Browsing by Author "Nakiyingi, Lydia"
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Item Acute Hypoxaemic Respiratory Failure In A Low-Income Country: A Prospective Observational Study Of Hospital Prevalence And Mortality(BMJ Open Respiratory Research, 2020) Kwizera, Arthur; Nakibuuka, Jane; Nakiyingi, Lydia; Sendagire, Cornelius; Tumukunde, Janat; Katabira, Catherine; Ssenyonga, Ronald; Kiwanuka, Noah; Kateete, David Patrick; Joloba, Moses; Kabatoro, Daphne; Atwine, Diana; Summers, CharlotteLimited data exist on the epidemiology of acute hypoxaemic respiratory failure (AHRF) in low-income countries (LICs). We sought to determine the prevalence of AHRF in critically ill adult patients admitted to a Ugandan tertiary referral hospital; determine clinical and treatment characteristics as well as assess factors associated with mortality.We conducted a prospective observational study at the Mulago National Referral and Teaching Hospital in Uganda. Critically ill adults who were hospitalised at the emergency department and met the criteria for AHRF (acute shortness of breath for less than a week) were enrolled and followed up for 90 days. Multivariable analyses were conducted to determine the risk factors for death.A total of 7300 patients was screened. Of these, 327 (4.5%) presented with AHRF. The majority (60 %) was male and the median age was 38 years (IQR 27–52). The mean plethysmographic oxygen saturation (SpO2) was 77.6% (SD 12.7); mean SpO2/FiO2 ratio 194 (SD 32) and the mean Lung Injury Prediction Score (LIPS) 6.7 (SD 0.8). Pneumonia (80%) was the most common diagnosis. Only 6% of the patients received mechanical ventilatory support. In-hospital mortality was 77% with an average length of hospital stay of 9.2 days (SD 7). At 90 days after enrolment, the mortality increased to 85%. Factors associated with mortality were severity of hypoxaemia (risk ratio (RR) 1.29 (95% CI 1.15 to 1.54), p=0.01); a high LIPS (RR 1.79 (95% CI 1.79 1.14 to 2.83), p=0.01); thrombocytopenia (RR 1.23 (95% CI 1.11 to 1.38), p=0.01); anaemia (RR 1.15 (95% CI 1.01 to 1.31), p=0.03) ; HIV co-infection (RR 0.84 (95% CI 0.72 to 0.97), p=0.019) and male gender (RR 1.15 (95% CI 1.01 to 1.31) p=0.04).The prevalence of AHRF among emergency department patients in a tertiary hospital in an LIC was low but was associated with very high mortality. Pneumonia was the most common cause of AHRF. Mortality was associated with higher severity of hypoxaemia, high LIPS, anaemia, HIV co-infection, thrombocytopenia and being male.Item Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda(BMC Cardiovascular Disorders, 2022) Baruch Baluku, Joseph; Nabwana, Martin; Nalunjogi, Joanitah; Muttamba, Winters; Mubangizi, Ivan; Nakiyingi, Lydia; Ssengooba, Willy; Olum, Ronald; Bongomin, Felix; Andia-Biraro, Irene; Worodria, WilliamTuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. Methods In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. Results Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had ≥ 1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14– 3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06). Conclusion There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.Item Evaluation of Cepheid’s Xpert MTB/RIF Test on Pleural Fluid in the Diagnosis of Pleural Tuberculosis in a High Prevalence HIV/TB Setting(PLoS ONE, 2014) Lusiba, John K.; Nakiyingi, Lydia; Kirenga, Bruce J.; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L.; Mayanja-Kizza, HarrietDiagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid’s Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Methods: Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Results: Of the 116 participants [female 50%, mean age 34 (SD 613], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Conclusion: Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.Item Evaluation of in-house PCR for diagnosis of smear-negative pulmonary tuberculosis in Kampala, Uganda(BMC Research Notes, 2012) Nakiyingi, Lydia; Kateete, David P.; Ocama, Ponsiano; Worodria, William; Sempa, Joseph B.; Asiimwe, Benon B.; Katabazi, Fred A.; Katamba, Achilles; Huang, Laurence; Joloba, Moses L.; Mayanja-Kizza, HarrietNucleic acid amplification tests (NAATs) have offered hope for rapid diagnosis of tuberculosis (TB). However, their efficiency with smear-negative samples has not been widely studied in low income settings. Here, we evaluated in-house PCR assay for diagnosis of smear-negative