Hospital, Southwestern Uganda.

Background: Pregnancy management using medications has been challenging for both healthcare providers and pregnant women, given the fear of teratogenicity effects and the potential for fetal harm. In the developing world, poor health-seeking behavior of patients, delayed initiation of antenatal care (ANC), and low level of educational status of mothers could contribute to the issue of drug safety in pregnancy. Aim: The aim of the study was to determine the prevalence and factors associated with potentially harmful medication use in pregnancy. Methods: A cross-sectional study was conducted from April 1 to June 6, 2021, including 209 pregnant women on ANC follow-up at a referral hospital in Southwestern Uganda. The simple random sampling technique was employed to select study participants. Interviewer-administered questionnaires were used to collect the history of medication use since conception and then the participant's ANC card was reviewed to determine prescribed drug regimens and their indications. Statistical Package for the Social Sciences version 23.0 was used for analysis. Results: Out of the 1,422 medications used by 209 women, 665 (42.2%) were category C, and 182 (11.5%) were category A. A total of 92 (44.0%) pregnant women used at least one potentially harmful medication during the current pregnancy. Having more than average monthly income (adjusted odds ratio [aOR] = 2.32 [1.04, 5.14 at 95% confidence interval (CI)]), having a chronic disease (aOR = 3.24 [1.17, 8.97 at 95% C.I]), using 7 and more medications (aOR = 9.12 [4.11, 20.24 at 95% CI]), and use of herbal medicines (aOR = 4.50 [2.10, 9.87 at 95% CI]) were shown to be risk factors. Conclusion: The proportion of pregnant women that used at least one potentially harmful medication is higher than in previous studies. Having comorbidities and taking more medications increase the risk of receiving a potentially harmful medication during pregnancy. Relevance to Patients: This study identified the gaps in the use of medicines during pregnancy which will enable the development and implementation of protocols for optimizing prescribing practices in pregnant women by focusing on the safety of the fetus.

Antimicrobial Bioactivity and GC-MS Analysis of Different Extracts of Corchorus olitorius L Leaves.

Results: Crude extracts of Corchorus olitorius L leaves and their TLC-separated components demonstrated bioactivity against Staphylococcus aureus (14 mm), Streptococcus pneumoniae (16 mm), and Escherichia coli (11 mm) but neither against Candida albicans nor Mycobacteria tuberculosis. However, the overall zones of inhibition were smaller compared to the positive control (≥18 mm). GC-MS analysis of the active components revealed the presence of methyl esters. Conclusion: Corchorus olitorius L is bioactive against both Gram-negative and Gram-positive bacteria but neither against fungi nor mycobacteria. The bioactivity is attributable to the presence of methyl esters. Since methyl esters already have proven bioactivity in some studies, they could be further studied and optimized for possible pharmaceutical use. Further, to provide a more comprehensive antimicrobial spectrum of Corchorus olitorius L in Uganda, purified active components could be investigated using a wider range of organisms.

Phytochemical Analysis, Acute Toxicity, as well as Antihyperglycemic and Antidiabetic Activities of Corchorus olitorius L. Leaf Extracts.

Backgroundand Aim. Diabetes mellitus is a metabolic disorder that has no known cure with continuous endeavors to find a therapy for the condition. According to some studies, traditional leafy vegetables could prevent and manage diabetes by modifying the carbohydrate and lipid metabolism. In this study, a phytochemical analysis, acute toxicity, as well as antihyperglycemic and antidiabetic activity testing of the methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. was performed. Materials and Methods. Methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. were prepared by serial extraction. Phytochemical analysis was performed following standard methods. 52 mice were separated into 13 groups (A-M) of 4 and received extracts' doses ranging from 1000 mg/kg to 5000 mg/kg for the acute toxicity testing. For the antihyperglycemic and antidiabetic activities testing, 48 rats were divided into 8 groups of 6 and received 500 mg/kg of each extract. 10 mg/kg of glibenclamide and distilled water were used as controls. Data were analyzed using Prism GraphPad version 8.0.2 (263). Results. Phytochemical analysis revealed the presence of alkaloids, reducing sugars, saponins, and terpenoids. There were no acute toxicity signs observed in this study. Corchorus olitorius L. extracts demonstrated moderate antihyperglycemic and antidiabetic activities. The methanolic extract exhibited the highest degree of antihyperglycemic activity. However, there was no statistically significant difference between the extracts and the negative control (p > 0.05), but with glibenclamide (p < 0.01). Conclusion. Corchorus olitorius L. is a safe and potential postprandial antidiabetic vegetable that could minimize the rise in blood glucose after a meal. We therefore recommend further investigations into the antidiabetic properties of the vegetable using purified extracts.

Predictors of hospital-acquired adverse drug reactions: a cohort of Ugandan older adults.

BACKGROUND: Globally, it is estimated that the number of older adults will become 2 billion by 2050. The identification of the predictors of adverse drug reaction (ADR) in hospitalized older patients is crucial to the development of prediction tools and preventive strategies to mitigate the burden of ADRs. This study aimed to determine the predictors of hospital-acquired ADR occurrence among hospitalized older adults in a low-income country. METHODS: We conducted a prospective cohort of older adults admitted to medical, oncology, and surgery wards at Mbarara Regional Referral Hospital (MRRH) for a consecutive 6 months where each patient was followed up daily from admission to discharge. We used Edwards and Aronson's definition of ADR and the Naranjo ADR Causality Scale. We employed Beer's criteria and Lexicomp to determine potentially inappropriate medications, and drug interactions, respectively. We conducted univariate and multivariable logistic regression using Statistical Package for the Social Science (SPSS) Version 23.0. RESULTS: Out of 523 participants with median (Inter Quartile Range) age of 67 (62-76) years, 256 (48.9%) experienced at least one ADR. Independent predictors of occurrence of hospital acquired ADRs included age of 60-75 (Adjusted odds ratio (AOR) = 1.97, 95% C.I: 1.14-3.41; p value = 0.015) compared to > 75 years, previous ADR in 1 year (AOR = 2.43, 95% C.I: 1.42-4.17; p value = 0.001), potentially inappropriate medication (AOR = 4.56, 95% C.I: 2.70-7.70; p value< 0.001), polypharmacy (AOR = 3.29, 95% C.I: 1.98-5.46; p value< 0.001)), having a Charlison Comorbidity Index (CCI) ≥ 6 (AOR = 8.47, 95% C.I: 4.85-14.99; p value< 0.001), having heart failure (AOR = 2.83, 95% C.I: 1.34-6.02; p value = 0.007) or kidney disease (AOR = 1.95, 95% C.I: 1.05-3.61; p value = 0.034) and a hospital stay > 10 days (AOR = 3.53, 95% C.I: 1.89-6.61; p value< 0.001) compared to < 5 days. CONCLUSION: The current prevalence of ADR is higher than previously reported in high-income countries. Disease-related factors followed by medication-related factors were shown to be the most important predictors of hospital-acquired ADRs. CCI and PIM showed the strongest association with ADR. The predictors of ADRs identified in our study were generally comparable with those reported by previous studies. PLAIN LANGUAGE TITLE: Conditions that predispose older patients to experience harmful effects from their medications while in hospital. Identifying the conditions that predispose older adults to incur harmful effects of their medications helps to plan on how best to predict, take precautions and closely follow up on them and thus, to prevent these undesirable outcomes. This study aimed to identify these conditions which determine which older adults are higher risk to incur these harmful undesirable effects of medicines. Everydayduring their hospital stay, we closely followed older patients who were 60 years and above from their entry to the hospital wards until they left the hospital. We interviewed the participants, reviewed their medication files and we also examined them physically to identify any unwanted and harmful outcome from their current medications. Out of 523 participants, almost half of them experienced at least one harmful or undesired effect related to their medicine. Conditions which predisposed them to experience a harmful effect from their medicines included being in age bracket of 60-75 years, having a history of experiencing harmful outcomes from medicines in the previous 1 year, taking a medication which was listed as potentially inappropriate for older adults, taking 5 or more medications concurrently, having a lower 10 years survival chance, having heart or kidney disease and a hospital stay > 10 days.

Development and Validation of 'Prediction of Adverse Drug Reactions in Older Inpatients (PADROI)' Risk Assessment Tool.

