Self-reported gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs in female students with dysmenorrhoea at Makerere University: prevalence, discontinuation and associated factors. a cross sectional study.

BACKGROUND: Primary dysmenorrhoea occurs in up to 50% of menstruating females. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used therapeutic remedies for dysmenorrhoea in Uganda. However, NSAIDs are associated with a 3-5 fold increase in the risk of gastrointestinal (GI) adverse drug effects. OBJECTIVES: We aimed to determine the prevalence and associated factors of self-reported NSAID-related GI adverse effects in female students who use NSAIDs in managing dysmenorrhoea-associated pain at Makerere University. DESIGN: A cross-sectional study. SETTING: Makerere University's main campus, situated North of Kampala, Uganda. PARTICIPANTS: 314 female students pursuing an undergraduate programme at Makerere University and residing in different halls of residence and hostels. OUTCOMES: Social demographic data, menstrual history and treatment data. RESULTS: Overall, 314 valid responses were received from female students with a median age of 22 years (IQR: 18-29 years). The median age at menarche was 13 years (IQR: 9-18 years). 41% (n=129/314) of the respondents had used medication for dysmenorrhoea and 32% (n=41/129) of whom reported NSAID-associated GI adverse effects with nausea being the most frequently reported (44%, n=18/41)Factors independently associated with GI adverse effects were: age at menarche (p=0.026), duration of menstruation (p=0.030) and use of ibuprofen (p=0.005). Females taking ibuprofen for dysmenorrhoea were about four times as likely to have NSAID-associated GI adverse effects (adjusted OR 3.87, 95% CI 1.51 to 9.91) than those who did not receive ibuprofen. Logistic regression was used to determine factors associated with self-reported adverse effects of NSAIDs among the female students. A p<0.05 was considered statistically significant. CONCLUSION: We found a considerably high prevalence of NSAID-related GI adverse effects driven by factors such as age at menarche and ibuprofen use.

Navigating duplication in pharmacovigilance databases: a scoping review.

OBJECTIVES: Pharmacovigilance databases play a critical role in monitoring drug safety. The duplication of reports in pharmacovigilance databases, however, undermines their data integrity. This scoping review sought to provide a comprehensive understanding of duplication in pharmacovigilance databases worldwide. DESIGN: A scoping review. DATA SOURCES: Reviewers comprehensively searched the literature in PubMed, Web of Science, Wiley Online Library, EBSCOhost, Google Scholar and other relevant websites. ELIGIBILITY CRITERIA: Peer-reviewed publications and grey literature, without language restriction, describing duplication and/or methods relevant to duplication in pharmacovigilance databases from inception to 1 September 2023. DATA EXTRACTION AND SYNTHESIS: We used the Joanna Briggs Institute guidelines for scoping reviews and conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Two reviewers independently screened titles, abstracts and full texts. One reviewer extracted the data and performed descriptive analysis, which the second reviewer assessed. Disagreements were resolved by discussion and consensus or in consultation with a third reviewer. RESULTS: We screened 22 745 unique titles and 156 were eligible for full-text review. Of the 156 titles, 58 (47 peer-reviewed; 11 grey literature) fulfilled the inclusion criteria for the scoping review. Included titles addressed the extent (5 papers), prevention strategies (15 papers), causes (32 papers), detection methods (25 papers), management strategies (24 papers) and implications (14 papers) of duplication in pharmacovigilance databases. The papers overlapped, discussing more than one field. Advances in artificial intelligence, particularly natural language processing, hold promise in enhancing the efficiency and precision of deduplication of large and complex pharmacovigilance databases. CONCLUSION: Duplication in pharmacovigilance databases compromises risk assessment and decision-making, potentially threatening patient safety. Therefore, efficient duplicate prevention, detection and management are essential for more reliable pharmacovigilance data. To minimise duplication, consistent use of worldwide unique identifiers as the key case identifiers is recommended alongside recent advances in artificial intelligence.

Dyslipidemia among adult people living with HIV on dolutegravir - based antiretroviral therapy at a private tertiary hospital in Kampala, Uganda: burden and determinants.

BACKGROUND: Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting. METHODS: We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3-82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1-76.7) followed by high TG (20.2%, 95%CI: 16.3-24.9), high TC (12.0%, 95%CI: 9.0-15.9) and high LDL (6.5%, 95%CI: 4.3-9.6). Female sex (aPR:1.55, 95%CI: 1.32-1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04-1.53, p = 0.018) were significantly associated with dyslipidemia. CONCLUSION: We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.

