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1.  Clinical significance of normal chest radiographs among HIV-seropositive patients with suspected tuberculosis in Uganda 
Respirology (Carlton, Vic.)  2011;16(5):836-841.
Background and objectives
The frequency, aetiologies, and outcomes of normal chest radiographs (CXRs) among HIV-seropositive patients with suspected pulmonary tuberculosis (TB) have been infrequently described.
Methods
Consecutive HIV-seropositive adults hospitalized for cough of ≥ 2 weeks duration at Mulago Hospital (Kampala, Uganda), between September 2007 and July 2008, were enrolled. Baseline CXRs were obtained on admission. Patients with sputum smears that were negative for acid-fast bacilli (AFB) were referred for bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was examined for mycobacteria, Pneumocystis jirovecii, and other fungi. Patients were followed for two months after enrolment.
Results
Of the 334 patients, 54 (16%) had normal CXRs. These patients were younger (median age 30 vs. 34 years, P=0.002), had lower counts of CD4+ T lymphocytes (median 13 vs. 57 cells/μL, P<0.001), and were less likely to be smear positive for AFB (17% vs. 39%, P=0.002) than those with abnormal CXRs. Pulmonary TB was the most frequent diagnosis (44%) among those with normal CXRs, followed by unknown diagnoses, pulmonary aspergillosis, and pulmonary cryptococcosis. The frequency of normal CXRs was 12% among pulmonary TB patients. There was a trend towards increased two-month mortality among patients with normal CXRs compared to those with abnormal CXRs (40% vs. 29%, P=0.15).
Conclusions
Normal CXR findings were common among HIV-seropositive patients with suspected TB, especially those who were young, those with low CD4+ T cell counts, and those with sputum smears that were negative for AFB. Mortality was high among those with normal CXRs. Normal CXR findings should not preclude further diagnostic evaluation in this population.
doi:10.1111/j.1440-1843.2011.01981.x
PMCID: PMC3126910  PMID: 21518124
clinical epidemiology; critical care medicine; immunodeficiency; radiology and other imaging; tuberculosis
2.  Chest radiographic findings of pulmonary tuberculosis in severely immunocompromised patients with the human immunodeficiency virus 
The British Journal of Radiology  2012;85(1014):e130-e139.
Objective
We describe chest radiograph (CXR) findings in a population with a high prevalence of human immunodeficiency virus (HIV) and tuberculosis (TB) in order to identify radiological features associated with TB; to compare CXR features between HIV-seronegative and HIV-seropositive patients with TB; and to correlate CXR findings with CD4 T-cell count.
Methods
Consecutive adult patients admitted to a national referral hospital with a cough of duration of 2 weeks or longer underwent diagnostic evaluation for TB and other pneumonias, including sputum examination and mycobacterial culture, bronchoscopy and CXR. Two radiologists blindly reviewed CXRs using a standardised interpretation form.
Results
Smear or culture-positive TB was diagnosed in 214 of 403 (53%) patients. Median CD4+ T-cell count was 50 cells mm–3 [interquartile range (IQR) 14–150]. TB patients were less likely than non-TB patients to have a normal CXR (12% vs 20%, p=0.04), and more likely than non-TB patients to have a diffuse pattern of opacities (75% vs 60%, p=0.003), reticulonodular opacities (45% vs 12%, p<0.001), nodules (14% vs 6%, p=0.008) or cavities (18% vs 7%, p=0.001). HIV-seronegative TB patients more often had consolidation (70% vs 42%, p=0.007) and cavities (48% vs 13%, p<0.001) than HIV-seropositive TB patients. TB patients with a CD4+ T-cell count of ≤50 cells mm–3 less often had consolidation (33% vs 54%, p=0.006) and more often had hilar lymphadenopathy (30% vs 16%, p=0.03) compared with patients with CD4 51–200 cells mm–3.
Conclusion
Although different CXR patterns can be seen in TB and non-TB pneumonias there is considerable overlap in features, especially among HIV-seropositive and severely immunosuppressed patients. Providing clinical and immunological information to the radiologist might improve the accuracy of radiographic diagnosis of TB.
doi:10.1259/bjr/70704099
PMCID: PMC3474111  PMID: 21976629
3.  Ultrasound findings in cases of extrapulmonary TB in patients with HIV infection in Jeddah, Saudi Arabia 
Objective
To report ultrasound (US), laboratory and chest radiograph (CXR) findings of patients with extra-pulmonary tuberculosis (EPTB) and discuss the diagnostic relevance of US in EPTB in high-risk individuals.
Methods
In this retrospective study, we described a cohort of 39 patients with a primarily immigrant background diagnosed with HIV and EPTB in Saudi Arabia and evaluated the role of US in their clinical management. All inpatient files of those diagnosed with EPTB who were HIV positive and had at least one US exam and one CXR exam performed were identified; results and outcomes were extracted.