BACKGROUND: Adverse drug reactions (ADR) detection and prediction methods in hospitalized older adults remain imprecise. The identification of the risk factors for ADRs in this group of patients is crucial to develop plausible prediction models. OBJECTIVE: This study aimed at developing and validating a "Prediction of ADR in Older Inpatients (PADROI)" risk assessment tool in hospitalized older adults. METHODS AND MATERIALS: We had previously conducted a derivational study that aimed to determine the risk factors of ADRs in hospitalized older adults. We developed the PADROI model as a potential ADR risk assessment tool incorporating 8 predictors each given a score by rounding off the respective adjusted odds ratios (AORs) to the nearest whole number. Subsequently, we conducted another prospective cohort among adults aged 60 years and older admitted to Gynecology and Obstetrics, Medical, Oncology, Surgery, and Psychiatry wards at Mbarara Regional Referral Hospital (MRRH) from July 5 to September 17, 2021. RESULTS: A total of 124 participants, 70 females and 54 males aged 60-95 years, were included in this validation cohort; 62 of them experienced 90 ADRs. When applied to the derivational cohort, the area under receiver operating characteristic curve (AUROC) for the PADROI model was shown to be 0.896 (0.869-0.923; at 95% CI). In the validation study, AUROC of PADROI was 0.917 (0.864-0.971 at 95% CI; p < 0.001). Overall, PADROI correctly predicted 91.7% of those who experienced an ADR. CONCLUSION: Using the adjusted odds ratios from our derivational cohort, we developed an ADR prediction tool (PADROI) that achieved an excellent AUROC (0.917), high sensitivity (87.1%) and specificity (90.3%). The current model demonstrated a high potential for clinical applicability which can be strengthened if similar results are reproduced in larger and multi-centered studies.

Prevalence, Incidence, and Characteristics of Adverse Drug Reactions Among Older Adults Hospitalized at Mbarara Regional Referral Hospital, Uganda: A Prospective Cohort Study.

BACKGROUND: Adverse drug reactions (ADRs) are associated with significant clinical and economic effects. Among the elderly population, the risk for ADRs is even higher. Data of ADR prevalence and incidence among the elderly population in Uganda and many low- and middle-income countries are lacking. OBJECTIVE: This study determined the prevalence, incidence, and characteristics of ADRs among hospitalized elderly patients at Mbarara Regional Referral Hospital (MRRH), Uganda. METHODS AND MATERIALS: We conducted a prospective cohort of older adults admitted to medical, oncology, and surgery wards at MRRH for consecutive 6 months. The primary data were obtained by interviewing patients and caregivers and reviewing patient medication charts, taking vital signs, and physical examinations. We used Edwards and Aronson's definition of ADR and the Naranjo ADR Causality Scale. We conducted descriptive statistics and the Kolmogorov-Smirnov test using SPSS Version 23.0. RESULTS: We studied a total of 523 older adults 60 to 103 years of age. During their hospital stay, 256 (48.9%) of the patients experienced at least one ADR. A total of 365 ADRs were identified during 4702 person-days of follow-up. The incidence of ADRs was 78 ADRs/1000 person-days. ADRs affecting the gastrointestinal tract were the most frequently (40.6%) identified categories. Probable and type A ADRs accounted for 260 (71.2%) and 305 (83.6%) of the total incidents, respectively. Overall, 237 (64.9%) of the ADRs were rated as mild, whereas 10 (2.8%) of them as severe. Lastly, 165 (45.2%) of the ADRs were categorized as preventable. CONCLUSION: Almost half of the hospitalized patients aged 60 to 103 years experienced at least one ADR during their hospital stay, which is higher than has been previously documented. Almost three-thirds of the ADRs were probable, about 4 out of 5 were type A and almost two-thirds were mild. Nearly half of the ADRs were preventable.

Prevalence, characteristics and predicting risk factors of adverse drug reactions among hospitalized older adults: A systematic review and meta-analysis.

BACKGROUND: Occurrence of adverse drug reactions is a major global health problem mostly affecting older adults. Identifying the magnitude and predictors of adverse drug reactions is crucial to developing strategies to mitigate the burden of adverse drug reactions. This study's objectives were to estimate and compare the prevalences of adverse drug reactions, to characterize them and to identify the predictors among hospitalized older adults. METHODS: A comprehensive systematic literature search including both prevalence and risk factors of adverse drug reactions in hospitalized older adults was conducted using PubMed, Scopus and Google Scholar, involving all articles published in English. Descriptive statistics and comparison of means was performed using SPSS version 20.0 and metaprop command was performed in STATA version 13.0. Heterogeneity was assessed using I 2 statistic. RESULTS: A total of 18 studies, involving 80,695 participants with a median age of 77 years, were included in this study. The pooled prevalence of adverse drug reaction was 22% (95% confidence interval: 17%, 28%; I 2 = 99.23%). Among high-income countries, the prevalence of adverse drug reactions was 29% (95% confidence interval: 16%, 42%) as compared to 19% (95% confidence interval: 14%-25%) in low and middle-income countries (p value = 0.176). Of the 620 adverse drug reactions categorized, most were type A (89%), which are generally predictable and preventable. Two-thirds (795, 67%) of the adverse drug reactions were probable and most (1194, 69%) were mild or moderate. The majority (60%) of the categorized adverse drug reactions were preventable and less than one-third (31%) were severe. The most consistently reported predictors of adverse drug reactions in hospitalized older patients were medication-related factors, including polypharmacy and potentially inappropriate medications followed by disease-related factors-renal failure, complex comorbidity, heart failure and liver failure. CONCLUSION: Almost one-quarter of all hospitalized older adults experienced at least one adverse drug reaction during their hospital stay. The majority of the adverse drug reactions were preventable. Medication-related factors were the most consistently reported predictors of adverse drug reactions followed by disease-related factors.

Traditional Medicinal Vegetables in Northern Uganda: An Ethnobotanical Survey.

BACKGROUND: A wide range of indigenous vegetables grow in Uganda especially during rainy seasons but scarcely during droughts, except those that are commercially grown. Although a number of these vegetables have medicinal values, they have not been satisfactorily studied besides conservation. Therefore, we conducted a cross-sectional ethnobotanical survey in Northern Uganda in order to document traditional medicinal vegetables and their uses. METHODS: Qualitative and quantitative approaches of data collection and analysis were employed using semistructured, interviewer-administered questionnaires as well as key informant interviews following international ethical codes. Fidelity levels and informant consensus factors were also calculated. RESULTS: 13 traditional vegetables belonging to 10 families were reported to serve as folk medicines. The most dominant families were Fabaceae (23.08%) and Solanaceae (15.38%). The most often used vegetables were Corchorus spp., Hibiscus spp., and Asystasiagangeticafor musculoskeletal (51%), gastrointestinal (34.3%), and malaria (31.8%). The vegetables were cultivated in the backyard and the leaves stewed for the different ailments. The informant consensus factor was the highest for Corchorus spp., in the treatment of joint pain/stiffness (0.92-1) while the highest fidelity level was (60.42%) for Amaranthus spp., in the management of anemia. CONCLUSIONS: Northern Uganda has numerous traditional vegetables with medicinal benefits. Diseases treated range from gastrointestinal to reproductive through musculoskeletal abnormalities. The community obtains vegetable leaves from the backyard and stews them regularly for the medicinal purposes with no specific dosage. Therefore, we recommend studies to verify in laboratory models the efficacy of these vegetables and standardize the dosages.

Influence of boarding secondary school environment on HIV positive students in South Western Uganda.

BACKGROUND: The number of human immunodeficiency virus (HIV) positive adolescents in secondary school has increased over the years. Little is known on how the students cope to the pressures and demands of their academic and health lives in the boarding secondary schools. This study explored the factors surrounding their anti-retroviral therapy adherence as well as their experiences. METHODS: We did a qualitative study that employed in-depth interviews amongst purposively selected 19 HIV positive adolescent students in boarding secondary school and seven key informants. Key informants were members of boarding secondary school staff directly taking care of the adolescents living with human immune virus and had spent at least two academic terms in that school. The study participants were recruited from four health facilities in Bushenyi district, southwestern Uganda, and key informants from five boarding secondary schools in Bushenyi. These were engaged in in-depth interviews using an interview guide. Data was transcribed, coded and the content analyzed thematically. RESULTS: Adolescents living with human immunodeficiency virus in boarding secondary school face challenges similar to adolescents outside boarding school settings. However, some challenges are unique to them. Students faced numerous barriers which made it difficult to adhere to their medication. Stigmatization in its different forms was also a major challenge amongst students. Willingness disclosure of serostatus was beneficial to the students since it guaranteed support while at school; facilitating adherence and better living. However, students were uneasy to disclose their status. Some students adopted negative coping mechanisms such as telling lies, escaping from school, and class to access medication. CONCLUSIONS: Adolescents in boarding secondary schools face similar challenges as compared to their counterparts with some being unique to them. Few school mechanisms help these students to cope while at school. Limited disclosure has proven useful but some adolescents have opted not to disclose their status and hence used negative coping mechanisms. These challenges need to be addressed and a safe environment to encourage limited disclosure should be made.

Acute and repeated-dose toxicity of Echinops kebericho Mesfin essential oil.

Echinops kebericho Mesfin is used for the management of various diseases and fumigation during child birth. This study investigated acute and repeated-dose toxicity of E. kebericho M. essential oils (EOs). The study was conducted in Swiss albino mice. Organ weight, histopathology and clinical chemistry were analyzed. The dose and duration of treatment were defined in accordance with Organization for Economic Co-operation and Development (OECD) guideline. No mortality was observed in acute oral dose toxicity study up to 2000 mg/kg per body weight. Compared to control group, treated groups did not show significant abnormalities in body weight and most parameters of clinical chemistry parameters and relative organ weight in repeated-dose toxicity study. However, urea, albumin, aspartate aminotransferase, and relative organ weight of right kidney showed variations in treated groups compared to control group. All treated groups and control group showed normal histology except lymphocytic infiltrates observed on the kidney with 200 mg/kg treated female group. The current study revealed that EO of E. kebericho M. could be considered well tolerated in acute and repeated-dose exposure. Further, teratogenic, mutagenic, carcinogenic, and sub-chronic and chronic toxicity studies are warranted.

Off-label antibiotic use among paediatric in-patients: a mixed-method prospective study at a tertiary hospital in southwestern Uganda.

Background The off-label use of drugs to treat children is a global practice attributed to the traditional exclusion of children from clinical trials mainly due to practical and ethical reasons. Off-label drug use carries both benefits and risks, but data regarding this use pattern are scanty in sub-Saharan Africa. Objective To determine the incidence and predictors of off-label antibiotic use in children less than 5 years admitted at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. Setting A prospective drug utilisation study was conducted among in-patients at the Paediatric Ward of MRRH from May to June 2019. Methods Clinical records and treatment notes of all children aged 0 to 59 months with at least one antibiotic prescription during the admission period were reviewed and included for data collection. Key informant interviews were conducted with physicians attending to patients in the Paediatric Ward. Main outcome measure Off-label use and potential predictors of off-label antibiotic use. Results Of 427 children admitted to the Paediatric Ward, 165 (38.6%) received 366 antibiotic prescriptions. However, 359 prescriptions belonging to 162 patients were analyzed. Off-label prescriptions occurred in 18.9% (95% CI: 14.9-23.0) of antibiotic prescriptions. Two categories of off-label prescriptions were found: off-label frequency of administration (n = 55, 80.9%), and off-label doses (n = 13, 19.1%). Ceftriaxone was the most common antibiotic prescribed at off-label doses, (n = 6, 8.8%) while ampicillin was the most common antibiotic prescribed with an off-label frequency of administration, (n = 39, 57.3%). Infants (1-23 months) received the majority (47.1%) of off-label antibiotic prescriptions; neonates (0-28 days) received 27.9%, and children (24-59 months) received 25% of the prescriptions. Controlling for sex and disease severity, age category remained significantly associated with off-label antibiotic use on multivariate analysis. Conclusion Off-label frequency of administration was the major category of off-label drug use, while off-label dose was the minor category. Age was a significant factor for off-label antibiotic prescription, with infants receiving the highest number of off-label prescriptions. Attending physicians identified several justifiable circumstances that warrant off-label antibiotic use and support emerging "well-founded" off-label uses of antibiotics in different paediatric age groups.

Antifungal Activity of the Essential Oil of Echinops kebericho Mesfin: An In Vitro Study.

