Copy number variants (CNVs) are the gain or loss of DNA segments in the genome that can vary in dosage and length. CNVs comprise a large proportion of variation in human genomes and impact health ...conditions. To detect rare CNV associations, kernel-based methods have been shown to be a powerful tool due to their flexibility in modeling the aggregate CNV effects, their ability to capture effects from different CNV features, and their accommodation of effect heterogeneity. To perform a kernel association test, a CNV locus needs to be defined so that locus-specific effects can be retained during aggregation. However, CNV loci are arbitrarily defined and different locus definitions can lead to different performance depending on the underlying effect patterns. In this work, we develop a new kernel-based test called CONCUR (i.e., copy number profile curve-based association test) that is free from a definition of locus and evaluates CNV-phenotype associations by comparing individuals' copy number profiles across the genomic regions. CONCUR is built on the proposed concepts of "copy number profile curves" to describe the CNV profile of an individual, and the "common area under the curve (cAUC) kernel" to model the multi-feature CNV effects. The proposed method captures the effects of CNV dosage and length, accounts for the numerical nature of copy numbers, and accommodates between- and within-locus etiological heterogeneity without the need to define artificial CNV loci as required in current kernel methods. In a variety of simulation settings, CONCUR shows comparable or improved power over existing approaches. Real data analyses suggest that CONCUR is well powered to detect CNV effects in the Swedish Schizophrenia Study and the Taiwan Biobank.
Unplanned hospital readmissions represent a significant health care value problem with high costs and poor quality of care. A significant percentage of readmissions could be prevented if clinical ...inpatient teams were better able to predict which patients were at higher risk for readmission. Many of the current clinical decision support models that predict readmissions are not configured to integrate closely with the electronic health record or alert providers in real-time prior to discharge about a patient’s risk for readmission. We report on the implementation and monitoring of the Epic electronic health record—“Unplanned readmission model version 1”—over 2 years from 1/1/2018–12/31/2019. For patients discharged during this time, the predictive capability to discern high risk discharges was reflected in an AUC/C-statistic at our three hospitals of 0.716–0.760 for all patients and 0.676–0.695 for general medicine patients. The model had a positive predictive value ranging from 0.217–0.248 for all patients. We also present our methods in monitoring the model over time for trend changes, as well as common readmissions reduction strategies triggered by the score.
ObjectiveFor the diagnosis of COVID-19, the yield of nasopharyngeal (NP) swabs is unclear, and bronchoalveolar lavage (BAL) is obtained to confirm the diagnosis. We assessed the utilisation of ...bronchoscopy for COVID-19 diagnosis in a multicenter study and compared the diagnostic yield of BAL versus NP swabs.MethodsThis retrospective study included all patients who were admitted with clinical presentation concerning for COVID-19 and underwent BAL from 1 March to 31 July 2020 at four tertiary care centres in North America. We also compared concordance of BAL with NP swabs for diagnosis of COVID-19 infection.ResultsFifty-three patients, with clinical suspicion for COVID-19 and admitted for respiratory failure, underwent bronchoscopy to collect BAL for SARS-CoV-2 testing. During the same period, 2039 bronchoscopies were performed on patients not infected with COVID-19. Of 42 patients with NP swabs and BAL collected within ≤7 days, 1 was NP swab negative but positive by BAL for SARS-CoV-2 (n=1/42 (2.4%)). Across a wide array of testing platforms, the overall agreement between NP swabs and BAL results was 97.6% (95% CI: 93.0% to 100%) with Cohen’s k of 0.90 (95% CI: 0.69 to 1.00). The sensitivity, specificity, positive and negative predictive values of NP swabs compared with BAL were 83.3% (95% CI: 53.5% to 100%), 100%, 100% and 97.3% (95% CI: 92.1% to 100%), respectively.ConclusionsBAL was used infrequently to assess COVID-19 in busy institutions. NP swabs have a high concordance with BAL for COVID-19 testing, but negative NP swabs should be confirmed with BAL when clinical suspicion is high.
We assessed the effect of implementing a protocol-directed strategy to determine when patients can be liberated from venovenous extracorporeal membrane oxygenation on extracorporeal membrane ...oxygenation duration, time to initiation of first sweep-off trial, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and survival to hospital discharge.
Single-center retrospective before and after study.
The medical ICU at an academic medical center.
One-hundred eighty patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at a single institution from 2013 to 2019.
