Association between biomarkers of inflammation and dyslipidemia in drug resistant tuberculosis in Uganda.

BACKGROUND: Active tuberculosis (TB) significantly increases the risk of cardiovascular disease, but the underlying mechanisms remain unclear. This study aimed to investigate the association between inflammation biomarkers and dyslipidemia in patients with drug-resistant TB (DR-TB). METHODS: This was a secondary analysis of data from a cross-sectional multi-center study in Uganda conducted 2021. Participants underwent anthropometric measurements and laboratory tests included a lipid profile, full haemogram and serology for HIV infection. Dyslipidemia was defined as total cholesterol > 5.0 mmol/l and/or low-density lipoprotein cholesterol > 4.14 mmol/l, and/or triglycerides (TG) ≥ 1.7 mmol/l, and/or high density lipoprotein cholesterol (HDL-c) < 1.03 mmol/l for men and < 1.29 mmol/l for women. Biomarkers of inflammation were leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil/lymphocyte (NLR), platelet/lymphocyte, and lymphocyte/monocyte (LMR) ratios, mean corpuscular volume (MCV), and the systemic immune inflammation index (SII) (neutrophil × platelet/lymphocyte). Modified Poisson Regression analysis was used for determining the association of the biomarkers and dyslipidemia. RESULTS: Of 171 participants, 118 (69.0%) were co-infected with HIV. The prevalence of dyslipidemia was 70.2% (120/171) with low HDL-c (40.4%, 69/171) and hypertriglyceridemia (22.5%, 38/169) being the most common components. Patients with dyslipidemia had significantly higher lymphocyte (P = 0.008), monocyte (P < 0.001), and platelet counts (P = 0.014) in addition to a lower MCV (P < 0.001) than those without dyslipidemia. Further, patients with dyslipidemia had lower leucocyte (P < 0.001) and neutrophil (P = 0.001) counts, NLR (P = 0.008), LMR (P = 0.006), and SII (P = 0.049). The MCV was inversely associated with low HDL-C (adjusted prevalence ratio (aPR) = 0.97, 95% CI 0.94-0.99, P = 0.023) but was positively associated with hypertriglyceridemia (aPR = 1.04, 95% CI 1.00-1.08, P = 0.052). CONCLUSIONS: Individuals with dyslipidemia exhibited elevated lymphocyte, monocyte, and platelet counts compared to those without. However, only MCV demonstrated an independent association with specific components of dyslipidemia. There is need for further scientific inquiry into the potential impact of dyslipidemia on red cell morphology and a pro-thrombotic state among patients with TB.

"Swallowing these drugs every day, you get tired": a mixed-methods study to identify Barriers and facilitators to retention and HIV Viral Load suppression among the Adolescents living with HIV in TASO Mbale and TASO Soroti centers of excellence.

Background: Adolescents aged 10-19, living with HIV (ALHIV) lag behind in attaining optimal viral load suppression (VLS) rates and retention in care, an important impediment to reaching epidemic control. This study aimed to identify barriers and facilitators to both VLS and retention among in the sub-population who seek care from TASO Mbale and TASO Soroti centers of excellence, to facilitate adaptation of the operation triple zero in the setting. Methods: We used a mixed methods approach, extracting secondary data on ALHIV who were active in care during April-June 2022 quarter to determine one year retention in care. Analysis was done in STATA Corp, 15.0. We used logistic regression to determine associated factors and adjusted odds ratio (aOR) to report level of predictability, using 95% confidence interval (CI) and P<0.05 for statistical significance. For qualitative component, purposive sampling of 59 respondents was done. Focused group discussions, key informant interviews, and in-depth interviews were used to collect data. Thematic content analysis was done using Atlas ti. Results: There were 533 ALHIV, with 12-month retention rate of 95.9% and VLS rate of 74.9%. Predictors for good VLS included good adherence [aOR:95%CI 0.066(0.0115, 0.38) P=0.02], being on first line treatment [aOR:95%CI 0.242 (0.0873,0.6724) P=0.006]. For retention, they include being a school going [aOR:95%CI 0.148(0.024,0.9218) P=0.041], multi month dispensing aOR:95%CI 32.6287(5.1446,206.9404) P<0.001, OVC enrolment aOR:95%CI 0.2625(0.083, 0.83) P=0.023]. Meanwhile key barriers included: individual ones such as internal stigma, lack of transport and treatment/drug fatigue; facility-level such as prolonged waiting time and lack of social activities; community level include stigma and discrimination, inadequate social support and food shortage. In terms of facilitators, individual level ones include good adherence and knowledge of one's HIV status; facility-level such as provision of adolescent friendly services and community-level such as social support and decent nutrition. Conclusions: VLS rate was sub-optimal mainly due to poor adherence. HIV programs could utilize the barriers and facilitators identified to improve VLS. Conversely, retention rate at one year was good, likely due to provision of adolescent friendly health services. ALHIV and their caregivers need to be empowered to sustain retention and improve VLS. Contributions to science: By accentuating the barriers and facilitators to retention and VLS among the ALHIV, we ensure HIV programs continue to prioritize effective interventions and discard others as the epidemic evolves. To this, our findings strategically validate the effectiveness of provision of adolescent friendly services and client-centered care in attaining good retention rate.Secondly, being a mixed-methods study, complementarily adds value to the existing body of knowledge on barriers and facilitators while reminding programmers that VLS remains sub-optimal and more efforts are necessary.Finally, different stakeholders could use our findings to advocate for more resources to address some of the barriers such as food shortage, empowerment of ALHIV and caregivers and strengthening skilling programs for ALHIV, especially the out-of-school.

