Browsing by Subject "Prognosis"

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    Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis
    (2016) Gupta-Wright, Ankur; Peters, Jurgens A; Flach, Clare; Lawn, Stephen D
    BackgroundSimple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay’s prognostic value.MethodsWe searched MEDLINE and Embase databases using comprehensive search terms for ‘HIV’, ‘TB’, ‘LAM’ and ‘sub-Saharan Africa’. Identified studies were reviewed and selected according to predefined criteria.ResultsWe identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44%) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6months, overall case fatality rates among HIV-TB cases varied between 7% and 53%. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95% confidence interval 1.6–3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95% confidence interval 1.4–4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count.ConclusionsWe have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0603-9) contains supplementary material, which is available to authorized users.
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    Development and validation of a prognostic score during tuberculosis treatment
    (2017) Pefura-Yone, Eric Walter; Balkissou, Adamou Dodo; Poka-Mayap, Virginie; Fatime-Abaicho, Hadja Koté; Enono-Edende, Patrick Thierry; Kengne, André Pascal
    BACKGROUND: Death under care is a major challenge for tuberculosis (TB) treatment programs. We derived and validated a simple score to predict mortality during tuberculosis treatment in high endemicity areas. METHODS: We used data for patients aged ≥15 years, diagnosed and treated for tuberculosis at the Yaounde Jamot Hospital between January 2012 and December 2013. Baseline characteristics associated with mortality were investigated using logistic regressions. A simple prognosis score (CABI) was constructed with regression coefficients for predictors in the final model. Internal validation used bootstrap resampling procedures. Models discrimination was assessed using c-statistics and calibration assessed via calibration plots and the Hosmer and Lemeshwow (H-L) statistics. The optimal score was based on the Youden's index. RESULTS: A total of 2250 patients (men 57.2%) with a mean age of 35.8 years were included; among whom 213 deaths (cumulative incidence 9.5%) were recorded. Clinical form of tuberculosis (C), age (A, years), adjusted body mass index (B, BMI, kg/m2) and status for HIV (Human immunodefiency virus) infection (I) were significant predictors in the final model (p < 0.0001) which was of the form Death risk = 1/(1 + e - (-1.3120 + 0.0474 ∗ age - 0.1866 ∗ BMI + 1.1637 (if smear negative TB) + 0.5418(if extra - pulmonary TB) + 1.3820(if HIV+))). The c-statistic was 0.812 in the derivation sample and 0.808 after correction for optimism. The calibration was good [H-Lχ2 = 6.44 (p = 0.60)]. The optimal absolute risk threshold was 4.8%, corresponding to a sensitivity of 81% and specificity of 67%. CONCLUSIONS: The preliminary promising findings from this study require confirmation through independent external validation studies. If confirmed, the model derived could facilitate the stratification of TB patients for mortality risk and implementation of additional monitoring and management measures in vulnerable patients.
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    Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort
    (2017) Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Vogt, Monica; Gupta-Wright, Ankur; Nicol, Mark P; Meintjes, Graeme
    Abstract Background We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Methods Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Results Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75). Conclusions Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.
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    Endovascular cerebral aneurysm treatment : Long-term outcomes
    (2008) Le Feuvre, David; Taylor, Allan
    Endovascular treatment was confirmed by the International Subarachnoid aneurysm Trial1 as the treatment of choice for intracranial “berry” aneurysms. The durability of coiling and the relevance of stable neck remnants next needed to be addressed. Methods We retrospectively assessed the follow-up angiograms of patients, who presented with subarachnoid haemorrhages or IIIrd nerve palsies and had berry aneurysms treated endovascularly between 2002 and 2003, Patients were phoned to assess their wellbeing and to see whether they were back at work or not. Angiograms were assessed to ascertain percentage of aneurysm coiled at initial procedure and then stability was assessed by percentage change in the residual on later angiograms. Results Over a 1-year period 75 patients were treated endovascularly. 100% occlusion was attainable in 52% at the initial procedure and although the number of patients who attended their 3-month and 1year follow-up angiograms were 40 and 34 respectively there was a trend toward progressive thrombosis to 65% and then 82% respectively. In only 1 of the neck remnants was there growth at the 3-month angiogram. One patient bled having missed his 3-month follow-up angiogram. Although only 40% of the patients were contactable at 4 years there was no re-bleeds amongst them. Conclusion Coiling is durable as shown by our results over a 4 year period and while neck remnants may be observed any growth should be viewed as unstable and treated either endovascularly or surgically if required.
