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Siedner, Mark

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Siedner

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Mark

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Siedner, Mark
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Now showing 1 - 10 of 29
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    Impact of a clinical program using weekly Short Message Service (SMS) on antiretroviral therapy adherence support in South Africa: a retrospective cohort study
    (BioMed Central, 2017) Georgette, Nathan; Siedner, Mark; Petty, Carter R.; Zanoni, Brian; Carpenter, Stephen; Haberer, Jessica
    Background: In randomized controlled trials, short message service (SMS) programs have improved adherence to HIV antiretroviral therapy (ART). In response, the World Health Organization recommended use of SMS programs to support ART. However, there is limited data on real-world implementations of SMS programs. Methods: We conducted a retrospective cohort study of an SMS program to improve ART adherence in a government-run HIV clinic in rural South Africa. We analyzed data from all adult patients who 1) enrolled at the clinic before the observation period (July 2013 through June 2014), 2) had ≥1 ART prescriptions in the observation period, and 3) had data on phone number availability (N = 2255). Our main outcome measure was prescription coverage, defined as the presence of a valid ART prescription for each day observed. We fit generalized linear mixed models adjusted for pre-program prescription coverage, demographics, and ART duration, dosing, and regimen. Results: Exposure to the SMS program was independently associated with greater prescription coverage (AOR = 1.23, 95% CI 1.13–1.34, P < 0.001) compared with non-exposure, although the absolute increase in prescription coverage was small (4.7 days of ART prescription coverage per average patient per year). Among a subset of patients (n = 725) whose pre-program prescription coverage was <100%, the corresponding mean expected absolute increase in prescription coverage was 8.2 days per year. Conclusions: Our primary finding was that an SMS reminder program implemented in routine clinical care was associated with a small increase in prescription coverage of uncertain clinical significance.
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    Comparative Effectiveness of Induction Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: A Network Meta-Analysis
    (Oxford University Press, 2015) Campbell, Jeffrey; Kanters, Steve; Bennett, John E.; Thorlund, Kristian; Tsai, Alexander; Mills, Edward J.; Siedner, Mark
    Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis.
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    Prevalence of lower extremity Peripheral artery disease among adult diabetes patients in Southwestern Uganda
    (BioMed Central, 2014) Okello, Samson; Millard, Alexander; Owori, Rogers; Asiimwe, Stephen Bambeiha; Siedner, Mark; Rwebembera, Joselyn; Wilson, Laurence Anthony; Moore, Christopher Charles; Annex, Brian Herb
    Background: Peripheral artery disease (PAD) is a major complication of atherosclerosis. PAD can be diagnosed with low-cost diagnostic techniques and is associated with significant morbidity and mortality. While the major epidemiologic risk factors for PAD have been established in the western world, data from resource-poor countries are limited. We performed a cross-sectional study to determine the prevalence and correlates of PAD among patients with diabetes at Mbarara Referral Hospital in southwestern Uganda. Methods: We consecutively enrolled diabetes patients aged 50 years or greater presenting to the outpatient clinic. We collected blood for fasting lipid profile, HIV serology, and glycosylated hemoglobin, measured blood pressure and ankle brachial index, and administered the Edinburgh Claudication Questionnaire (ECQ). We also surveyed patients for other PAD risk factors. We used logistic regression to determine correlates of PAD. Results: We enrolled 229 diabetes patients. The median age of 60 years (IQR 55–66), and 146 (63.7%) were female. Fifty five patients (24%) had PAD (ABI of ≤ 0.9). Of these, 48 /55 (87.27%) had mild PAD (ABI 0.71-0.9) while 7/55 (12.73%) had moderate to severe PAD (ABI < 0.7). Amongst those with PAD, 24/55 (43.64%) reported claudication by the ECQ. Correlates of PAD included female sex (AOR 2.25, 95% CI 1.06 - 4.77, p = 0.034), current high blood pressure (AOR 2.59, 95% CI 1.25-5.33, p = 0.01), and being on a sulfonylurea–glibenclamide (AOR 3.47, 95% CI 1.55 - 7.76, p = 0.002). Conclusion: PAD was common in diabetic patients in southwestern Uganda. Given its low cost and ease of measurement, ABI deserves further assessment as a screening tool for both PAD and long term cardiovascular risk amongst diabetics in this region.
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    Disinhibition in Risky Sexual Behavior in Men, but Not Women, during Four Years of Antiretroviral Therapy in Rural, Southwestern Uganda
    (Public Library of Science, 2013) Kembabazi, Annet; Bajunirwe, Francis; Hunt, Peter W.; Martin, Jeffrey N.; Muzoora, Conrad; Haberer, Jessica E.; Bangsberg, David R.; Siedner, Mark
    Background: In resource-rich areas, risky sexual behavior (RSB) largely diminishes after initiation of anti-retroviral therapy, with notable exceptions among some populations who perceive a protected benefit from anti-retroviral therapy (ART). Yet, there is limited data about long-term trends in risky sexual behavior among HIV-infected people in sub-Saharan Africa after initiation of anti-retroviral therapy. Methods: We administered questionnaires every three months to collect sexual behavior data among patients taking ART in southwestern Uganda over four years of follow-up time. We defined RSB as having unprotected sex with an HIV-negative or unknown status partner, or unprotected sex with a casual partner. We fit logistic regression models to estimate changes in RSB by time on ART, with and without adjustment for calendar year and CD4 count. Results: 506 participants were enrolled between 2005 and 2011 and contributed a median of 13 visits and 3.5 years of observation time. The majority were female (70%) and median age was 34 years (interquartile range 29–39). There was a decrease in the proportion of men reporting RSB from the pre-ART visit to the first post-ART visit (16.2 to 4.3%, p<0.01) but not women (14.1 to 13.3%, p = 0.80). With each year of ART, women reported decreasing RSB (OR 0.85 per year, 95%CI 0.74–0.98, p = 0.03). In contrast, men had increasing odds of reporting RSB with each year of ART to near pre-treatment rates (OR 1.41, 95%CI 1.14–1.74, p = 0.001), which was partially confounded by changes in calendar time and CD4 count (AOR = 1.24, 95%CI 0.92–1.67, p = 0.16). Conclusions: Men in southwestern Uganda reported increasing RSB over four years on ART, to levels approaching pre-treatment rates. Strategies to promote long-term safe sex practices targeted to HIV-infected men on ART might have a significant impact on preventing HIV transmission in this setting.
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    The Missing Men: HIV Treatment Scale-Up and Life Expectancy in Sub-Saharan Africa
    (Public Library of Science, 2015) Tsai, Alexander; Siedner, Mark
    In a Perspective accompanying Bor and colleagues, Alexander Tsai and Mark Siedner discuss the gender gap in ART uptake and HIV mortality in Africa.
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    A combination SMS and transportation reimbursement intervention to improve HIV care following abnormal CD4 test results in rural Uganda: a prospective observational cohort study
    (BioMed Central, 2015) Siedner, Mark; Santorino, Data; Lankowski, Alexander J.; Kanyesigye, Michael; Bwana, Mwebesa B.; Haberer, Jessica; Bangsberg, David R.
    Background: Up to 50 % of HIV-infected persons in sub-Saharan Africa are lost from care between HIV diagnosis and antiretroviral therapy (ART) initiation. Structural barriers, including cost of transportation to clinic and poor communication systems, are major contributors. Methods: We conducted a prospective, pragmatic, before-and-after clinical trial to evaluate a combination mobile health and transportation reimbursement intervention to improve care at a publicly operated HIV clinic in Uganda. Patients undergoing CD4 count testing were enrolled, and clinicians selected a result threshold that would prompt early return for ART initiation or further care. Participants enrolled in the pre-intervention period (January – August 2012) served as a control group. Participants in the intervention period (September 2012 – November 2013) were randomized to receive daily short message service (SMS) messages for up to seven days in one of three formats: 1) messages reporting an abnormal result directly, 2) personal identification number-protected messages reporting an abnormal result, or 3) messages reading “ABCDEFG” to confidentially convey an abnormal result. Participants returning within seven days of their first message received transportation reimbursements (about $6USD). Our primary outcomes of interest were time to return to clinic and time to ART initiation. Results: There were 45 participants in the pre-intervention period and 138 participants in the intervention period (46, 49, and 43 in the direct, PIN, and coded groups, respectively) with low CD4 count results. Median time to clinic return was 33 days (IQR 11–49) in the pre-intervention period and 6 days (IQR 3–16) in the intervention period (P < 0.001); and median time to ART initiation was 47 days (IQR 11–75) versus 12 days (IQR 5–19), (P < 0.001). In multivariable models, participants in the intervention period had earlier return to clinic (AHR 2.32, 95 %CI 1.53 to 3.51) and earlier time to ART initiation (AHR 2.27, 95 %CI 1.38 to 3.72). All three randomized message formats improved time to return to clinic and time to ART initiation (P < 0.01 for all comparisons versus the pre-intervention period). Conclusions: A combination of an SMS laboratory result communication system and transportation reimbursements significantly decreased time to clinic return and time to ART initiation after abnormal CD4 test results. Trial registrations Clinicaltrials.gov NCT01579214, approved 13 April 2012. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0397-1) contains supplementary material, which is available to authorized users.
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    Remoteness and maternal and child health service utilization in rural Liberia: A population–based survey
    (Edinburgh University Global Health Society, 2015) Kenny, Avi; Basu, Gaurab; Ballard, Madeleine; Griffiths, Thomas; Kentoffio, Katherine; Niyonzima, Jean Bosco; Sechler, G. Andrew; Selinsky, Stephen; Panjabi, Rajesh; Siedner, Mark; Kraemer, John D.
    Background: This study seeks to understand distance from health facilities as a barrier to maternal and child health service uptake within a rural Liberian population. Better understanding the relationship between distance from health facilities and rural health care utilization is important for post–Ebola health systems reconstruction and for general rural health system planning in sub–Saharan Africa. Methods: Cluster–sample survey data collected in 2012 in a very rural southeastern Liberian population were analyzed to determine associations between quartiles of GPS–measured distance from the nearest health facility and the odds of maternal (ANC, facility–based delivery, and PNC) and child (deworming and care seeking for ARI, diarrhea, and fever) service use. We estimated associations by fitting simple and multiple logistic regression models, with standard errors adjusted for clustered data. Findings: Living in the farthest quartile was associated with lower odds of attending 1–or–more ANC checkup (AOR = 0.04, P < 0.001), 4–or–more ANC checkups (AOR = 0.13, P < 0.001), delivering in a facility (AOR = 0.41, P = 0.006), and postnatal care from a health care worker (AOR = 0.44, P = 0.009). Children living in all other quartiles had lower odds of seeking facility–based fever care (AOR for fourth quartile = 0.06, P < 0.001) than those in the nearest quartile. Children in the fourth quartile were less likely to receive deworming treatment (AOR = 0.16, P < 0.001) and less likely (but with only marginal statistical significance) to seek ARI care from a formal HCW (AOR = 0.05, P = 0.05). Parents in distant quartiles more often sought ARI and diarrhea care from informal providers. Conclusions: Within a rural Liberian population, distance is associated with reduced health care uptake. As Liberia rebuilds its health system after Ebola, overcoming geographic disparities, including through further dissemination of providers and greater use of community health workers should be prioritized.
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    Evaluation of the modified colorimetric resazurin microtiter plate-based antibacterial assay for rapid and reliable tuberculosis drug susceptibility testing
    (BioMed Central, 2014) Katawera, Victoria; Siedner, Mark; Boum II, Yap
    Background: The resazurin microtiter assay (classic REMA), a colorimetric liquid culture-based drug susceptibility assay for Mycobacterium tuberculosis (MTB), has been endorsed by the World Health Organization. The assay requires 8-16 days to obtain results, delaying management of drug resistant tuberculosis patients. A modified REMA which allows results in as little as 24 hours for bacterial strains, has been developed and validated using Staphylococcus aureus, but has not yet been evaluated for MTB. Therefore we assessed the performance of the modified REMA for rifampicin (RIF) and isoniazid (INH) susceptibility, using the classic REMA as the reference standard. We also compared simplicity (from the technicians’ point of view), time taken to obtain results (rank-sum testing), specificity and Kappa statistics of the two methods. Results: The modified REMA, which is a one-step procedure, was found to be simpler to perform and results were obtained in a significantly shorter time (5 versus 9 days, p < 0.0001) compared to the classic REMA due to addition of indicator and strain at the same time. The specificity of the modified REMA was low {46.8% (35.5% - 58.4%) for RIF and 13.9% (7.2% - 23.5%) for INH}. Kappa statistics were 16.0% for RIF and 2.0% for INH. Low specificity and kappa statistics are due to indicator reduction by the strains before complete drug activity. Conclusion: Although modified REMA is faster and simpler compared to classic REMA, it is not reliable for MTB drug susceptibility testing.
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    Evaluation of the SD BIOLINE HIV/syphilis Duo assay at a rural health center in Southwestern Uganda
    (BioMed Central, 2014) Omoding, Daniel; Katawera, Victoria; Siedner, Mark; Boum, Yap
    Background: Point-of-care tests have the capacity to improve healthcare delivery by reducing costs and delay associated with care. A novel point-of-care immunochromatographic test for dual diagnosis of both HIV and syphilis by detecting IgG, IgM and IgA antibodies to HIV, and specific and recombinant Treponema pallidum antigens has recently been developed, but has not been evaluated in rural field settings. We evaluated the performance of the SD Bioline Syphilis/HIV Duo (Duo) assay at a healthcare center in rural Uganda. Methods: A convenience sample of pregnant women attending Kinoni Health Centre IV from March to May, 2013 was enrolled. Venous blood was collected and centrifuged for plasma isolation. Samples were tested with the Duo assay and compared with the Treponema pallidum hemaglutination assay and paired HIV rapid antibody tests as the reference standards. The ease of use and time required for the Duo assay were also assessed by laboratory technicians. Results: Two hundred twenty women were enrolled with a mean age of 25.00 years (SD 5.41). The sensitivity and specificity of the Duo assay were 100% (95% CI 79.0 – 100%) and 100% (95% CI 97.6 – 100.0) respectively, for syphilis, and, 100% (75.9 – 100%) and 99.5% (96.8 – 99.9%) respectively, for HIV. The duo kit was found to be faster and easier to use than the current HIV and syphilis testing techniques. Conclusion: The sensitivity and specificity of the SD Bioline HIV/Syphilis Duo test were excellent in a field setting in Uganda. The Duo assay should be further evaluated in alternate populations and with point-of-care specimens (e.g. whole blood from finger stick specimens), but shows promise as a tool for improved HIV and syphilis surveillance, diagnosis, and treatment in field settings.
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    Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy
    (Public Library of Science, 2014) Lankowski, Alexander J.; Tsai, Alexander; Kanyesigye, Michael; Bwana, Mwebesa; Haberer, Jessica; Wenger, Megan; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.; Siedner, Mark
    Background: There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance: Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.