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.

Improving retention and HIV viral load suppression among adolescents living with HIV in TASO Soroti and TASO Mbale centers of excellence using Operation Triple Zero model: a before and after study protocol.

BACKGROUND: Retention in care and HIV viral load suppression remains sub-optimal among HIV positive adolescents in many settings including TASO Uganda, despite the implementation of interventions such as regimen optimization and community-based approaches like multi-month drug dispensing. To this end, the implementation of additional intervention is urgently required to address gaps in current programming which include inadequate centralization of the HIV positive adolescents and their caregivers in the designs. This study, thus, proposes to adapt and implement the Operation Triple Zero (OTZ) model in TASO Soroti and Mbale centers to improve both retention and viral load suppression among the adolescents living with HIV. METHODOLOGY: A before and after study design is preferred, employing both qualitative and quantitative approaches. To identify barriers and facilitators to retention and HIV viral load suppression among the HIV positive adolescents, secondary data, focused group discussions, and key informant interviews will be used to understand perspectives of the adolescents, their caregivers, and the health-workers. The Consolidated Framework for Implementation Research (CFIR) will help in designing the intervention, while Knowledge to Action (K2A) will support the adaptation process. To test the intervention, Reach, Effectiveness, Adaption, Implementation and Maintenance (RE-AIM) framework will be used. A paired t-test will be used to compare means of retention and viral load suppression in the before and after study periods. DISCUSSION: This study aims at adapting and implementing the OTZ model in TASO Soroti and Mbale Centers of Excellence (COEs) to attain optimal retention and HIV viral load suppression rates among the HIV positive adolescents in care. Uganda is yet to adapt the touted OTZ model and findings from this study will be important in providing the necessary lessons to inform a policy shift for potential scale up of the model. Furthermore, results of this study could provide additional evidence for the effectiveness of OTZ in attaining optimal HIV treatment outcomes among the adolescents living with HIV.

The Effect of COVID-19 Restrictions on General and HIV Positive Inpatient Admissions and Treatment Outcomes: An Uncontrolled Before-and-after Study at a Ugandan Tertiary Hospital.

Measures to contain the Corona Virus Disease 2019 (COVID-19) pandemic curtailed access to prevention and treatment services for endemic infectious diseases like HIV. We used an uncontrolled before-and-after study design to compare general and HIV positive (HIV+) inpatient outcomes at a tertiary hospital in Uganda, using electronic records of medical inpatients. Data was downloaded, cleaned in Microsoft Excel, and exported to STATA for analysis. We determined the difference in number of admissions and median length of hospital stay using Mann-Whitney U test; and difference in median survival and incidence rates of mortality using Kaplan - Meier statistics, between the pre- and peri-COVID-19 groups. Of 7506 patients admitted to Kiruddu NRH, 50.8% (3812) were female and 18.7% (1,401) were aged 31-40 years, and 18.8% (1,411) were HIV+. Overall, 24.6% (1849) died. Total admissions were lower (2192 vs. 5314 patients), overall mortality rate higher (41.8% vs. 17.6%, p < 0.01), median length of hospital stay longer (6 vs. 4 days, p < 0.01) and median survival shorter (11 vs. 20 days, Chi-square = 252.05, p < 0.01) in the peri- than in pre-COVID-19 period. The adjusted hazard ratio (aHR) of death was 2.08 (95% CI: 1.85-2.23, p < 0.01) in the peri- compared to the pre-COVID-19 period. These differences were more pronounced in HIV + patients. Compared to pre-COVID-19, the peri-COVID-19 period registered lower inpatient admissions but poorer treatment outcomes for general and HIV + inpatients. Emerging epidemic responses should minimize disruption to inpatient care, especially for HIV + individuals.

HIV, tuberculosis, diabetes mellitus and hypertension admissions and premature mortality among adults in Uganda from 2011 to 2019: is the tide turning?

BACKGROUND: The growing burden of diabetes mellitus (DM) and hypertension (HTN) on the background of endemic Human Immuno-deficiency Virus (HIV) and tuberculosis (TB) is a concern in low- and middle-income countries. We aimed to describe annual trends in admissions, mortality rates and premature mortality (years of potential life lost-YPLLs) due to HIV, tuberculosis (TB), diabetes mellitus (DM) and hypertension (HTN) in Uganda. METHODS: We conducted a retrospective cohort study, retrieving electronic records of adults admitted to Mulago and Kiruddu national referral hospitals medical wards between 1st January 2011 and 31st December 2019. We used STATA BE 17.0 and GraphPad Prism 8.0.2 to compute total admissions, inpatient crude mortality rates, and YPLLs; and demonstrate trends using Mann-Kendall test. RESULTS: Of 108,357 admissions, 55,620 (51.3%) were female, 15,300 (14.1%) were recorded in 2012, and 22,997 (21.2%) were aged 21-30 years. HIV, TB, DM and HTN accounted for 26,021 (24.0%); 9537 (8.8%); 13,708 (12.7) and 13,252 (12.2%) of all admissions, respectively. Overall inpatient mortality was 16.7% (18,099/108,357), 53.5% (9674/18,099) were male, 21.5% (3898) were aged 31-40 years and 2597 (14.4%) were registered in 2013. HIV, TB, DM and HTN accounted for 35.6% (6444), 14.6% (2646), 9.1% (1648) and 11.8% (2142) of all deaths, respectively. Total admissions (Kendall's tau-B = - 0.833, p < 0.001) and deaths declined (Kendall's tau-B = - 0.611, p = 0.029). A total of 355,514 (mean = 20.8 years, SD 30.0) YPLLs were recorded, of which 54.6% (191,869) were in males; 36.2% (128,755) were among those aged 21-30 years and were recorded in 2012 (54,717; 15.4%). HIV, TB, DM and HTN accounted for 46.5% (165,352); 19.5% (69,347); 4.8% (16,991) and 4.5% (16,167) of YPLLs, respectively. Proportionate contribution of HIV to deaths and YPLLs declined, remained stagnant for TB; and increased for both DM and HTN. CONCLUSION: TB and HIV account for higher though declining, while DM and HTN account for lower albeit rising morbidity and premature mortality among adult medical patients in Uganda. TB prevention and treatment; and DM/HTN service integration in HIV care should be optimized and scaled up.

Tetanus in Uganda: Clinical Outcomes of Adult Patients Hospitalized at a Tertiary Health Facility Between 2011 and 2020.

