The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Early impact of guideline publication on angiotensin-receptor neprilysin inhibitor use among patients hospitalized for heart failure.

BACKGROUND: On May 20, 2016, US professional organizations in cardiology published joint treatment guidelines recommending the use of angiotensin-receptor neprilysin inhibitor (ARNI) for eligible patients with heart failure with reduced ejection fraction (HFrEF). Using data from the Get With The Guidelines-Heart Failure registry, we evaluated the early impact of this update on temporal trends in ARNI prescription. METHODS: We analyzed patients with HFrEF who were eligible for ARNI prescription (EF ≤40%, no contraindications) and hospitalized from February 20, 2016, through August 19, 2016-allowing for 13weeks before and after guideline publication. We quantified trends in ARNI use associated with guidelines publication with an interrupted time-series design using logistic regression and accounting for correlations within hospitals using general estimating equation methods. RESULTS: Of 7,200 eligible patient hospitalizations, 51.9% were discharged in the period directly preceding publication of the guidelines, and 48.1% were discharged after. Odds ratios of ARNI prescription at discharge were significantly higher in the postguideline period compared with the preguideline period in adjusted models (adjusted odds ratio 1.29, 95% CI 1.06-1.57, P=.01). However, there was no significant interaction between observed and expected ARNI use after guideline publication (Pinteraction=.14). Results were consistent using a 6-month before and after time frame. CONCLUSIONS: The model suggested a small increase in ARNI use in HF patients being discharged from the hospital immediately after guideline release. However, the publication of national guidelines recommending ARNI use seemed to have little influence on the adoption of this evidence-based medication in the first 3 to 6months.

Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass.

To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.

Association of Implantable Device Measured Physical Activity With Hospitalization for Heart Failure.

OBJECTIVES: The purpose of this study was to evaluate the association of physical activity (PA) level and longitudinal PA trajectory with a composite heart failure hospitalization and mortality endpoint over a 5-year follow-up period following implantation. BACKGROUND: Low device measured PA early after implantation of an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) is associated with poor outcomes. METHODS: We linked daily PA data from the Boston Scientific ALTITUDE dataset of patients with ICD or CRT-D implantation to Medicare claims data. We used a joint model to investigate the association of the composite endpoint with 1) the time-varying point estimate of PA and 2) the time-varying trajectory/slope of PA during follow-up. RESULTS: Among 20,927 patients with median activity level 85 min/day, 14.1% and 49.6% experienced the composite endpoint at 1 and 5 years. Adjusted joint model results showed that there was a 1.13 (95% confidence interval: 1.12 to 1.13)-fold increase in the hazard of the composite endpoint for 75 min of daily PA relative to 85 min of PA; and a within-patient 10-min decrease in average daily PA over an 8-week period from 85 to 75 min was associated with a hazard ratio of 4.02 (95% confidence interval: 3.82 to 4.22) for the composite endpoint. CONCLUSIONS: Patients with large decreases in PA have significantly higher risk of experiencing heart failure hospitalization or death. PA data from implantable devices may identify patients before clinical decompensation.

Ischemic and Bleeding Outcomes in Patients With Atrial Fibrillation and Contraindications to Oral Anticoagulation.

OBJECTIVES: This study sought to describe clinical outcomes among patients with atrial fibrillation (AF) and contraindications to oral anticoagulation (OAC). BACKGROUND: Treatment with OAC prevents stroke and death in patients with AF, but may be contraindicated among patients at high bleeding risk. METHODS: This was an observational, longitudinal analysis of a nationally representative 5% Medicare sample of patients with chronic AF and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) score ≥2. They were stratified by both the presence of high bleeding risk contraindications to OAC and by OAC use. We assessed 3-year ischemic and bleeding outcomes using multivariable Cox proportional hazards models adjusted for relevant patient characteristics. RESULTS: Among 26,684 AF patients not treated with OAC, 8,283 (31%) had a high bleeding risk contraindication, primarily a blood dyscrasia (75%) or history of gastrointestinal bleeding (40%). Without OAC, patients with contraindications had worse ischemic and bleeding outcomes at 3 years compared with those without contraindications. We also identified 12,454 patients with OAC contraindications who received OAC. Compared with patients not receiving OAC, use of OAC was associated with reduced mortality (adjusted hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.76 to 0.83), stroke (adjusted HR: 0.90; 95% CI: 0.83 to 0.99), and all-cause hospitalization (adjusted HR: 0.93; 95% CI: 0.90 to 0.96) but increased risk of intracranial hemorrhage (adjusted HR: 1.42; 95% CI: 1.17 to 1.72). CONCLUSIONS: High bleeding risk contraindications to OAC are common among older patients with AF, and these patients have higher mortality compared with untreated patients without OAC contraindications. The use of OAC in these patients is associated with lower rates of all-cause stroke, hospitalization, and death but higher risk of intracranial hemorrhage.

Invasive lionfish reduce native fish abundance on a regional scale.

Invasive lionfish pose an unprecedented threat to biodiversity and fisheries throughout Atlantic waters off of the southeastern United States, the Caribbean, and the Gulf of Mexico. Here, we employ a spatially replicated Before-After-Control-Impact analysis with temporal pairing to quantify for the first time the impact of the lionfish invasion on native fish abundance across a broad regional scale and over the entire duration of the lionfish invasion (1990-2014). Our results suggest that 1) lionfish-impacted areas off of the southeastern United States are most prevalent off-shore near the continental shelf-break but are also common near-shore and 2) in impacted areas, lionfish have reduced tomtate (a native forage fish) abundance by 45% since the invasion began. Tomtate served as a model native fish species in our analysis, and as such, it is likely that the lionfish invasion has had similar impacts on other species, some of which may be of economic importance. Barring the development of a control strategy that reverses the lionfish invasion, the abundance of lionfish in the Atlantic, Caribbean, and Gulf of Mexico will likely remain at or above current levels. Consequently, the effect of lionfish on native fish abundance will likely continue for the foreseeable future.