Results
Thirty-nine patients were diagnosed with HIV-associated EPTB between January 2008 and March 2012 and fulfilled the search criteria. Disseminated TB was diagnosed in 32 patients, pleural TB in 15, TB meningitis in 9 and TB pericarditis in 5. Enlarged abdominal lymph nodes were the single most frequent US finding seen in 61%, followed by pleural effusions (38%), liver (36%) and spleen (31%) lesions. CXR were normal in 38% of the patients.
Conclusions
As EPTB infections in HIV positive patients can be treated effectively if diagnosed early, we suggest that US should be integrated in diagnostic algorithms for EPTB.
doi:10.1016/S2222-1808(14)60306-6
PMCID: PMC4027353
HIV; Extra-pulmonary tuberculosis; Ultrasound; Diagnosis
4.  Screening Strategies for Tuberculosis Prevalence Surveys: The Value of Chest Radiography and Symptoms 
PLoS ONE  2012;7(7):e38691.
Background
We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.
Methods
All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.
Results
Presence of any abnormality on CXR had 94% (95%CI 88–98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68–77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for ‘any TB symptom’ which had 90% (95%CI 84–95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30–34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97–100) sensitivity. Specificity was 65% (95%CI 61–68). Sequential application of first a symptom screen for ‘any symptom’, followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.
Conclusion
CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.
doi:10.1371/journal.pone.0038691
PMCID: PMC3391193  PMID: 22792158
5.  The role and performance of chest X-ray for the diagnosis of tuberculosis: A cost-effectiveness analysis in Nairobi, Kenya 
Background
The objective of this study was to establish 1) the performance of chest X-ray (CXR) in all suspects of tuberculosis (TB), as well as smear-negative TB suspects and 2) to compare the cost-effectiveness of the routine diagnostic pathway using Ziehl-Neelsen (ZN) sputum microscopy followed by CXR if case of negative sputum result (ZN followed by CXR) with an alternative pathway using CXR as a screening tool (CXR followed by ZN).
Methods
From TB suspects attending a chest clinic in Nairobi, Kenya, three sputum specimens were examined for ZN and culture (Lowenstein Jensen). Culture was used as gold standard. From each suspect a CXR was made using a four point scoring system: i: no pathology, ii: pathology not consistent for TB, iii: pathology consistent for TB and iv: pathology highly consistent for TB. The combined score i + ii was labeled as "no TB" and the combined score iii + iv was labeled as "TB". Films were re-read by a reference radiologist. HIV test was performed on those who consented. Laboratory and CXR costs were used to compare for cost-effectiveness.
Results
Of the 1,389 suspects enrolled, for 998 (72%) data on smear, culture and CXR was complete. 714 films were re-read, showing a 89% agreement (kappa value = 0.75 s.e.0.037) for the combined scores "TB" or "no-TB". The sensitivity/specificity of the CXR score "TB" among smear-negative suspects was 80%/67%. Using chest CXR as a screening tool in all suspects, sensitivity/specificity of the score "any pathology" was 92%, respectively 63%. The cost per correctly diagnosed case was for the routine process $8.72, compared to $9.27 using CXR as screening tool. When costs of treatment were included, CXR followed by ZN became more cost-effective.
Conclusion
The diagnostic pathway ZN followed by CXR was more cost-effective as compared to CXR followed by ZN. When cost of treatment was also considered CXR followed by ZN became more cost-effective. The low specificity of chest X-ray remains a subject of concern. Depending whether CXR was performed on all suspects or on smear-negative suspects only, 22%–45% of patients labeled as "TB" had a negative culture. The introduction of a well-defined scoring system, clinical conferences and a system of CXR quality control can contribute to improved diagnostic performance.
doi:10.1186/1471-2334-5-111
PMCID: PMC1326228  PMID: 16343340
6.  Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the role of chest x-ray and sputum culture 
Background
Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients.
Methods
Ambulatory HIV-positive subjects with CD4 counts ≥ 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture.
Results
Among 1176 subjects 136 (12%) were treated for presumptive TB. These patients were more frequently male than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower median CD4 counts (319/μL vs. 425/μL, respectively; p < .0001). Among the 136 patients treated for TB, 38 (28%) had microbiologic confirmation, including 13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated patients in whom the only positive finding was an abnormal CXR. Blood cultures were negative in all patients.
Conclusion
Many ambulatory HIV-infected patients with CD4 counts ≥ 200/mm3 are treated for presumptive TB. Our data suggest that optimal detection requires comprehensive evaluation, including CXR and sputum culture on both symptomatic and asymptomatic subjects.
doi:10.1186/1471-2334-8-32
PMCID: PMC2323005  PMID: 18325120
7.  National Guidelines Not Always Followed When Diagnosing Smear-Negative Pulmonary Tuberculosis in Patients with HIV in Botswana 
PLoS ONE  2014;9(2):e88654.
