The impact of performance feedback reports on physician ordering behavior in the use of computed tomography pulmonary angiography (CTPA).

PURPOSE: The increased utilization, and potential overutilization, of computed tomography pulmonary angiography (CTPA) is a well-recognized issue within emergency departments (EDs). The objective of this study is to determine the impact of performance feedback reports on CTPA ordering behavior among ED physicians. METHODS: We conducted a prospective study of the impact of individualized performance feedback reports on the ordering behavior of physicians working at two high-volume community EDs in Ontario, Canada. We generated individualized reports (or "Dashboards") for each ED physician containing detailed feedback and peer comparison for each physician's CTPA ordering. Our baseline pre-intervention period was January 1 to December 31, 2018, and our intervention period was January 1, 2019, to December 31, 2021. We tracked individual and group ordering behavior through the study period. Our primary outcomes are impact of feedback on (1) overall group ordering rate and (2) overall diagnostic yield. Secondary analysis was done to determine the impact of the intervention on those physicians with the highest CTPA utilization rate. RESULTS: There was no statistically significant difference in the diagnostic yield of the included physicians in either of the years of the intervention period. There was a statically significant increase in the utilization rate for CTPA from 2018 to 2020 and 2021 from 5.9 to 7.9 and 11.4 CTPAs per 1000 ED visits respectively (p < 0.5). CONCLUSION: Our study found no consistent significant impact of individualized feedback and peer comparison on physician ordering of CTPAs. This points to a potentially greater impact of environmental and institutional factors, as opposed to physician-targeted quality improvement measures, on physician ordering behavior.

Utilization of serum D-dimer assays prior to computed tomography pulmonary angiography scans in the diagnosis of pulmonary embolism among emergency department physicians: a retrospective observational study.

BACKGROUND: A variety of evidence-based algorithms and decision rules using D-Dimer testing have been proposed as instruments to allow physicians to safely rule out a pulmonary embolism (PE) in low-risk patients. OBJECTIVE: To describe the prevalence of D-Dimer utilization among emergency department (ED) physicians and its impact on positive yields and utilization rates of Computed Tomography Pulmonary Angiography (CTPA). METHODS: Data was collected on all CTPA studies ordered by ED physicians at three sites during a 2-year period. Using a chi-square test, we compared the diagnostic yield for those patients who had a D-Dimer prior to their CTPA and those who did not. Secondary analysis was done to examine the impact of D-Dimer testing prior to CTPA on individual physician diagnostic yield or utilization rate. RESULTS: A total of 2811 CTPAs were included in the analysis. Of these, 964 CTPAs (34.3%) were ordered without a D-Dimer, and 343 (18.7%) underwent a CTPA despite a negative D-Dimer. Those CTPAs preceded by a D-Dimer showed no significant difference in positive yields when compared to those ordered without a D-Dimer (9.9% versus 11.3%, p = 0.26). At the individual physician level, no statistically significant relationship was found between D-Dimer utilization and CTPA utilization rate or diagnostic yield. CONCLUSION: This study provides evidence of suboptimal adherence to guidelines in terms of D-Dimer screening prior to CTPA, and forgoing CTPAs in patients with negative D-Dimers. However, the lack of a positive impact of D-Dimer testing on either CTPA diagnostic yield or utilization rate is indicative of issues relating to the high false-positive rates associated with D-Dimer screening.

Nicotinamide mononucleotide impacts HIV-1 infection by modulating immune activation in T lymphocytes and humanized mice.

BACKGROUND: HIV-1-associated immune activation drives CD4+ T cell depletion and the development of acquired immunodeficiency syndrome. We aimed to determine the role of nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD) co-enzyme, in CD4+ T cell modulation during HIV-1 infection. METHODS: We examined HIV-1 integrated DNA or transcribed RNA, intracellular p24 protein, and T cell activation markers in CD4+ T cells including in vitro HIV-1-infected cells, reactivated patient-derived cells, and in HIV-1-infected humanized mice, under NMN treatment. RNA-seq and CyTOF analyses were used for investigating the effect of NMN on CD4+ T cells. FINDINGS: We found that NMN increased the intracellular NAD amount, resulting in suppressed HIV-1 p24 production and proliferation in infected CD4+ T cells, especially in activated CD25+CD4+ T cells. NMN also inhibited CD25 expression on reactivated resting CD4+ T cells derived from cART-treated people living with HIV-1 (PLWH). In HIV-1-infected humanized mice, the frequency of CD4+ T cells was reconstituted significantly by combined cART and NMN treatment as compared with cART or NMN alone, which correlated with suppressed hyperactivation of CD4+ T cells. INTERPRETATION: Our results highlight the suppressive role of NMN in CD4+ T cell activation during HIV-1 infection. It warrants future clinical investigation of NMN as a potential treatment in combination with cART in PLWH. FUNDING: This work was supported by the Hong Kong Research Grants Council Theme-Based Research Scheme (T11-706/18-N), University Research Committee of The University of Hong Kong, the Collaborative Research with GeneHarbor (Hong Kong) Biotechnologies Limited and National Key R&D Program of China (Grant2021YFC2301900).

Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.