High-throughput RNA isoform sequencing using programmed cDNA concatenation.

Full-length RNA-sequencing methods using long-read technologies can capture complete transcript isoforms, but their throughput is limited. We introduce multiplexed arrays isoform sequencing (MAS-ISO-seq), a technique for programmably concatenating complementary DNAs (cDNAs) into molecules optimal for long-read sequencing, increasing the throughput >15-fold to nearly 40 million cDNA reads per run on the Sequel IIe sequencer. When applied to single-cell RNA sequencing of tumor-infiltrating T cells, MAS-ISO-seq demonstrated a 12- to 32-fold increase in the discovery of differentially spliced genes.

Reduction of Inappropriate Antibiotic Use and Improved Outcomes by Implementation of an Algorithm-Based Clinical Guideline for Nonpurulent Skin and Soft Tissue Infections.

STUDY OBJECTIVE: Clinicians currently do not reliably adhere to antibiotic treatment guidelines, resulting in unnecessary patient exposure to broad-spectrum antimicrobials. Our objective is to determine whether a treatment intervention for the management of nonpurulent skin and soft tissue infections increases clinician adherence and improves patient outcomes. METHODS: Between January 1 and December 31, 2017, patients presenting to 2 emergency departments (EDs) and who had received a diagnosis of a nonpurulent skin and soft tissue infection were enrolled and assigned to a pre- or postintervention cohort with a treatment intervention implemented on June 1. Primary outcomes were percentage of ED providers following the guidelines and percentage of patients admitted to the hospital. Secondary outcomes were patient self-reported treatment failure and hospital readmission. RESULTS: There were 1,360 patients, 665 in the preintervention and 695 in the postintervention cohorts. After algorithm implementation, guideline adherence increased (43.0% versus 55.1%; P<.001) and number of patients admitted to the hospital declined (36.5% versus 12.0%; P<.001). In addition, patients reported fewer treatment failures (26.8% versus 16.5%; P=.02) and fewer readmissions (22.3% versus 12.7%; P=.013). After multivariate adjustment, guideline adherence increased by 22% (adjusted relative risk [RR] 1.22; 95% confidence interval [CI] 1.10 to 1.37), whereas hospital admissions were reduced by 26% (adjusted RR 0.74; 95% CI 0.64 to 0.87). In addition, the risks of treatment failure and readmission were reduced by 46% (adjusted RR 0.64; 95% CI 0.43 to 0.97) and 45% (adjusted RR 0.55; 95% CI 0.34 to 0.87), respectively. CONCLUSION: Among patients with a nonpurulent skin and soft tissue infection, implementing an easy-to-follow treatment algorithm can reduce unnecessary antibiotic exposure by increasing clinician guideline adherence while reducing patient treatment failure rates.