BACKGROUND: Echinops kebericho is an endemic medicinal plant in Ethiopia widely used in the treatment of infectious and noninfectious diseases. Essential oils are known for their antibacterial, antifungal, antiviral, insecticidal, and antioxidant properties. This study evaluated the antifungal activity of essential oil from E. kebericho against four common pathogenic fungi and two standard strains. METHODS: The essential oil was obtained by hydrodistillation. The antifungal screening was done by agar well diffusion method. Minimal inhibitory concentrations (MICs) were determined by broth microdilution. Minimal fungicidal concentrations (MFCs) were determined by subculturing fungal strains with no visible growth onto a Sabouraud dextrose agar (SDA) plate. RESULTS: Candida albicans and Cryptococcus neoformans were highly sensitive while Aspergillus flavus did not show sensitivity up to 1 mg/ml of essential oil; MICs ranged from 0.083 mg/ml to 0.208 mg/ml. Concentration and fungal species showed significant dose-dependent associations (p < 0.0001) with antifungal activity. The MICs of essential oil were comparable to those of the standard drug (fluconazole) against C. glabrata and C. krusei. The lowest MFC of the essential oil was observed against Candida parapsilosis (0.145 mg/ml) while the highest MFC was against Candida krusei (0.667 mg/ml). CONCLUSION: Echinops kebericho essential oil showed noteworthy antifungal activity against Cryptococcus neoformans, Candida albicans, and Candida glabrata and could be a potential candidate for further antifungal drug development.

Caring for people with dementia in rural Uganda: qualitative study of caregiving burden experienced by informal and formal caregivers.

BACKGROUND: The rising incidence of Alzheimer's disease among older-age adults worldwide has been accompanied by an increase in caregiving burden. Limited work has examined the lived experiences of both formal and informal caregivers of people living with dementia in low-income countries. METHODS: We conducted one-on-one, in-depth qualitative interviews with a purposive sample of 10 informal caregivers and 5 formal caregivers of people living with dementia in Mbarara, Uganda. They were interviewed about their experiences caring for people with dementia until thematic saturation was reached. All interviews were audio recorded, transcribed into English, and thematically analysed. RESULTS: Two primary themes emerged from the data: patient factors influencing caregiving burden (problematic behaviours, such as wandering and aggression) and patient physical health and cognitive deterioration (namely, loss of memory and incontinence). Psychosocial and economic aspects of caregiving burden included financial costs, family conflicts, anxiety, stigma, and substance misuse. CONCLUSIONS: Both formal and informal caregivers of people living with dementia experience physical, financial, and psychological stressors. Interventions aimed at reducing these stressors would benefit caregivers as well as improve quality of care for people living with dementia.

Caregiving burden and mental health problems among family caregivers of people with dementia in rural Uganda.

BACKGROUND: Alzheimer's disease and related dementias are associated with increasing health burden in low- and middle-income countries. Less well-recognized is the potential health burden experienced by other affected individuals, such as family caregivers. In this study, we sought to profile the burden of care and its association with symptoms of depression and anxiety among informal caregivers of people living with dementia in rural southwestern Uganda. METHOD: We conducted a cross-sectional study of 232 family caregivers of people with dementia. The key measured variables of interest were caregiving burden (Zarit Burden Index) and symptoms of depression and anxiety (Depression Anxiety Stress Scales). We fitted multivariable regression models specifying depression and anxiety symptoms as the primary outcomes of interest and caregiving burden as the primary explanatory variable of interest. RESULTS: Family caregivers of people with dementia experience significant caregiving burden, with each item on the Zarit Burden Index endorsed by more than 70% of study participants. Nearly half [108 (47%)] of caregivers had Zarit Burden Interview scores >60, suggestive of severe caregiving burden. In multivariable regression models, we estimated a statistically significant positive association between caregiving burden and symptoms of both depression [b = 0.42; 95% confidence interval (CI) 0.34-0.49] and anxiety (b = 0.37; 95% CI 0.30-0.45). CONCLUSION: Family caregivers of people with dementia in rural Uganda experience a high caregiving burden, which is associated with symptoms of depression and anxiety. Interventions aimed at reducing caregiving burden may have important collateral mental health benefits.

Acute and sub-acute toxicity of Echinops kebericho decoction in rats.

BACKGROUND: Echinops kebericho is widely used for treatment of a variety of diseases including infectious, non-infectious disease and fumigation during child birth. Antibacterial, antimalarial, anti-leshimania, anti-diarrheal and insect repellent activities have been elucidated. Its toxicity profile is not yet investigated and thus this study was to investigate acute and sub-acute toxicity of E. kebericho decoctions. METHODS: Acute toxicity study was performed in female Wistar albino rats with single oral dose and followed up to 14 days. The sub-acute oral dose toxicity studies were conducted in rats of both sexes in accordance with the repeated dose 28-day oral toxicity study in rodent OECD guidelines. Physical observations were made regularly during the study period while body weight was measured weekly. Organ weight, histopathology, clinical chemistry and hematology data were collected on the 29th day. Results were presented as mean ± standard deviation. One-way analysis of variance (ANOVA) was performed if assumptions were met; otherwise Kruskal-Wallis analysis was performed. RESULT: Oral administration of E. kebericho decoction showed no treatment-related mortality in female rats up to the dose of 5000 mg/kg. In sub-acute toxicity studies, no significant treatment-related abnormalities were observed compared to negative controls. Food consumption, body weight, organ weight, hematology, clinical chemistry, and histopathology did not show significant variation between controls and treatment groups. However, creatinine, relative lung weight, triglycerides, and monocytes were lower in treated compared to control groups. Significant variations between male and female groups in food consumption, relative organ weight, hematology, clinical chemistry were observed. Histolo-pathology of high-dose treated groups showed fatty liver. CONCLUSION: Echinops kebericho showed LD50 of greater than 5000 mg/kg in acute toxicity study and is well tolerated up to the dose of 600 mg/kg body weight in sub-acute toxicity study.

Antibacterial Activities of Echinops kebericho Mesfin Tuber Extracts and Isolation of the Most Active Compound, Dehydrocostus Lactone.

Echinops kebericho Mesfin is traditionally used for the treatment of various infectious diseases. This study investigated antibacterial activity of the essential oil (EO) and the different fractions of ethanol extract. The most active component was isolated and identified. Isolation and purification was accomplished using chromatographic techniques while identification was done by spectroscopic method. Minimum inhibitory concentration (MIC) was determined using the broth micro-dilution method. In bioactive-guided isolation, percent inhibition was determined using optical density (OD) measurement. The MICs of the essential oil ranged from 78.125 µg/ml to 625 µg/ml, and its activity was observed against methicillin-resistant Staphylococcus aureus (MRSA, NCTC 12493). Ethyl acetate fraction showed high activity against MRSA (NCTC 12493), MIC = 39.075 µg/ml followed by Enterococcus faecalis (ATCC 49532), MIC = 78.125 µg/ml and was least active against Klebsiella pneumoniae (ATCC 700603), MIC = 1,250 µg/ml. MIC of hexane fraction ranged from 156.2 µg/ml to Escherichia coli (ATCC 49532) to 1,250 µg/ml to E. coli (NCTC 11954). The MICs of chloroform fraction ranged from 312.5 to 2500 µg/ml; while butanol fraction could be considered pharmacologically inactive as its MIC value was 2,500 µg/ml for all and no activity against E. coli (NCTC 11954). Dehydrocostus lactone was successfully isolated and identified whose MIC was 19.53 µg/ml against MRSA. Dehydrocostus lactone isolated from E. kebericho M. showed noteworthy antibacterial activity which lends support to ethnopharmacological use of the plant. Further optimization should be done to improve its antibacterial activities and pharmacokinetic profile.

Essential oils as topical anti-infective agents: A systematic review and meta-analysis.

OBJECTIVE: This study summarized evidence on the efficacy and safety of essential oils (EOs) in the treatment of topical infections. DESIGN AND SETTING: Systematic review of clinical trials conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. Electronic databases of the Cochrane, PubMed, EMBASE, Web of Science, and Scopus were searched from inception to November 2018. INTERVENTION: Essential oil of any type, standard treatment and placebo. MAIN OUTCOME MEASURES: Outcomes of the study include total acne count, acne severity index, reduction in total acne surface area, number of non-inflammatory acne lesions and inflammatory acne lesions, microbial cure rate, microbial decolonization rate, and new microbial emergence. RESULTS: Non-significant but higher proportion of MRSA was cleared in EOs group (69% [95%CI: 34%, 96%]) compared to routine care (45% [95%CI: 36%, 53%]). Essential oils significantly lowered level of new MRSA emergence (9% [95% CI: 5%, 14%], I2 = 86.59%) compared to routine care (53% [95%CI: 30%, 75%], I2 = 86.59%). Four of the five studies on acne treatment showed equal or superior efficacy of EOs and the remaining one showed inferior efficacy to a control. In treatment of topical fungal infections, efficacy of essential oils were non-inferior compared to a standard treatment but superior to a placebo. CONCLUSION: Essential oils could be considered as alternative treatment for acne, decolonization of MRSA, and topical fungal infections, yet the low quality and heterogeneity among the studies calls for further studies.