A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan.

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.

OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose chest CT (OPTIMACT) trial-statistical analysis plan.

BACKGROUND: A chest X-ray is a standard imaging procedure in the diagnostic work-up of patients suspected of having non-traumatic pulmonary disease. Compared to a chest X-ray, an ultra-low-dose (ULD) chest computed tomography (CT) scan provides substantially more detailed information on pulmonary conditions. To what extent this translates into an improvement in patient outcomes and health care efficiency is yet unknown. The OPTimal IMAging strategy in patients suspected of non-traumatic pulmonary disease at the emergency department: chest X-ray or ultra-low-dose chest CT (OPTIMACT) study is a multicenter, pragmatic, non-inferiority randomized controlled trial designed to evaluate replacement of chest X-ray by ULD chest CT in the diagnostic work-up of such patients, in terms of patient-related health outcomes and costs. During randomly assigned periods of 1 calendar month, either conventional chest X-ray or ULD chest CT scan was used as the imaging strategy. This paper presents in detail the statistical analysis plan of the OPTIMACT trial, developed prior to data analysis. METHODS/RESULTS: Functional health at 28 days is the primary clinical outcome. Functional health at 28 days is measured by the physical component summary scale of the Short Form (SF)-12 questionnaire version 1. Secondary outcomes are mental health (mental component summary scale of the SF-12), length of hospital stay, mortality within 28 days, quality-adjusted life year equivalent during the first 28 days (derived from the EuroQol five-dimension, five-level instrument), correct diagnoses at emergency department discharge as compared to the final post hoc diagnosis at day 28, number of patients in follow-up because of incidental findings on chest X-ray or ULD chest CT, and health care costs. CONCLUSIONS: After this pragmatic trial we will have precise estimates of the effectiveness of replacing chest X-ray with ULD chest CT in terms of patient-related health outcomes and costs. TRIAL REGISTRATION: Netherlands National Trial Register: NTR6163. Registered on 6 December 2016.

Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005­December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

UTILITY OF ROUTINE CHEST RADIOGRAPHS IN KENYA.

BACKGROUND: Many otherwise healthy Kenyans are required to obtain chest radiographs as part of routine medical examination to exclude pulmonary TB, a condition of significant public health concern. Many of these people are required to have these radiographs taken yearly as part of routine check-up. No local data is available to support this practice. Though a quick procedure to perform and readily available throughout the country, chest radiograph exposes the individual to a dose of ionising radiation. Ionising radiation is associated with increased risk of malignancy. The cost is also substantial. OBJECTIVE: To determine the prevalence of radiological findings consistent with PTB among routine medical examination chest radiographs. DESIGN: A cross-sectional descriptive study. SETTINGS: Department of Radiology Kenyatta National Hospital, Department of Imaging and Radiation Medicine, University of Nairobi, Plaza Imaging Solutions, a private radiology practice in Nairobi and Department of Radiology, the Nairobi Hospital. SUBJECTS: Four hundred and two chest radiographs of patients presenting for routine medical examinations were analysed. RESULTS: Sixty three radiographs had abnormal but clinically insignificant findings (16%). Only one radiograph (0.25%) had radiological features of PTB. The rest were reported as normal (84%). CONCLUSION: In this study, the diagnostic yield for the intended purpose (to include/ exclude PTB) was extremely low (0.25%). It is recommended that routine chest radiographs as screening tools for active pulmonary tuberculosis be reconsidered due to poor diagnostic yield. The authors propose a bigger nation wide study before a policy decision can be proposed.

Costs and consequences of additional chest x-ray in a tuberculosis prevention program in Botswana.

RATIONALE: Isoniazid preventive therapy is effective in reducing the risk of tuberculosis (TB) in persons living with HIV (PLWH); however, screening must exclude TB disease before initiating therapy. Symptom screening alone may be insufficient to exclude TB disease in PLWH because some PLWH with TB disease have no symptoms. The addition of chest radiography (CXR) may improve disease detection. OBJECTIVES: The objective of the present analysis was to compare the costs and effects of the addition of CXR to the symptom screening process against the costs and effects of symptom screening alone. METHODS: Using data from Botswana, a decision analytic model was used to compare a "Symptom only" policy against a "Symptom+CXR" policy. The outcomes of interest were cost, death, and isoniazid- and multidrug-resistant TB in a hypothetical cohort of 10,000 PLWH. MEASUREMENTS AND MAIN RESULTS: The Symptom+CXR policy prevented 16 isoniazid- and 0.3 multidrug-resistant TB cases; however, because of attrition from the screening process, there were 98 excess cases of TB, 15 excess deaths, and an additional cost of U.S. $127,100. The Symptom+CXR policy reduced deaths only if attrition was close to zero; however, to eliminate attrition the cost would be U.S. $2.8 million per death averted. These findings did not change in best- and worst-case scenario analyses. CONCLUSIONS: In Botswana, a policy with symptom screening only preceding isoniazid-preventive therapy initiation prevents more TB and TB-related deaths, and uses fewer resources, than a policy that uses both CXR and symptom screening.

Cost effectiveness of interferon-gamma release assay versus chest X-ray for tuberculosis screening of BCG-vaccinated elderly populations.

BACKGROUND: The prevalence of tuberculosis (TB) in the elderly is higher than that in the general population, and elderly populations are considered a high-risk group. Currently, annual TB screening of Bacille Calmette-Guérin (BCG)-vaccinated people aged over 65 years is performed by an annual chest x-ray examination (CXR) in Japan. Interferon-gamma release assays (QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube [QFT]) are new alternatives to the tuberculin skin test to diagnose latent TB infection (LTBI) that have no cross-reactivity with the BCG vaccine. We evaluated the cost effectiveness of QFT versus CXR versus no screening in BCG-vaccinated elderly populations. METHODS: We constructed a Markov model to evaluate the cost effectiveness of QFT, CXR, and no screening. The target population was a hypothetical cohort of 1000 immunocompetent 65-year-olds, using a societal perspective and a lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%. RESULTS: In the base-case analysis, a no-screening strategy resulted in the lowest cost ($US303.51; 14.6475 quality-adjusted life-years [QALYs]) compared with CXR ($US393.22; 14.6477 QALYs) and QFT ($US525.45; 14.6516 QALYs) [year 2008 values]. The sensitivity of QFT, as well as the prevalence of TB and LTBI, influenced the cost effectiveness; when the sensitivity of QFT was higher than 0.89, QFT became more cost effective than providing no screening. As the prevalence of LTBI and TB increased, the QFT strategy became progressively more cost effective. CONCLUSIONS: Providing no routine TB screening is currently the most cost-effective strategy for BCG-vaccinated elderly populations in Japan. There appears to be little role for CXR in TB screening of elderly populations. These findings may be applicable to other countries with intermediate and high TB risks when choosing optimal TB screening of elderly populations.

Tuberculosis screening of travelers to higher-incidence countries: a cost-effectiveness analysis.

BACKGROUND: Travelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence. METHODS: Decision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented. RESULTS: For all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to $161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence. CONCLUSION: A single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection.

Population-based chest X-ray screening for pulmonary tuberculosis in people living with HIV/AIDS, An Giang, Vietnam.

SETTING: Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) program, An Giang Province, Vietnam. OBJECTIVE: To evaluate the coverage and yield of a chest radiography (CXR) screening program for tuberculosis (TB) among people living with HIV/AIDS (PLHA), risk factors for a TB CXR, inter-rater reliability of CXR readings and direct costs. DESIGN: Retrospective review of routine public health program records and CXRs. RESULTS: An increasing proportion of PLHAs received a screening CXR each year of the program (range 21% in 2001 to 61% in 2004, P<0.001). Of 876 screening CXRs performed, 191 (22%) were classified as suspicious for active TB ('TB CXR'). Compared to PLHAs with a CXR not suspicious for active TB, PLHAs with a TB CXR were more likely to be aged between 24 and 64 years, male and previously treated for TB (P<0.01 for each comparison). Agreement between the expert and local program CXR readings was 81% (kappa 0.50). Direct costs were approximately US$40 per TB suspect identified. Among TB suspects, <10% were followed up with sputum smear examination and enrolled for treatment. CONCLUSION: In An Giang Province, a large proportion of PLHAs are screened for TB annually, and one in five persons screened is classified as a TB suspect based on CXR. Annual CXRs may be a high-yield, inexpensive method for TB screening in PLHAs, but the follow-up of TB suspects to confirm diagnosis and initiate treatment is crucial.

The futility of universal pre-employment chest radiographs.

In a developmental center, a preemployment chest x-ray was required for all job applicants. We scrutinized the pros and cons of this practice through a review of the medical literature and our experience, and discussion with our colleagues. We concluded that such chest x-ray caused unwarranted radiation exposure, did not produce compliance with the tuberculosis laws, gave a false sense of security regarding workers' compensation risk management, was contrary to established occupational medicine practice guidelines, and was unnecessary and wasteful. We discontinued such chest x-rays. The purpose of the pre-employment examination should remain narrowly job related. Even long-established procedures require periodic utilization review.

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 dollars, compared to 9.27 dollars 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.

[Discussing the current situation of tuberculosis case-finding by mass miniature radiography in Japan].

The system of tuberculosis (TB) case-finding by mass miniature radiography (MMR) was established and expanded for almost all Japanese citizens in the 1950s. And, as stipulated by the TB Prevention Law, periodic mass screenings for schools, inhabitants, employees and institutions have been carried out. Among those aged over 25 years, the proportion of people screened by MMR was estimated to be 60.3%. This means that about 54 million people aged over 25 years are receiving medical service with MMR every year. However, the detection rates of TB cases by MMR have declined markedly compared with those in 1950s. As of 1998, the detection rate was 0.03 per 1,000 for school children and students, 0.06 per 1,000 for employees, and 0.16 per 1,000 for inhabitants. The proportion of cases detected by MMR among newly notified TB cases was 12.8% in 1998, and this ratio has been almost constant for the last 10 years. This ratio was greater among young adult TB cases. Approximately 20% of notified TB cases aged 20-39 years were detected by MMR for employees. Although the purpose of MMR is to find the cases before discharging TB bacilli, 35.1% of the cases were bacteriologically confirmed, and this proportion was greater among elderly TB cases. The Japan Anti-Tuberculosis Association (JATA) has been carrying out MMR for a long time. Eight selected branches of JATA that has been doing high quality case-finding reported 228 TB cases out of 965,440 inhabitants aged over 40 years examined by MMR in 1996. Based on these results, the cost per TB case detected by MMR was calculated. The cost was 4.4 millions yen (yen) per case for all forms of TB, yen 2.3 millions for male, yen 8.4 millions for female, yen 7.3 millions for those aged 40-49 years and yen 1.8 millions for those aged over 80 years. TB detection rate by MMR for inhabitants was correlated with TB incidence rate in various areas, and based on this correlation, the cost was calculated for various incidence rates. For all forms of TB, the cost was yen 4.0 millions per case for an incidence rate of 30 per 100,000, and yen 6.7 millions for an incidence rate of 20 per 100,000. MMR is not economically cost-effective even among elderly people and in areas with incidence rate less than 50 per 100,000, because the medical expense for a TB patient treated under hospitalization for 2 months and outpatient's clinic for 4 months is approximately yen 0.9 millions in 1996. The decision making in continuation or abolition or limitation of MMR should be discussed from a wide range of cost-effectiveness analyses as well as from the view of public health service and willingness of people. For the purpose of decision making, this study provides the detection rates; the costs stratified by sex, age and incidence; and the proportion of cases detected by MMR among newly notified TB cases by age-group and bacteriological status.

Lung cancer screening: will the controversy extend to its cost-effectiveness?

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in the US. It has been shown that when treated in its early stages, survival rates improve. Despite this, controversy remains regarding screening for the early detection of lung cancer, primarily because mortality reductions were not observed in the trials that studied chest x-ray and sputum cytology. Nevertheless, renewed interest in screening, due in part to better screening options, has prompted further research exploring the potential cost-effectiveness of implementing lung cancer screening programs. This article provides a critical review of the literature of economic evaluations of lung cancer screening programs. The focus of this review is the methodology implemented in these studies. Based on an electronic search of the literature (Pubmed, Medline and CancerLit) from Sep 1988-Sep 2001, seven articles that quantified the cost-effectiveness of lung cancer screening programs were identified. For most of the studies, the cost-effectiveness aspect was a minor component with little or no description of the methods. Although some studies focused more on estimating the economic efficiency of screening, their methodology was weak and still not well documented. Only two studies implemented fully a cost-effectiveness analysis and provided the necessary level of detail. If consensus can be reached regarding the clinical benefit of lung cancer screening, future studies related to cost-effectiveness would have to be implemented on much sounder methodology. The publications reviewed do provide preliminary support for the economic efficiency of screening for lung cancer.