TB using Lowenstein-Jensen (LJ) culture as the baseline test. Two hundred and five pulmonary TB (PTB) suspects with smear-negative sputum samples, admitted on a short stay emergency ward at Mulago Hospital in Kampala, Uganda, were enrolled. Two smear-negative sputum samples were obtained from each PTB suspect and processed simultaneously for identification of MTBC using in-house PCR and LJ culture. Results: Seventy two PTB suspects (35%, 72/205) were LJ culture positive while 128 (62.4%, 128/205) were PCR-positive. The sensitivity and specificity of in-house PCR for diagnosis of smear-negative PTB were 75% (95% CI 62.6-85.0) and 35.9% (95% CI 27.2-45.3), respectively. The positive and negative predictive values were 39% (95% CI 30.4-48.2) and 72.4% (95% CI 59.1-83.3), respectively, while the positive and negative likelihood ratios were 1.17 (95% CI 0.96-1.42) and 0.70 (95% CI 0.43-1.14), respectively. One hundred and seventeen LJ culturenegative suspects (75 PCR-positive and 42 PCR-negative) were enrolled for follow-up at 2 months. Of the PCR-positive suspects, 45 (60%, 45/75) were still alive, of whom 29 (64.4%, 29/45) returned for the follow-up visit; 15 (20%, 15/75) suspects died while another 15 (20%, 15/75) were lost to follow-up. Of the 42 PCR-negative suspects, 22 (52.4%, 22/42) were still alive, of whom 16 (72.7%, 16/22) returned for follow-up; 11 (26.2%, 11/42) died while nine (21.4%, 9/42) were lost to follow-up. Overall, more PCR-positive suspects were diagnosed with PTB during follow-up visits but the difference was not statistically significant (27.6%, 8/29 vs. 25%, 4/16, p = 0.9239). Furthermore, mortality was higher for the PCR-negative suspects but the difference was also not statistically significant (26.2% vs. 20% p = 0.7094). Conclusion: In-house PCR correlates poorly with LJ culture for diagnosis of smear-negative PTB. Therefore, in-house PCR may not be adopted as an alternative to LJ culture.Item The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study(Critical care medicine, 2012) Jacob, Shevin T; Banura, Patrick; Baeten, Jared M.; Moore, Christopher C.; Meya, David; Nakiyingi, Lydia; Burke, Rebecca; Horton, Cheryl Lynn; Iga, Boaz; Mayanja-Kizza, Harriet; for the Promoting Resource-Limited Interventions for Sepsis Management in Uganda (PRISM-U) Study Group The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention studyIn sub-Saharan Africa, sepsis is an important cause of mortality but optimal sepsis management including fluid resuscitation, early antibiotic administration and patient monitoring is limited by a lack of supplies and skilled health workers.To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda.A prospective before and after study of an intervention cohort (n=426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n=245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals.Early sepsis management provided by a dedicated study medical officer comprised of fluid resuscitation, early antibiotics and regular monitoring in the first 6 hours of hospitalization.Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006).The majority (86%) of patients in both cohorts were HIV-infected. Median fluid volume provided in the first 6 hours of hospitalization was higher in intervention than observation cohort patients (3000 vs. 500 mL, p<0.001) and a greater proportion of intervention cohort patients received antibacterial therapy in less than one hour (67% vs 30.4%, p<0.001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs 45.7%, log-rank p=0.005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted HR=0.74, 95% CI=0.55–0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered.Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital.Item Internal Medicine Clerkship Amidst COVID-19 Pandemic: A Cross-Sectional Study of the Clinical Learning Experience of Undergraduate Medical Students at Makerere University, Uganda(Advances in Medical Education and Practice, 2021) Bongomin, Felix; Olum, Ronald; Nakiyingi, Lydia; Lalitha, Rejani; Ssinabulya, Isaac; Sekaggya- Wiltshire, Christine; Ocama, Ponsiano; Byakika-Kibwika, PaulineThe coronavirus-2019 (COVID-19) pandemic continues to impose a significant impact on medical education. We aimed to describe the clinical learning experience of undergraduate medical students undertaking internal medicine clerkship during the COVID-19 pandemic at Makerere University, Uganda. Methods: A descriptive, cross-sectional study among medical students in clinical years of study pursuing the Bachelor of Medicine and Bachelor of Surgery undergraduate degree program was conducted in November 2020. Only 3rd (junior clerks) and 5th (senior clerks) year medical students whose internal medicine clerkships were interrupted by the COVID-19 pandemic were studied. Results: Data of 188 (95%) eligible clinical year students; junior (101, 54.0%) and senior (86, 46.0%) were analysed. Median age was 24 (range: 22–42) years. Majority (70.1%) were male and Ugandan nationals (94.1%). Sixty-four (30.3%) students reported inadequate personal protective equipment, 152 (81.7%) felt at risk of contracting COVID-19, and 127 (67.9%) said it was difficult to observe COVID-19 standard operating procedures. Twentytwo students (11.9%) were discouraged from pursuing a career in internal medicine. Overall, most students reported good or excellent clinical experience pre-COVID-19 era compared to during the COVID-19 era (4.0 vs 3.5, p<0.0001). Senior clerks significantly believed that the time allocated for the rotation was adequate (p<0.0001) and they were able to complete their study objectives (p<0.001), compared to the junior clerks. Senior clerks believed that learning was difficult when combined with junior clerks (p=0.013). About half of the students (51.4%, n=95) reported clinical teaching should remain as it was in the pre- COVID-19 era. Conclusion: The COVID-19 pandemic has had a significantly negative effect on the clinical learning experience of the students. There is need to review the current teaching and learning methods to suit teaching and learning during pandemics of highly infectious diseases to ensure safe and effective learning experience.Item Misdiagnosis of Chronic Pulmonary Aspergillosis as Pulmonary Tuberculosis at a Tertiary Care Center in Uganda: A Case Series(Journal of medical case reports, 2021) Kwizera, Richard; Katende, Andrew; Bongomin, Felix; Nakiyingi, Lydia; Kirenga, Bruce J.Diagnosis of chronic pulmonary aspergillosis (CPA) is based on a combination of clinical symptomatology, compatible chest imaging findings, evidence of Aspergillus infection and exclusion of alternative diagnosis, all occurring for more than 3 months. Recently, a rapid, highly sensitive and specific point-of-care lateral flow device (LFD) has been introduced for the detection of Aspergillus-specific immunoglobulin (Ig)G, especially in resource-limited settings where CPA is underdiagnosed and often misdiagnosed as smear-negative pulmonary tuberculosis (PTB). Therefore, in our setting, where tuberculosis (TB) is endemic, exclusion of PTB is an important first step to the diagnosis of CPA. We used the recently published CPA diagnostic criteria for resource-limited settings to identify patients with CPA in our center. Three Ugandan women (45/human immunodeficiency virus (HIV) negative, 53/HIV infected and 18/HIV negative), with a longstanding history of cough, chest pain, weight loss and constitutional symptoms, were clinically and radiologically diagnosed with PTB and empirically treated with an anti-tuberculous regimen despite negative microbiological tests. Repeat sputum Mycobacteria GeneXpert assays were negative for all three patients. On further evaluation, all three patients met the CPA diagnostic criteria with demonstrable thick-walled cavities and fungal balls (aspergilomas) on chest imaging and positive Aspergillus-specific IgG/IgM antibody tests. After CPA diagnosis, anti-TB drugs were safely discontinued for all patients, and they were initiated on capsules of itraconazole 200 mg twice daily with good treatment outcomes. The availability of simple clinical diagnostic criteria for CPA and a LFD have the potential to reduce misdiagnosis of CPA and in turn improve treatment outcomes in resource-limited settings.Item Mycobacterium tuberculosis Bacteremia in a Cohort of HIV-Infected Patients Hospitalized with Severe Sepsis in Uganda–High Frequency, Low Clinical Sand Derivation of a Clinical Prediction Score(PloS one, 2013) Jacob, Shevin T.; Pavlinac, Patricia B.; Nakiyingi, Lydia; Banura, Patrick; Baeten, Jared M.; Morgan, Karen; Magaret, Amalia; Manabe, Yuka; Reynolds, Steven J.; Liles, W. Conrad; Wald, Anna; Joloba, Moses L.; Mayanja-Kizza, Harriet; Michael Scheld, W.When manifested as Mycobacterium tuberculosis (MTB) bacteremia, disseminated MTB infection clinically mimics other serious blood stream infections often hindering