Measuring clinical outcomes of highly multiplex molecular diagnostics for respiratory infections: A systematic review and conceptual framework.

Objectives: To review methodologies and outcomes reporting among these studies and to develop a conceptual framework of outcomes to assist in guiding studies and production of clinical metrics. Data sources: PubMed and Embase from January 1, 2012, thru December 1, 2021. Study eligibility criteria: Studies evaluating highly multiplex molecular respiratory diagnostics and their impact on either clinical or economic outcomes. Methods: A systematic literature review (SLR) of methodologies and outcomes reporting was performed. A qualitative synthesis of identified SLRs and associated primary studies was conducted to develop conceptual framework for outcomes. Results: Ultimately, 4 systemic literature reviews and their 12 associated primary studies were selected for review. Most primary studies included patient outcomes focusing on antimicrobial exposure changes such as antibiotic (80%) and antiviral use (50%) or occupancy changes such as hospital length of stay (60%). Economic outcomes were infrequently reported, and societal outcomes, such as antibiotic resistance impact, were absent from the reviewed literature. Qualitative evidence synthesis of reported outcomes yielded a conceptual framework of outcomes to include operational, patient, economic, and societal domains. Conclusions: Our review highlights the significant heterogeneity in outcomes reporting among clinical impact studies for highly multiplex molecular respiratory diagnostics. Furthermore, we developed a conceptual framework of outcomes domains that may act as a guide to improve considerations in outcomes selection and reporting when evaluating clinical impact of these tests. These improvements may be important in synthesizing the evidence for informing clinical decision making, guidelines, and financial reimbursement.

Rapid multiplex PCR for respiratory viruses reduces time to result and improves clinical care: Results of a systematic review and meta-analysis.

OBJECTIVES: The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting. METHODS: We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing. RESULTS: Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07). CONCLUSIONS: Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting.

Bone morphogenetic protein-2 delivery from polyelectrolyte multilayers enhances osteogenic activity on nanostructured titania.

Incomplete osseointegration is primary cause of failure for orthopedic implants. New biomaterials that present stable signals promoting osteogenesis could reduce failure rates of orthopedic implants. In this study bone morphogenetic protein-2 (BMP-2) was delivered from titania nanotubes (Nt) modified with chitosan/heparin polyelectrolyte multilayers (PEMs). The surfaces were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. BMP-2 release from the surfaces was measured in vitro for up to 28 days. After an initial burst release of BMP-2 during the first 2 days, most of the BMP-2 remained on the surface. To determine the osteogenic properties of these surfaces, they were seeded with rat bone marrow cells; alkaline phosphatase (ALP) activity, total protein, calcium deposition, and osteocalcin were measured up to 4 weeks in vitro. When compared to Nt surfaces, the surfaces with BMP-2 induce greater osteocalcin and calcium deposition. PEMs provide sustained presentation of BMP-2, from a biomimetic surface. This enhances the osteogenic properties of the surface without requiring supraphysiologic growth factor dose. This growth factor delivery strategy could be used to improve bone healing outcomes and reduce complications for recipients of orthopedic implants.