Improving Clerkship to Enhance Patients' Quality of care (ICEPACQ): a baseline study.

BACKGROUND: Proper and complete clerkships for patients have long been shown to contribute to correct diagnosis and improved patient care. All sections for clerkship must be carefully and fully completed to guide the diagnosis and the plan of management; moreover, one section guides the next. Failure to perform a complete clerkship has been shown to lead to misdiagnosis due to its unpleasant outcomes, such as delayed recovery, prolonged inpatient stay, high cost of care and, at worst, death. OBJECTIVE: The objectives of the study were to determine the gap in clerkship, the impact of incomplete clerkship on the length of hospital stay, to explore the causes of the gap in clerkship of the patients and the strategies which can be used to improve clerkship of the patients admitted to, treated and discharged from the gynecological ward in Mbale RRH. METHODOLOGY: This was a mixed methods study involving the collection of secondary data via the review of patients' files and the collection of qualitative data via key informant interviews. The files of patients who were admitted from August 2022 to December 2022, treated and discharged were reviewed using a data extraction tool. The descriptive statistics of the data were analyzed using STATA version 15, while the qualitative data were analyzed via deductive thematic analysis using Atlas ti version 9. RESULTS: Data were collected from 612 patient files. For qualitative data, a total of 8 key informant interviews were conducted. Social history had the most participants with no information provided at all (83.5% not recorded), with biodata and vital sign examination (20% not recorded) having the least number. For the patients' biodata, at least one parameter was recorded in all the patients, with the greatest gap noted in terms of recording the nearest health facility of the patient (91% not recorded). In the history, the greatest gap was noted in the history of current pregnancy (37.5% not provided at all); however, there was also a large gap in the past gynecological history (71% not recorded at all), past medical history (71% not recorded at all), past surgical history (73% not recorded at all) and family history (80% not recorded at all). The physical examination revealed the greatest gap in the abdominal examination (43%), with substantial gaps in the general examination (38.5% not recorded at all) and vaginal examination (40.5% not recorded at all), and the vital sign examination revealed the least gap. There was no patient who received a complete clerkship. There was a significant association between clerkships and the length of hospital stay. The causes of the gap in clerkships were multifactorial and included those related to the hospital, those related to the health worker, those related to the health care system and those related to the patient. The strategies to improve the clerkship of patients also included measures taken by health care workers, measures taken by hospitals and measures taken by the government. CONCLUSION AND RECOMMENDATION: There is a gap in the clerkships of patients at the gynecological ward that is recognized by the stakeholders at the ward, with some components of the clerkship being better recorded than others, and no patients who received a complete clerkship. There was a significant association between clerkships and the length of hospital stay. The following is the recommended provision of clerkship tools, such as the standardized clerkship guide and equipment for patient examination, continuous education of health workers on clerkships and training them on how to use the available tools, the development of SOPs for patient clerkships, the promotion of clerkship culture and the supervision of health workers.

Incidence of home delivery among women living with HIV in Lira, Northern Uganda: a prospective cohort study.

BACKGROUND: Home delivery has been associated with mother-to-child transmission of HIV and remains high among HIV-infected women. Predictors for home delivery in the context of HIV have not been fully studied and understood in Northern Uganda. We therefore aimed to find out the incidence and risk factors for home delivery among women living with HIV in Lira, Northern Uganda. METHODS: This prospective cohort study was conducted between August 2018 and January 2020 in Lira district, Northern Uganda. A total of 505 HIV infected women receiving antenatal care at Lira regional referral hospital were enrolled consecutively and followed up at delivery. We used a structured questionnaire to obtain data on exposures which included: socio-demographic, reproductive-related and HIV-related characteristics. Data was analysed using Stata version 14.0 (StataCorp, College Station, Texas, U.S.A.). We estimated adjusted risk ratios using Poisson regression models to ascertain risk factors for the outcome of interest which was home delivery (which is delivering an infant outside a health facility setting under the supervision of a non-health worker). RESULTS: The incidence of home delivery among women living with HIV was 6.9% (95%CI: 4.9-9.5%). Single women were more likely to deliver at home (adjusted risk ratio = 4.27, 95%CI: 1.66-11). Women whose labour started in the night (night time onset of labour ARR = 0.39, 95%CI: 0.18-0.86) and those that were adherent to their ART (ARR = 0.33, 95%CI: 0.13-0.86) were less likely to deliver at home. CONCLUSION: Home delivery remains high among women living with HIV especially those that do not have a partner. We recommend intensified counselling on birth planning and preparedness in the context of HIV and PMTCT especially for women who are: separated, divorced, widowed or never married and those that are not adherent to their ART.