early diagnosis and initiation of potentially life-saving anti-tuberculosis therapy. In a cohort of hospitalized HIV-infected Ugandan patients with severe sepsis, we report the frequency, management and outcomes of patients with MTB bacteremia and propose a risk score based on clinical predictors of MTB bacteremia.We prospectively enrolled adult patients with severe sepsis at two Ugandan hospitals and obtained blood cultures for MTB identification. Multivariable logistic regression modeling was used to determine predictors of MTB bacteremia and to inform the stratification of patients into MTB bacteremia risk categories based on relevant patient characteristics.Among 368 HIV-infected patients with a syndrome of severe sepsis, eighty-six (23%) had MTB bacteremia. Patients with MTB bacteremia had a significantly lower median CD4 count (17 vs 64 lymphocytes/mm3, p<0.001) and a higher 30-day mortality (53% vs 32%, p = 0.001) than patients without MTB bacteremia. A minority of patients with MTB bacteremia underwent standard MTB diagnostic testing (24%) or received empiric anti-tuberculosis therapy (15%). Independent factors associated with MTB bacteremia included male sex, increased heart rate, low CD4 count, absence of highly active anti-retroviral therapy, chief complaint of fever, low serum sodium and low hemoglobin. A risk score derived from a model containing these independent predictors had good predictive accuracy [area under the curve = 0.85, 95% CI 0.80–0.89].Nearly 1 in 4 adult HIV-infected patients hospitalized with severe sepsis in 2 Ugandan hospitals had MTB bacteremia. Among patients in whom MTB was suspected, standard tests for diagnosing pulmonary MTB were inaccurate for correctly classifying patients with or without bloodstream MTB infection. A MTB bacteremia risk score can improve early diagnosis of MTB bacteremia particularly in settings with increased HIV and MTB co-infection.Item Possible Misdiagnosis of HIV associated Lymphoma as Tuberculosis among Patients attending Uganda Cancer Institute(AIDS research and therapy, 2017) Buyego, Paul; Nakiyingi, Lydia; Ddungu, Henry; Walimbwa, Stephen; Nalwanga, Damalie; Reynolds, Steven J.; Parkes‑Ratanshi, RosalindEarly diagnosis of HIV associated lymphoma is challenging because the definitive diagnostic procedure of biopsy, requires skills and equipment that are not readily available. As a consequence, diagnosis may be delayed increasing the risk of mortality. We set out to determine the frequency and risk factors associated with the misdiagnosis of HIV associated lymphoma as tuberculosis (TB) among patients attending the Uganda Cancer Institute (UCI). A retrospective cohort study design was used among HIV patients with associated lymphoma patients attending the UCI, Kampala, Uganda between February and March 2015. Eligible patient charts were reviewed for information on TB treatment, socio-demographics, laboratory parameters (Hemoglobin, CD4cells count and lactate dehydrogenase) and clinical presentation using a semi structured data extraction form. A total of 183 charts were reviewed; 106/183 were males (57.9%), the median age was 35 (IQR, 28–45). Fifty six (30.6%) patients had a possible misdiagnosis as TB and their median time on TB treatment was 3.5 (1–5.3) months. In multivariate analysis the presence of chest pain had an odd ratio (OR) of 4.4 (95% CI 1.89–10.58, p < 0.001) and stage III and IV lymphoma disease had an OR of 3.22 (95% CI 1.08–9.63, p < 0.037) for possible misdiagnosis of lymphoma as TB. A high proportion of patients with HIV associated lymphoma attending UCI are misdiagnosed and treated as TB. Chest pain and stage III and IV of lymphoma were associated with an increased risk of a possible misdiagnosis of lymphoma as TB.Item Predictors and outcomes of mycobacteremia among HIV-infected smear- negative presumptive tuberculosis patients in Uganda(BMC infectious Diseases, 2015) Nakiyingi, Lydia; Ssengooba, Willy; Nakanjako, Damalie; Armstrong, Derek; Kirenga, Bruce J.; Mayanja-Kizza, Harriet; Joloba, Moses L.; Ellner, Jerrold J.; Dorman, Susan E.; Manabe, Yukari C.Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting.Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment.Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28–39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065). Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm3), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting.Item Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology(PLoS ONE, 2015) Nakiyingi, Lydia; Nonyane, Bareng A. S.; Ssengooba, Willy; Kirenga, Bruce J.; Nakanjako, Damalie; Lubega, Gloria; Byakika-Kibwika, Pauline; Joloba, Moses L.; Ellner, Jerry J.; Dorman, Susan E.; Mayanja-Kizza, Harriet; Manabe, Yukari C.The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIVinfected smear-negative presumptive TB. We sought to determine predictors for MTB culture- positivity among these patients.Item Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes(Antibiotics, 2022) Okot Odongo, Charles; Nakiyingi, Lydia; Gatete Nkeramihigo, Clovis; Seifu, Daniel; Bisaso Kuteesa, RonaldMycobacterium tuberculosis is the leading cause of sepsis among HIV-infected adults, yet effective treatment remains a challenge. Efficacy of antituberculous drugs is optimized by high Area Under Curve to Minimum Inhibitory Concentration (AUC/MIC) ratios, suggesting that both the drug concentration at the disease site and time above MIC are critical to treatment outcomes. We elaborate on sepsis pathophysiology and show how it adversely affects antituberculous drug kinetics. Expanding distribution volumes secondary to an increased vascular permeability prevents the attainment of target Cmax concentrations for nearly all drugs. Furthermore, sepsis-induced metabolic acidosis promotes protonation, which increases renal clearance of basic drugs such as isoniazid and ethambutol, and hence AUCs are substantially reduced. Compared with the treatment of non-sepsis TB disease, these distorted kinetics underlie the poor treatment outcomes observed with bloodstream infections. In addition to aggressive hemodynamic management, an increase in both the dose and frequency of drug administration are warranted, at least in the early phase of treatment.Item Treatment Success and associated factors among patients with Pulmonary Tuberculosis attending Kampala Capital City Authority health facilities: A retrospective cohort study(medRxiv, 2022) Tumusiime, Cathbert; Katamba, Achilles; Nakiyingi, Lydia; Kalyango, JoanTB treatment success remains low in Uganda at 82%, below the recommended WHO target (≥90%). Consequences of poor treatment outcome include; increased MDR-TB prevalence, treatment costs and death. Kampala Capital City Authority (KCCA) public health facilities are congested which compromises the care given to pulmonary tuberculosis patients (PTB) that affects the treatment success of patients. However, there is scarce information regarding factors that are associated with treatment success among PTB patients in KCCA public health facilities. General Objective: To determine the treatment success and associated factors among patients with pulmonary tuberculosis attending KCCA public health facilities in Kampala between July 2019 and June 2020. Methods: A retrospective cohort study that involved review of records for 772 PTB patients who were enrolled on TB treatment in five KCCA health facilities from July 2019 to June 2020. Data on sociodemographic and clinical factors was abstracted from health facility TB registers. Data was entered in epidata and analyzed using STATA_v14 software. A modified poison regression model with robust standard errors was used in analysis and risk ratios were reported. Results: Treatment success was 87.2% (CI: 84.2%-89.1%), PTB patients who cured accounted for 413 (53.5%) and 260 (33.7%) completed treatment. Factors associated with PTB treatment success were: being classified as a clinically diagnosed PTB patients (aRR= 0.8, CI: 0.53 - 0.94, P value =0.021) and having a positive HIV/AIDS status (aRR= 0.7, CI: 0.43 - 0.88, P value =0.006) reduced treatment success and having a community volunteer as a treatment supporter was associated with increased treatment success (aRR= 1.2, CI: 1.06 - 3.28, P value =0.028). Conclusion: Over 80% of PTB patients in KCCA public health facilities achieve treatment success although this is still below the WHO target. Factors associated with TB treatment success include; being classified as a clinically diagnosed PTB patient, having a positive HIV/AIDS status as factors that reduce treatment success and having a community volunteer as a treatment supporter improves treatment success. Efforts such as consistent follow-ups should be encouraged among clinically diagnosed and HIV/AIDS positive PTB patients. Additionally, community volunteers should be empowered to support PTB patients.