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.

Prevalence and factors associated with adverse drug events among patients on dolutegravir-based regimen at the Immune Suppression Syndrome Clinic of Mbarara Regional Referral Hospital, Uganda: a mixed design study.

BACKGROUND: In low income countries such as Uganda progress has been made towards achieving the United Nations AIDS programme 95-95-95 target however efforts are still impeded by pretreatment drug resistance and adverse drug events (ADEs) hence introduction of dolutegravir-based antiretroviral therapy as first-line treatment due to a higher genetic barrier to resistance, better tolerability and safety profile. However, recent studies have raised concerns regarding its safety in real-clinical settings due to ADEs and being a recently introduced drug there is need to actively monitor for ADEs, hence this study aimed to establish the prevalence and factors associated with ADEs among patients on dolutegravir-based regimen at the Immune Suppression Syndrome (ISS) Clinic- Mbarara Regional Referral Hospital (MRRH). METHODS: A mixed design study was conducted at ISS Clinic-MRRH among 375 randomly selected patients who had been exposed to DTG-based regimen for at-least 12 weeks. These were interviewed to obtain data on socio-demographics, dietary habits and their files reviewed for ADEs. Data entry was done using Epi-data 3.0 and exported to SPSS 25.0 for analysis. Prevalence was determined as a percentage, and ADE associated factors assessed using bivariate analysis, those found significant were further subjected to multivariate analysis and considered significant at P < 0.05. RESULTS: The prevalence of ADEs among patients on DTG-based regimen was found to be 33.1% (124/375) with 5.6% (7/124) participants discontinued from treatment due ADEs, 4 due to hyperglycemia and 3 liver toxicity. The commonly experienced ADE was allergy at 36.3%. Male sex (AOR 1.571, 95% CI 1.433-1.984), WHO stage one at entry to care (AOR 4.586, 95% CI 1.649-12.754), stage two (AOR 4.536, 95% CI 1.611-12.776), stage three (AOR 3.638, 95% CI 1.262-10.488), were significantly associated with ADEs. Patients with undetectable viral load at initiation of DTG-based regimen were 67.6% less likely to experience ADEs (AOR = 0.324, 95% CI 0.1167-0.629). CONCLUSION: This study reports a prevalence of 33.1% of ADEs among patients on DTG-based regimen. The most commonly experienced ADE was allergy. Male sex, early HIV disease stage at entry into care and detectable viral load at initiation of DTG-based regimen were significantly associated with ADEs. It is crucial to actively monitor patients with these characteristics for ADEs.

The effect of prescription patterns on the performance of the pharmacy department of a Regional Referral Hospital, Uganda.

Background: Poor drug prescription patterns (PP) result in irrational medicine use, avoidable stock outs and drug expiries. Objective: This study primarily assessed the effects of PP on the performance of the pharmacy department (PD) of Mbarara Regional Referral Hospital (MRRH) Uganda. Methods: This was a mixed method cross-sectional study conducted in the outpatient department (OPD) of MRRH, questionnaires were administered to 86 prescribers and 300 patient prescriptions were reviewed. Ethical clearance was granted and informed consent of patients. Data were analysed, presented in the form of graphs, tables. Results: The overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officersThe overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officers. Conclusion: Prescription pattern affected the performance of the PD of MRRH, calling for its continued monitoring to ensure that guidelines are upheld, EML and UCG are availed and utilized.

A cross-sectional assessment of the effects of select training modalities on vaccine cold chain management.

Background: Vaccines offer arguably the most cost-effective public health intervention. Vaccine supply chain management which is a critical building block faces many Human resources challenges mainly due to the special attributes of vaccines. Objective: This study attempted to measure the effect of training on vaccine cold chain handler knowledge and practices. Methods: A cross-sectional research design, using predominantly quantitative data collection techniques, was used. Facilities that have offered vaccination services for more than a year and report through the HMIS system were eligible for selection. Observation checklists and structured questionnaires were used. SPSS was used to analyse data. Results: Vaccine cold chain management among the study group had an average score of 65.33% range (31-85%). The average knowledge score among the study respondents was 62.42% with a range (45-95%). The knowledge of respondents generally increases with an additional increase in the number of training modalities. Conclusions: The status of VCCM is at about 65.33% below the target of 80% set by the EVM. The trainings have an effect on both knowledge of handlers and their practice especially when deployed in a multi-pronged design and thus these trainings need to be aligned to achieve synergy. ABBREVIATIONS: CCE, Cold Chain Equipment; DHIS2, District Health Information Systems 2; DHO, District Health Officer; DPT, Diphtheria, Pertussis, Tetanus; DVS, District Vaccine Stores; EPI, Expanded Program for Immunisation; EVM, Effective Vaccine Management; FEFO, First Expiry First Out; GAVI, Global Alliance for Vaccines and Immunisation; HMIS, Health Information Management Systems; IRC, International Rescue Committee; KII, Key Informant Interview; LIAT, logistics indicator assessment tool; PATH, Program for Appropriate Technology in Health; PHC, Primary Health Care; QPPU, Quantification and Planning and Procurement Unit; SOPs, Standard Operating Procedures; SPSS, Statistical Package for Social Sciences; UNEPI, Uganda National Expanded Program for Immunisation; UNICEF, United Nations Children's Fund; VPD, Vaccine Preventable Diseases; VVM, Vaccine Vial Monitors; WHO, World Health Organisation.

In-vivo and in-silico studies revealed the molecular mechanisms of Colocasia esculenta phenolics as novel chemotherapy against benign prostatic hyperplasia via inhibition of 5α-reductase and α1-adrenoceptor.

Benign Prostatic Hyperplasia (BPH) is a major cause of lower urinary tract infections and erectile dysfunction thus a major contributor to lowering the quality of life among older men. In this study, we investigated the molecular mechanism of Colocasia esculenta (CE) as a novel agent for BPH chemotherapy. In vivo, we assigned 45 male Wistar albino rats about 6 weeks old into 9 experimental groups (n = 5). BPH was induced in groups 2-9 with 3 mg/kg of Testosterone Propionate (TP) subcutaneously. Group 2 (BPH) was not treated. Group 3 was treated with 5 mg/kg Finasteride (standard drug). Group 4-9 were treated each with 200 mg/kg body weight (b.w) of CE crude tuber extracts/fractions (ethanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous). At the end of treatment, we sampled the rats' serum to check the level of PSA. In silico, we conducted a molecular docking of the crude extract of CE phenolics (CyP) previously reported, targeting 5α-Reductase and α1-Adrenoceptor linked to the BPH progressions. We adopted the standard inhibitors/antagonists (5α-reductase: finasteride; α1-adrenoceptor: tamsulosin) of the target proteins as controls. Furthermore, the pharmacological properties of the lead molecules were studied in terms of ADMET using swissadme and pKCSM resources, respectively. Results showed that administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA levels whereas CE crude extracts/fractions significantly (p < 0.05) lowered the serum PSA level. Also, fourteen of the CyPs bind to at least one or two of the target proteins with their binding affinity of between - 9.3 to - 5.6 kcal/mol and - 6.9 to - 4.2 kcal/mol, respectively. The CyPs possess better pharmacological properties compared to the standard drugs. Therefore, they have the potentials to be enlisted for clinical trials towards the management of BPH.

Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats.

BACKGROUND: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. METHODS: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. RESULTS: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. CONCLUSION: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

Prevalence and Risk Factors of Nephrotoxicity Among Adult Cancer Patients at Mbarara Regional Referral Hospital.

BACKGROUND: Nephrotoxicity is common among cancer patients, yet some anti-cancer drugs, for example, platinum derivatives, are nephrotoxic and have narrow therapeutic indices. If nephrotoxicity is not managed, it can progress to kidney injury, which results in unregulated blood pressure, hormonal imbalance, electrolyte imbalance, body fluid imbalance and death. However, the burden of nephrotoxicity among adult cancer patients in Uganda is not documented in the literature. OBJECTIVE: This study assessed the prevalence and risk factors of nephrotoxicity among cancer patients receiving chemotherapy at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). METHODS: The study was a cross-sectional study carried out at the MRRHCU, Uganda. All the 206 adult cancer patients who received at least three cycles of chemotherapy and fulfilled the inclusion criteria were included. A data collection form was used to collect data, which was recorded into Microsoft Excel version 2013. Data were analyzed using Stata version 12.1. RESULTS: Of the 206 participants, 74 (35.9%) developed nephrotoxicity with majority in stage 1 (n = 83, 40.3%) and stage 2 (n = 55, 26.7%). In the multivariate logistic regression of risk factors for nephrotoxicity, age >50 years old (aOR: 1.80, 95% CI: 1.06, 1.91; p > 0.001), hypertension (aOR: 1.71, 95% CI: 1.74, 1.94; p = 0.011) and use of platinum agents (aOR: 2.04, 95% CI: 1.82, 3.34; p = 0.002) were significant independent risk factors of nephrotoxicity. CONCLUSION: About one-third (1/3) of the adult cancer patients at MRRHCU develop nephrotoxicity, which indicates a high burden of nephrotoxicity. The prevention of progression of nephrotoxicity from grades 0, 1 or 2 to grade 3 or 4 is therefore necessary, especially among the patients with risk factors, such as hypertension and age >50 years old and use of platinum agents.

Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox.

BACKGROUND: Aloe vera and Aloe ferox have over the years been among the most sought-after Aloe species in the treatment of ailments worldwide. This review provides categorized literature on the phytochemical and scientifically proven toxicological profiles of A. vera and A. ferox to facilitate their exploitation in therapy. MAIN BODY OF THE ABSTRACT: Original full-text research articles were searched in PubMed, ScienceDirect, Research gate, Google Scholar, and Wiley Online Library using specific phrases. Phenolic acids, flavonoids, tannins, and anthraquinones were the main phytochemical classes present in all the two Aloe species. Most of the phytochemical investigations and toxicity studies have been done on the leaves. Aloe vera and Aloe ferox contain unique phytoconstituents including anthraquinones, flavonoids, tannins, sterols, alkaloids, and volatile oils. Aloe vera hydroalcoholic leaf extract showed a toxic effect on Kabir chicks at the highest doses. The methanolic, aqueous, and supercritical carbon dioxide extracts of A. vera leaf gel were associated with no toxic effects. The aqueous leaf extract of A. ferox is well tolerated for short-term management of ailments but long-term administration may be associated with organ toxicity. Long-term administration of the preparations from A. vera leaves and roots was associated with toxic effects. SHORT CONCLUSION: This review provides beneficial information about the phytochemistry and toxicity of A. vera and A. ferox and their potential in the treatment of COVID-19 which up to date has no definite cure. Clinical trials need to be carried out to clearly understand the toxic effects of these species.

Antibiotic prescription practices among prescribers for children under five at public health centers III and IV in Mbarara district.

INTRODUCTION: Rational use of medicines requires that patients receive medications appropriate to their clinical needs. Irrational prescription of antibiotics has been reported in many health systems across the world. In Uganda, mainly nurses and assistant medical officers (Clinical officers) prescribe for children at level III and IV primary care facilities (health center II and IV). Nurses are not primarily trained prescribers; their antibiotic prescription maybe associated with errors. There is a need to understand the practices of antibiotic prescription among prescribers in the public primary care facilities. We therefore determined antibiotic prescription practices of prescribers for children under five years at health center III and IV in Mbarara district, South Western Uganda. METHODS: This was a retrospective descriptive cross-sectional study. We reviewed outpatient records of children <5 years of age retrospectively. Information obtained from the outpatient registers were captured in predesigned data abstraction form. Health care providers working at health centers III and IV were interviewed using a structured questionnaire. They provided information on socio-demographic, health facility, antibiotic prescription practices and availability of reference tools. Data was analyzed using STATA software version 13∙0. RESULTS: There were 1218 outpatients records of children under five years reviewed and 35 health care providers interviewed. The most common childhood illness diagnosed was upper respiratory tract infection. It received the most antibiotic prescription (53%). The most commonly prescribed oral antibiotics were cotrimoxazole and amoxicillin, and ceftriaxone and benzyl penicillin were the commonest prescribed injectable antibiotics. Up to 68.4% of the antibiotic prescription was irrational. No prescriber or facility factors were associated with irrational antibiotic prescription practices. CONCLUSION: Upper respiratory tract infection is the most diagnosed condition in children under five years with Cotrimoxazole and Amoxicillin being the most commonly prescribed antibiotics. Antibiotics are being prescribed irrationally at health centers III and IV in Mbarara District. Training and support supervision of prescribers at health centers III and IV in Mbarara district need to be prioritized by the district health team.

Anticonvulsant and anxiolytic activity of the leaf aqueous and ethanolic extracts of Melanthera scandens in a rat model.

Modern drug therapy of epilepsy is complicated by the inability of drugs to control seizures in some patients and side effects that range in severity from minimal impairment of the central nervous system to death from aplastic anemia or hepatic failure. Medicinal plants used in traditional medicine for the treatment of epilepsy have been scientifically shown to possess promising anticonvulsant activities in animal models for screening for anticonvulsant activity and can be a source of newer anticonvulsants. The aim of this study was to investigate the preliminary phytochemical properties, anticonvulsant and anxiolytic activities of Melanthera scandens aqueous and ethanolic extracts. Phytochemicals from the aqueous and ethanolic extracts were screened by standard methods. Anticonvulsant activity was evaluated against pentylenetetrazol (PTZ)-induced seizure model in rats. The effect of the extract at oral dose levels of 250, 500 and 1000 mg/kg was evaluated in an experimental rat model, using diazepam (5 mg/kg) as positive control. Anxiolytic activity was performed using elevated plus maze method. Phytochemical screening revealed that M. scandens extracts contain carbohydrates, flavonoids, saponins, glycosides, tannins, terpenoids, phenols and phytosterols. The aqueous extract at a dose of 500 mg/kg significantly increased seizure latency (P=0.0023), while the ethanolic extract did not have a significant effect on seizure latency. Both extracts significantly reduced the seizure severity (P= 0.0155), and provided up to 100% protection against PTZ induced death at 1000 mg/kg. Both extracts had no significant effect on the duration of PTZ induced seizures. Both extracts were found to increase the number of entries and the time spent in the open arms of the maze at a dose of 250 mg/kg, indicating anxiolytic activity, which was not seen at higher doses (500 and 1000 mg/kg). The total numbers of entries into the closed arm were significantly reduced at 500 and 1000 mg/kg oral doses of both extracts, indicating a reduction in locomotor activity of the rats. The results obtained in this study suggest that both the aqueous and ethanolic extracts of M. scandens possess anticonvulsant and anxiolytic activities in a rat model.

Tackling sexually transmitted infection burden in Ugandan communities living in the United Kingdom: a qualitative analysis of the socio-cultural interpretation of disease and condom use.

BACKGROUND: Despite being in a different country and social environment, Ugandans living in the UK still reportedly have the lowest rates of condom usage and one of the highest incidences of STIs in UK. In Uganda, STIs and HIV prevalence has been reported to be on the increase. Understanding peoples' beliefs and the attitudes that influence their behavior is a key factor to effectively designing control programs. METHODS: A qualitative study that interviewed 37 purposively selected Ugandans living in the UK was conducted. Lay theories and interpretations were derived using thematic analysis. RESULTS: Condoms generally carried a lot of stigma and were perceived for use primarily in extramarital affairs and pregnancy control. HIV/AIDS was most feared due to its perceived socio-psychological or physical effects unlike other STIs described as "non-threatening" due to wide availability of "quality" treatment in UK. Notions of trust, the purpose of relationships, symptom recognition and partner selection greatly influenced decisions to undertake consistent condom use. CONCLUSIONS: The socio-cultural understanding of STIs, sex, trust and relationships are symbolic in influencing consistent condom use among Ugandans. This indicates a need to acknowledge community beliefs and values about sexual health and design messages about STIs and condoms that would help eliminate these serious condom-related misconceptions.