Epidemiology of adverse drug reactions to antihypertensive, antithrombotic and antidiabetic medications among adult inpatients at a National Referral Hospital, Uganda.

INTRODUCTION: Treatment for hypertension, thrombosis and type 2 diabetes mellitus is long term and usually requires a combination of drugs which increases the risk of adverse drug reactions (ADRs). This study aimed to establish the prevalence at admission, incidence during hospitalization and characteristics of ADRs linked to antihypertensive, antithrombotic and antidiabetic drugs among adult inpatients in Uganda. METHODS: We conducted a secondary analysis of data from a previously assembled prospective cohort study in Uganda's Mulago National Referral Hospital. We reviewed the files of inpatients who received antihypertensive, antithrombotic and/or antidiabetic medications prior to and/or during hospitalization. The modified Schumock and Thornton Preventability Scale, the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events and the World Health Organization - Uppsala Monitoring Centre seriousness criteria were used to characterize the ADRs. RESULTS: More than a quarter (27%, 42/155) of the inpatients experienced an ADR at admission or during hospitalization. The point prevalence of ADRs at admission was 8% (13/155) and the incidence of ADRs during hospitalization was 23% (36/155). Forty-one percent (35/86) of the ADRs were serious and the majority (59%, 51/86) were preventable. CONCLUSION: One in 13 inpatients experienced an ADR on admission and one in four experienced an ADR that developed during hospitalization. Clinicians ought to prescribe medicines with lower ADR risk profile for cardiovascular and/or diabetic patients whenever possible.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

BACKGROUND: The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. METHODS: In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%ß respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. RESULTS: Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%ß at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%ß at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %ß from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively. CONCLUSION: We demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.

Hospital admissions attributed to adverse drug reactions in tertiary care in Uganda: burden and contributing factors.

Background: Adverse drug reactions (ADRs) contribute to the burden of disease globally and of particular concern are ADR-related hospital admissions. Objectives: This study sought to determine the burden, characteristics, contributing factors and patient outcomes of ADRs that were the primary diagnosis linked to hospital admission among inpatients in Uganda. Design: We conducted a cross-sectional secondary analysis of data from a prospective cohort study of adult inpatients aged 18 years and older at Uganda's Mulago National Referral Hospital from November 2013 to April 2014. Methods: We reviewed clinical charts to identify inpatients with an ADR as one of the admitting diagnoses and, if so, whether or not the hospital admission was primarily attributed to the ADR. Logistic regression was used to determine factors associated with hospital admissions primarily attributed to ADRs. Results: Among 762 inpatients, 14% had ADRs at hospital admission and 7% were primarily hospitalized due to ADRs. A total of 235 ADRs occurred among all inpatients and 57% of the ADRs were the primary diagnosis linked to hospital admission. The majority of ADRs occurred in people living with HIV and were attributed to antiretroviral drugs. HIV infection [aOR (adjusted odds ratio) = 2.97, 95% confidence interval (CI): 1.30-6.77], use of antiretroviral therapy (aOR = 5.46, 95% CI: 2.56-11.68), self-medication (aOR = 2.27, 95% CI: 1.14-4.55) and higher number of drugs used (aOR = 1.13, 95% CI: 1.01-1.26) were independently associated with hospital admissions attributed to ADRs. Conclusion: Antiretroviral drugs were often implicated in ADR-related hospital admissions. HIV infection (whether managed by antiretroviral therapy or not), self-medication and high pill burden were associated with hospital admissions attributable to ADRs. The high HIV burden in Sub-Saharan Africa increases the risk of ADR-related hospitalization implying the need for emphasis on early detection, monitoring and appropriate management of ADRs associated with hospital admission in people living with HIV.

