Browsing by Author "Badri, Motasim"

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    Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting
    (Public Library of Science, 2009) Dheda, Keertan; Van-Zyl Smit, Richard N; Sechi, Leonardo A; Badri, Motasim; Meldau, Richard; Symons, Gregory; Khalfey, Hoosein; Carr, Igshaan; Maredza, Alice; Dawson, Rodney
    BACKGROUND: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. METHODS: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal FINDINGS: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. CONCLUSION: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings.
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    Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples
    (Public Library of Science, 2010) Dheda, Keertan; Davids, Virginia; Lenders, Laura; Roberts, Teri; Meldau, Richard; Ling, Daphne; Brunet, Laurence; Smit, Richard van Zyl; Peter, Jonathan; Green, Clare; Badri, Motasim; Sechi, Leonardo; Sharma, Surendra; Hoelscher, Michael; Dawson, Rodney
    BACKGROUND: The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB®-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated. METHODS: LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis. RESULTS: Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm 3 (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%-100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm 3 were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species. CONCLUSIONS: These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm 3 , who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection.
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    Cost-effectiveness of highly active antiretroviral therapy in South Africa
    (Public Library of Science, 2005) Badri, Motasim; Maartens, Gary; Mandalia, Sundhiya; Bekker, Linda-Gail; Penrod, John R; Platt, Robert W; Wood, Robin; Beck, Eduard J
    Healthcare costs for HIV-infected South African adults on HAART compared with costs for HIV-infected controls not on HAART. Authors conclude HAART is cost effective.
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    Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis
    (BioMed Central Ltd, 2010) Pooran, Anil; Booth, Helen; Miller, Robert F; Scott, Geoff; Badri, Motasim; Huggett, Jim F; Rook, Graham; Zumla, Alimuddin; Dheda, Keertan
    BACKGROUND: Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-gamma-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs of adverse drug reactions and directly compares two commercially available versions of the IGRA: the Quantiferon-TB-Gold-In-Tube (QFT-GIT) and T-SPOT.TB. METHODS: A LTBI screening model directed at screening contacts was used to perform a cost-effectiveness analysis, from a UK healthcare perspective, taking into account the risk of isoniazid-related hepatotoxicity and post-exposure TB (2 years post contact) using the TST, QFT-GIT and T-SPOT.TB IGRAs. RESULTS: Examining costs alone, the TST/IGRA dual screening strategies (TST/T-SPOT.TB and TST/QFT-GIT; GBP162,387 and GBP157,048 per 1000 contacts, respectively) cost less than their single strategy counterparts (T-SPOT.TB and QFT-GIT; GBP203,983 and GBP202,921 per 1000 contacts) which have higher IGRA test costs and greater numbers of persons undergoing LTBI treatment. However, IGRA alone strategies direct healthcare interventions and costs more accurately to those that are truly infected.Subsequently, less contacts need to be treated to prevent an active case of TB (T-SPOT.TB and QFT-GIT; 61.7 and 69.7 contacts) in IGRA alone strategies. IGRA single strategies also prevent more cases of post-exposure TB. However, this greater effectiveness does not outweigh the lower incremental costs associated with the dual strategies. Consequently, when these costs are combined with effectiveness, the IGRA dual strategies are more cost-effective than their single strategy counterparts. Comparing between the IGRAs, T-SPOT.TB-based strategies (single and dual; GBP39,712 and GBP37,206 per active TB case prevented, respectively) were more cost-effective than the QFT-GIT-based strategies (single and dual; GBP42,051 and GBP37,699 per active TB case prevented, respectively). Using the TST alone was the least cost-effective (GBP47,840 per active TB case prevented). Cost effectiveness values were sensitive to changes in LTBI prevalence, IGRA test sensitivities/specificities and IGRA test costs. CONCLUSION: A dual strategy is more cost effective than a single strategy but this conclusion is sensitive to screening test assumptions and LTBI prevalence.
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    Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa
    (Public Library of Science, 2013) Shean, Karen; Streicher, Elizabeth; Pieterson, Elize; Symons, Greg; van Zyl Smit, Richard; Theron, Grant; Lehloenya, Rannakoe; Padanilam, Xavier; Wilcox, Paul; Victor, Tommie C; van Helden Paul; Groubusch Martin; Warren, Robin; Badri, Motasim; Dheda, Keertan
    BACKGROUND: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. METHODS: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)]. FINDINGS: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). CONCLUSION: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB.
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    Hyperglycaemic crisis in the Eastern Cape province of South Africa: High mortality and association of hyperosmolar ketoacidosis with a new diagnosis of diabetes
    (2010) Ekpebegh, C O; Longo-Mbenza, B; Akinrinmade, A; Blanco-Blanco, E; Badri, Motasim; Levitt, N S
    Objectives. To describe the frequencies, presenting characteristics (demographic, clinical and biochemical) and outcomes (duration of admission and mortality rates) for various types of hyperglycaemic crisis. Methods. Retrospective review of medical records of patients with hyperglycaemic crisis admitted to Nelson Mandela Academic Hospital, Mthatha, E Cape, from 1 January 2008 to 31 December 2009. Outcome measures were duration of admission and mortality. Results. Data were available for 269 admissions (response rate 81.0%), 169 females and 100 males. Admissions for hyperglycaemia (HG, N=119), and non-hyperosmolar diabetic ketoacidosis (NHDKA, N=97) were more frequent than those for hyperosmolar hyperglycaemic state (HHS, N=29) and hyperosmolar diabetic ketoacidosis (HDKA, N=24). Duration of admission was similar in all groups. Mortality was high in all groups, but was higher in patients with HDKA (37.5%, risk ratio (RR) 3.88, 95% confidence interval (CI) 1.41 - 10.67, p=0.009), HHS (31.0%, RR 2.91, 95% CI 1.09 - 7.75, p=0.033) and HG (19.5%, RR 1.56, 95% CI 0.75 - 3.21, p=0.236) than in those with NHDKA (13.4%). HDKA (62.5%) was associated with new-onset diabetes more often than NHDKA (27.8%), HHS (44.8%) or HG (17.6%) (p<0.0001). An altered level of consciousness was more frequent in HDKA than NHDKA admissions (RR 5.71, 95% CI 1.90 – 17.17, p=0.002).
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    ICU-Associated Acinetobacter baumannii Colonisation/Infection in a High HIV-Prevalence Resource-Poor Setting
    (Public Library of Science, 2012) Ntusi, Ntobeko B A; Badri, Motasim; Khalfey, Hoosain; Whitelaw, Andrew; Oliver, Stephen; Piercy, Jenna; Raine, Richard; Joubert, Ivan; Dheda, Keertan
    BACKGROUND: There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa. METHODS: We reviewed the case records of patients with A.baumannii colonisation/infection admitted into the adult respiratory and surgical ICUs in Cape Town, South Africa, from January 1 to December 31 2008. In contrast to colonisation, infection was defined as isolation of A.baumannii from any biological site in conjunction with a compatible clinical picture warranting treatment with antibiotics effective against A.baumannii . RESULTS: The incidence of A.baumannii colonisation/infection in 268 patients was 15 per 100 person-years, with an in-ICU mortality of 26.5 per 100 person-years. The average length of stay in ICU was 15 days (range 1-150). A.baumannii was most commonly isolated from the respiratory tract followed by the bloodstream. Independent predictors of mortality included older age (p = 0.02), low CD4 count if HIV-infected (p = 0.038), surgical intervention (p = 0.047), co-morbid Gram-negative sepsis (p = 0.01), high APACHE-II score (p = 0.001), multi-organ dysfunction syndrome (p = 0.012), and a positive blood culture for A.baumannii (p = 0.017). Of 21 A.baumannii colonised/infected HIV-positive persons those with clinical AIDS (CD4<200 cells/mm 3 ) had significantly higher in-ICU mortality and were more likely to have a positive blood culture. Conclusion In this resource-poor setting A.baumannii infection in critically ill patients is common and associated with high mortality. HIV co-infected patients with advanced immunosuppression are at higher risk of death.
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    Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study
    (BioMed Central Ltd, 2010) Sinxadi, Phumla; van der Walt, Jan-Stefan; McIlleron, Helen; Badri, Motasim; Smith, Peter; Dave, Joel; Levitt, Naomi; Maartens, Gary
    BACKGROUND: Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides. METHODS: Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy. RESULTS: There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m2 and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79). CONCLUSIONS: There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.
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    The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study
    (BioMed Central Ltd, 2009) Shaboodien, Gasnat; Engel, Mark E; Syed, Faisal; Poulton, Joanna; Badri, Motasim; Mayosi, Bongani
    BACKGROUND: The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10-12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV). METHODS: A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. RESULTS: The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/muL vs. 176/muL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67-8.06, p = 0.11). CONCLUSION: The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.