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    Glycosyltransferase gene expression profiles classify cancer types and propose prognostic subtypes
    (2016) Ashkani, Jahanshah; Naidoo, Kevin J
    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.
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    Outcome prediction in intensive care with special reference to cardiac surgery
    (1995) Turner, John Scott
    The development, use, and understanding of severity of illness scoring systems has advanced rapidly in the last decade; their weaknesses and limitations have also become apparent. This work follows some of this development and explores some of these aspects. It was undertaken in three stages and in two countries. The first study investigated three severity of illness scoring systems in a general Intensive Care Unit (ICU) in Cape Town, namely the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the Therapeutic Intervention Scoring System (TISS), and a locally developed organ failure score. All of these showed a good relationship with mortality, with the organ failure score the best predictor of outcome. The TISS score was felt to be more likely to be representative of intensiveness of medical and nursing management than severity of illness. The APACHE II score was already becoming widely used world-wide and although it performed less well in some diagnostic categories (for example Adult Respiratory Distress Syndrome) than had been hoped, it clearly warranted further investigation. Some of the diagnosis-specific problems were eliminated in the next study which concentrated on the application of the APACHE II score in a cardiothoracic surgical ICU in London. Although group predictive ability was statistically impressive, the predictive ability of APACHE II in the individual patient was limited as only very high APACHE II scores confidently predicted death and then only in a small number of patients. However, there were no deaths associated with an APACHE II score of less than 5 and the mortality was less than 1 % when the APACHE II score was less than 10. Finally, having recognised the inadequacies in mortality prediction of the APACHE II score in this scenario, a study was undertaken to evaluate a novel concept: a combination of preoperative, intraoperative, and postoperative (including APACHE II and III) variables in cardiac surgery patients admitted to the same ICU. The aim was to develop a more precise method of predicting length of stay, incidence of complications, and ICU and hospital outcome for these patients. There were 1008 patients entered into the study. There was a statistically significant relationship between increasing Parsonnet (a cardiac surgery risk prediction score), APACHE II, and APACHE III scores and mortality. By forward stepwise logistic regression a model was developed for the probability of hospital death. This model included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale. Predictive performance was evaluated by calculating the area under the receiver operating characteristic (ROC) curve. The derived model had an area under the ROC curve 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying 0.84. It was concluded that a combination of intraoperative and postoperative variables can improve predictive ability.
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    Prognostic indicators in the World Health Organization’s algorithm for seriously ill HIV-infected inpatients with suspected tuberculosis
    (BioMed Central, 2018-02-12) Griesel, Rulan; Stewart, Annemie; van der Plas, Helen; Sikhondze, Welile; Mendelson, Marc; Maartens, Gary
    Background: Criteria for the 2007 WHO algorithm for diagnosing tuberculosis among HIV-infected seriously ill patients are the presence of one or more danger signs (respiratory rate > 30/min, heart rate > 120/min, temperature > 39 °C, and being unable to walk unaided) and cough ≥ 14 days. Determining predictors of poor outcomes among HIV-infected inpatients presenting with WHO danger signs could result in improved treatment and diagnostic algorithms. Methods: We conducted a prospective cohort study of inpatients presenting with any duration of cough and WHO danger signs to two regional hospitals in Cape Town, South Africa. The primary outcome was all-cause mortality up to 56 days post-discharge, and the secondary outcome a composite of any one of: hospital admission for > 7 days, died in hospital, transfer to a tertiary level or tuberculosis hospital. We frst assessed the WHO danger signs as predictors of poor outcomes, then assessed the added value of other variables selected a priori for their ability to predict mortality in common respiratory opportunistic infections (CD4 count, body mass index (BMI), being on antiretroviral therapy (ART), hypotension, and confusion) by comparing the receiver operating characteristic (ROC) area under the curve (AUC) of the two multivariate models. Results: 484 participants were enrolled, median age 36, 66% women, 53% had tuberculosis confrmed on culture. The 56-day mortality was 13.2%. Inability to walk unaided, low BMI, low CD4 count, and being on ART were independently associated with poor outcomes. The multivariate model of the WHO danger signs showed a ROC AUC of 0.649 (95% CI 0.582–0.717) for predicting 56-day mortality, which improved to ROC AUC of 0.740 (95% CI 0.681–0.800; p = 0.004 for comparison between the two ROC AUCs) with the multivariate model including the a priori selected variables. Findings were similar in sub-analyses of participants with culture-positive tuberculosis and with cough duration ≥ 14 days. Conclusion: The study design prevented a rigorous evaluation of the prognostic value of the WHO danger signs. Our prognostic model could result in improved algorithms, but needs to be validated.
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    The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study
    (2015) Nglazi, Mweete D; Bekker, Linda‐Gail; Wood, Robin; Kaplan, Richard
    BackgroundThe implementation of collaborative TB-HIV services is challenging. We, therefore, assessed TB treatment outcomes in relation to HIV infection and antiretroviral therapy (ART) among TB patients attending a primary care service with co-located ART and TB clinics in Cape Town, South Africa.MethodsIn this retrospective cohort study, all new TB patients aged ≥ 15years who registered and initiated TB treatment between 1 October 2009 and 30 June 2011 were identified from an electronic database. The effects of HIV-infection and ART on TB treatment outcomes were analysed using a multinomial logistic regression model, in which treatment success was the reference outcome.ResultsThe 797 new TB patients included in the analysis were categorized as follows: HIV- negative, in 325 patients (40.8%); HIV-positive on ART, in 339 patients (42.5%) and HIV-positive not on ART, in 133 patients (16.7%). Overall, bivariate analyses showed no significant difference in death and default rates between HIV-positive TB patients on ART and HIV-negative patients. Statistically significant higher mortality rates were found among HIV-positive patients not on ART compared to HIV-negative patients (unadjusted odds ratio (OR) 3.25; 95% confidence interval (CI) 1.53–6.91). When multivariate analyses were conducted, the only significant difference between the patient categories on TB treatment outcomes was that HIV-positive TB patients not on ART had significantly higher mortality rates than HIV-negative patients (adjusted OR 4.12; 95% CI 1.76–9.66). Among HIV-positive TB patients (n = 472), 28.2% deemed eligible did not initiate ART in spite of the co-location of TB and ART services. When multivariate analyses were restricted to HIV-positive patients in the cohort, we found that being HIV-positive not on ART was associated with higher mortality (adjusted OR 7.12; 95% CI 2.95–18.47) and higher default rates (adjusted OR 2.27; 95% CI 1.15–4.47).ConclusionsThere was no significant difference in death and default rates between HIV-positive TB patients on ART and HIV negative TB patients. Despite the co-location of services 28.2% of 472 HIV-positive TB patients deemed eligible did not initiate ART. These patients had a significantly higher death and default rates.
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    The utility of a shortened palliative care screening tool to predict death within 12 months – a prospective observational study in two south African hospitals with a high HIV burden
    (2019-11-13) Raubenheimer, Peter J; Day, Cascia; Abdullah, Faried; Manning, Katherine; Cupido, Clint; Peter, Jonny
    Abstract Background Timely identification of people who are at risk of dying is an important first component of end-of-life care. Clinicians often fail to identify such patients, thus trigger tools have been developed to assist in this process. We aimed to evaluate the performance of a identification tool (based on the Gold Standards Framework Prognostic Indicator Guidance) to predict death at 12 months in a population of hospitalised patients in South Africa. Methods Patients admitted to the acute medical services in two public hospitals in Cape Town, South Africa were enrolled in a prospective observational study. Demographic data were collected from patients and patient notes. Patients were assessed within two days of admission by two trained clinicians who were not the primary care givers, using the identification tool. Outcome mortality data were obtained from patient folders, the hospital electronic patient management system and the Western Cape Provincial death registry which links a unique patient identification number with national death certificate records and system wide electronic records. Results 822 patients (median age of 52 years), admitted with a variety of medical conditions were assessed during their admission. 22% of the cohort were HIV-infected. 218 patients were identified using the screening tool as being in the last year of their lives. Mortality in this group was 56% at 12 months, compared with 7% for those not meeting any criteria. The specific indicator component of the tool performed best in predicting death in both HIV-infected and HIV-uninfected patients, with a sensitivity of 74% (68–81%), specificity of 85% (83–88%), a positive predictive value of 56% (49–63%) and a negative predictive value of 93% (91–95%). The hazard ratio of 12-month mortality for those identified vs not was 11.52 (7.87–16.9, p < 0.001). Conclusions The identification tool is suitable for use in hospitals in low-middle income country setting that have both a high communicable and non-communicable disease burden amongst young patients, the majority under age 60.