Background
Diagnosis of smear negative pulmonary tuberculosis (SNPTB) is challenging, especially in patients with HIV. The Botswana National Tuberculosis Program (BNTP) guidelines give guidance in diagnosing and treating SNPTB. Patients with chronic cough should be screened for TB by 3 sputum smear investigations. If negative, a chest x-ray (CXR) should be performed. If negative for TB, antimicrobial treatment for other infections should be started. We investigated the clinicians’ use of the guidelines in clinical practice.
Methods
Data regarding the medical history (coughing period), requested and conducted investigations concerning tuberculosis diagnosis (sputum smear or culture or CXR) or alternative diagnoses (sputum microscopy or blood or sputum culture for diagnosis of other organisms), in SNPTB HIV-positive patients (outpatients and admitted patients) from 2006–2009 in a district hospital in Botswana were extracted from all available hospital medical records. Additionally, a survey was done in all doctors diagnosing SNPTB in this hospital using a self-administered questionnaire with questions regarding the application of the BNTP guidelines in practice. Descriptive analyses of collected data were performed to test the compliance to the guidelines.
Results
Data from medical records showed that in 47.0% (132/281) of patients, TB treatment was started without microbiological results from sputum smears. Other methods to rule out or confirm PTB were used in 2.1% (6/281); and 99.6% (280/281) of SNPTB patients had received a CXR. The survey in 7 clinicians found that all always used CXR, and all clinicians requested three sputum results only sometimes. Six out of 7 clinicians started antibiotics before starting TB treatment. Reasons clinicians gave for difficulties in following the guidelines included inability of patients to produce sputum; and laboratory delays in releasing sputum results.
Conclusion
Between 2006 and 2009 a high proportion of SNPTB diagnoses in a district hospital in Botswana were not supported by laboratory investigation.
doi:10.1371/journal.pone.0088654
PMCID: PMC3925109  PMID: 24551128
8.  Blood Absolute T Cell Counts may Predict 2-Month Treatment Response in Patients with Pulmonary Tuberculosis 
Disease markers  2010;28(6):343-352.
Background and objective: Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients.
Methods:Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were investigated.
Results: A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3+ T cells (p = 0.016) and CD8+ T cells (p = 0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0–1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37–32.77) and bilateral lung involvemment on CXR (OR 13.114, 95% CI 1.87–92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC) = 0.855, p < 0.001) whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC = 0.676, p = 0.015).
Conclusions: A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance.
doi:10.3233/DMA-2010-0714
PMCID: PMC3833334  PMID: 20683148
Pulmonary tuberculosis; slow responders; absolute T cell counts; prediction score
9.  High Tuberculosis Prevalence in a South African Prison: The Need for Routine Tuberculosis Screening 
PLoS ONE  2014;9(1):e87262.
Background
Tuberculosis is a major health concern in prisons, particularly where HIV prevalence is high. Our objective was to determine the undiagnosed pulmonary tuberculosis (“undiagnosed tuberculosis”) prevalence in a representative sample of prisoners in a South African prison. In addition we investigated risk factors for undiagnosed tuberculosis, to explore if screening strategies could be targeted to high risk groups, and, the performance of screening tools for tuberculosis.
Methods and Findings
In this cross-sectional survey, male prisoners were screened for tuberculosis using symptoms, chest radiograph (CXR) and two spot sputum specimens for microscopy and culture. Anonymised HIV antibody testing was performed on urine specimens. The sensitivity, specificity and predictive values of symptoms and investigations were calculated, using Mycobacterium tuberculosis isolated on sputum culture as the gold standard.
From September 2009 to October 2010, 1046 male prisoners were offered enrolment to the study. A total of 981 (93.8%) consented (median age was 32 years; interquartile range [IQR] 27–37 years) and were screened for tuberculosis. Among 968 not taking tuberculosis treatment and with sputum culture results, 34 (3.5%; 95% confidence interval [CI] 2.4–4.9%) were culture positive for Mycobacterium tuberculosis. HIV prevalence was 25.3% (242/957; 95% CI 22.6–28.2%). Positive HIV status (adjusted odds ratio [aOR] 2.0; 95% CI 1.0–4.2) and being an ex-smoker (aOR 2.6; 95% CI 1.2–5.9) were independently associated with undiagnosed tuberculosis. Compared to the gold standard of positive sputum culture, cough of any duration had a sensitivity of 35.3% and specificity of 79.6%. CXR was the most sensitive single screening modality (sensitivity 70.6%, specificity 92.2%). Adding CXR to cough of any duration gave a tool with sensitivity of 79.4% and specificity of 73.8%.
Conclusions
Undiagnosed tuberculosis and HIV prevalence was high in this prison, justifying routine screening for tuberculosis at entry into the prison, and intensified case finding among existing prisoners.
doi:10.1371/journal.pone.0087262
PMCID: PMC3907552  PMID: 24498059
10.  Significant variation in presentation of pulmonary tuberculosis across a high resolution of CD4 strata 
BACKGROUND
The human immunodeficiency virus (HIV) alters the presentation of pulmonary tuberculosis (PTB), but it remains unclear whether alterations occur at a CD4 cell threshold or throughout HIV infection.
OBJECTIVE
To better understand the relationship between CD4 count and clinical and radiographic presentation of PTB.
SETTING AND DESIGN
Initial presentations of culture-confirmed PTB patients evaluated at a Ugandan national TB referral center and an affiliated research unit were compared by HIV status and across 11 CD4 cell count strata: 0–50 to >500 cells/µl.
RESULTS
A total of 873 HIV-infected PTB cases were identified. Among HIV-infected PTB cases with CD4 < 50, 21% had a normal chest X-ray (CXR) vs. 2% with CD4 > 500, with a continuous trend across CD4 strata (test for trend, P < 0.001). All radiographic manifestations of PTB displayed significant trends across CD4 strata. HIV-infected vs. non-HIV-infected patients had no significant difference in CXR findings of miliary patterns or pleural effusion at CD4 > 100, normal CXR or fibrosis at CD4 > 150, adenopathy at CD4 > 250, and cavitation or upper lung disease at CD4 > 300. Twenty-three per cent of co-infected cases with CD4 < 50 and 1% with CD4 > 500 had negative acid-fast bacilli (AFB) smears, with a significant trend between (P < 0.001).
CONCLUSION
Variations in CXR appearance and AFB smear correlate with CD4 decline in significant, continuous trends.
PMCID: PMC3033769  PMID: 20843421
tuberculosis; HIV; CD4; chest X-ray
11.  Pulmonary imaging of pandemic influenza H1N1 infection: relationship between clinical presentation and disease burden on chest radiography and CT 
The British Journal of Radiology  2010;83(992):645-651.
The potential for pulmonary involvement among patients presenting with novel swine-origin influenza A (H1N1) is high. To investigate the utility of chest imaging in this setting, we correlated clinical presentation with chest radiographic and CT findings in patients with proven H1N1 cases. Subjects included all patients presenting with laboratory-confirmed H1N1 between 1 May and 10 September 2009 to one of three urban hospitals. Clinical information was gathered retrospectively, including symptoms, possible risk factors, treatment and hospital survival. Imaging studies were re-read for study purposes, and CXR findings compared with CT scans when available. During the study period, 157 patients presented with subsequently proven H1N1 infection. Hospital admission was necessary for 94 (60%) patients, 16 (10%) were admitted to intensive care and 6 (4%) died. An initial CXR, carried out for 123 (78%) patients, was abnormal in only 40 (33%) cases. Factors associated with increased likelihood for radiographic lung abnormalities were dyspnoea (p<0.001), hypoxaemia (p<0.001) and diabetes mellitus (p = 0.023). Chest CT was performed in 21 patients, and 19 (90%) showed consolidation, ground-glass opacity, nodules or a combination of these findings. 4 of 21 patients had negative CXR and positive CT. Compared with CT, plain CXR was less sensitive in detecting H1N1 pulmonary disease among immunocompromised hosts than in other patients (p = 0.0072). A normal CXR is common among patients presenting to the hospital for H1N1-related symptoms without evidence of respiratory difficulties. The CXR may significantly underestimate lung involvement in the setting of immunosuppression.
doi:10.1259/bjr/53692814
PMCID: PMC3473510  PMID: 20551254
12.  The Sensitivity and Specificity of Using a Computer Aided Diagnosis Program for Automatically Scoring Chest X-Rays of Presumptive TB Patients Compared with Xpert MTB/RIF in Lusaka Zambia 
PLoS ONE  2014;9(4):e93757.
Objective
To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert).
Method
Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤60) or abnormal (CAD score>60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM).
Results
Of 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2–100), 23.2% (95%CI 18.2–28.9), 33.0% (95%CI 27.6–38.7) and 100% (95% 93.9–100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66–0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert CT(r = 0.37, p<0.0001).
Conclusions
To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.
doi:10.1371/journal.pone.0093757
PMCID: PMC3976315  PMID: 24705629
13.  Tuberculosis Screening by Tuberculosis Skin Test or QuantiFERON®-TB Gold In-Tube Assay among an Immigrant Population with a High Prevalence of Tuberculosis and BCG Vaccination 
PLoS ONE  2013;8(12):e82727.
Rationale
Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth.
Objectives
1. Compare the sensitivity of QuantiFERON ®-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR.
Methods
We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR.
Results
The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15–19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants.
