Mobile integrated health-community paramedicine programs' effect on emergency department visits: An exploratory meta-analysis.

INTRODUCTION: Mobile Integrated Health Community Paramedicine (MIH-CP) programs are designed to increase access to care and reduce Emergency Department (ED) and Emergency Medical Services (EMS) usage. Previous MIH-CP systematic reviews reported varied interventions, effect sizes, and a high prevalence of biased methods. We aimed to perform a meta-analysis on MIH-CP effect on ED visits, and to evaluate study designs' effect on reported effect sizes. We hypothesized biased methods would produce larger reported effect sizes. METHODS: We searched Pubmed, Embase, CINAHL, and Scopus databases for peer-reviewed MIH-CP literature from January 1, 2000, to July 24, 2021. We included all full-text English studies whose program met the National Associations of Emergency Medical Technicians definition, reported ED visits, and had an MIH-CP related intervention and outcome. We established risk ratios for each included study through interpreting the reported data. We performed a random-effects and cumulative meta-analysis of ED visit data, tests of heterogeneity, and a moderator analysis to assess for factors influencing the magnitude of observed effect. RESULTS: We identified 16 studies that reported ED visit data and included 12 in our meta-analysis. All studies were observational; 3 used matched controls, 6 pre-post controls, and 3 without controls. 7 studies' intervention were diversion/triage while 5 studies intervened with health education/home primary care services. Pooled risk ratio for our data set was 0.56 (95% confidence interval 0.42-0.74). Cumulative meta-analysis revealed that as of 2018 MIH-CP programs began to show consistent reductions in ED visits. Significant heterogeneity was seen among studies, with I-squared >90%. Moderator analysis showed reduced heterogeneity for matched-control studies. CONCLUSION: Our data revealed MIH-CP programs were associated with a reduced risk of ED visits. Study design did not have a statistically significant influence on effect size, though it did influence heterogeneity. We would recommend future studies continue to use high levels of control to produce reliable data with lower heterogeneity.

A Systematic Review of Methodologies and Outcome Measures of Mobile Integrated Health-Community Paramedicine Programs.

INTRODUCTION: Mobile integrated health-community paramedicine (MIH-CP) uses patient-centered, mobile resources in the out-of-hospital environment to increase access to care and reduce unnecessary emergency department (ED) usage. The objective of this systematic review is to characterize the outcomes and methodologies used by MIH-CP programs around the world and assess the validity of the ways programs evaluate their effectiveness. METHODS: The PubMed, Embase, CINAHL, and Scopus databases were searched for peer-reviewed literature related to MIH-CP programs. We included all full-length studies whose programs met the National Association of Emergency Medical Technicians definition, had MIH-CP-related interventions, and measured outcomes. We excluded all non-English papers, abstract-only, and incomplete studies. RESULTS: Our initial literature review identified 6434 titles. We screened 178 full-text studies to assess for eligibility and identified 33 studies to include in this review. These 33 include four randomized controlled trials, 17 cohort studies, eight 8 case series, and four 4 cross-sectional studies. Of the 29 non-randomized trials, five used matched controls, 13 used pre-post, and 11 used no controls. Outcomes measured were hospital usage (24 studies), ED visits (15), EMS usage (23), patient satisfaction (8), health-related outcomes (8), and cost (9). Studies that evaluated hospital usage reported one of several outcome measures: hospital admissions (11), ED length of stay (3), and hospital readmission rate (2). EMS usage was measured by ambulance transports (12) and EMS calls (10). Cost outcomes observed were ambulance transport savings (7), ED visit savings (4), hospital admission savings (3), and cost per quality-adjusted life year (2). CONCLUSION: Most studies assessing MIH-CP programs reported success of their interventions. However, significant heterogeneity of outcome measures and varying quality of study methodologies exist among studies. Future studies designed with adequately matched controls and applying uniform core metrics for cost savings and health care usage are needed to better evaluate the effectiveness of MIH-CP programs.

C3-Symmetric Aromatic Core of Griffithsin Is Essential for Potent Anti-HIV Activity.

Lectins, carbohydrate-binding proteins of nonimmune origin, bind to carbohydrates and glycan shields present on the surfaces of cells and viral spike proteins. Lectins thus hold great promise as therapeutic and diagnostic proteins, exemplified by their potent antiviral activities and the desire to engineer synthetic carbohydrate receptors based on lectin recognition principles. Here, we describe a new carbohydrate-binding architectural motif─namely, a C3-symmetric tyrosine-based aromatic core, present in the therapeutic lectin griffithsin (GRFT). By using structure-based amino acid substitutions, X-ray crystallography, molecular dynamics (MD) simulations, and HIV-1 neutralization assays, we show that this core is critical for potent (pM) antiviral activity and nanomolar binding to the glycan shield largely consisting of high mannose glycans. Crystal structures and MD simulations show that CH-π interactions stabilize the aromatic cluster to maintain the three pseudo-symmetric carbohydrate-binding sites, nonaromatic amino acid substitutions (Tyr to Ala) abrogate antiviral activity, and increasing the aromatic CH-π edge-to-centroid interface via a Tyr to Trp substitution yields a GRFT variant with improved potency and increased residence time of Man-9 observed in MD simulations. NMR titrations of a Tyr-to-Ala variant indicate that disruption of the aromatic prevents the intermolecular crosslinking between two equivalents of Man-9 and one carbohydrate-binding face observed in wild-type GRFT and known to be critical for picomolar potency of this lectin. This C3-symmetric aromatic core defines a new recognition motif for the design of carbohydrate receptors and suggests principles for engineering known lectins to have increased affinity and stability.

Coculture of Marine Invertebrate-Associated Bacteria and Interdisciplinary Technologies Enable Biosynthesis and Discovery of a New Antibiotic, Keyicin.

Advances in genomics and metabolomics have made clear in recent years that microbial biosynthetic capacities on Earth far exceed previous expectations. This is attributable, in part, to the realization that most microbial natural product (NP) producers harbor biosynthetic machineries not readily amenable to classical laboratory fermentation conditions. Such "cryptic" or dormant biosynthetic gene clusters (BGCs) encode for a vast assortment of potentially new antibiotics and, as such, have become extremely attractive targets for activation under controlled laboratory conditions. We report here that coculturing of a Rhodococcus sp. and a Micromonospora sp. affords keyicin, a new and otherwise unattainable bis-nitroglycosylated anthracycline whose mechanism of action (MOA) appears to deviate from those of other anthracyclines. The structure of keyicin was elucidated using high resolution MS and NMR technologies, as well as detailed molecular modeling studies. Sequencing of the keyicin BGC (within the Micromonospora genome) enabled both structural and genomic comparisons to other anthracycline-producing systems informing efforts to characterize keyicin. The new NP was found to be selectively active against Gram-positive bacteria including both Rhodococcus sp. and Mycobacterium sp. E. coli-based chemical genomics studies revealed that keyicin's MOA, in contrast to many other anthracyclines, does not invoke nucleic acid damage.

Investigation of Interspecies Interactions within Marine Micromonosporaceae Using an Improved Co-Culture Approach.

With respect to bacterial natural products, a significant outcome of the genomic era was that the biosynthetic potential in many microorganisms surpassed the number of compounds isolated under standard laboratory growth conditions, particularly among certain members in the phylum Actinobacteria. Our group, as well as others, investigated interspecies interactions, via co-culture, as a technique to coax bacteria to produce novel natural products. While co-culture provides new opportunities, challenges exist and questions surrounding these methods remain unanswered. In marine bacteria, for example, how prevalent are interspecies interactions and how commonly do interactions result in novel natural products? In an attempt to begin to answer basic questions surrounding co-culture of marine microorganisms, we have tested both antibiotic activity-based and LC/MS-based methods to evaluate Micromonosporaceae secondary metabolite production in co-culture. Overall, our investigation of 65 Micromonosporaceae led to the identification of 12 Micromonosporaceae across three genera that produced unique metabolites in co-culture. Our results suggest that interspecies interactions were prevalent between marine Micromonosporaceae and marine mycolic acid-containing bacteria. Furthermore, our approach highlights a sensitive and rapid method for investigating interspecies interactions in search of novel antibiotics, secondary metabolites, and genes.