Potential of Zanthoxylum leprieurii as a source of active compounds against drug resistant Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis (TB) is still a global health problem mainly due to development of resistance and co-infection with the Human immune Virus (HIV). Treatment of multi and extensively drug resistant TB requires use of second line drugs which are less efficacious, expensive and very toxic. This has necessitated a need to search for new treatment regimens especially from medicinal plants. Zanthoxylum leprieurii, a plant species from Rutaceae is used locally in the treatment of tuberculosis in Uganda. The aim of the study was to isolate, identify and characterize bio active compounds from Z. leprieurii stem bark with antimycobacterial activity. METHODS: Crude extracts, fractions and compounds from air dried stem bark of Z. leprieurii were tested against pan sensitive (H37rv), isoniazid resistant (TMC 301) and rifampicin resistant (TMC 331) strains of M. tuberculosis using micro plate alamar blue assay. Isolation of active compounds was done by using column chromatography and thin layer chromatography. They were analysed using nuclear magnetic resonance spectroscopy and mass spectroscopy. RESULTS: The methanol extract had minimum inhibitory concentrations (MIC) of 47.5, 75.3 and 125.0 µg/ml on the pan sensitive strain, rifampicin resistant and isozianid resistant strains of M. tuberculosis respectively. The chloroform extract had MIC values of 260 µg/ml agnaist the pan sensitive strain and 156 µg/ml on the rifampicin resistant strain. Of the sixteen fractions from the methanol extract, fraction Za4 (MIC = 6.3 µg/mL, 23.0 µg/mL, 11.7 µg/mL) and Za6 (MIC = 11.7 µg/mL 31.2 µg/ml, 31.2 µg/ml) were the most active. Three acridone alkaloids; hydroxy-1, 3-dimethoxy-10-methyl-9-acridone (1), 1-hydroxy-3-methoxy-10-methyl-9-acridone (2) and 3-hydroxy-1, 5, 6-trimethoxy-9-acridone (3) were isolated from Za4 and Za6. The MIC of compound 3 was found to be 5.1 µg/ml, 4.5 µg/ml and 3.9 µg/ml on H37rv, TMC 331 and TMC 301 while that of 1 was found to be 1.5 µg/ml, 8.3 µg/ml and 3.5 µg/ml respectively. CONCLUSION: The results of this study suggest that Z. leprieurii is active on resistant strains of M. tuberculosis and could be a potential source of new leads against resistant tuberculosis. It also verifies the local use of the plant in treatment of tuberculosis.

Factors predicting home storage of medicines in Northern Uganda.

BACKGROUND: Medicines are kept in households Worldwide for first aid, treatment of chronic or acute disease conditions. This promotes inappropriate use of medicines and hence the associated risks. The study explored the factors which predict availability and utilization of medicines in households of Northern Uganda. METHOD: A cross sectional survey of 892 households was performed from November-to-December 2012. Five data collectors administered the questionnaires, respondents were requested to bring out any medicines present in their households. Demographic characteristics, drug name, quantity, source, formulation, legibility of drug labels and reasons why the medicines were being kept at home was collected. Data was analyzed using STATA 12.0 at 95% level of significance. RESULTS: Of the households visited, 35.1% (313/892) had drugs. Paracetamol (11.8%), coartem (11.3%), cotrimoxazole (10%), amoxicillin (9.2%) and metronidazole (8.2%) were the major medicines found. Antibacterial drugs were the most commonly (40.1%) kept type of drugs. The medicines present in households were for on-going treatment (48%); 'leftover' (30.5%) and anticipated future use (21.6%). Symptoms of malaria (34.1%) were common in households which had drugs. The medicines kept in homes were mainly from the private sector 60.5% (497/821). The rate of home drug storage was higher 85.3% (267/313) amongst the educated individuals. There was high prevalence 76% (238/313) of self-medication among respondents in households which stored drugs. The average number of medicines in each household was 6 ± 5 with majority (68.1%) having between 1-10 drugs. Previous successful treatment (OR: 1.3; 95% CI: 0.95-1.77), regular income (OR: 1.8; 95% CI: 1.2-2.6) and sex (OR: 0.63; 95% CI: 0.5-0.9) predicted storage of medicines in households in northern Uganda. CONCLUSION: Over a third of households in Northern Uganda store medicines with antibacterial agents being the most common. Self-medication is common among individuals in households which keep drugs. Past successful treatment, regular income and sex predict community home drug storage.

A consortium approach to competency-based undergraduate medical education in Uganda: process, opportunities and challenges.

BACKGROUND: Uganda, like the rest of Africa, is faced with serious health challenges including human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS), other infectious diseases and increasing non-communicable diseases, yet it has a significant shortage of health workers. Even the few health workers available may lack desired competencies required to address current and future health challenges. Reducing Uganda's disease burden and addressing health challenges requires Ugandan medical schools to produce health workers with the necessary competencies. This study describes the process which a consortium of Ugandan medical schools and the Medical Education Partnership for Equitable Services to all Ugandans (MESAU) undertook to define the required competencies of graduating doctors in Uganda and implement competency-based medical education (CBME). METHODS: A retrospective qualitative study was conducted in which document analysis was used to collect data employing pre-defined checklists, in a desktop or secondary review of various documents. These included reports of MESAU meetings and workshops, reports from individual institutions as well as medical undergraduate curricula of the different institutions. Thematic analysis was used to extract patterns from the collected data. RESULTS: MESAU initiated the process of developing competencies for medical graduates in 2011 using a participatory approach of all stakeholders. The process involved consultative deliberations to identify priority health needs of Uganda and develop competencies to address these needs. Nine competence domain areas were collaboratively identified and agreed upon, and competencies developed in these domains. DISCUSSION: Key successes from the process include institutional collaboration, faculty development in CBME and initiating the implementation of CBME. The consortium approach strengthened institutional collaboration that led to the development of common competencies desired of all medical graduates to address priority health challenges in Uganda. It is important that the MESAU consortium continues engaging all stakeholders in medical education to support the implementation and sustainability of CBME in Uganda.

Can an integrated intervention package including peer support increase the proportion of health facility births? A cluster randomised controlled trial in Northern Uganda.

OBJECTIVE: To assess the effect of an integrated intervention package compared with routine government health services on the frequency of health facility births. SETTING: Three subcounties of Lira district in Northern Uganda. DESIGN: A cluster randomised controlled trial where a total of 30 clusters were randomised in a ratio of 1:1 to intervention or standard of care. PARTICIPANTS: Pregnant women at ≥28 weeks of gestation. INTERVENTIONS: Participants in the intervention arm received an integrated intervention package of peer support, mobile phone messaging and birthing kits during pregnancy while those in the control arm received routine government health services ('standard of care'). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of women giving birth at a health facility in the intervention arm compared with the control arm. Secondary outcomes were perinatal and neonatal deaths. RESULTS: In 2018-2019, 995 pregnant women were included in 15 intervention clusters and 882 in 15 control clusters. The primary outcome was ascertained for all except one participant who died before childbirth. In the intervention arm, 754/994 participants (76%) gave birth at a health facility compared with 500/882 (57%) in the control arm. Participants in the intervention arm were 35% more likely to give birth at a health facility compared with participants in the control arm, (risk ratio 1.35 (95% CI 1.20 to 1.51)) and (risk difference 0.20 (95% CI 0.13 to 0.27)). Adjusting for baseline differences generated similar results. There was no difference in secondary outcomes (perinatal or neonatal mortality or number of postnatal visits) between arms. CONCLUSION: The intervention was successful in increasing the proportion of facility-based births but did not reduce perinatal or neonatal mortality. TRIAL REGISTRATION NUMBER: NCT02605369.

Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda.

Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.

Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats.

Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.

Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study.

BACKGROUND: HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection. METHODS: 197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes for CYP2B6 (*6, *11), CYP3A5 (*3, *6, *7), ABCB1 (c.3435C>T and c.4036 A/G rs3842), CYP2A6 (*9, *17) and NR1I3 rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score. RESULTS: During the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment. CYP2B6*6 and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency of CYP2B6*6 genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2. CONCLUSIONS: Efavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations and CYP2B6 genotype but not by rifampicin based anti-TB co-treatment.

Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda.

BACKGROUND: Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance of Plasmodium species to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda. METHODS: An ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor. RESULTS: A total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species were Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica and Mangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed. CONCLUSION: This study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.

