Trade-offs between cost and accuracy in active case-finding for tuberculosis: a dynamic modelling analysis

Background Active case-finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap, and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF, in ACF in a high burden setting? Methods and Findings We constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of two hypothetical approaches, following initial symptom screening: (i) ‘moderate accuracy’ testing employing a microscopy-like test (that is, lower cost but also lower accuracy) for bacteriological confirmation and (ii) ‘high accuracy’ testing employing an Xpert-like test (higher-cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of USD 20 million in a slum population of 2 million, high-accuracy testing would avert 1·14 (95% Bayesian credible intervals 0·75 – 1·99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: high-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of a high-accuracy are that: its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment; and its higher sensitivity contributes to the overall cases averted by ACF. Amongst limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, including variations in the accuracy of the reference standard under such conditions. Conclusions Our results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account, when designing cost-effective strategies for ACF

Compliance with Tuberculosis Screening in Irregular Immigrants

Tuberculosis (TB) is a serious public health problem in many regions of the world, especially in the poorest areas. For this reason, screening for active and latent forms must be considered when dealing with high-risk groups such as irregular immigrants in Western countries. We conducted a retrospective cohort study by recruiting subjects aged 6515 years who underwent a tuberculin skin test at a dedicated National Health Service Centre in a northern Italian province between 1 January 2012 and 31 December 2013. These participants were followed up until 31 December 2016. We aimed at evaluating an experimental protocol for active and latent tuberculosis screening, focusing on patient compliance, feasibility, and capability to detect clinical forms of the disease. We enrolled 368 irregular immigrants, i.e., immigrants not having a valid residence permit and who were therefore not entitled to choose a general practitioner. In total, 90.22% of these completed all the steps for the screening of active TB, while 87.33% also undertook screening for the latent form of the disease. Homelessness, self-reported prostitution, female sex, and employment status adversely affected compliance. Chronic alcohol consumption was associated with increased risk of no beginning or interruption of the procedures. All of the five patients with active TB successfully completed the treatment. Overall, adherence to the screening program was high compared to other studies in immigrants, possibly owing to organizational factors such as the availability of cultural mediators, the network between the different health services, the presence of dedicated nursing staff and a free-of-charge service. In addition, selected vulnerable subgroups should be targeted using tailored screening and follow-up programs

Modelling active case-finding strategies for tuberculosis in urban India

India harbours the world’s largest burden of tuberculosis, with approximately 27% of the estimated global burden. Although considerable measures have been taken since the roll-out of the End TB strategy, in 2015, to increase case detection and improve treatment quality, the overall quality of care remains poor and estimates on incidence remain highly uncertain, because of the poor notification rates, especially from the private healthcare sector, where nearly half of all individuals seek care. In 2017, India’s National Strategic Plan for Tuberculosis Elimination brought forward extremely ambitious targets of an 80% reduction in incidence by 2025. The first step of the plan proposes a scale-up of case-detection through active case-finding, in order to increase case notification rates and reduce the diagnostic and treatment initiation delays, often associated with tuberculosis care. The evidence for the value of active case-finding interventions for tuberculosis, however, is mixed and highlights a substantial geographical imbalance of studies. A recent systematic review has encouraged the implementation of targeted active case-finding interventions, suggesting these may have an important effect on the prevalence of disease. Despite this, there remains some scepticism around these interventions, which can be costly and difficult to implement on a large scale, and because of the diverse number of factors that can affect their impact. This thesis aims to investigate the value of routine active case-finding interventions in high-burden settings, implemented using available tools for screening and diagnosis. Epidemiological data is used in the development of the mathematical models used in the analyses, and costing information is included to allow an estimation of the financial implications of this undertaking.Open Acces

Severe quetiapine voluntary overdose successfully treated with a new hemoperfusion sorbent

Quetiapine overdose, although rare, is mainly linked with tachycardia, QTc-interval prolongation, somnolence, coma, hyperglycemia, and eventually hepatotoxicity and myocarditis. Extracorporeal techniques for quetiapine removal might be helpful, but only a few cases are reported in the literature. We here describe the case of a 27-year-old healthy woman, admitted to our Intensive Care Unit after voluntary quetiapine intake and successfully treated with CytoSorb hemoperfusion in combination with continuous renal replacement therapy (CRRT), in order to accelerate quetiapine elimination. This is the first published experience about the potential application of hemoadsorption therapies, as CytoSorb sorbent, in large overdoses of quetiapine and this approach might be feasible to rapidly remove the substance from blood, stabilizing the patient condition

Deferasirox in the management of iron overload in patients with myelofibrosis treated with ruxolitinib: The multicentre retrospective RUX‐IOL study

Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX-IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation