The Risk of Falsely Declaring Noninferiority of Novel Latent Tuberculosis Treatment in Large Trials.
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ABSTRACT:
SUBMITTER: Abubakar I
PROVIDER: S-EPMC7047458 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse.
| S-EPMC7302701 | biostudies-literature
Project description:In this Collection Review for the Novel Treatments for Tuberculosis Collection, Piero Olliaro and Michael Vaillant discuss the considerations when choosing a non-inferiority margin that is meaningful from statistical, ethical, clinical, and health standpoint.
| S-EPMC6625704 | biostudies-literature
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| S-EPMC10797496 | biostudies-literature
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| S-EPMC10797497 | biostudies-literature
Project description:We report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. We applied the method to 48 Mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease, and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015.
| S-EPMC5320671 | biostudies-literature
Project description:RATIONALE:Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES:To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS:Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS:Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS:Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).
| S-EPMC6624829 | biostudies-literature
Project description:Despite recent success in reducing its incidence, tuberculosis remains a considerable challenge in Canada, particularly among foreign-born and Indigenous populations. A key component of the strategy for controlling the disease is the treatment of latent tuberculosis infection. The standard treatment consists of isoniazid (INH) daily for nine months. In recent years, shorter regimens have been developed in the hope of increasing rates of treatment acceptance and completion. Of these, the shortest and most recently developed is a combination of INH and rifapentine taken once weekly for 12 doses (3HP), typically using directly observed therapy (DOT). This regimen has been approved by the Food and Drug Administration in the United States but is not yet authorized in Canada. Based on a rapidly expanding number of observational studies and randomized controlled trials, 12 weeks of 3HP appears to have similar efficacy to nine months of INH, a favourable adverse event profile and potentially improved rates of treatment completion. Although rates of treatment acceptance, the role of self-administered therapy and the regimen's cost-effectiveness within the Canadian context remain uncertain, 3HP is a promising alternative to existing treatments for LTBI.
| S-EPMC5764734 | biostudies-other
Project description:Preventing the development of tuberculosis (TB) in contacts of patients with multidrug-resistant TB (MDR-TB) by the treatment of latent TB infection (LTBI) is highly desirable. However, few safe, well tolerated, and effective drugs are available to treat MDR-LTBI and the published guidance is limited. Fortunately, six new chemical entities from four classes developed to treat TB have entered clinical trials in the past decade. We tested three of these drugs alone and in combination in an experimental paucibacillary LTBI chemotherapy model using BALB/c and C3HeB/FeJ mice immunized with a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG30) and then challenged with a low-dose aerosol of M. tuberculosis H37Rv. The regimens tested contained bedaquiline (TMC), PA-824 (Pa), sutezolid (PNU), and/or one of two fluoroquinolones. Control mice received rifampin (RIF) or isoniazid (INH). In BALB/c mice, TMC-containing regimens and the Pa-PNU combination were the most active test regimens and were at least as effective as RIF. Pa, PNU, and levofloxacin had activity comparable to that of INH. Virtually identical results were observed in C3HeB/FeJ mice. This study confirms the potent activity of TMC observed previously in BALB/c mice and highlights Pa alone or in combination with either PNU or a fluoroquinolone as a regimen worthy of evaluation in future clinical trials of MDR-LTBI. Given their closer pathological representation of human TB lesions, C3HeB/FeJ mice may become a preferred model for the experimental chemotherapy of LTBI. Future studies should evaluate additional clinically relevant LTBI regimens in this strain including relapse as an endpoint.
| S-EPMC4023781 | biostudies-literature
Project description:PurposeFew individuals that are latently infected with M. tuberculosis latent tuberculosis infection(LTBI) progress to active disease. We investigated risk factors for LTBI and active pulmonary tuberculosis (PTB) in Germany.MethodsHealthy household contacts (HHCs), health care workers (HCWs) exposed to M. tuberculosis and PTB patients were recruited at 18 German centres. Interferon-? release assay (IGRA) testing was performed. LTBI risk factors were evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors for tuberculosis were evaluated by comparing PTB patients with HHCs.ResultsFrom 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in 34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p = 0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI. In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual contact to a diseased partner and substance dependency (all p < 0.001). PTB was associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%; p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8 vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years follow-up.ConclusionsPositive IGRA responses are frequent among exposed HHCs and HCWs in Germany and are poor predictors for the development of active tuberculosis.
| S-EPMC5488071 | biostudies-literature
Project description:It is unknown whether patients with LTBI at high vs. low risk of developing active TB are currently adequately identified and treated in the US. In this study our objective was 1) To retrospectively apply the online calculator (tstin3d.com) to determine the probability of having LTBI and assign cumulative risk of progression. 2) Measure treatment outcomes in subjects with Low: 0-<10%, Intermediate: 10-<50% and High: 50-100% cumulative risk. We performed medical record review of tuberculin skin test and/or Interferon-γ release assay (IGRAs) positive patients with LTBI seen from 2010-2015. Of 125 subjects included, 51(41%), 46 (37%) and 28 (22%) subjects were in Low, Intermediate and High risk groups respectively. Tstin3d.com was useful in determining the probability of LTBI in tuberculin skin test positive US-born subjects. Overall treatment completion rate was 61% in 114 subjects with complete treatment information and similar completion rates were seen in the three groups (Low-60%, Intermediate-63% and High-57%). Provider assessment of important clinical risk factors was often incomplete. Logistic regression analysis showed no association of assessment of important risk factors with treatment completion. The major limitations of the calculator are the lack of an updated data on country-specific prevalence of TB disease as the global burden of TB continues to decrease as well as falsely high positive predictive values that due to "transiently" positive IGRA results in subjects from countries with low prevalence. Nonetheless, our findings suggest that tstin3d.com could be utilized in the US setting for improving providing awareness of risk stratification of patients with LTBI for short course treatment regimens based on risk.
| S-EPMC6237398 | biostudies-literature