Are antibiotic prescription practices in Eastern Uganda concordant with the national standard treatment guidelines? A cross-sectional retrospective study.

OBJECTIVES: This study aimed to evaluate the antibiotic prescription patterns of health workers in Eastern Uganda and more specifically whether they are in accordance with the Ugandan standard treatment guidelines and other indicators of appropriate antimicrobial prescription. METHODS: Patient data were obtained from the health management information system of the outpatient department registers of Soroti and Mbale Regional Referral Hospitals from 2016-2018. RESULTS: The prevalence of non-adherence to treatment guidelines when prescribing antibiotics was 82.6% (95% CI 81.4-83.7%). Guidelines were more likely to be adhered to when prescribing antibiotics for individuals aged 13-19 years compared with their counterparts aged 0-12 years [adjusted odds ratio (aOR) = 0.55, 95% CI 0.40-0.74]. When prescribing antibiotics for males, health workers were twice as likely not to adhere to guidelines compared with when prescribing for females (aOR = 2.09, 95% CI 1.61-2.72). When prescribing cephalosporins and nitroimidazoles, health workers were likely not to adhere to guidelines compared with when prescribing penicillin (cephalosporins, aOR = 1.92, 95% CI 1.28-2.86; nitroimidazoles, aOR = 1.70, 95% CI 1.09-2.65). Health workers were most likely not to follow guidelines when prescribing antibiotics in combination (two antibiotics, aOR = 1.27, 95% CI 1.03-1.56). CONCLUSION: Non-adherence to treatment guidelines for an indicated diagnosis and inappropriate antibiotic prescription are significantly prevalent in Eastern Uganda. Health workers were more likely not to follow guidelines when prescribing for males, children up to 12 years of age and when prescribing cephalosporins, nitroimidazoles or double antibiotic combinations.

Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda.

BACKGROUND: In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population. METHODS: This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis. RESULTS: The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (≥39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65). CONCLUSION: The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers.

Experiences and views of healthcare professionals on the prescription of antibiotics in Eastern Uganda: A qualitative study.

OBJECTIVES: This study aimed to explore the experiences and views of healthcare professionals on antibiotic prescription in Eastern Uganda. METHODS: This was an exploratory qualitative study using semi-structured interviews. Participants included 16 healthcare professionals from Mbale and Soroti Regional Referral Hospitals. Additionally, two workshops were held (one in each hospital) with a total of 56 healthcare professionals to discuss the findings. Thematic analysis was used to analyse the data. RESULTS: Healthcare professionals' prescriptions are influenced by (i) healthcare workers' perceptions and practices, (ii) patients' perceptions and beliefs, and (iii) contextual factors. Healthcare workers' prescriptions depend on the presence of bacterial infection and the severity of the condition, the availability and cost of medication, previous experience with antibiotic prescribing, patient characteristics, and trial and error. They also have limited knowledge and share little information on the use of antibiotics with patients. Patient factors included demand for a particular antibiotic, inability to afford expensive drugs, and limited knowledge about antibiotic use and resistance. Contextual factors that contributed to antibiotic prescribing were an overburdened healthcare system, the influence of pharmaceutical companies and pharmacies, the use of (treatment) guidelines, and difficulties with laboratory services. CONCLUSION: This study showed that healthcare professionals are aware of the problem of antibiotic resistance but do not feel ownership of the problem. Instead, they rather blame the overburdened system, local drug shops, pharmacies, drug representatives and patients. There is a need for a multisectoral and holistic approach toward fighting antibiotic resistance.

Incidence and determinants of perinatal mortality among women with obstructed labour in eastern Uganda: a prospective cohort study.

BACKGROUND: In Uganda, the incidence and determinants of perinatal death in obstructed labour are not well documented. We determined the incidence and determinants of perinatal mortality among women with obstructed labour in Eastern Uganda. METHODS: Between July 2018 and September 2019, 584 with obstructed labour were recruited and followed up to the 7th day postnatal. Information on maternal characteristics, obstetric factors and laboratory parameters was collected. Each patient received the standard perioperative care. We used a generalized linear model for the Poisson family, with a log link and robust variance estimation to determine the association between the exposure variables and perinatal death. RESULTS: Of the 623 women diagnosed with obstructed labour, 584 met the eligibility criteria. There were 24 fresh still births (FSB) and 32 early neonatal deaths (ENND) giving an FSB rate of 43.8 (95% CI 28.3-64.4) deaths per 1000 total births; early neonatal death rate of 58.4 (95% CI 40.3-81.4) deaths per 1000 and an overall perinatal mortality rate of 102.2 (95% CI 79.4-130.6) deaths in the first 7 days of life. A mother being referred in active labour adjusted risk ratio of 2.84 (95% CI: 1.35-5.96) and having high blood lactate levels at recruitment adjusted risk ratio 2.71 (95% CI: 1.26-4.24) were the determinants of perinatal deaths. CONCLUSIONS: The incidence of perinatal death was four times the regional and national average. Babies to women referred in active labour and those with high maternal blood lactate were more likely to die.

Effect of pre-operative bicarbonate infusion on maternal and perinatal outcomes among women with obstructed labour in Mbale hospital: A double blind randomized controlled trial.

INTRODUCTION: Oral bicarbonate solution is known to improve both maternal and perinatal outcomes among women with abnormal labour (dystocia). Its effectiveness and safety among women with obstructed labour is not known. OBJECTIVE: To determine the effect and safety of a single-dose preoperative infusion of sodium bicarbonate on maternal and fetal blood lactate and clinical outcomes among women with obstructed labour (OL) in Mbale hospital. METHODS: We conducted a double blind, randomised controlled trial from July 2018 to September 2019. The participants were women with OL at term (≥37 weeks gestation), carrying a singleton pregnancy with no other obstetric emergency, medical comorbidity or laboratory derangements. INTERVENTION: A total of 477 women with OL were randomized to receive 50ml of 8.4% sodium bicarbonate (238 women) or 50 mL of 0.9% sodium chloride (239 women). In both the intervention and controls arms, each participant was preoperatively given a single dose intravenous bolus. Every participant received 1.5 L of normal saline in one hour as part of standard preoperative care. OUTCOME MEASURES: Our primary outcome was the mean difference in maternal venous blood lactate at one hour between the two arms. The secondary outcomes were umbilical cord blood lactate levels at birth, neonatal sepsis and early neonatal death upto 7 days postnatal, as well as the side effects of sodium bicarbonate, primary postpartum hemorrhage, maternal sepsis and mortality at 14 days postpartum. RESULTS: The median maternal venous lactate was 6.4 (IQR 3.3-12.3) in the intervention and 7.5 (IQR 4.0-15.8) in the control group, with a statistically non-significant median difference of 1.2 mmol/L; p-value = 0.087. Vargha and Delaney effect size was 0.46 (95% CI 0.40-0.51) implying very little if any effect at all. CONCLUSION: The 4.2g of preoperative intravenous sodium bicarbonate was safe but made little or no difference on blood lactate levels. TRIAL REGISTRATION: PACTR201805003364421.

Prevalence of antibiotic-resistant bacteria among patients in two tertiary hospitals in Eastern Uganda.

OBJECTIVE: The aim of this study was to determine the prevalence and antibiotic resistance patterns of bacterial isolates from inpatients and outpatients in Mbale and Soroti regional referral hospitals in Eastern Uganda. METHODS: A retrospective analysis of culture and antibiotic sensitivity test results from the microbiology laboratories of the two tertiary hospitals was conducted for a 3-year period (January 2016-December 2018). RESULTS: Microbiology records of 3092 patients were reviewed and analysed, with 1305 (42.1%) samples yielding clinical isolates. The most prevalent isolates were Escherichia coli (n = 442; 33.9%), Staphylococcus aureus (n = 376; 28.8%), Klebsiella pneumoniae (n = 237; 18.2%), and Streptococcus pneumoniae (n = 76; 5.8%). High rates of antimicrobial resistance were detected across both Gram-negative and Gram-positive bacteria. Escherichia coli and K. pneumoniae were resistant to several agents such as amoxicillin/clavulanate (83.5%; 64.6%), cefotaxime (74.2%; 52.7%), ciprofloxacin (92.1%; 27.8%), gentamicin (51.8%; 76%), imipenem (3.2%; 10.5%), tetracycline (98%; 74.5%), and trimethoprim-sulfamethoxazole (74.1%; 74.3%), respectively. Staphylococcus aureus and S. pneumoniae exhibited the following resistance profile: cefoxitin (44.4%; 40.9%), chloramphenicol (69.1%; 27.6%) clindamycin (21.5%; 24.4%), gentamicin (83.2%; 66.9%), penicillin (46.5%; -) tetracycline (85.6%; 97.6%), trimethoprim-sulfamethoxazole (88%; 91.3%), and vancomycin (41.2%; -). CONCLUSION: We observed high resistance rates to antibiotics among the majority of microorganisms that were isolated from the samples collected from patients in Eastern Uganda. Furthermore, measures should be undertaken locally to improve microbiology diagnostics and to prevent the spread of antibiotic-resistant strains as this impedes the optimal treatment of bacterial infections and narrows the choice of effective therapeutic options.