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    Performance of serum C-reactive protein as a screening test for smear-negative tuberculosis in an ambulatory high HIV prevalence population
    (Public Library of Science, 2011) Wilson, Douglas; Badri, Motasim; Maartens, Gary
    BACKGROUND: Delayed diagnosis has contributed to the high mortality of sputum smear-negative tuberculosis (SNTB) in high HIV prevalence countries. New diagnostic strategies for SNTB are urgently needed. C-reactive protein (CRP) is a non-specific inflammatory protein that is usually elevated in patients with tuberculosis, but its role in the diagnosis of tuberculosis is uncertain. METHODOLOGY/PRINCIPAL FINDINGS: To determine the diagnostic utility of CRP we prospectively evaluated the performance of CRP as a screening test for SNTB in symptomatic ambulatory tuberculosis suspects followed up for 8 weeks in KwaZulu-Natal, South Africa. Confirmed tuberculosis was defined as positive culture or acid-fast bacilli with granulomata on histology, and possible tuberculosis as documented response to antitubercular therapy. The CRP quotient was defined as a multiple of the upper limit of normal of the serum CRP result. Three hundred and sixty four participants fulfilled entry criteria: 135 (37%) with confirmed tuberculosis, 114 (39%) with possible tuberculosis, and 115 (24%) without tuberculosis. The median CRP quotient was 15.4 (IQR 7.2; 23.3) in the confirmed tuberculosis group, 5.8 (IQR 1.4; 16.0) in the group with possible tuberculosis, and 0.7 (IQR 0.2; 2.2) in the group without tuberculosis ( p <0.0001). The CRP quotient above the upper limit of normal had sensitivity 0.98 (95% CI 0.94; 0.99), specificity 0.59 (95% CI 0.50; 0.68), positive predictive value 0.74 (95% CI 0.67; 0.80), negative predictive value 0.96 (95% CI 0.88; 0.99), and diagnostic odds ratio 63.7 (95% CI 19.1; 212.0) in the confirmed tuberculosis group compared with the group without tuberculosis. Higher CRP quotients improved specificity at the expense of sensitivity. Significance In high HIV prevalence settings a normal CRP could be a useful test in combination with clinical evaluation to rule out tuberculosis in ambulatory patients. Point-of-care CRP should be further evaluated in primary care clinics.
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    Pregnancy-associated heart failure: a comparison of clinical presentation and outcome between hypertensive heart failure of pregnancy and idiopathic peripartum cardiomyopathy
    (Public Library of Science, 2015) Ntusi, Ntobeko B A; Badri, Motasim; Gumedze, Freedom; Sliwa, Karen; Mayosi, Bongani M
    AIMS: There is controversy regarding the inclusion of patients with hypertension among cases of peripartum cardiomyopathy (PPCM), as the practice has contributed significantly to the discrepancy in reported characteristics of PPCM. We sought to determine whether hypertensive heart failure of pregnancy (HHFP) (i.e., peripartum cardiac failure associated with any form of hypertension) and PPCM have similar or different clinical features and outcome. Methods and RESULTS: We compared the time of onset of symptoms, clinical profile (including electrocardiographic [ECG] and echocardiographic features) and outcome of patients with HHFP (n = 53; age 29.6 ± 6.6 years) and PPCM (n = 30; age 31.5 ± 7.5 years). The onset of symptoms was postpartum in all PPCM patients, whereas it was antepartum in 85% of HHFP cases (p<0.001). PPCM was more significantly associated with the following features than HHFP (p<0.05): twin pregnancy, smoking, cardiomegaly with lower left ventricular ejection fraction on echocardiography, and longer QRS duration, QRS abnormalities, left atrial hypertrophy, left bundle branch block, T wave inversion and atrial fibrillation on ECG. By contrast, HHFP patients were significantly more likely (p<0.05) to have a family history of hypertension, hypertension and pre-eclampsia in a previous pregnancy, tachycardia at presentation on ECG, and left ventricular hypertrophy on echocardiography. Chronic heart failure, intra-cardiac thrombus and pulmonary hypertension were found significantly more commonly in PPCM than in HHFP (p<0.05). There were 5 deaths in the PPCM group compared to none among HHFP cases (p = 0.005) during follow-up. CONCLUSION: There are significant differences in the time of onset of heart failure, clinical, ECG and echocardiographic features, and outcome of HHFP compared to PPCM, indicating that the presence of hypertension in pregnancy-associated heart failure may not fit the case definition of idiopathic PPCM.
