In this comparative biomarker study, we analysed 1768 serial sputum samples from 178 patients at 4 sites in Southeast Africa. We show that tuberculosis Molecular Bacterial Load Assay (TB-MBLA) reduces time-to-TB-bacillary-load-result from days/weeks by culture to hours and detects early patient treatment response. By day 14 of treatment, 5% of patients had cleared bacillary load to zero, rising to 58% by 12th week of treatment. Fall in bacillary load correlated with mycobacterial growth indicator tube culture time-to-positivity (Spearmans r=−0.51, 95% CI (−0.56 to −0.46), p<0.0001). Patients with high pretreatment bacillary burdens (above the cohort bacillary load average of 5.5log10eCFU/ml) were less likely to convert-to-negative by 8th week of treatment than those with a low burden (below cohort bacillary load average), p=0.0005, HR 3.1, 95% CI (1.6 to 5.6) irrespective of treatment regimen. TB-MBLA distinguished the bactericidal effect of regimens revealing the moxifloxacin—20 mg rifampicin regimen produced a shorter time to bacillary clearance compared with standard-of-care regimen, p=0.008, HR 2.9, 95% CI (1.3 to 6.7). Our data show that the TB-MBLA could inform clinical decision making in real-time and expedite drug TB clinical trials.
BackgroundLung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis.The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice?MethodsA randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation. Adults aged 50–75 who are at high risk of lung cancer and healthy enough to undergo potentially curative therapy (Performance Status 0–2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening.Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis will be offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray will be used to determine the speed and the need for contrast in the first screening CT. Participants who are found to have lung cancer will be followed-up to assess both time to diagnosis and stage of disease at diagnosis.DiscussionThe study will determine the clinical and cost effectiveness of EarlyCDT®-Lung Test for early lung cancer detection and assess its suitability for a large-scale, accredited screening service. The study will also assess the potential psychological and behavioural harms arising from false positive or false negative results, as well as the potential benefits to patients of true negative EarlyCDT lung test results. A cost-effectiveness model of lung cancer screening based on the results of the EarlyCDT Lung Test study will be developed.Trial registration NCT01925625. August 19, 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3175-y) contains supplementary material, which is available to authorized users.
Vincent J Vezzaa, Adrian Butterwortha, Perrine Lasserrea, Ewen O Blaira, Alexander MacDonalda, Stuart Hannaha, Christopher Rinaldib, Paul A Hoskissonc, Andrew C Wardd, Alistair Longmuire, Steven Setforde, Eoghan CW Farmerf, Michael...
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