Conclusions
During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population. 
doi:10.1371/journal.pone.0082727
PMCID: PMC3868593  PMID: 24367546
14.  Performance of Clinical Algorithms for Smear-Negative Tuberculosis in HIV-Infected Persons in Ho Chi Minh City, Vietnam 
Background. Tuberculosis (TB) disease diagnosis in Vietnam relies on symptom screening, chest radiography (CXR), and acid fast bacilli (AFB) sputum smear which have a poor sensitivity in HIV patients. We evaluated the performance of clinical algorithms in screening and diagnosing AFB smear-negative TB in HIV patients. Methods. We enrolled 399 HIV-positive patients seeking care at a HIV clinic in Ho Chi Minh City (HCMC), Vietnam. Participants' demographics, medical history, common TB symptoms, CXR, and laboratory tests were collected. Results. Of 399 HIV patients, 390 had initial AFB-negative smears and 22/390 patients had positive cultures. Symptom screening missed 54% (12/22) of smear-negative pulmonary TB (PTB) cases. Multivariate analysis found CD4+ cell level and CXR were significant PTB predictors. An algorithm combining four TB symptoms and TST presented a high sensitivity (100%), but poorly specific (24%) diagnostic performance for smear-negative PTB. Conclusion. Up to 54% of PTB cases in the HIV-infected population may be missed in the routine screening and diagnostic procedures used in Vietnam. Symptom screening was a poor overall diagnostic measure in detecting smear-negative TB in HIV patients. Our study results suggest that routine sputum cultures should be implemented to achieve a more accurate diagnosis of TB in HIV patients.
doi:10.1155/2012/360852
PMCID: PMC3512270  PMID: 23227329
15.  The clinical value of daily routine chest radiographs in a mixed medical–surgical intensive care unit is low 
Critical Care  2005;10(1):R11.
Introduction
The clinical value of daily routine chest radiographs (CXRs) in critically ill patients is unknown. We conducted this study to evaluate how frequently unexpected predefined major abnormalities are identified with daily routine CXRs, and how often these findings lead to a change in care for intensive care unit (ICU) patients.
Method
This was a prospective observational study conducted in a 28-bed, mixed medical–surgical ICU of a university hospital.
Results
Over a 5-month period, 2,457 daily routine CXRs were done in 754 consecutive ICU patients. The majority of these CXRs did not reveal any new predefined major finding. In only 5.8% of daily routine CXRs (14.3% of patients) was one or more new and unexpected abnormality encountered, including large atelectases (24 times in 20 patients), large infiltrates (23 in 22), severe pulmonary congestion (29 in 25), severe pleural effusion (13 in 13), pneumothorax/pneumomediastinum (14 in 13), and malposition of the orotracheal tube (32 in 26). Fewer than half of the CXRs with a new and unexpected finding were ultimately clinically relevant; in only 2.2% of all daily routine CXRs (6.4% of patients) did these radiologic abnormalities result in a change to therapy. Subgroup analysis revealed no differences between medical and surgical patients with regard to the incidence of new and unexpected findings on daily routine CXRs and the effect of new and unexpected CXR findings on daily care.
Conclusion
In the ICU, daily routine CXRs seldom reveal unexpected, clinically relevant abnormalities, and they rarely prompt action. We propose that this diagnostic examination be abandoned in ICU patients.
doi:10.1186/cc3955
PMCID: PMC1550788  PMID: 16420655
16.  The value of end-of-treatment chest radiograph in predicting pulmonary tuberculosis relapse 
SUMMARY
SETTING
Patients with cavitary pulmonary tuberculosis (TB) on baseline chest radiograph (CXR) who remain culture-positive after 8 weeks of treatment are at high risk of relapse. The role of end-of-treatment (EOT) CXR in predicting relapse is unclear.
OBJECTIVE
To determine whether EOT CXR independently predicts TB relapse.
DESIGN
We conducted a secondary analysis of a randomized trial of intermittent treatment using rifapentine in the continuation phase of TB treatment among 1004 human immunodeficiency virus seronegative adults with culture-proven pulmonary TB.
RESULTS
Relapse occurred in 17.3% of subjects with persistent cavity on EOT CXR, in 7.6% of subjects with a cavity that resolved by EOT, and 2.5% (P = 0.002 for trend) of subjects who never had a cavity. In multivariable analysis, patients with persistent cavity on EOT CXR were significantly more likely to relapse than patients with no cavity on baseline or 2-month CXR (hazard ratio [HR] 4.22, 95%CI 2.00–8.91), and were more likely to relapse than subjects whose early cavity had resolved by EOT CXR (HR 1.92, 95%CI 1.09–3.39).
CONCLUSION
A persistent cavity after 6 months of TB treatment was independently associated with disease relapse after controlling for other variables. EOT CXR may help predict those likely to relapse.
PMCID: PMC3785322  PMID: 18713505
tuberculosis; relapse; chest radiograph
17.  Prevalence and Predictors of Tuberculosis Coinfection among HIV-Seropositive Patients Attending the Aminu Kano Teaching Hospital, Northern Nigeria 
Journal of Epidemiology  2009;19(2):81-87.
Background
The HIV/AIDS epidemic has been accompanied by a severe epidemic of tuberculosis (TB), although the prevalence of coinfection is largely unknown, especially in developing countries, including Nigeria. The aim of this study was to determine the prevalence and predictors of TB coinfection among HIV-seropositive Nigerians.
Methods
The case files of HIV/AIDS patients attending Aminu Kano Teaching Hospital, Nigeria from January to December 2006 were reviewed.
Results
A total of 1320 HIV/AIDS patients had complete records and were reviewed, among which 138 (10.5%) were coinfected with TB (95% CI, 8.9% to 12.2%). Pulmonary TB was diagnosed in 103 (74.6%) patients, among whom only 18 (17.5%) were sputum-positive. Fifty (36.2%) coinfected patients had some type of extrapulmonary TB (EPTB); 15 had both pulmonary TB and EPTB. Among the 35 patients with EPTB only, 20 (57.1%) had abdominal TB, 5 (14.3%) had TB adenitis, 5 (14.3%) had spinal TB, 3 (8.6%) were being monitored for tuberculous meningitis, and 1 (2.9%) each had renal TB and tuberculous adrenalitis. The highest prevalence of TB, 13.7% (n = 28), was seen among patients aged 41–50 years. TB coinfection was significantly associated with marital status, WHO clinical stage, and CD4 count. Marital status (OR, 2.1; 95% CI, 1.28–3.59; P = 0.04), WHO clinical stage at presentation (4.81; 1.42–8.34; P = 0.001), and baseline CD4 count (2.71; 1.51–6.21; P = 0.02) remained significant predictors after adjustment for confounding.
Conclusions
The moderately high prevalence of TB among HIV-seropositive patients underscores the urgent need for strategies that lead to rapid identification and treatment of coinfection with active or latent TB.
doi:10.2188/jea.JE20080026
PMCID: PMC3924118  PMID: 19265273
tuberculosis; HIV; coinfection; prevalence; Kano; Nigeria
18.  The effect of a tuberculosis chest X-ray image reference set on non-expert reader performance 
European Radiology  2013;23:2459-2468.
Objectives
In low-resource settings, limitations in diagnostic accuracy of chest X-rays (CXR) for pulmonary tuberculosis (PTB) relate partly to non-expert interpretation. We piloted a TB CXR Image Reference Set (TIRS) to improve non-expert performance in an operational setting in Malawi.
Methods
Nineteen doctors and clinical officers read 60 CXR of patients with suspected PTB, at baseline and using TIRS. Two officers also used the CXR Reading and Recording System (CRRS). Correct treatment decisions were assessed against a “gold standard” of mycobacterial culture and expert performance.
Results
TIRS significantly increased overall non-expert sensitivity from 67.6 (SD 14.9) to 75.5 (SD 11.1, P = 0.013), approaching expert values of 84.2 (SD 5.2). Among doctors, correct decisions increased from 60.7 % (SD 7.9) to 67.1 % (SD 8.0, P = 0.054). Clinical officers increased in sensitivity from 68.0 % (SD 15) to 77.4 % (SD 10.7, P = 0.056), but decreased in specificity from 55.0 % (SD 23.9) to 40.8 % (SD 10.4, P = 0.049). Two officers made correct treatment decisions with TIRS in 62.7 %. CRRS training increased this to 67.8 %.
Conclusion
Use of a CXR image reference set increased correct decisions by doctors to treat PTB. This tool may provide a low-cost intervention improving non-expert performance, translating into improved clinical care. Further evaluation is warranted.
Key Points
• Tuberculosis treatment decisions are influenced by CXR findings, despite improved laboratory diagnostics.
• In low-resource settings, CXR interpretation is performed largely by non-experts.
• We piloted the effect of a simple reference training set of CXRs.
• Use of the reference set increased the number of correct treatment decisions. This effect was more marked for doctors than clinical officers.
• Further evaluation of this simple training tool is warranted.
Electronic supplementary material
The online version of this article (doi:10.1007/s00330-013-2840-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s00330-013-2840-z
PMCID: PMC3738845  PMID: 23652843
Radiography; Tuberculosis; Malawi; Sensitivity and Specificity; Teaching
19.  Is routine chest radiography indicated following chest drain removal after cardiothoracic surgery? 
A best evidence topic was written according to a structured protocol. The question addressed was whether routine chest radiography is indicated following chest drain removal in patients undergoing cardiothoracic surgery. A total of 356 papers were found using the reported searches; of which, 6 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were mean duration of drains left in situ, timing of drain removal, pathology detected on chest radiographs (CXRs), interventions following imaging and clinical assessment, complications in patients not undergoing routine CXRs and the cost saving of omitting routine CXRs. One large cohort study reported the detection of pathology in 79% of clinically indicated CXRs in comparison to 40% of routine CXRs (P = 0.005). Ninety-five per cent of the non-routine CXR cohort remained asymptomatic and required no intervention. One large observational study reported the detection of new pneumothoraces in 9.3% of patients, 70.3% of which were barely perceptible. Intervention following CXR was required in 0.25% and only one medium-sized pneumothorax would have been potentially missed without CXR. Another large observational study reported intervention following CXR in 1.9% and the presence of relevant clinical signs and symptoms to be a significant predictor of major intervention (P < 0.01). A smaller observational study reported no pathology detected or intervention following CXR in 98% and the cost saving of omitting a single CXR at £10 000 per annum. Another small observational study reported only 7% of CXRs to be clinically indicated with a false-positive rate of 100%, and a false-negative rate of 7% in CXRs not clinically indicated. The smallest study reported no complications in the non-CXR cohort and only one patient undergoing intervention in the routine CXR cohort. We conclude that there is evidence that routine post drain removal CXR provides no diagnostic or therapeutic advantage over clinically indicated CXR or simple clinical assessment. The best evidence studies reported the detection of pathology on routine CXR ranging from 2 to 40% compared with 79% in clinically indicated CXRs (P = 0.005). Whilst the rate of intervention following routine CXR was as high as 4% in the smallest study, clinical signs and symptoms suggestive of pathology were a significant predictor of major re-intervention (P < 0.01).
doi:10.1093/icvts/ivs037
PMCID: PMC3352714  PMID: 22392935
Chest drain; Chest radiography
20.  Comparison of thermodilution measured extravascular lung water with chest radiographic assessment of pulmonary oedema in patients with acute lung injury 
Background
Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are characterized by pulmonary oedema, measured as extravascular lung water (EVLW). The chest radiograph (CXR) can potentially estimate the quantity of lung oedema while the transpulmonary thermodilution method measures the amount of EVLW. This study was designed to determine whether EVLW as estimated by a CXR score predicts EVLW measured by the thermodilution method and whether changes in EVLW by either approach predict mortality in ALI/ARDS.
Methods
Clinical data were collected within 48 hours of ALI/ARDS diagnosis and daily up to 14 days on 59 patients with ALI/ARDS. Two clinicians scored each CXR for the degree of pulmonary oedema, using a validated method. EVLW indexed to body weight was measured using the single indicator transpulmonary thermodilution technique.
Results
The CXR score had a modest, positive correlation with the EVLWI measurements (r = 0.35, p < 0.001). There was a 1.6 ml/kg increase in EVLWI per 10-point increase in the CXR score (p < 0.001, 95% confidence interval 0.92-2.35). The sensitivity of a high CXR score for predicting a high EVLWI was 93%; similarly the negative predictive value was high at 94%; the specificity (51%) and positive predictive value (50%) were lower. The CXR scores did not predict mortality but the EVLW thermodilution did predict mortality.
Conclusion
EVLW measured by CXR was modestly correlated with thermodilution measured EVLW. Unlike CXR findings, transpulmonary thermodilution EVLWI measurements over time predicted mortality in patients with ALI/ARDS.
doi:10.1186/2110-5820-3-25
PMCID: PMC3846630  PMID: 23937970
Extravascular lung water; Chest radiograph; Acute lung injury; Acute respiratory distress syndrome
21.  National Profile and Treatment Outcomes of Patients with Extrapulmonary Tuberculosis in Bénin 
PLoS ONE  2014;9(4):e95603.
Background
In sub-Saharan Africa, there is a dearth of published literature on extrapulmonary tuberculosis (EPTB).
Objective
To describe demographic, diagnostic and HIV-status characteristics of patients with EPTB in Bénin, their treatment outcomes, and among those who completed their treatment in the Centre National Hospitalier de Pneumo-Phtisiologie (CNHP-P), the proportion whose bodyweight increased during treatment.
Material and Findings
This was a retrospective cohort study with comparisons made between EPTB and new smear-positive pulmonary tuberculosis (NPTB) patients diagnosed in the country from January to December 2011. There were 383 EPTB patients (9% of all TB cases) with a mean age of 35 years, male/female ratio of 1.3 and important regional variation. There were significantly more females (p = 0.001), children <15years (p<0.001) and HIV-positive patients (p = 0.005) with EPTB compared with NPTB. Pleural effusion, spinal and lymph node tuberculosis accounted for 66% of all EPTB. Children <15 years represented 16% of cases, with lymph node disease being most common among them (p<0.001). Of 130 EPTB patients registered in CNHP-P, 7% had a confirmed bacteriological/histological diagnosis. There were 331 (86%) patients who successfully completed treatment. More patients with EPTB were lost-to-follow-up compared with NPTB (p<0.001) with all these patients from one region. The best treatment completion rates were in children <15 years (OR:3.5, 95%CI:1.0–14.8) while patients with pleural effusion and ascites had the worst outcomes. Of 72 HIV-coinfected patients, 88% were on antiretroviral therapy (ART). HIV-positive status was associated with poor outcomes while those on ART fared better. In the CNHP-P, more than 80% who completed their treatment showed an increase in bodyweight and this was more evident in HIV-positive compared with HIV-negative patients (p = 0.03).
Conclusion
Patients with EPTB generally do well in Bénin, although the TB Programme would benefit through more attention to accurate diagnosis and earlier start of ART in HIV-infected patients.
doi:10.1371/journal.pone.0095603
PMCID: PMC3995824  PMID: 24755603
22.  Site of Extrapulmonary Tuberculosis is Associated with HIV Infection 
The site of extrapulmonary tuberculosis infection has a known effect on mortality. Authors use a large clinical case series to identify previously unconfirmed risk factors that are associated with site of extrapulmonary tuberculosis infection.
Background. In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB.
Methods. We retrospectively reviewed 320 cases of EPTB from 1995–2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease.
Results. Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18–89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4).
Conclusions. Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.
doi:10.1093/cid/cis303
PMCID: PMC3493181  PMID: 22423123
23.  Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study 
Background
Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients.
Methods
A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis.
Results
The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB.
Conclusion
Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.
doi:10.1186/1471-2334-8-8
PMCID: PMC2245948  PMID: 18218115
24.  Pulmonary staging in colorectal cancer--is computerised tomography the answer? 
INTRODUCTION: Pulmonary staging in colorectal cancer (CRC) has traditionally been carried out by means of plain chest radiograph (CXR), although computerised tomography (CT) imaging of the chest is increasingly being performed for this purpose. The aim of this study was to assess the value of pre-operative thoracic CT for pulmonary staging in CRC. PATIENTS AND METHODS: Data were collected prospectively on all patients referred into hospital over a 20-month study period for double contrast barium enema evaluation of symptoms suggestive of an underlying CRC. Patients with a CRC went on to have a staging intravenous, contrast-enhanced CT of the chest, abdomen and pelvis prior to an out-patient appointment with a colorectal surgeon. The CXRs of those patients in whom a radiological abnormality was seen on thoracic CT were reviewed blindly by an independent consultant radiologist. RESULTS: A total of 403 barium enemas were performed, of which 38 demonstrated a CRC (9%). In those patients diagnosed with CRC, nine (24%) had an abnormality on thoracic CT. Four patients with positive thoracic CTs had chemotherapy and or radiotherapy with no surgery. One patient underwent colectomy, and 2 patients who had primary lung tumours as opposed to metastases also underwent colectomies. One patient received palliative care only. In addition, one of the patients underwent multiple, non-diagnostic thoracic investigations prior to a diagnosis of sarcoidosis being made and then proceeding to surgery. An independent consultant radiologist reviewed seven out of the nine CXRs of patients with an abnormality on thoracic CT without knowledge of the clinical diagnosis, and reported three of the CXRs to be normal. CONCLUSIONS: Thoracic CT appears to improve the accuracy of pulmonary staging in CRC allowing a more appropriate level of intervention. However, CT is likely to identify more benign radiological abnormalities than CXR alone, and investigations should not occur to the detriment of treating the primary tumour.
doi:10.1308/003588405X60579
PMCID: PMC1963965  PMID: 16176690
25.  Extrapulmonary tuberculosis in non-human immunodeficiency virus-infected adults in an endemic region 
Annals of Thoracic Medicine  2007;2(3):118-121.
AIMS:
Extrapulmonary tuberculosis (EPTB) still constitutes an important clinical problem. We aimed to evaluate the incidence and features of extrapulmonary tuberculosis.
MATERIALS AND METHODS:
We retrospectively evaluated 14,266 tuberculosis patients diagnosed between January 1999 and December 2003 in a tertiary care hospital in Istanbul. As many as 2,435 patients (17.1%) with EPTB were evaluated for the incidence and features.
RESULTS:
Of the 14,266 patients, 4,154 were female (29%) and 10,112 were male (71%) and were aged between 14 and 86 years with a mean age of 35 ± 14 years. As many as 660 (17.9%) patients were diagnosed as EPTB in 1999, 568 (17.8%) in 2000, 357 (13.7%) in 2001, 462 (22%) in 2002 and 388 (14.5%) in 2003. EPTB presented most commonly as pleurisy (66%), followed by lymphadenitis (23%). Lymphadenitis and pleurisy were more commonly observed among female TB patients (60%) and among male TB patients (59%) respectively. EPTB showed a significant female predilection (26.8%) compared to male patients (13.1%). Multi-organ involvement was observed in 37 (1.5%) patients (two organs in 33 and three organs in 4). As many as 197 (8%) EPTB cases had pulmonary tuberculosis simultaneously.
CONCLUSIONS:
EPTB still constitutes an important clinical problem. The rates of EPTB have remained constant despite the decline in pulmonary tuberculosis cases. In the current study, we present our experience of the incidence and features of EPTB patients without HIV infection. In this study, EPTB cases constituted one-fifth of all tuberculosis cases presented to our center in the study period.
doi:10.4103/1817-1737.33700
PMCID: PMC2732087  PMID: 19727358
Extrapulmonary tuberculosis; gender; incidence; tuberculosis

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