Genetic variations in ABCB1 and CYP3A5 as well as sex influence quinine disposition among Ugandans.

Quinine is one of the most effective antimalarial drugs, although its clinical use is limited as a result of its narrow safety margin. Quinine is a substrate of the polymorphic p-glycoprotein and CYP3A4/3A5. This study aimed to examine the effects of genetic variations in ABCB1 and CYP3A5 genes, sex, demographic, and biochemical variables (serum albumin, creatinine, alanine aminotransferase and albumin) on quinine disposition among Ugandans. Quinine (600 mg) was orally administered to 140 healthy volunteers. Quinine and its metabolite 3-hydroxyquinine concentrations were determined from 16-hour postdose plasma by high-performance liquid chromatography. CYP3A5 activity was measured using quinine/3-hydroxyquinine ratio (metabolic ratio). Genotyping for a total of 20 single nucleotide polymorphisms in ABCB1 (n = 13) and CYP3A5 (n = 7) was done using Taqman and minisequencing on microarray. There were 20.5- and 13-fold variations in body weight-adjusted plasma quinine concentrations (mean +/- standard deviation, 5.26 +/- 2.5 mumol/L; range, 0.88-18.10 mumol/L) and quinine-to-3-hydroxyquinine metabolic ratio (mean +/- standard deviation, 7.68 +/- 3.3 mumol/L; range, 1.66-22.3 mumol/L), respectively. Weight-adjusted plasma quinine concentration was significantly influenced by sex and ABCB1 haplotype. There was a significant sex difference in quinine metabolic ratio, women being faster metabolizers than men (P = 0.01). CYP3A5 genotype/haplotype significantly (P = 0.03) influenced quinine disposition with a clear CYP3A5*1 gene dose effect. The result confirms that quinine disposition is influenced mainly by sex as well as by ABCB1 and CYP3A5 genotypes. Despite being fast metabolizers, women display higher quinine bioavailability than men in Uganda. This may have clinical significance in determining an individual's susceptibility to quinine-associated adverse reactions such as cinchonism.

Measuring adherence to antiretroviral treatment in resource-poor settings: the feasibility of collecting routine data for key indicators.

BACKGROUND: An East African survey showed that among the few health facilities that measured adherence to antiretroviral therapy, practices and definitions varied widely. We evaluated the feasibility of collecting routine data to standardize adherence measurement using a draft set of indicators. METHODS: Targeting 20 facilities each in Ethiopia, Kenya, Rwanda, and Uganda, in each facility we interviewed up to 30 patients, examined 100 patient records, and interviewed staff. RESULTS: In 78 facilities, we interviewed a total of 1,631 patients and reviewed 8,282 records. Difficulties in retrieving records prevented data collection in two facilities. Overall, 94.2% of patients reported perfect adherence; dispensed medicine covered 91.1% of days in a six month retrospective period; 13.7% of patients had a gap of more than 30 days in their dispensed medication; 75.8% of patients attended clinic on or before the date of their next appointment; and 87.1% of patients attended within 3 days.In each of the four countries, the facility-specific median indicators ranged from: 97%-100% for perfect self-reported adherence, 90%-95% of days covered by dispensed medicines, 2%-19% of patients with treatment gaps of 30 days or more, and 72%-91% of appointments attended on time. Individual facilities varied considerably.The percentages of days covered by dispensed medicine, patients with more than 95% of days covered, and patients with a gap of 30 days or more were all significantly correlated with the percentages of patients who attended their appointments on time, within 3 days, or within 30 days of their appointment. Self reported recent adherence in exit interviews was significantly correlated only with the percentage of patients who attended within 3 days of their appointment. CONCLUSIONS: Field tests showed that data to measure adherence can be collected systematically from health facilities in resource-poor settings. The clinical validity of these indicators is assessed in a companion article. Most patients and facilities showed high levels of adherence; however, poor levels of performance in some facilities provide a target for quality improvement efforts.

