A Collaborative Partnership between the Multicenter Handoff Collaborative and an Electronic Health Record Vendor.

OBJECTIVES: The operating room is a specialized, complex environment with many factors that can impede effective communication during transitions of care between anesthesia clinicians. We postulated that an efficient, accessible, standardized tool for intraoperative handoffs built into standard workflow would improve communication and handoff safety. Most institutions now use an electronic health record (EHR) system for patient care and have independently designed intraoperative handoff tools, but these home-grown tools are not scalable to other organizations and lack vendor-supported features. The goal of this project was to create a standardized, intraoperative handoff tool supported by EHR functionality. METHODS: The Multicenter Handoff Collaborative, with support from the Anesthesia Patient Safety Foundation, created a working group of frontline anesthesia experts to collaborate with a development team from the EHR vendor (Epic Systems) to design a standardized intraoperative handoff tool. Over 2 years, the working group identified the critical elements for the tool and software usability, and the EHR team designed a standardized intraoperative handoff tool that is accessible to any institution using this EHR. RESULTS: The first iteration of the intraoperative handoff tool was released in August 2019, with a second version in February 2020. The tool is standardized but customizable by individual institutions. CONCLUSION: We demonstrate that work on complex health care processes critical to patient safety, such as handoffs, can be performed on a national scale through cross-industry collaboration. Frontline experts can partner with health care industry vendors to design, build, and release a product on an accelerated timeline.

Dynamics of weak and strong collisions: highly vibrationally excited pyrazine (E = 37900 cm(-1)) with DCl.

The outcome of energy transfer due to single collisions between highly vibrationally excited pyrazine (E = 37,900 cm(-1)) and DCl is measured for the appearance of individual low-J rotational states of DCl using high-resolution transient IR absorption. Appearance profiles from double-Gaussian transient lineshapes were measured for a number of DCl states with J = 2-12. These data give information on the recoil velocity distributions, appearance rates, and populations of individual states of the scattered molecules. These data complement previous studies on high-J state DCl scattering (Li, Z.; Korobkova, E.; Werner, K.; Shum, L.; Mullin, A. S. J. Chem. Phys. 2005, 123, 174306), and together, they provide a full description of the V-RT collisions with DCl that quench pyrazine(E). Scattered DCl (v = 0) molecules with J = 2-21 are rotationally hot with T(rot) = 880 +/- 100 K. Center-of-mass translational energy distributions are T(rel) approximately 700 K for J < 15. Broader velocity distributions are observed for the J = 15-20 states. The rate constant for V-RT energy transfer is 4.6 x 10(-10) cm(3) molecule(-1) s(-1). This value is a lower limit to the overall rate constant for energy transfer and corresponds to approximately 85% of the Lennard-Jones collision rate. We estimate scattering into the DCl (v = 1) state occurs in approximately 1% of collisions. The energy transfer probability distribution P(DeltaE) is presented and yields DeltaE = 888 cm(-1).

Modification of globin gene expression by RNA targeting strategies.

OBJECTIVE: Sickle cell anemia is a genetic blood disease resulting from production of mutant beta-globin (beta(S)) and has severe clinical consequences. It is known that a higher cellular gamma-globin level, e.g., higher ratio of cellular gamma-globin to beta(S)-globin (gamma/beta(S) ratio), inhibits sickle hemoglobin (HbS) polymerization tendency. Hence, therapeutic treatment of sickle cell anemia has been focused on introducing gamma-globin gene into red blood cells to increase the cellular gamma/beta(S) ratio. Here, we have introduced ribozymes and small interfering RNAs (siRNAs) against beta(S)-globin mRNA into blood cells as a means to increase the gamma/beta(S) ratio. MATERIALS AND METHODS: Single and multiribozymes against beta(S)-globin mRNA have been tested in vitro and in human erythroleukemia K562beta(S) cells that stably express exogenous beta(S)-globin gene. Primary human hematopoietic progenitor cells were also transfected with multiribozyme and the gamma/(gamma + beta) ratio determined and compared with cells transfected with long hairpin beta-globin cDNA and synthetic siRNA genes. RESULTS: We have found that the multiribozyme zb21A containing two ribozyme units effectively reduces beta(S)-globin mRNA both in vitro and in K562beta(S) cells. The gamma-globin mRNA to beta(S)-globin mRNA ratio in the multiribozyme transfected cells is about a factor of 2 more than that in the control cells. We have also found that the gamma/(gamma + beta) ratio in the transfected hematopoietic progenitor cells is increased by more than twofold in cells treated with multiribozyme zb21A or siRNA ib5. CONCLUSION: Our results suggest that introducing multiribozymes or siRNAs into red blood cells is comparable in their effectiveness to increase the ratio of cellular gamma-globin mRNA to beta- or beta(S)-globin mRNA, providing possible strategies to increase the effectiveness of gamma-globin gene transfer as gene therapy for treatment of patients with sickle cell anemia.

Nitration and inactivation of IDO by peroxynitrite.

IDO induction can deplete L-tryptophan in target cells, an effect partially responsible for the antimicrobial activities and antiallogeneic T cell responses of IFN-gamma in human macrophages, dendritic cells, and bone marrow cells. L-tryptophan depletion and NO production are both known to have an antimicrobial effect in macrophages, and the interaction of these two mechanisms is unclear. In this study we found that IDO activity was inhibited by the peroxynitrite generator, 3-(4-morpholinyl)sydnonimine, in PMA-differentiated cytokine-induced THP-1 (acute monocytic leukemia) cells and IFN-gamma-stimulated PBMCs, whereas IDO protein expression was unaffected compared with that in untreated cells. Nitrotyrosine was detected in immunoprecipitated (IP)-IDO from PMA-differentiated cytokine-induced THP-1 cells treated with 3-(4-morpholinyl)sydnonimine, but not from untreated cells. Treatment of IP-IDO and recombinant IDO (rIDO) with peroxynitrite significantly decreased enzyme activity. Nitrotyrosine was detected in both peroxynitrite-treated IP-IDO and rIDO, but not in either untreated IP-IDO or rIDO. Peptide analysis by liquid chromatography/electrospray ionization and tandem mass spectrometry demonstrated that Tyr15, Tyr345, and Tyr353 in rIDO were nitrated by peroxynitrite. The levels of Tyr nitration and the inhibitory effect of peroxynitrite on IDO activity were significantly reduced in the Tyr15-to-Phe mutant. These results indicate that IDO is nitrated and inactivated by peroxynitrite and that nitration of Tyr15 in IDO protein is the most important factor in the inactivation of IDO.

Hospitalizations for varicella in the United States, 1988 to 1999.

BACKGROUND: Varicella epidemiology is changing with increasing use of the varicella vaccine. METHODS: To describe the epidemiology of severe varicella disease before and after vaccine introduction, data from the National Hospital Discharge Survey (NHDS) for 1988 to 1999 were analyzed. Incidental cases of varicella in persons hospitalized for a different indication were excluded. RESULTS: In the prevaccination era (1988 to 1995), there were 10 632 varicella hospitalizations annually. The most common complications were viral pneumonitis (20.9%), fluid/electrolyte disturbances (19.3%) and soft tissue infections (17.8%). Most (89.1%) persons had no severe underlying immunocompromising conditions. The mean length of hospitalization was 5.4 days, corresponding to approximately 57 000 days of hospitalization annually. In the first years after vaccine licensure (1996 to 1999), vaccine coverage reached 59%. Although not statistically significant, there was a trend toward decreased hospitalizations and a decline in mean length of hospitalization. CONCLUSIONS: Varicella morbidity was higher in the prevaccination era than previously reported. Although no significant decline is evident, a trend toward decreased hospitalizations is emerging in the first years after vaccine introduction.