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1.  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
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.  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
4.  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
5.  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
6.  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
7.  Focused assessment with sonography for HIV-associated tuberculosis (FASH): a short protocol and a pictorial review 
Background
Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings.
Methods
A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed.
Results
The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high.
Conclusion
FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future.
doi:10.1186/2036-7902-4-21
PMCID: PMC3554543  PMID: 23171481
HIV; TB; Co-infection; Ultrasound; Focused assessment; Resource-limited setting.
8.  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
9.  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
10.  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
11.  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
12.  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
13.  Chest radiography in general practice: indications, diagnostic yield and consequences for patient management 
Background
Chest radiography (CXR) is frequently performed in Western societies. There is insufficient knowledge of its diagnostic value in terms of changes in patient management decisions in primary care.
Aim
To assess the influence of CXR on patient management in general practice.
Design of study
Prospective cohort study.
Setting
Seventy-eight GPs and three general hospitals in the Netherlands.
Method
Patients (n = 792) aged ≥18 years referred by their GPs for CXR were included. The main outcome was change in patient management assessed by means of questionnaires filled in by GPs before and after CXR.
Results
Mean age of the patients was 57.3±16.2 years and 53% were male. Clinically relevant abnormalities were found in 24% of the CXRs. Patient management changed in 60% of the patients following CXR. Main changes included: fewer referrals to a medical specialist (from 26 to 12%); reduction in initiation or change in therapy (from 24 to 15%); and more frequent reassurance (from 25 to 46%). However, this reassurance was not perceived as such in a quarter of these patients. A change in patient management occurred significantly more frequently in patients with complaints of cough (67%), those who exhibited abnormalities during physical examination (69%), or those with a suspected diagnosis of pneumonia (68%).
Conclusion
Patient management by the GP changed in 60% of patients following CXR. CXR substantially reduced the number of referrals and initiation or change in therapy, and more patients were reassured by their GP. Thus, CXR is an important diagnostic tool for GPs and seems a cost-effective diagnostic test.
PMCID: PMC1874520  PMID: 16882374
chest radiography; general practice; patient care management
14.  Therapy duration and long-term outcomes in extra-pulmonary tuberculosis 
BMC Infectious Diseases  2014;14:115.
Background
Tuberculosis is classified as either pulmonary or extra-pulmonary (EPTB). While much focus has been paid to pulmonary tuberculosis, EPTB has received scant attention. Moreover, EPTB is viewed as one wastebasket diagnosis, as “the other” which is not pulmonary.
Methods
This is a retrospective cohort study of all patients treated for EPTB in the state of Texas between January 2000 and December 2005, who had no pulmonary disease. Clinical and epidemiological factors were abstracted from electronic records of the Report of Verified Case of Tuberculosis. The long-term outcome, which is death by December 2011, was established using the Social Security Administration Death Master File database. Survival in EPTB patients was compared to those with latent tuberculosis, as well as between different types of EPTB, using Cox proportional hazard models. A hybrid of the machine learning method of classification and regression tree analyses and standard regression models was used to identify high-order interactions and clinical factors predictive of long-term all-cause mortality.
Results
Four hundred and thirty eight patients met study criteria; the median study follow-up period for the cohort was 7.8 (inter-quartile range 6.0-10.1) years. The overall all-cause mortality rate was 0.025 (95% confidence interval [CI]: 0.021-0.030) per 100 person-year of follow-up. The significant predictors of poor long-term outcome were age (hazard ratio [HR] for each year of age-at-diagnosis was 1.05 [CI: 1.04-1.06], treatment duration, type of EPTB and HIV-infection (HR = 2.16; CI: 1.22, 3.83). Mortality in genitourinary tuberculosis was no different from latent tuberculosis, while meningitis had the poorest long-term outcome of 46.2%. Compared to meningitis the HR for death was 0.50 (CI: 0.27-0.91) for lymphatic disease, 0.42 (CI: 0.21-0.81) for bone/joint disease, and 0.59 (CI: 0.27-1.31) for peritonitis. The relationship between mortality and therapy duration for each type of EPTB was a unique “V” shaped curve, with the lowest mortality observed at different therapy durations for each, beyond which mortality increased.
Conclusions
EPTB is comprised of several different diseases with different outcomes and durations of therapy. The “V” shaped relationship between therapy duration and outcome leads to the hypothesis that longer duration of therapy may lead to higher patient mortality.
doi:10.1186/1471-2334-14-115
PMCID: PMC3943436  PMID: 24580808
Extra-pulmonary tuberculosis; Therapy duration; Survival; Peritoneal; Meningitis
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.  Utility of routine chest radiographs in a medical–surgical intensive care unit: a quality assurance survey 
Critical Care  2001;5(5):271-275.