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    Prevalence, hemodynamics, and cytokine profile of effusive-constrictive pericarditis in patients with tuberculous pericardial effusion
    (Public Library of Science, 2013) Ntsekhe, Mpiko; Matthews, Kerryn; Syed, Faisal F; Deffur, Armin; Badri, Motasim; Commerford, Patrick J; Gersh, Bernard J; Wilkinson, Katalin A; Wilkinson, Robert J; Mayosi, Bongani M
    BACKGROUND: Effusive constrictive pericarditis (ECP) is visceral constriction in conjunction with compressive pericardial effusion. The prevalence of proven tuberculous ECP is unknown. Whilst ECP is distinguished from effusive disease on hemodynamic grounds, it is unknown whether effusive-constrictive physiology has a distinct cytokine profile. We conducted a prospective study of prevalence and cytokine profile of effusive-constrictive disease in patients with tuberculous pericardial effusion. METHODS: From July 2006 through July 2009, the prevalence of ECP and serum and pericardial levels of inflammatory cytokines were determined in adults with tuberculous pericardial effusion. The diagnosis of ECP was made by combined pericardiocentesis and cardiac catheterization. RESULTS: Of 91 patients evaluated, 68 had tuberculous pericarditis. The 36/68 patients (52.9%; 95% confidence interval [CI]: 41.2-65.4) with ECP were younger (29 versus 37 years, P=0.02), had a higher pre-pericardiocentesis right atrial pressure (17.0 versus 10.0 mmHg, P<0.0001), serum concentration of interleukin-10 (IL-10) (38.5 versus 0.2 pg/ml, P<0.001) and transforming growth factor-beta (121.5 versus 29.1 pg/ml, P=0.02), pericardial concentration of IL-10 (84.7 versus 20.4 pg/ml, P=0.006) and interferon-gamma (2,568.0 versus 906.6 pg/ml, P=0.03) than effusive non-constrictive cases. In multivariable regression analysis, right atrial pressure > 15 mmHg (odds ratio [OR] = 48, 95%CI: 8.7-265; P<0.0001) and IL-10 > 200 pg/ml (OR=10, 95%CI: 1.1, 93; P=0.04) were independently associated with ECP. CONCLUSION: Effusive-constrictive disease occurs in half of cases of tuberculous pericardial effusion, and is characterized by greater elevation in the pre-pericardiocentesis right atrial pressure and pericardial and serum IL-10 levels compared to patients with effusive non-constrictive tuberculous pericarditis.
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    Risk factors for falls in older adults in a South African Urban Community
    (BioMed Central, 2016-02-24) Kalula, Sebastiana Zimba; Ferreira, Monica; Swingler, George H; Badri, Motasim
    Background: Studies on falls in older adults have mainly been conducted in high income countries. Scant, if any, information exists on risk factors for falls in the older population of sub-Saharan African countries. Methods: A cross-sectional survey and a 12-month follow-up study were conducted to determine risk factors for falls in a representative multi-ethnic sample of 837 randomly selected ambulant community-dwelling subjects aged ≥65 years in three suburbs of Cape Town, South Africa. Logistic regression models were fitted to determine the association between (1) falls and (2) recurrent falls occurring during follow-up and their potential socio-demographic, self-reported medical conditions and physical assessment predictors. Results: Prevalence rates of 26.4 % for falls and 11 % for recurrent falls at baseline and 21.9 % for falls and 6.3 % for recurrent falls during follow-up. In both prospective analyses of falls and recurrent falls, history of previous falls, dizziness/vertigo, ethnicity (white or mixed ancestry vs black African) were significant predictors. However, poor cognitive score was a significant predictor in the falls analysis, and marital status (unmarried vs married) and increased time to perform the timed Up and Go test in the recurrent fall analysis but not in both. Other than the timed Up and Go test in recurrent falls analysis, physical assessment test outcomes were not significant predictors of falls. Conclusion: Our study provides simple criteria based on demographic characteristics, medical and physical assessments to identify older persons at increased risk of falls. History taking remains an important part of medical practice in the determination of a risk of falls in older patients. Physical assessment using tools validated in developed country populations may not produce results needed to predict a risk of falls in a different setting.
