How to make PROMs work: qualitative insights from leaders at United States hospitals with successful PROMs programs.

PURPOSE: Elucidate facilitators, barriers, and key lessons learned regarding the implementation of system-wide clinical patient-reported outcome measure (PROM) programs among United States (US) healthcare leaders. METHODS: We conducted semi-structured interviews with 35 US healthcare leaders, including chief-level executives, data directors, PROM directors, and department chairs involved in PROM implementation across seven diverse healthcare systems from February to June 2020. Transcripts were coded, evaluated for qualitative themes, and categorized according to the consolidated framework for implementation research (CFIR). RESULTS: According to US hospital leaders with experience in existing clinical PROM programs, there are facilitators and barriers to implementation success in each CFIR domain. Allowing clinicians to select PROM measures and ensuring a user-friendly data platform (intervention); adapting data collection to patient home environments (outer setting); informing clinicians of the multi-faceted use of PROM data for research, clinical care, and business (inner setting); implementing PROM education earlier into clinician training (characteristics of individuals); and establishing specialty-agnostic PROM implementation teams (process) were among key facilitators to implementation success. CONCLUSION: Leaders of geographically and clinically diverse PROM programs in the US identify common themes that facilitate successful implementation. Drivers of success depend on factors within and outside the clinical environment. These findings may serve to guide both establishing new PROM programs and refining existing PROM programs.

Examining the First Peer-to-Peer Mentorship Program (F1Doctors) for International Medical Students.

In this study, we report international medical students in the United States and conduct an analysis of the first, peer-to-peer, national mentorship program for international medical students and international pre-med applicants in the US (F1Doctors). We used analyzed survey data collected through F1Doctors and the Association of American Medical Colleges yearly matriculation reports. Results indicated that the average college grade point average (GPA) and Medical College Admission Test score (MCAT) of international applicants was higher than that of all applicants. Additionally, non-US applicants reported facing numerous unique challenges such as limited access to extracurricular opportunities and difficulty finding mentors who are familiar with the application process. International applicants have the potential to increase the diversity of healthcare professionals, and F1Doctors is the first platform to support international healthcare applicants in the US.

Analysis of self-initiated visits for cervical trauma at urgent care centers and subsequent emergency department referral.

BACKGROUND: Following trauma involving the cervical spine (c-spine), patients often seek care at urgent care centers (UCCs) or emergency departments (EDs). PURPOSE: The purpose was to assess whether UCCs could effectively image acute self-selected c-spine trauma without referral to the ED as well as to estimate costs differences between UCC and ED imaging assessment. MATERIALS AND METHODS: This retrospective study identified patients receiving c-spine imaging at UCCs affiliated with a large academic hospital system from 5/1/-8/31/2021. Patients receiving c-spine X-rays with an indication of trauma following low acuity injury, at UCCs were compared to patients receiving any c-spine imaging in the main campus ED. Medical record numbers were cross-referenced to identify patients receiving imaging at both a UCC and ED within 24 h and within 7 days. Work relative value units (wRVUs) for each UCC and ED imaging type were calculated. For the hypothetical scenario of patients presenting to the ED in the absence of UCC, patients were assumed to receive c-spine computed tomography (CT) without contrast per "usually appropriate" designation by the American College of Radiology Appropriateness Criteria®. RESULTS: Among 143 self-selected, low acuity, patients who received c-spine X-rays at UCCs with an indication of trauma, one required referral to the ED within 24 h and two required referrals to the ED within 7 days. During the 4-month study period, 105.94 wRVUs ($3696.25) were saved by performing a c-spine X-ray in an UCC instead of a CT in the ED, extrapolated to 317.82 wRVUs ($11,088.74) per year. Using the average total costs of an UCC visit versus an ED visit, a total $145,976 was estimated to be saved during the study period or $437,928 per year. CONCLUSION: Offering access for patient-initiated visits at UCCs for low-acuity c-spine trauma may help reduce the need for an ED visit, reducing imaging and healthcare visit costs. SUMMARY STATEMENT: Urgent Care Centers (UCCs) reduced the need for an Emergency Department (ED) referral visit in nearly 100% of self-selected, low acuity, patients with cervical trauma.

Insights into the evolution and drug susceptibility of Babesia duncani from the sequence of its mitochondrial and apicoplast genomes.

Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.

The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation.

The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for survival of Plasmodium falciparum within human erythrocytes. Accordingly, a PA analog α-PanAm showed potent activity against blood stage parasites in vitro; however, its efficacy in vivo and its mode of action remain unknown. We developed a new synthesis route for α-PanAm and showed that the compound is highly effective against blood stages of drug-sensitive and -resistant P. falciparum strains, inhibits development of P. berghei in hepatocytes, and at doses up to 100 mg/kg also inhibits blood stage development of P. chabaudi in mice. We used yeast and its pantothenate kinase Cab1 as models to characterize mode of action of α-PanAm and found that α-PanAm inhibits yeast growth in a PA-dependent manner, and its potency increases dramatically in a yeast mutant with defective pantothenate kinase activity. Biochemical analyses using 14C-PA as a substrate demonstrated that α-PanAm is a competitive inhibitor of Cab1. Interestingly, biochemical and mass spectrometry analyses also showed that the compound is phosphorylated by Cab1. Together, these data suggest that α-PanAm exerts its antimicrobial activity by direct competition with the natural substrate PA for phosphorylation by the pantothenate kinase.

Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions.

Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution.

Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone.

Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis.