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Optimizing Tuberculosis Diagnosis in Human Immunodeficiency Virus-Infected Inpatients Meeting the Criteria of Seriously Ill in the World Health Organization Algorithm.

ABSTRACT: Background:The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill human immunodeficiency virus (HIV)-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients. Methods:We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defined danger signs. Culture-positive tuberculosis from any site was the reference standard. A priori selected variables were assessed for univariate associations with tuberculosis. The most predictive variables were assessed in a multivariate logistic regression model and used to establish a clinical prediction rule for diagnosing tuberculosis. Results:We enrolled 484 participants. The median age was 36 years, 65.5% were female, the median CD4 count was 89 cells/µL, and 35.3% were on antiretroviral therapy. Tuberculosis was diagnosed in 52.7% of participants. The c-statistic of our clinical prediction rule (variables: cough ?14 days, unable to walk unaided, temperature >39°C, chest radiograph assessment, hemoglobin, and white cell count) was 0.811 (95% confidence interval, .802-.819). The classic tuberculosis symptoms (fever, night sweats, weight loss) added no discriminatory value in diagnosing tuberculosis. Xpert MTB/RIF assay sensitivity was 86.3% and specificity was 96.1%. Conclusions:Our clinical prediction rule had good diagnostic utility for tuberculosis among seriously ill HIV-infected inpatients. Xpert MTB/RIF assay, incorporated into the updated 2016 WHO algorithm, had high sensitivity and specificity in this population. Our findings could facilitate improved diagnosis of tuberculosis among seriously ill HIV-infected inpatients in resource-constrained settings.

SUBMITTER: Griesel R

PROVIDER: S-EPMC5905585 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Optimizing Tuberculosis Diagnosis in Human Immunodeficiency Virus-Infected Inpatients Meeting the Criteria of Seriously Ill in the World Health Organization Algorithm.

Griesel Rulan R Stewart Annemie A van der Plas Helen H Sikhondze Welile W Rangaka Molebogeng X MX Nicol Mark P MP Kengne Andre P AP Mendelson Marc M Maartens Gary G

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180401 9

<h4>Background</h4>The World Health Organization (WHO) algorithm for the diagnosis of tuberculosis in seriously ill human immunodeficiency virus (HIV)-infected patients lacks a firm evidence base. We aimed to develop a clinical prediction rule for the diagnosis of tuberculosis and to determine the diagnostic utility of the Xpert MTB/RIF assay in seriously ill HIV-infected patients.<h4>Methods</h4>We conducted a prospective study among HIV-infected inpatients with any cough duration and WHO-defin ...[more]

PMID: 29126226

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Project description: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 first 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 confirmed 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.

Project description:Tuberculosis, bacterial community-acquired pneumonia (CAP), and Pneumocystis jirovecii pneumonia (PJP) are the three commonest causes of hospitalisation in HIV-infected adults. Prompt diagnosis and treatment initiation are important to reduce morbidity and mortality, but are hampered by limited diagnostic resources in resource poor settings. C-reactive protein (CRP) and procalcitonin have shown diagnostic utility for respiratory tract infections, however few studies have focussed on their ability to distinguish between tuberculosis, CAP, and PJP in HIV-infected inpatients.We evaluated the diagnostic accuracy of CRP and procalcitonin, compared with composite reference standards, to discriminate between the three target infections in adult HIV-infected inpatients in two district level hospitals in Cape Town, South Africa. Participants were admitted with current cough and danger signs in accordance with the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study clinicians were blinded to CRP and procalcitonin results.Two hundred forty-eight participants met study case definitions: 133 with tuberculosis, 61 with CAP, 16 with PJP, and 38 with mixed infection. In the 210 particpants with single infections the differences in median CRP and procalcitonin concentrations between the three infections were statistically significant, but distributions overlapped considerably. CRP and procalcitonin concentrations were highest in the CAP group and lowest in the PJP group. CRP and procalcitonin cut-offs with sensitivities of ?90% were found for all three target infection pairs, but corresponding specificities were low. Highest receiver operating characteristic areas under the curve for CRP and procalcitonin were for PJP versus tuberculosis and PJP versus CAP (0.68 and 0.71, and 0.74 and 0.69 respectively).CRP and procalcitonin showed limited value in discriminating between the three target infections due to widely overlapping distributions, but diagnostic accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings show limitations for CRP and procalcitonin, particularly for discriminiation of tuberculosis form CAP, however they may have greater diagnostic utility as part of a panel of biomarkers or in clinical prediction rules.