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    A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis
    (BioMed Central Ltd, 2011) Heckmann, Jeannine; Rawoot, Amanullah; Bateman, Kathleen; Renison, Rudi; Badri, Motasim
    BACKGROUND:Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements. METHODS: The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG. RESULTS: Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019). CONCLUSIONS: This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems.TRIAL REGISTRATION:SANCTR:DOH-27-0411-2436
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    Stroke outcomes in a socio-economically disadvantaged urban community
    (2011) De Villiers, Linda; Badri, Motasim; Ferreira, Monica; Bryer, Alan
    AIMS: To determine survival, disability and functional outcomes of stroke patients following their discharge from an acute stroke unit in an urban community with limited rehabilitative resources. METHODS: Stroke patients were recruited from a district hospital in Cape Town and followed-up for 6 months. Clinical characteristics, demographic and socioeconomic data, and disability and function as measured by modified Rankin Score (mRS), modified Barthel Index (mBI) at recruitment and 3 follow-up visits, were recorded. RESULTS: The study included 196 patients. Median age was 60 (IQR 51 - 69) years, 135 (68.9%) were female, 57.7% black, 42.3% coloured, and 45 (23%) died within 6 months. At discharge, median mBI score was 7 (IQR 3 - 12) and median mRS 4 (IQR 3 - 5). In the multivariate regression models, only function (mBI OR 0.88, 95% confidence interval (CI) 0.79 - 0.96, p<0.0001) and disability (mRS 0R 2.34, 95%CI 1.20 - 4.54, p<0.0001) were independently associated with risk of death. Shack housing was independently associated with moderate or severe disability (odds ratio 3.42, 95%CI 1.22 - 9.59, p=0.02). Despite limited rehabilitation resources, 67% of survivors had mild to moderate disability at 6 months. CONCLUSION: Apart from initial stroke severity, risk factors for poor survival were a severe disability category and the presence of impaired swallowing at discharge. Shack housing was independently associated with poor functional outcomes. These findings should be helpful in allocating home-based care and inpatient rehabilitation resources to high-risk groups to improve outcomes.
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    The burden and risk factors for adverse drug events in older patients - a prospective cross-sectional study
    (2006) Tipping, Brent; Kalula, Sebastiana; Badri, Motasim
    Objective. To determine the burden and risk factors for adverse drug events (ADEs) in older patients. Design. A prospective cross-sectional study. Methods. Patients (65 years and older) presenting to the tertiary Emergency Unit of Groote Schuur Hospital, Cape Town, between February and May 2005, were assessed for wellestablished ADEs, as defined by the South African Medicines Formulary. Logistic regression models were fitted to determine drugs and other factors associated with the likelihood of developing ADEs. Results. ADEs were identified in 104 of the 517 (20%) presentations. The most frequently involved drug classes were cardiovascular (34%), anticoagulant (27%), analgesic (19%) and antidiabetic (9%). Patients who developed ADEs were more likely to have five or more prescription drugs (p < 0.0001), more than three clinical problems (p = 0.001), require admission (p = 0.04), and report compliance with medication (p = 0.02) than those who did not. Drugs shown to independently confer increased risk of ADEs were angiotensin-converting enzyme inhibitors (RR = 2.6, 95% CI: 1.3 - 5.2, p = 0.009), non-steroidal anti-inflammatory drugs (RR = 4.1, 95% CI: 2.1 - 8.0, p < 0.0001) and warfarin (RR = 3.1, 95% CI: 1.6 - 6.3, p = 0.0014). Conclusion. ADEs contribute significantly to the burden of elderly care in the Emergency Unit. In a setting such as ours, increased pill burden and certain drug classes are likely to result in increased risk of ADEs in the older population group.
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    Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting
    (BioMed Central Ltd, 2008) Badri, Motasim; Lawn, Stephen D; Wood, Robin
    BACKGROUND:Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. METHODS: In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL > 1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (DeltaCD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up. RESULTS: During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179), VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003), DeltaCD4 counts (r = - 0.11, P < 0.01), and most strongly with CD4 count slopes (r = - 0.30, P < 0.001). However, the distributions of the absolute CD4 counts, DeltaCD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P = 0.99, P = 0.92 and P = 0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%). CONCLUSION: CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.
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    Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa
    (Biomed Central Ltd, 2007) Lawn, Stephen; Bangani, Nonzwakazi; Vogt, Monica; Bekker, Linda-Gail; Badri, Motasim; Ntobongwana, Marjorie; Dockrell, Hazel; Wilkinson, Robert; Wood, Robin
    BACKGROUND:Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates. METHODS: IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done. RESULTS: ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls. CONCLUSION: The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation.