American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2017
Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of M. tuberculosis Infection.
Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (Mtb) infection, which predisposes individuals to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability. ⋯ Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition (an increase from IFN-γ <0.2 to >0.7 IU/ml) would allow more definitive detection of recent Mtb infection and potentially improve identification of those more likely to develop disease.
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Am. J. Respir. Crit. Care Med. · Sep 2017
ReviewApplying Precision Medicine to Trial Design Using Physiology: Extracorporeal CO2 Removal for ARDS.
In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). ⋯ To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.
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Am. J. Respir. Crit. Care Med. · Sep 2017
Randomized Controlled TrialHigh-Dose Vitamin D3 During Tuberculosis Treatment in Mongolia: A Randomised Controlled Trial.
Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. ⋯ Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).
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Am. J. Respir. Crit. Care Med. · Sep 2017
Comparative StudyAssessing the Generalizability of the National Lung Screening Trial: Comparison of Stage 1 Patients.
The findings of the NLST (National Lung Screening Trial) are the basis for screening high-risk individuals according to age and smoking history. Although screening is covered for eligible Medicare beneficiaries, the generalizability of the NLST in the elderly population has been questioned. ⋯ Elderly patients with minimal comorbid conditions meeting the inclusion criteria of the NLST who underwent surgery had excellent postoperative outcomes and similar lung cancer-specific 5-year survivorship. In those with significant comorbidities or those not undergoing surgery, competing causes of death may diminish the benefit, and there is no evidence to recommend screening in this group.