Background: Tetanus is a vaccine-preventable infectious disease associated with high mortality rates. Increased vaccination coverage globally and locally has resulted in substantial declines in the number of individuals diagnosed with tetanus. We report annual trends in tetanus admissions and deaths over a decade at a national referral hospital in Uganda. Methods: This was a retrospective cohort study, using data from an electronic database of patients admitted to medical wards at a national referral hospital between 2011 and 2020. Data were abstracted on demographic characteristics, that is, length of hospital stay and mortality outcome. Admission and mortality rate trends were analyzed using the Mann-Kendall's trend test, whereas Kaplan-Meier survival curves were used to compare gender survival rates. Results: During the study period, 459 individuals were admitted with tetanus. Of these, 85.8% (394 of 459) were males, and 26.1% (120 of 459) were aged 20 years or less. Overall, 48.8% (224 of 459) participants died, 85.3% (191 of 224) of whom were males (85.3%, n = 191), although females had a higher mortality rate (50.8%, 33 of 65 vs 48.5%, 191 of 394). Those aged 31-40 years accounted for 23.7% (53 of 224) of the deaths; and 88.7% (197 of 224) of the deaths occurred within the first 7 days of admission. The total number of tetanus admissions declined (TauA = -.6444, P = .0116). However, mortality rates remained stable (TauA = .0222, P > .999). The average length of hospital stay was 8.1 days (standard deviation, 7.5; range, 1-46). Conclusions: Although tetanus admissions declined, mortality rate remained high. Males were disproportionately affected. We recommend quality-of-care audits for inpatient care improvement and more research on the determinants of infection and mortality to inform vaccination for at-risk men.

Incidence of tuberculosis among PLHIV on antiretroviral therapy who initiated isoniazid preventive therapy: A multi-center retrospective cohort study.

INTRODUCTION: Isoniazid preventive therapy (IPT) is effective in treating tuberculosis (TB) infection and hence limiting progression to active disease. However, the durability of protection, associated factors and cost-effectiveness of IPT remain uncertain in low-and-middle income countries, Uganda inclusive. The Uganda Ministry of health recommends a single standard-dose IPT course for eligible people living with HIV (PLHIV). In this study we determined the incidence, associated factors and median time to TB diagnosis among PLHIV on Antiretroviral therapy (ART) who initiated IPT. MATERIALS AND METHODS: We conducted a retrospective cohort study at eleven The AIDS Support Organization (TASO) centers in Uganda. We reviewed medical records of 2634 PLHIV on ART who initiated IPT from 1st January 2016 to 30th June 2018, with 30th June 2021 as end of follow up date. We analyzed study data using STATA v.16. Incidence rate was computed as the number of new TB cases divided by the total person months. A Frailty model was used to determine factors associated with TB incidence. RESULTS: The 2634 individuals were observed for 116,360.7 person months. IPT completion rate was 92.8%. Cumulative proportion of patients who developed TB in this cohort was 0.83% (22/2634), an incidence rate of 18.9 per 100,000 person months. The median time to TB diagnosis was 18.5 months (minimum- 0.47; maximum- 47.3, IQR: 10.1-32.4). World Health Organization (WHO) HIV clinical stage III (adjusted hazard ratio (aHR) 95%CI: 3.66 (1.08, 12.42) (P = 0.037) and discontinuing IPT (aHR 95%CI: 25.96(4.12, 169.48) (p = 0.001)), were associated with higher odds of TB diagnosis compared with WHO clinical stage II and IPT completion respectively. CONCLUSION: Incidence rates of TB were low overtime after one course of IPT, and this was mainly attributed to high completion rates.

Missed opportunities in tuberculosis investigation and associated factors at public health facilities in Uganda.

BACKGROUND: The incidence of tuberculosis (TB) is high in Uganda; yet, TB case detection is low. The population-based survey on the prevalence of TB in Uganda revealed that only 16% of presumptive TB patients seeking care at health facilities were offered sputum microscopy or chest-X ray (CXR). This study aimed to determine the magnitude of, and patient factors associated with missed opportunities in TB investigation at public health facilities of Wakiso District in Uganda. METHODS: A facility-based cross-sectional survey was conducted at 10 high volume public health facilities offering comprehensive TB services in Wakiso, Uganda, among adults (≥18 years) with at least one symptom suggestive of TB predefined according to the World Health Organisation criteria. Using exit interviews, data on demographics, TB symptoms, and clinical data relevant to TB diagnosis were collected. A missed opportunity in TB investigation was defined as a patient with symptoms suggestive of TB who did not have sputum and/or CXR evaluation to rule out TB. Poisson regression analysis was performed to determine factors associated with missed opportunities in TB investigation. RESULTS: Two hundred forty-seven (247) patients with presumptive TB exiting at antiretroviral therapy (ART) clinics (n = 132) or general outpatient clinics (n = 115) at public health facilities were recruited into this study. Majority of participants were female (161/247, 65.2%) with a mean + SD age of 35.1 + 11.5 years. Overall, 138 (55.9%) patients with symptoms suggestive of TB disease did not have sputum and/or CXR examinations. Patients who did not inform health workers about their TB related symptoms were more likely to miss a TB investigation (adjusted prevalence ratio (aPR): 1.68, 95%CI; 1.36-2.08, P < 0.001). However, patients who reported duration of cough of 2 weeks or more were less likely to be missed for TB screening (aPR; 0.69, 95%CI; 0.56-0.86, p < 0.001). CONCLUSION: There are substantial missed opportunities for TB diagnosis in Wakiso District. While it is important that patients should be empowered to report symptoms, health workers need to proactively implement the WHO TB symptom screen tool and complete the subsequent steps in the TB diagnostic cascade.

Diabetic Complications and Associated Factors: A 5-Year Facility-Based Retrospective Study at a Tertiary Hospital in Rwanda.

INTRODUCTION: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from defects in insulin production, insulin action, or both. Despite advances in DM diagnosis and management, the incidence of DM-related complications remains high. This study aimed to determine patterns of common complications and associated factors among hospitalized patients in Rwanda. METHODS: A cross-sectional study, with retrospective chart review, was conducted at CHUK from July to August, 2021. Charts for DM patients admitted from January 2016 to December 2020 were considered while those inaccessible at the time of data collection were excluded. Linear regression model was used to assess the relationship between dependent and independent variables with a p < 0.05 considered statistically significant. RESULTS: A total of 246 charts were reviewed. The median age was 56 years (IQR: 14-90). More than half of participants (n = 135; 54.9%) were females; majority from the Central region (n = 138; 56.7%). Recorded DM risk factors included alcohol intake (n = 81; 48.5%); smoking (n = 40; 24.2%), obesity (n = 43; 52.4%), and family history of DM (n = 27; 56.3%). Majority (n = 153; 84.5%) had type 2 DM and (n = 147; 69%) had known their diagnosis for at least 6 years. Hypertension (n = 124, 50.4%), acute hyperglycemic state (n = 59, 24%), nephropathy (n = 58, 23.6%), and stroke (n = 38, 15.4%) were frequently reported complications. Nearly all participants (n = 81, 95.2%) with complications had poor glycemic control. Alcohol intake, age ≥45 years, and T1DM were associated with higher odds of DM complications (aOR = 8, 95% CI = 2-32.6, p = 0.003, aOR = 6.2, 95% CI = 1.4-27.6, p = 0.016 and aOR = 14.1, 95% CI = 1.2-161.5, p = 0.034, respectively). Duration of DM (p = 0.001) was significant at bivariate analysis. CONCLUSION: DM complications were prevalent among the studied population with poor glycemic control mainly influenced by alcohol consumption and duration of DM. Expansion of integrated DM and hypertension screening services to lower-level centers is needed to reduce the associated morbidity and mortality.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study.

INTRODUCTION: Systematic screening for TB among patients presenting to care and among high risk populations is recommended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches implemented by a large urban TB project in central Uganda. METHODS: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (numbers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and community TB registers. RESULTS: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). CONCLUSION: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years.

Comparative yield of different active TB case finding interventions in a large urban TB project in central Uganda: a descriptive study

Introduction: Systematic screening for TB among patients presenting to care and among high risk populations is recom- mended to improve TB case finding. We aimed to describe the comparative yield of three TB screening approaches imple- mented by a large urban TB project in central Uganda. Methods: We abstracted data on the screening cascade from 65 health facilities and their surrounding communities (num- bers screened, with presumptive TB, receiving a diagnostic test and diagnosed with TB) from the different clinic and com- munity TB registers. Results: From January 2018 to December 2019, 93,378 (24%) of all patients screened at health facilities had presumptive TB; 77,381 (82.9%) received a diagnostic test and 14,305 (18.5%) were diagnosed with TB. The screening yield (the number of patients diagnosed with TB out of all patients screened) was 0.3% and was three times higher among men than women (0.6% vs 0.2% p<0.01). During targeted community screening interventions, 9874 (21.1%) of all patients screened had presumptive TB; 7034 (71.2%) of these received a diagnostic test and 1699 (24.2%) were diagnosed with TB. The screening yield was higher among men, (3.7% vs 3.3% p<0.01) and highest among children 0-14 (4.8% vs 3.2% p<0.01). Conclusion: Targeted community TB screening interventions improve access to TB diagnosis for men and children 0-14 years

Tolerability of oral itraconazole and voriconazole for the treatment of chronic pulmonary aspergillosis: A systematic review and meta-analysis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) requires prolonged treatment with itraconazole or voriconazole. However, adverse events (AEs) are common with the use of these agents, with the need to discontinue the offending drug in a significant proportion of the patients. The aim of this study was to evaluate the frequency of adverse events of itraconazole and voriconazole for the treatment of CPA. METHODS: We searched Embase and Medline to select clinical studies providing information on AEs to itraconazole or voriconazole for the treatment of CPA from inception to May 2020. Reviews, single case reports, and case series reporting less than 10 patients were excluded. Random effect meta-analysis was performed using STATA 16.0. RESULTS: We included 9 eligible studies with an overall total of 534 CPA patients enrolled. Of these, 69% (n = 366) were treated with voriconazole and 31% (n = 168) with itraconazole. The median daily dose of both itraconazole and voriconazole used was 400mg. In a pooled analysis, AEs were observed in 36% (95% CI: 20-52%, N = 366) of patients on voriconazole and 25% (95% CI: 18 to 31%, N = 168) in those treated with itraconazole. Discontinuation rate due to AEs was the same for both drugs; 35% (47/366) and 35% (15/168) for voriconazole and itraconazole, respectively. There were 70 AEs reported with itraconazole use, the commonest being cardiotoxicity (29%). Skin AEs (28%) were the most frequent among the 204 AEs reported with voriconazole use. None of the studies compared the tolerability of itraconazole head-to-head with voriconazole. CONCLUSIONS: AEs due itraconazole and voriconazole are common and may lead to discontinuation of treatment in a significant proportion of patients. This information can be used to educate patients prior to commencement of these antifungal therapies. PROSPERO REGISTRATION NUMBER: CRD42020191627.

Attendance and Utilization of Antenatal Care (ANC) Services: Multi-Center Study in Upcountry Areas of Uganda.

INTRODUCTION: Globally every year 529,000 maternal deaths occur, 99% of this in developing countries. Uganda has high maternal and neonatal morbidity and mortality ratios, typical of many countries in sub-Saharan Africa. Recent findings reveal maternal mortality ratio of 435:100,000 live births and neonatal mortality rate of 29 deaths per 1000 live births in Uganda; these still remain a challenge. Women in rural areas of Uganda are two times less likely to attend ANC than the urban women. Most women in Uganda have registered late ANC attendance, averagely at 5.5 months of pregnancy and do not complete the required four visits. The inadequate utilization of ANC is greatly contributing to persisting high rates of maternal and neonatal mortality in Uganda. This study was set to identify the factors associated with late booking and inadequate utilization of Antenatal Care services in upcountry areas of Uganda. METHOD: Cross-sectional study design with mixed methods of interviewer administered questionnaires, focus group discussions and key informant interviews. Data was entered using Epidata and analyzed using Stata into frequency tables using actual tallies and percentages. Ethical approval was sought from SOM-REC MakCHS under approval number "#REC REF 2012-117" before conducting the study. RESULTS: A total of four hundred one were enrolled with the majority being in the age group 20 - 24 years (mean age, 25.87 ± 6.26). Health workers played a great role (72.04%), followed by the media (15.46%) and friends (12.50%) in creating awareness about ANC. A significant number of respondents went to TBAs with reasons such as "near and accessible", "my husband decided", and "they are the only people I know". 37.63% of the respondents considered getting an antenatal Card as an importance of ANC. 71 (19.67%) respondents gave a wrong opinion (late) on booking time with reasons like demands at work, no problems during pregnancy, advised by friends, just to get a card, long distance and others didn't know. Almost half of the respondents never knew the recommended number of visits. Religion, occupation, level of education, and parity were found to influence place of ANC attendance, number of ANC visits and booking time. Husbands were necessary to provide financial support, accompany their wives ANC clinic, and ensure that they complete the visits. But their response was poor due to: fear of routine investigations and constrained economically. CONCLUSION: The study findings show the actual rural setting of ANC services attendance and utilization. Much sensitization has to be done specifically in these rural areas to empower pregnant women and their husbands as to improve ANC attendance and utilization.