Project description:BackgroundDespite the perceived ethical, personal and health service benefits of advance care planning (ACP), the extent to which older and seriously ill Australian inpatients have considered future health decisions remains uncertain. This study aimed to determine in a sample of older and seriously ill inpatients, the proportion who had: 1) engaged in four advance care planning (ACP) activities; 2) not engaged in ACP activities but wanted to; and 3) reasons why they had not engaged.MethodsCross-sectional face-to-face standardised interview survey with inpatients in a tertiary referral centre who were either: aged 80+ years; aged 55+ years with progressive chronic disease(s); or judged by treating clinicians as having a life expectancy of less than 12?months. Patients indicated whether they had engaged in four ACP activities: (1) appointed medical substitute-decision-maker(s), (2) recorded end-of-life wishes in an advance directive or care plan; and talked about their end-of-life wishes with their: (3) support persons and/or (4) doctors. Patients who had not engaged in activities were asked whether they wished this to occur and reasons why.ResultsOne hundred eighty-six inpatients consented to the study (80% of approached). Of these, 9% (n?=?16) had engaged in four ACP activities; 27% (n?=?50) had not engaged in any. Half (n?=?94, 52%) had appointed a medical substitute-decision-maker, 27% (n?=?50) had recorded wishes in an advance directive or care plan, 51% (n?=?90) had talked about their end-of-life wishes with support persons and 27% (n?=?48) had talked with their doctor. Patients who wanted to, but had not, engaged in the four ACP activities were unaware they could record wishes or appoint decision-makers, or indicated providers had not initiated conversations.ConclusionRelatively few inpatients had engaged in all four ACP activities. More inpatients had discussed end of life issues with family and appointed substitute decision makers, than completed written documents or talked with doctors. Community education and a more active role for community and hospital-based providers in supporting patients and families to collaboratively resolve end-of-life decisions may increase the probability wishes are known and followed.

Project description:BackgroundWorld Health Organization (WHO) released region-specific cardiovascular disease (CVD) risk prediction charts recently, but the extent to which the charts can apply to Chinese population is unknown. We aimed to validate the WHO CVD risk charts for East Asia, and evaluate their practicability combining with China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) equations among Chinese adults.MethodsThe China-PAR cohort with 93,234 participants aged 40-80 years was followed up during 1992-2015, including 29,337 participants from three sub-cohorts with follow-up period of over 10 years. We validated the WHO CVD risk charts using the China-PAR cohort by assessment of the predicted number of events, C index, calibration χ², and calibration plots, further elaborated the concordance between the China-PAR equations and the WHO risk charts.FindingsDuring an average follow-up of 13•64 years, 1849 incident CVD cases were identified from 29,337 participants. Both the laboratory-based and non-laboratory-based charts overestimated CVD events by 59% and 58% in men, and by 72% and 85% in women, respectively. However, 92% of participants identified as high risk by the China-PAR equations could be successfully detected by the laboratory-based charts at the cut-off point of 10%. We also observed that the non-laboratory-based charts demonstrated the poor performance for diabetic population, with high proportion of high-risk individuals (17% for men, 31% for women) would be missed.InterpretationAlthough the WHO CVD risk charts for East Asia apparently overestimated CVD risk among Chinese population, they could be pragmatic pre-selection tools, as potential supplement to the China-PAR equations. The widespread use of the WHO risk charts along with the China-PAR equations might facilitate the implementation of the risk-based CVD prevention in China.FundingFull funding sources are listed at the end of the paper (see Acknowledgments).

Dataset Information

Optimizing Tuberculosis Diagnosis in Human Immunodeficiency Virus-Infected Inpatients Meeting the Criteria of Seriously Ill in the World Health Organization Algorithm.

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Optimizing Tuberculosis Diagnosis in Human Immunodeficiency Virus-Infected Inpatients Meeting the Criteria of Seriously Ill in the World Health Organization Algorithm.

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