Prevalence and contributing factors of hospital admissions attributed to adverse drug reactions in Uganda Introduction: Adverse drug reactions (ADRs) are a big problem in many parts of the world and of particular concern is a situation where patients are admitted primarily because of an ADR. We sought to determine the burden, characteristics, contributing factors and patient outcomes of ADRs that were the primary diagnosis linked to hospital admission in Uganda. Methods: We analysed data collected from a prospective cohort study of adult inpatients aged 18 years and older at Uganda's Mulago National Referral Hospital from November 2013 to April 2014. We reviewed clinical charts to identify inpatients in whom an ADR was one of the admitting diagnoses and, if so, whether or not the ADR was the primary diagnosis linked to hospital admission. We used statistical tests to assess for contributing factors of hospital admissions attributable to ADRs. Results: Among 762 inpatients, 108 had ADRs at admission and 56 were primarily admitted due to ADRs. A total of 235 ADRs occurred among all inpatients and 135 of the ADRs were the primary diagnosis linked to hospital admission. The majority of ADRs occurred in people living with HIV and were linked to antiretroviral drugs. HIV infection, use of antiretroviral therapy, self-medication and higher number of drugs used were associated with hospital admissions primarily attributed to ADRs. Conclusion: To prevent hospital admissions attributed to ADRs, patients need to be warned against self-medication, health workers and patients need to be reminded of the importance of early detection, monitoring and appropriate management of ADRs among the HIV-infected (whether managed by ART or not) and those patients taking many drugs.

Blood glucose outcomes of anti-retroviral therapy naïve Ugandan people with HIV with pre-diabetes mellitus initiated on dolutegravir for 48 weeks.

Background: The Uganda ministry of Health recommends frequent blood glucose monitoring for the first six months on dolutegravir, in people with HIV (PWH) having pre-diabetes mellitus (pre-DM). We sought to determine if indeed PWH with pre-diabetes started on dolutegravir had worse blood glucose outcomes at 48 weeks compared to those with normal blood glucose. Methods: In this matched cohort study, we compared 44 PWH with pre-DM and 88 PWH with normal blood glucose at baseline. The primary outcome was change in mean fasting blood glucose (FBG) from baseline to week 48 and 2-hour blood glucose (2hBG) from baseline to week 36 compared between the two groups. Results: There was significant increase in FBG in PWH with normal blood glucose (mean change in FBG(FBG): 3.9mg/dl, 95% confidence interval (95% CI): (2.2, 5.7), p value (p) = < 0.0001) and decrease in those with pre-DM (FBG: -6.1mg/dl, 95%CI (-9.1, -3.2), p = < 0.0001) at 48 weeks. 2hBG at 36 weeks was significantly lower than at baseline in both groups with the magnitude of reduction larger in those with pre-DM at 12 weeks (adjusted differences in mean drop in 2hBG (a2hBG): -19.69mg/dl, 95%CI (-30.19, -9.19), p = < 0.0001) and 36 weeks (a2hBG: -19.97mg/dl, 95%CI (-30.56, -9.39), p = < 0.0001). Conclusion: We demonstrated that Ugandan ART naïve PWH with pre-diabetes at enrollment have consistent improvement in both fasting blood glucose and glucose tolerance over 48 weeks on dolutegravir. Intensified blood glucose monitoring of these patients in the first six months of dolutegravir may be unnecessary.

Dolutegravir use over 48 weeks is not associated with worsening insulin resistance and pancreatic beta cell function in a cohort of HIV-infected Ugandan adults.

Background The Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance. Methods In this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%ß respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance. Results Of the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%ß at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%ß at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %ß from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively.

The prevalence and factors associated with mental disorders in a community setting in central Uganda.

BACKGROUND: Mental disorders are known to predict poverty, morbidity and mortality. In resource limited settings, low levels of mental health literacy (MHL) and high mental illness stigma (MIS) have been sighted as possible factors that may impede access to mental health care. However, little has been done to examine the association between mental disorders and these factors (MHL and MIS) in sub-Saharan Africa. METHODS: We assessed for the prevalence of major depressive disorders (MDD), substance use disorders (SUD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), documented MHL and MIS among 814 participants from 24 villages in central Uganda. We conducted regression analyses to examine the association between the prevalence of mental disorders, demographic factors as well as MIS and MHL. RESULTS: Over two thirds of the participants 581 (70%) were female. The mean age of the participants was 38 years (SD± 13.5). The prevalence of mental disorders ranged from 6.8-32%. Participants who were older were less likely to screen positive for GAD (OR 0.98; 0.96-0.99), female gender was protective against SUD (OR 0.46; 0.3-0.68) and those with MDD had lower education level (OR 0.23; 0.1-0.53). The mean MIS score was 11.3 (SD± 5.4) with a range of 6-30 and the mean MHL score was 21.7 (SD ±3.0) with a range of 10-30. MIS was negatively associated with GAD [ß = -1.211 (-2.382 to -0.040)]. There no statistically significant association between MHL and a mental disorder. CONCLUSION: There was a high prevalence of mental disorders in the community that we studied. Adequate resources should be allocated to address this burden.

Facilitators and Barriers to Uptake of the Med Safety Mobile App for Adverse Drug Reaction Reporting by Health Workers in Uganda: A Qualitative Study.

INTRODUCTION: Adverse drug reactions (ADRs) are an important public health challenge worldwide; however, pharmacovigilance systems are plagued by under-reporting. Mobile technologies, including mobile applications such as Med Safety, could strengthen ADR reporting. We explored the acceptability, and factors that could influence uptake of, Med Safety for ADR reporting by health workers in Uganda. METHODS: The study took place between July and September 2020 in 12 HIV clinics in Uganda and employed a qualitative exploratory research design. We conducted 22 in-depth interviews and 3 mixed-gender focus group discussions (49 participants) with a diverse range of health workers. We analysed the data using a thematic approach. RESULTS: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app. Uptake of the app was favoured by the younger, technology proficient, health worker demographic; the app's offline and two-way risk communication functionalities; availability of free internet hotspots at some health facilities; goodwill and willingness of health workers to report ADRs; and the cumbersome nature of conventional ADR reporting tools. Potential barriers to the uptake of Med Safety were the perceived lengthy processes of initial app registration and completion of multiple screens during ADR reporting; challenges with health workers' smartphones (incompatibility with application, no space for more applications, low battery charge); high cost of internet data; poor internet connectivity; difficulty in recognising ADRs, language barrier and poor feedback to ADR reporters. CONCLUSION: There was goodwill among the health workers to adopt Med Safety for ADR reporting and the majority would recommend the app to other health workers. Training with practice increased acceptability of the app and should be integral in all future app roll-out campaigns. The identified facilitators and barriers could be used to appropriately guide future research and implementation to promote the uptake of Med Safety for pharmacovigilance in low- and middle-income countries.

Blood glucose trajectories and incidence of diabetes mellitus in Ugandan people living with HIV initiated on dolutegravir.

BACKGROUND: Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. METHODS: Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. RESULTS: The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): - 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: - 7.26 mg/dl, IQR: - 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. CONCLUSION: We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Pharmacovigilance in low- and middle-income countries: A review with particular focus on Africa.

Low- and middle-income countries (LMIC) face unique challenges with regard to the establishment of robust pharmacovigilance systems capable of generating data to inform healthcare policy and practice. These include the limited integration and reliability of pharmacovigilance systems across LMIC despite recent efforts to harmonize pharmacovigilance rules and regulations in several regional economic communities. There are particular challenges relating to the need to translate reporting tools into numerous local languages and the low numbers of healthcare providers relative to number of patients, with very short consultation times. Additional factors frequent in LMIC include high uptake of herbal and traditional medication, mostly by self-medication; disruptive political conflicts jeopardizing fragile systems; and little or no access to drug utilization data, which makes it difficult to reliably estimate the true risks of medicines use. Pharmacovigilance activities are hindered by the scarcity of well-trained personnel with little or no budgetary support from national governments; high turnover of pharmacovigilance staff whose training involves a substantial amount of resources; and little awareness of pharmacovigilance among healthcare workers, decision makers and consumers. Furthermore, little collaboration between public health programmes and national medicines regulatory authorities coupled with limited investment in pharmacovigilance activities, especially during mass drug administration for neglected tropical diseases and mass vaccinations, produces major challenges in establishing a culture where pharmacovigilance is systematically embedded. Very low spontaneous reporting rates with poor quality reports hinders robust signal detection analyses. This review summarises the specific challenges and areas of progress in pharmacovigilance in LMIC with special focus on the situation in Africa.

An Evaluation of Antibiotic Prescription Rationality at Lower Primary Healthcare Facilities in Three Districts of South-Western Uganda.

Purpose: Antimicrobial resistance is now one of the leading five causes of death globally. This study evaluated the rationality of antibiotic prescriptions at lower primary care levels in three districts of Southwestern Uganda. Methods: This prospective cross-sectional study reviewed 9899 antibiotic prescriptions at 39 health centers following a drug delivery cycle by National Medical Stores in three phases (19 days each on average). Phase 1 started 3 days after delivery, mid-way (Phase 2) and towards the end (Phase 3). The proportion of rationally prescribed antibiotics was determined using a modified criterion by Badar and in reference to Uganda Clinical Guidelines (UCG). Using multivariate logistic regression, the factors associated with rational prescription were determined with 95% confidence intervals. Results: Seven of every 10 antibiotic prescriptions were irrational. Half the prescriptions were made by unauthorized personnel (nurses) and many of the pediatric prescriptions (916, 46.5%) did not bear body weight measurements to guide appropriate dosing. Also, the proportion of rational prescriptions in reference to UCG, 2016 was very low (3387, 34.2%). However, a high proportion of antibiotic prescriptions were legibly written (9462, 95.7%), prescribed by generic names (9083, 91.8%) and had a diagnosis (9677, 97.8%) indicated. Multivariate logistic analysis showed that; availability of medicines (phase 1) (phase 2 AOR=1.14, 95% CI:1.02-1.28, phase 3, AOR=1.23, 95% CI:1.1-1.38), legibly written prescription (AOR=0.61, 95% CI: 0.47-0.78), indication of a date on the prescription (AOR=0.56, 95% CI0.38-0.81) and being a medical officer were factors associated with rational antibiotic prescription. Conclusion: We observed a high rate of irrational prescription in the study sites and the majority of these were by unauthorized personnel. A review of antibiotic use policies and focused interventions is crucial in these settings.

Using community influencer groups to address COVID-19 misinformation and vaccine hesitancy in Uganda: a protocol for a prospective quasi-experimental study.

INTRODUCTION: Coronovirus disease 2019 (COVID-19) misinformation has been reported globally and locally. This has the potential to influence public risk perception and reduce the acceptance of the COVID-19 vaccine. This study aims to determine the prevalence of COVID-19 misinformation and vaccine hesitancy in Buikwe district. The study will also pilot a social mobilisation intervention using community influencers and determine its effect on COVID-19 misinformation and vaccine hesitancy. METHODS AND ANALYSIS: The study will be conducted using a quasi-experimental study design, in which two villages will be assigned to the intervention arm and two villages assigned controls. A mixed-methods technique employing both quantitative and qualitative methods will be employed. Data will be collected from healthy men and women aged 18 years and older who reside in the selected villages. The study will be implemented in three phases. First, a baseline study of 12 in-depth interviews with key informants and 6 focus group discussions and a household survey among 632 participants will be done. Second, an intervention employing dialogue-based social mobilisation approach using 10-man community groups per village will be developed and implemented. These will be trained and facilitated to educate and sensitise their communities about COVID-19. Third, an end-line household survey done after 6-months of intervention implementation in the four villages to assess the effect of the intervention on COVID-19 misinformation and vaccine hesitancy. Post-intervention qualitative evaluation will be done after the endline quantitative assessment. Preliminary analysis of the endline quantitative analysis will inform any revisions of the discussion guides. Qualitative data collected will be analysed using thematic content analysis while quantitative data will be analysed using χ2 tests or logistic regression, by intention-to-treat analysis. ETHICS AND DISSEMINATION: The study was reviewed for ethics and approved by the Makerere University School of Health Sciences Research Ethics Committee, reference number MakSHSREC-2020-45 and the Uganda National Council of Science and Technology, reference number HS1140ES. Study finding shall be presented to the district and national COVID-19 task force and at scientific gatherings and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: PACTR202102846261362.

Patient experiences of sexual dysfunction after transition to dolutegravir-based HIV treatment in mid-Western Uganda: a qualitative study.

BACKGROUND: The literature on dolutegravir (DTG)-based HIV treatment has focused on assessing therapeutic efficacy particularly with regard to viral load suppression. However, little empirical attention has been devoted to understanding the effects of DTG on quality of life, in particular sexual health and functioning in PLHIV. This study focused on understanding patient experiences of sexual dysfunction, after transition to DTG-based regimens in Rwenzori region in Mid-Western Uganda. METHODS: We adopted a qualitative exploratory research design. Between August and September 2021, we conducted sixteen in-depth interviews and six focus group discussions (48 participants) with patients reporting 'new' sexual dysfunction after transition to DTG-based regimens at seven health facilities in mid-Western Uganda. Data were analyzed by thematic approach. RESULTS: Decreased libido was reported in both sexes of patients within weeks of transition to DTG-based regimens. Diminished interest in sex was more frequently reported among women while men complained of a marked reduction in the frequency of sex. Women reported loss of psycho-social attraction to their long-term male partners. Erectile dysfunction was common among men in this sample of patients. Patients described their experiences of sexual dysfunction as an affront to their socially-constructed gender identities. Patients described tolerating sexual adverse drug reactions (ADRs) as a necessary tradeoff for the extension in life granted through antiretroviral therapy. A number of women reported that they had separated from their spouses as a result of perceived drug-induced sexual dysfunction. Marital strife and conflict arising from frustration with sexual-partner dysfunction was frequently reported by participants in both sexes. Several participants indicated experiencing insecurity in their heterosexual relationships due to difficulties in sexual functioning. CONCLUSION: Sexual dysfunction following transition to DTG-based regimens is common in both sexes of PLHIV, who indicated that they had no prior experience of difficulties in sexual health. Our findings demonstrate that sexual ADRs negatively impact self-esteem, overall quality of life and impair gender relations. DTG-related sexual health problems merit increased attention from HIV clinicians. Further research is warranted to assess the prevalence of DTG-associated sexual dysfunction in patients in Uganda.

Smell and Taste Symptoms Among Patients With Mild and Moderately Severe COVID-19 Infection in Uganda.

Objective: Patients with coronavirus disease 2019 (COVID-19) may present with smell/taste dysfunctions in addition to the most frequent symptoms (fever, cough, and shortness of breath) or as the first symptom or even the only symptom. There is paucity of documentation of prevalence and characteristics of smell/taste dysfunction in COVID-19 in sub-Saharan Africa. The aim of this study was to determine the prevalence of smell/taste symptoms in our setting to institute local evidence-based practice. Study Design: Cross-sectional study. Setting: COVID-19 treatment centers in Uganda. Methods: Patients hospitalized for COVID-19 at 3 treatment sites from November 2020 to March 2021 were recruited. Following written informed consent, their demographics, comorbidities, and smell/taste symptoms data were collected using a questionnaire. Results: Of 614 patients recruited, 409 (63.8%) had mild symptoms and 232 (36.2%) had moderate to severe symptoms; 64.3% were male, and the mean age was 48.6 ± 15.51 years. In total, 23.1% were health responders and 12.2% had contact with a positive case. Smell and taste impairment was seen in 425 (66.3%) patients, second to cough (71.6%). Smell and taste impairment was seen in 162 (38.1%) as the first symptom, in 128 (30%) as the only symptom, and significantly more in those with mild COVID-19 symptoms (P < .001). Conclusion: COVID-19 manifests with various symptoms, including impairment of smell and taste. This study shows that smell and taste impairment is common and can be the first and only symptom in less severe COVID-19 infections. Therefore, inclusion in the Ministry of Health guidelines is strongly recommended.

Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial.

INTRODUCTION: Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance-monitoring the effects of medicines-is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union's Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda's National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown. METHODS AND ANALYSIS: A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only. ETHICS AND DISSEMINATION: Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia. TRIAL REGISTRATION NUMBER: PACTR202009822379650.

Implementation of a peer support intervention to promote the detection, reporting and management of adverse drug reactions in people living with HIV in Uganda: a protocol for a quasi-experimental study.

INTRODUCTION: Patients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda's pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report ADRs and improve ADR management through linkage to care. We seek to test the feasibility and effect of a peer support intervention on ADR reporting by PLHIV receiving combination antiretroviral therapy (cART) in Uganda; identify barriers and facilitators to the intervention; and characterise ADR reporting and management. METHODS AND ANALYSIS: This is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months. ETHICS AND DISSEMINATION: The study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia. TRIAL REGISTRATION NUMBER: ISRCTN75989485.

High Burden of Adverse Drug Reactions to Isoniazid Preventive Therapy in People Living With HIV at 3 Tertiary Hospitals in Uganda: Associated Factors.

