BackgroundThere are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. MethodsA total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum followup of 10 years until December 31, 2015, was completed for all participants.

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Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).OBJECTIVE To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. DESIGN, SETTING, AND PARTICIPANTSRandomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.INTERVENTIONS Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. MAIN OUTCOMES AND MEASURESThe primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. RESULTS Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).CONCLUSIONS AND RELEVANCE Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

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In baseline lung cancer CT screening, half of participants with lung nodules have more than one nodule. Lung cancer probability does not significantly change with the number of nodules. Baseline nodule count will not help to differentiate between benign and malignant nodules. Each nodule found in lung cancer screening should be assessed separately independent of the presence of other nodules.

BACKGROUND We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. RESULTS AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration <4 ng/L in patients with an onset of chest pain >3 h (direct rule-out) or a 0-h hs-cTnI-Access concentration <5 ng/L and an absolute change within 2 h <5 ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3–100) and sensitivity of 99.4% (95% CI, 96.5–99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1–79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3–100) and sensitivity of 97.7% (95% CI, 92.0–99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8–86) in the validation cohort. CONCLUSIONS Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. TRIAL REGISTRATION APACE, NCT00470587; ADAPT, ACTRN1261100106994; IMPACT, ACTRN12611000206921.