Dataset Information

Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment.

ABSTRACT: Background:Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases. Methods:Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate-TB burden country over a 5-year period. We defined "missed TB" or "not-missed TB" patients as those who started anti-TB therapy after or before positive mycobacterial culture results, respectively. Results:Of 258 patients, 134 (52%) were classified in the missed TB group, and 124 (48%) in the not-missed TB group. Positive results of molecular tests including MTB polymerase chain reaction and/or Xpert TB/RIF were only obtained in the not-missed TB group (54/106, 54%). The median diagnostic delay in the missed TB group was longer than in the other group (30 vs 6 days; P < .001). In the missed TB group, the most common working diagnoses were pneumonia (46, 34%) and lung metastasis of malignancy (40, 30%). Typical radiologic findings for TB, such as upper lobe predominance and centrilobular nodules with tree-in-bud appearance, were less common in the missed TB group than in the other group. Old age (odds ratio [OR], 1.03), solid organ transplant (OR, 3.46), solid tumor (OR, 3.83), and hematologic malignancy (OR, 4.04) were independently associated with missed TB. Conclusions:Care is needed to differentiate pauci-bacillary TB, especially in immunocompromised patients with the mentioned risk factors, even without the usual radiologic features of TB. Additional rapid diagnostic tests to rule out pauci-bacillary TB are urgently needed.

SUBMITTER: Park JH

PROVIDER: S-EPMC6366656 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment.

Park Joung Ha JH Choe Jooae J Bae Moonsuk M Choi Sungim S Jung Kyung Hwa KH Kim Min Jae MJ Chong Yong Pil YP Lee Sang-Oh SO Choi Sang-Ho SH Kim Yang Soo YS Woo Jun Hee JH Jo Kyung-Wook KW Shim Tae Sun TS Kim Mi Young MY Kim Sung-Han SH

Open forum infectious diseases 20190117 2

<h4>Background</h4>Pauci-bacillary pulmonary tuberculosis (TB) can be delayed to diagnose and start anti-TB therapy, especially in immunocompromised patients. We therefore evaluated the clinical and radiologic features of these delayed cases.<h4>Methods</h4>Immunocompromised adult patients with pauci-bacillary pulmonary TB were retrospectively enrolled in a tertiary hospital in an intermediate-TB burden country over a 5-year period. We defined "missed TB" or "not-missed TB" patients as those who ...[more]

PMID: 30775402

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Project description:BackgroundEarly diagnosis and treatment of pulmonary tuberculosis (PTB) is essential for an effective control of the tuberculosis (TB) epidemic. Delayed diagnosis and treatment of TB increases the chance of complications and mortality for the patients, and enhances TB transmission in the population. Therefore, the aim of this study was to characterize patient, healthcare and total delay in diagnosing PTB and assess the effect of clinical and sociodemographic factors on the time until first contact with healthcare or reaching a PTB diagnosis.MethodsRetrospective cohort study that included active PTB patients notified in the National Tuberculosis Surveillance System (SVIG-TB), between 2008 and 2017. Descriptive statistics, Kaplan-Meier estimates, logrank test and Cox proportional hazards model were used to characterize patient, healthcare and total delay and estimate the effect of clinical and sociodemographic variables on these delays. Significance level was set at 0.05.ResultsMedian patient, healthcare and total delays was 37 days (Interquartile range (IQR): 19-71), 8 days (IQR: 1-32) and 62 days (IQR: 38-102), respectively. The median patient delay showed a constant increase, from 33 days in 2008 to 44 days in 2017. The median total delay presented a similar trend, increasing from 59 days in 2008 to 70 days in 2017. Healthcare delay remained constant during the study period. More than half of the PTB cases (82.9%) had a delay > 1 month between symptom onset and diagnosis. In the final Cox model, alcohol abuse, unemployment and being from a high TB incidence country were factors significantly associated with longer patient delay, while being female, having more than 45 years, oncologic and respiratory diseases were associated with longer healthcare delay. Being female, having more than 45 years and being from a high TB incidence country were associated with longer total delay.ConclusionsPatient delay and total delay have increased in recent years. Older patients, patients with alcohol problems, other comorbidities, unemployed or from countries with high TB incidence would benefit from the development of specific public health strategies that could help reduce the delay in TB diagnosis observed in our study. This study emphasizes the need to promote awareness of TB in the general population and among the healthcare community, especially at ambulatory care level, in order to reduce the gap between beginning of symptoms and TB diagnosis.

Project description:ImportanceDelayed diagnosis of appendicitis is associated with worse outcomes than timely diagnosis, but clinical features associated with diagnostic delay are uncertain, and the extent to which delays are preventable is unclear.ObjectiveTo determine clinical features associated with delayed diagnosis of pediatric appendicitis, assess the frequency of preventable delay, and compare delay outcomes.Design, setting, and participantsThis case-control study included 748 children treated at 5 pediatric emergency departments in the US between January 1, 2010, and December 31, 2019. Participants were younger than 21 years and had a diagnosis of appendicitis.ExposuresIndividual features of appendicitis and pretest likelihood of appendicitis were measured by the Pediatric Appendicitis Risk Calculator (pARC).Main outcomes and measuresCase patients had a delayed diagnosis of appendicitis, defined as 2 emergency department visits leading to diagnosis and a case review showing the patient likely had appendicitis at the first visit. Control patients had a single emergency department visit yielding a diagnosis. Clinical features and pARC scores were compared by case-control status. Preventability of delay was assessed as unlikely, possible, or likely. The proportion of children with indicated imaging based on an evidence-based cost-effectiveness threshold was determined. Outcomes of delayed diagnosis were compared by case-control status, including hospital length of stay, perforation, and multiple surgical procedures.ResultsA total of 748 children (mean [SD] age, 10.2 [4.3] years; 392 boys [52.4%]; 427 White children [57.1%]) were included in the study; 471 (63.0%) had a delayed diagnosis of appendicitis, and 277 (37.0%) had no delay in diagnosis. Children with a delayed diagnosis were less likely to have pain with walking (adjusted odds ratio [aOR], 0.16; 95% CI, 0.10-0.25), maximal pain in the right lower quadrant (aOR, 0.12; 95% CI, 0.07-0.19), and abdominal guarding (aOR, 0.33; 95% CI, 0.21-0.51), and were more likely to have a complex chronic condition (aOR, 2.34; 95% CI, 1.05-5.23). The pretest likelihood of appendicitis was 39% to 52% lower in children with a delayed vs timely diagnosis. Among children with a delayed diagnosis, 109 cases (23.1%) were likely to be preventable, and 247 (52.4%) were possibly preventable. Indicated imaging was performed in 104 (22.0%) to 289 (61.3%) children with delayed diagnosis, depending on the imputation method for missing data on white blood cell count. Patients with delayed diagnosis had longer hospital length of stay (mean difference between the groups, 2.8 days; 95% CI, 2.3-3.4 days) and higher perforation rates (OR, 7.8; 95% CI, 5.5-11.3) and were more likely to undergo 2 or more surgical procedures (OR, 8.0; 95% CI, 2.0-70.4).Conclusions and relevanceIn this case-control study, delayed appendicitis was associated with initially milder symptoms but worse outcomes. These findings suggest that a majority of delayed diagnoses were at least possibly preventable and that many of these patients did not undergo indicated imaging, suggesting an opportunity to prevent delayed diagnosis of appendicitis in some children.

Project description:BackgroundIntrapulmonary pharmacokinetics may better explain response to tuberculosis (TB) treatment than plasma pharmacokinetics. We explored these relationships by modeling bacillary clearance in sputum in adult patients on first-line treatment in Malawi.MethodsBacillary elimination rates (BER) were estimated using linear mixed-effects modelling of serial time-to-positivity in mycobacterial growth indicator tubes for sputum collected during the intensive phase of treatment (weeks 0-8) for microbiologically confirmed TB. Population pharmacokinetic models used plasma and intrapulmonary drug levels at 8 and 16 weeks. Pharmacokinetic-pharmacodynamic relationships were investigated using individual-level measures of drug exposure (area-under-the-concentration-time-curve [AUC] and Cmax) for rifampicin, isoniazid, pyrazinamide, and ethambutol, in plasma, epithelial lining fluid, and alveolar cells as covariates in the bacillary elimination models.ResultsAmong 157 participants (58% human immunodeficiency virus [HIV] coinfected), drug exposure in plasma or alveolar cells was not associated with sputum bacillary clearance. Higher peak concentrations (Cmax) or exposure (AUC) to rifampicin or isoniazid in epithelial lining fluid was associated with more rapid bacillary elimination and shorter time to sputum negativity. More extensive disease on baseline chest radiograph was associated with slower bacillary elimination. Clinical outcome was captured in 133 participants, with 15 (11%) unfavorable outcomes recorded (recurrent TB, failed treatment, or death). No relationship between BER and late clinical outcome was identified.ConclusionsGreater intrapulmonary drug exposure to rifampicin or isoniazid in the epithelial lining fluid was associated with more rapid bacillary clearance. Higher doses of rifampicin and isoniazid may result in sustained high intrapulmonary drug exposure, rapid bacillary clearance, shorter treatment duration and better treatment outcomes.

Project description:OBJECTIVES:To develop a proof-of-concept "interpretable" deep learning prototype that justifies aspects of its predictions from a pre-trained hepatic lesion classifier. METHODS:A convolutional neural network (CNN) was engineered and trained to classify six hepatic tumor entities using 494 lesions on multi-phasic MRI, described in Part 1. A subset of each lesion class was labeled with up to four key imaging features per lesion. A post hoc algorithm inferred the presence of these features in a test set of 60 lesions by analyzing activation patterns of the pre-trained CNN model. Feature maps were generated that highlight regions in the original image that correspond to particular features. Additionally, relevance scores were assigned to each identified feature, denoting the relative contribution of a feature to the predicted lesion classification. RESULTS:The interpretable deep learning system achieved 76.5% positive predictive value and 82.9% sensitivity in identifying the correct radiological features present in each test lesion. The model misclassified 12% of lesions. Incorrect features were found more often in misclassified lesions than correctly identified lesions (60.4% vs. 85.6%). Feature maps were consistent with original image voxels contributing to each imaging feature. Feature relevance scores tended to reflect the most prominent imaging criteria for each class. CONCLUSIONS:This interpretable deep learning system demonstrates proof of principle for illuminating portions of a pre-trained deep neural network's decision-making, by analyzing inner layers and automatically describing features contributing to predictions. KEY POINTS:• An interpretable deep learning system prototype can explain aspects of its decision-making by identifying relevant imaging features and showing where these features are found on an image, facilitating clinical translation. • By providing feedback on the importance of various radiological features in performing differential diagnosis, interpretable deep learning systems have the potential to interface with standardized reporting systems such as LI-RADS, validating ancillary features and improving clinical practicality. • An interpretable deep learning system could potentially add quantitative data to radiologic reports and serve radiologists with evidence-based decision support.

Dataset Information

Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment.

Publications

Clinical Characteristics and Radiologic Features of Immunocompromised Patients With Pauci-Bacillary Pulmonary Tuberculosis Receiving Delayed Diagnosis and Treatment.

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