BACKGROUND: HIV is one of the most important risk factors of tuberculosis (TB)-related morbidity and mortality. Isoniazid preventive therapy (IPT) is recommended to prevent latent TB reactivation in patients with HIV. However, due to multiple therapies and comorbidities, these patients are predisposed to adverse drug reactions (ADRs) that lead to increased morbidity and mortality. The aim of this study was to determine the prevalence and associated factors of suspected IPT-linked ADRs in HIV-positive patients using IPT. METHODS: A cross-sectional study was conducted between February and March 2020 at 3 regional referral hospitals (RRHs) in central Uganda. We sampled 660 HIV-positive patients aged 10 years or older who received IPT between July and December 2019 inclusive. Patients were interviewed using a pretested structured questionnaire, and their treatment records were reviewed. A modified Poisson regression model with clustered robust standard errors was used to identify factors associated with suspected IPT-linked ADRs. RESULTS: The prevalence of the suspected ADRs was 51% (334 of the 660; 95% confidence interval [CI]: 18% to 83%). Patients self-reported 7-fold the number of suspected ADRs documented in the clinical files by the health care workers. Musculoskeletal symptoms were the most frequently experienced reaction (14%), followed by dizziness (13%) and peripheral neuropathy (11%). Serious suspected ADRs were experienced by 12% of the study participants; the most common were hepatotoxicity (26%), dizziness (23%), and neuropathy (17%). Female sex (aPR [adjusted prevalence ratio]: 0.92, 95% CI: = 0.88 to 0.95), study site (aPR: 1.09, 95% CI: = 1.09 to 1.18), level of education (aPR: 0.94, 95% CI: = 0.94 to 0.99), history of TB (aPR: 0.93, 95% CI: = 0.87 to 0.99), good IPT adherence (aPR: 1.16, 95% CI: = 1.05 to 1.29), and use of protease inhibitor (PI)-based antiretroviral therapy (aPR: 1.01, 95% CI: = 1.00 to 1.02) were significantly associated with suspected IPT-linked ADRs. CONCLUSION: The prevalence of suspected IPT-linked ADRs is high, and hepatotoxicity is the most commonly reported serious suspected ADR. Patients self-reported more suspected ADRs than those documented in clinical files by health care workers. Patient engagement could improve ADR detection and potentially strengthen the pharmacovigilance system. Patients with a high risk of ADR ought to be monitored regularly to enable early detection and management.

Provider perspectives on the acceptability and tolerability of dolutegravir-based anti-retroviral therapy after national roll-out in Uganda: a qualitative study.

BACKGROUND: The World Health Organization recommends dolutegravir (DTG) as the for first-line and second-line antiretroviral therapy (ART) worldwide. However, little is known about the acceptability and tolerability of DTG-based ART at routine points-of-care in Uganda. We set out to explore the perceptions of clinicians in ART clinics regarding the acceptability and tolerability of DTG-based ART since national roll-out in March 2018 in Uganda. METHODS: We adopted a qualitative exploratory design involving 49 participants. Between September 2020 and February 2021, we conducted 22 in-depth interviews with clinicians in the ART clinics of 12 purposively selected health facilities across Uganda. The selection of study sites ensured diversity in facility ownership-type (public/private), level of service delivery (tertiary/secondary/primary) and the four major geographic sub-regions of Uganda. We conducted three focus group discussions with 27 clinicians in the participating facilities. Data were analyzed by thematic approach. RESULTS: Clinicians in ART clinics acknowledged that DTG-based ART is well tolerated by the majority of their patients who appreciate the reduced pill burden, perceived less side effects and superior viral load suppression. However, they reported that a number of their patients experience adverse drug reactions (ADRs) after being transitioned to DTG. Hyperglycemia is, by far, the most commonly reported suspected ADR associated with DTG-based regimens and was cited in all but two participating facilities. Insomnia, weight gain and reduced libido are among the other frequently cited suspected ADRs. In addition, clinicians in ART clinics perceived some of the suspected ADRs as resulting from drug interactions between dolutegravir and isoniazid. Weak diagnostic capacities and shortage of associated commodities (e.g. glucometers and test kits) were reported as impediments to understanding the full extent of ADRs associated DTG-based ART. CONCLUSION: While DTG-based regimens were perceived by clinicians in ART clinics to be well tolerated by the majority of their patients, they also reported that a number of patients experience suspected ADRs key among which were hyperglycemia, insomnia and reduced libido. Based on the perspectives of clinicians, we recommend that future studies examine the prevalence of dolutegravir-induced hyperglycemia in patients in Uganda.