Exclusive breastfeeding among HIV exposed infants from birth to 14 weeks of life in Lira, Northern Uganda: a prospective cohort study.

BACKGROUND: Breastfeeding is important for growth, development and survival of HIV exposed infants. Exclusive breastfeeding reduces the risk of morbidity, mortality and increases HIV free survival of infants. Evidence on risk factors for inappropriate breastfeeding in Northern Uganda is limited. OBJECTIVE: This study determined the risk factors for non-exclusivity of breastfeeding in the first 14 weeks of life. METHODS: This prospective cohort study was conducted among 466 mother-infant pairs between August 2018 and February 2020 in Lira district, Northern Uganda. HIV infected pregnant women were enrolled and followed up at delivery, 6- and 14- weeks postpartum. We used a structured questionnaire to obtain data on socio-demographic, reproductive-related, HIV-related characteristics and exclusive breastfeeding. Data were analysed using Stata version 14.0 (StataCorp, College Station, Texas, USA.). We estimated adjusted risk ratios using modified Poisson regression models. RESULTS: The proportion of HIV exposed infants that were exclusively breastfed reduced with increasing age. Risk factors for non-exclusive breastfeeding included infants being born to HIV infected women who: were in the highest socioeconomic strata (adjusted risk ratio = 1.5, 95%CI: 1.01- 2.1), whose delivery was supervised by a non-health worker (adjusted risk ratio = 1.6, 95%CI: 1.01- 2.7) and who had not adhered to their ART during pregnancy (adjusted risk ratio = 1.3, 95%CI: 1.01- 1.7). CONCLUSIONS: HIV infected women: with highest socioeconomic status, whose delivery was not supervised by a health worker and who did not adhere to ART were less likely to practice exclusive breastfeeding. We recommend ART adherence and infant feeding counselling to be emphasised among HIV infected women who are at risk of having a home delivery, those with poor ART adherence and those of higher socioeconomic status. We also recommend integration of these services into other settings like homes, community and work places instead of limiting them to hospital settings. ABBREVIATIONS: HIV: Human Immunodeficiency Virus; ART: Antiretroviral therapy; HEI: HIV exposed infant; PMTCT: Prevention of mother-to-child transmission of HIV; MTCT: Mother-to-child transmission of HIV; AFASS: Acceptable, Feasible, Affordable, Sustainable and Safe; LRRH: Lira regional referral hospital; CI: confidence interval; ARR: Adjusted risk ratio; SD: Standard deviation; PCA: Principal component analysis.

Detectable HIV-RNA Viral Load Among HIV-Infected Pregnant Women on Treatment in Northern Uganda.

BACKGROUND / OBJECTIVES: Detectable HIV viral load among HIV-infected pregnant women remains a public health threat. We aimed to determine factors associated with detectable viral load among HIV-infected pregnant women in Lira, Northern Uganda. METHODS: We conducted a cross-sectional survey among 420 HIV-infected pregnant women attending Lira Regional Referral Hospital using a structured questionnaire and combined it with viral load tests from Uganda National Health Laboratories. We conducted multivariable logistic regression while adjusting for confounders to determine the factors associated with detectable viral load and we report adjusted odds ratios and proportion of women with viral load less than 50 copies/ml and above 1000 copies, respectively. RESULTS: The prevalence of detectable viral load (>50 copies/ml) was 30.7% (95%CI: 26.3% - 35.4%) and >1000 copies/ml was 8.1% (95% CI: 5.7% - 11.1%). Factors associated with detectable viral load were not belonging to the Lango ethnicity (adjusted odds ratio = 1.92, 95%CI: 1.05 - 3.90) and taking a second-line (protease inhibitor-based) regimen (adjusted odds ratio = 4.41, 95%CI: 1.13 - 17.22). CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: HIV-infected pregnant women likely to have detectable viral load included those taking a protease inhibitor-based regimen and those who were not natives of Lira. We recommend intensified clinical and psychosocial monitoring for medication compliance among HIV-infected pregnant women that are likely to have a detectable viral load to significantly lower the risk of vertical transmission of HIV in Lira specifically those taking a protease inhibitor-based regimen and those who are non-natives to the study setting. Much as the third 90% of the global UNAIDS 90-90-90 target has been achieved, the national implementation of PMTCT guidelines should be tailored to its contextual needs.