In 2016, our institution implemented a daily assessment of readiness for a trial off extracorporeal membrane oxygenation sweep gas ("sweep-off trial"). When patients met prespecified criteria, the respiratory therapist performed a sweep-off trial to determine readiness for discontinuation of venovenous extracorporeal membrane oxygenation.
Sixty-seven patients were treated before implementation of the sweep-off trial protocol, and 113 patients were treated after implementation. Patients managed using the sweep-off trial protocol had a significantly shorter extracorporeal membrane oxygenation duration (5.5 d 3-11 d vs 11 d 7-15.5 d;
< 0.001), time to first sweep-off trial (2.5 d 1-5 d vs 7.0 d 5-11 d;
< 0.001), duration of mechanical ventilation (15.0 d 9-31 d vs 25 d 21-33 d;
= 0.017), and ICU length of stay (18 d 10-33 d vs 27.0 d 21-36 d;
= 0.008). There were no observed differences in hospital length of stay or survival to hospital discharge.
In patients with acute respiratory distress syndrome managed with venovenous extracorporeal membrane oxygenation at our institution, implementation of a daily, respiratory therapist assessment of readiness for a sweep-off trial was associated with a shorter time to first sweep-off trial and shorter duration of extracorporeal membrane oxygenation. Among survivors, the postassessment group had a reduced duration of mechanical ventilation and ICU lengths of stay. There were no observed differences in hospital length of stay or inhospital mortality.
In pulmonary hypertension (PH), measurement of various echocardiographic parameters that assess right heart function is recommended by current clinical guidelines. Limited data exists on the combined ...value of clinical and echocardiographic parameters in precapillary PH in the modern era of therapy. We examined the association of clinical and echocardiographic parameters with surrogate outcomes (6-minute walk distance) and hard outcomes (hospitalization or death) in patients with precapillary PH. A cohort of patients with an established diagnosis of precapillary PH who underwent transthoracic echocardiography at the Duke Echo Lab were prospectively enrolled from 2010 to 2014. Univariable and multivariable models were constructed to examine the relation of clinical and echocardiographic parameters with surrogate and hard outcomes. Of the 98 patients with analyzable echocardiograms with good image quality, 85 were woman, mean age was 59.4 years, and 47% had ≥World Health Organization functional class III symptoms. The mean 6-minute walk distance was 354(±132) m, and 83% were on pulmonary arterial hypertension medications. At 24 months, the cumulative incidence rate for hospitalization or death was 47%. In univariable analyses, the REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) risk score (HR 1.72 per 1 SD (2.81) increment, 95% CI 1.34, 2.22; p=<0.001), RV global longitudinal strain (RVGLS) (HR 1.54 per 1 SD (5.31) worsening, 95% CI , 2.12; p=0.008) and log-2 NT proBNP (HR 1.43 per 1-fold increase, 95% CI 1.25, 1.63; p=<0.001) were significantly associated with hospitalization or death.
Patients with nonobstructive coronary artery disease (CAD) have worse outcomes compared with those without CAD; however, few studies have compared the intermediate- and long-term impact of CAD ...severity as a function of patient sex.
We evaluated 5-year and long-term all-cause mortality of women and men undergoing elective coronary angiography at a single center by degree of CAD: no CAD (1%-24% stenosis), nonobstructive CAD (25%-69% epicardial stenosis or 25%-49% left main stenosis), or obstructive CAD (epicardial stenosis ≥70% or left main stenosis ≥50%), both overall and after adjusting for baseline clinical risk factors using Cox proportional-hazards models.
Between January 1986 and July 2010, 8,766 women and 11,638 men underwent angiography and were followed for a median of 9.2 years. The majority (67%) of women had no CAD or nonobstructive CAD, whereas the majority of men had obstructive CAD (56%, P < .001). In both sexes, increasing CAD was associated with increased 5-year risk of mortality. Risk-adjusted hazard ratios (vs no CAD) for women were 1.36 (95% CI, 1.16-1.60) and 1.86 (1.61-2.16) for nonobstructive and obstructive CAD, respectively; corresponding hazard ratios for men were 1.24 (1.06-1.45) and 1.38 (1.20-1.59). After risk adjustment, 5-year mortality risk was higher in men than in women at all levels of CAD severity. The relationships between severity of CAD and mortality risk during long-term follow-up in women and men were similar to the 5-year relationships above.
Although women undergoing elective catheterization have less severe CAD than men, nonobstructive CAD is prevalent in both sexes and carries a worse prognosis than no CAD. These data suggest a need for further investigation to establish optimal therapies for this at-risk group of patients with nonobstructive CAD.
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