Objective
To determine the utility of routine chest radiographs (CXRs) in clinical decision-making in the intensive care unit (ICU).
Design
A prospective evaluation of CXRs performed in the ICU for a period of 6 months. A questionnaire was completed for each CXR performed, addressing the indication for the radiograph, whether it changed the patient's management, and how it did so.
Setting
A 14-bed medical–surgical ICU in a university-affiliated, tertiary care hospital.
Patients
A total of 645 CXRs were analyzed in 97 medical patients and 205 CXRs were analyzed in 101 surgical patients.
Results
Of the 645 CXRs performed in the medical patients, 127 (19.7%) led to one or more management changes. In the 66 surgical patients with an ICU stay <48 hours, 15.4% of routine CXRs changed management. In 35 surgical patients with an ICU stay ≥ 48 hours, 26% of the 100 routine films changed management. In both the medical and surgical patients, the majority of changes were related to an adjustment of a medical device.
Conclusions
Routine CXRs have some value in guiding management decisions in the ICU. Daily CXRs may not, however, be necessary for all patients.
PMCID: PMC83854  PMID: 11737902
chest radiograph; intensive care unit; quality assurance; routine radiography
17.  Evaluation of the 2007 WHO Guideline to Improve the Diagnosis of Tuberculosis in Ambulatory HIV-Positive Adults 
PLoS ONE  2011;6(4):e18502.
Background
In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB) in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays.
Methods and Findings
Cohort study of TB suspects in four tuberculosis (TB) clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9%) of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0%) agreed to be tested, 79 (7.0%) were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3%) with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB), 28.6% smear-positive PTB, 15.2% EPTB). The median time to TB treatment initiation was 5 days (IQR: 2–13 days), ranging from 2 days (IQR: 1–11.5 days) for EPTB, over 2.5 days (IQR: 1–4 days) for smear-positive PTB to 9 days (IQR: 3–17 days) for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%–73.6%) and 79.4% (95%CI: 74.8%–82.4%) respectively.
Conclusions
Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment initiation.
doi:10.1371/journal.pone.0018502
PMCID: PMC3071837  PMID: 21494694
18.  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
19.  INCREASED INCIDENCE OF TUBERCULOSIS IN PATIENTS OF SYSTEMIC SCLEROSIS ON DEXAMETHASONE PULSE THERAPY: A SHORT COMMUNICATION FROM KASHMIR 
Indian Journal of Dermatology  2008;53(1):24-25.
Background:
Systemic sclerosis is a multi-systemic autoimmune disorder affecting predominantly the skin, lungs, gut and kidneys.
Purpose:
To report the increased incidence of tuberculosis in patients of systemic sclerosis on dexamethasone pulse (DP) therapy.
Methods:
Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to a battery of investigations including complete hemogram (CBC) with erythrocyte sedimentation rate (ESR(F)), Chest X-ray CXR (PA view) Mantoux test and urine analysis. CBC, ESR and urine examination was done monthly and CXR were repeated six-monthly.
Findings:
Seven patients on DP therapy developed genitourinary tuberculosis. Four had pulmonary tuberculosis. One patient developed tubercular lymphadenitis, one patient succumbed to miliary tuberculosis.
Conclusion:
There is an increased incidence of tuberculosis amongst patients of systemic sclerosis on DP therapy.
Limitation of the Study:
There was no control group of systemic sclerosis patients not on DP therapy to rule out the confounding effect of the disease per se predisposing to tuberculosis as all our patients as a matter of routine were put on steroid pulse. Also, the increased incidence of tuberculosis was detected incidentally while on monthly follow-up.
doi:10.4103/0019-5154.39737
PMCID: PMC2784581  PMID: 19967014
Dexamethasone pulse; systemic sclerosis; tuberculosis
20.  PCR as a Diagnostic Tool for Extra-Pulmonary Tuberculosis 
Introduction: Extra-Pulmonary Tuberculosis (EPTB) accounts for approximately 40% of the tuberculosis cases. Though it is not communicable, it is a significant cause of morbidity. This study was conducted to know the efficacy of the Polymerase Chain Reaction (PCR) as an additional tool, along with the conventional methods, in the diagnosis of EPTB.
Material and Methods: Clinical samples were collected from suspected cases of EPTB. The Ziehl-Neelsen staining (ZNS), culture on the Lowenstein-Jensen medium (LJM) and PCR testing with the use of a commercial kit were performed on the homogenized samples.
Results: A total of 182 samples which were received for the molecular diagnosis of EPTB were also tested by ZNS and culture on LJM for the presence of Mycobacterium tuberculosis. Of these, 22 were positive by at least one of the tests which were used. PCR detected the maximum number of cases of EPTB, followed by culture. The results of PCR and the conventional tests were analyzed by using McNemar’s test for the correlated proportions-the exact method of ‘IBM SPSS Statistics 20’. The analysis showed a statistical significance.
Conclusions: Whenever they are feasible, using all the available tests in combination increases the laboratory detection rates of M. tuberculosis from clinical samples. PCR must be included in the diagnostic panel of EPTB.
doi:10.7860/JCDR/2013/5425.3075
PMCID: PMC3708187  PMID: 23905092
Tuberculosis; Extrapulmonary tuberculosis; PCR; Mycobacterium
21.  Extrapulmonary Tuberculosis: Mycobacterium tuberculosis Strains and Host Risk Factors in a Large Urban Setting in Brazil 
PLoS ONE  2013;8(10):e74517.
Background
Factors related to the development of extrapulmonary forms of tuberculosis (EPTB) are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB) strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil.
Methods and Findings
We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB) cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB) and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each. By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%) fell into patterns with no family assignment; 297 (48%) isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23-54.18) were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB.
Conclusions
These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics.
doi:10.1371/journal.pone.0074517
PMCID: PMC3788772  PMID: 24098337
22.  The interrelations of radiologic findings and mechanical ventilation in community acquired pneumonia patients admitted to the intensive care unit: a multicentre retrospective study 
Background
We evaluated patients admitted to the intensive care units with the diagnosis of community acquired pneumonia (CAP) regarding initial radiographic findings.
Methods
A multicenter retrospective study was held. Chest x ray (CXR) and computerized tomography (CT) findings and also their associations with the need of ventilator support were evaluated.
Results
A total of 388 patients were enrolled. Consolidation was the main finding on CXR (89%) and CT (80%) examinations. Of all, 45% had multi-lobar involvement. Bilateral involvement was found in 40% and 44% on CXR and CT respectively. Abscesses and cavitations were rarely found. The highest correlation between CT and CXR findings was observed for interstitial involvement. More than 80% of patients needed ventilator support. Noninvasive mechanical ventilation (NIV) requirement was seen to be more common in those with multi-lobar involvement on CXR as 2.4-fold and consolidation on CT as 47-fold compared with those who do not have these findings. Invasive mechanical ventilation (IMV) need increased 8-fold in patients with multi-lobar involvement on CT.
Conclusion
CXR and CT findings correlate up to a limit in terms of interstitial involvement but not in high percentages in other findings. CAP patients who are admitted to the ICU are severe cases frequently requiring ventilator support. Initial CT and CXR findings may indicate the need for ventilator support, but the assumed ongoing real practice is important and the value of radiologic evaluation beyond clinical findings to predict the mechanical ventilation need is subject for further evaluation with large patient series.
doi:10.1186/1476-0711-13-5
PMCID: PMC3898785  PMID: 24400646
Radiography; Thoracic; Pneumoniae; Imaging; Critical care
23.  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
24.  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
25.  Competency in Chest Radiography 
BACKGROUND
Accurate interpretation of chest radiographs (CXR) is essential as clinical decisions depend on readings.
OBJECTIVE
We sought to evaluate CXR interpretation ability at different levels of training and to determine factors associated with successful interpretation.
DESIGN
Ten CXR were selected from the teaching file of the internal medicine (IM) department. Participants were asked to record the most important diagnosis, their certainty in that diagnosis, interest in a pulmonary career and adequacy of CXR training. Two investigators independently scored each CXR on a scale of 0 to 2.
PARTICIPANTS
Participants (n = 145) from a single teaching hospital were third year medical students (MS) (n = 25), IM interns (n = 44), IM residents (n = 45), fellows from the divisions of cardiology and pulmonary/critical care (n = 16), and radiology residents (n = 15).
RESULTS
The median overall score was 11 of 20. An increased level of training was associated with overall score (MS 8, intern 10, IM resident 13, fellow 15, radiology resident 18, P<.001). Overall certainty was significantly correlated with overall score (r = .613, P<.001). Internal medicine interns and residents interested in a pulmonary career scored 14 of 20 while those not interested scored 11 (P = .027). Pneumothorax, misplaced central line, and pneumoperitoneum were diagnosed correctly 9%, 26%, and 46% of the time, respectively. Only 20 of 131 (15%) participants felt their CXR training sufficient.
CONCLUSION
We identified factors associated with successful CXR interpretation, including level of training, field of training, interest in a pulmonary career and overall certainty. Although interpretation improved with training, important diagnoses were missed.
doi:10.1111/j.1525-1497.2006.00427.x
PMCID: PMC1484801  PMID: 16704388
education; medical; radiography; thoracic; clinical competence; educational measurement

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