Canadian nurse initiated analgesia protocol to reduce delays in the emergency department: A quality improvement study.

BACKGROUND: Australian literature supports nurse-initiated opioid analgesia protocols may be effective, but this practice is not yet widely adopted in Canada. LOCAL PROBLEM: Previous quality audits of Emergency Departments (EDs) in Victoria (Canada) indicate long delays to administration of analgesia. METHODS: Two tertiary care hospitals in a Canadian city of approximately 400,000 people were chosen for a quality improvement initiative. A manual retrospective chart review was conducted on a total of 122 patients which was compared to data from 125 patients from a previous audit in 2019. INTERVENTIONS: ED nursing staff both hospitals were provided education and daily reminders to document pain score at triage, and to flag an acute analgesia opioid order set on the charts of patients with moderate or severe pain (greater than 4 out of 10 in the Numerical Rating Scale (NRS) or by triage nurse's clinical judgment). At Victoria General Hospital (VGH), nurses had the option of finding an emergency physician (EP) to sign the acute analgesia opioid order set, or independently administer IV opioids from a presigned order set without consulting an EP. At Royal Jubilee Hospital (RJH), nursing staff could only administer IV opioids from the order set after an EP was consulted. Median time to opioid analgesia after the intervention was compared to 2019 data for each hospital. RESULTS: Each hospital significantly reduced median time to administration of opioids: VGH achieved 45.6 % reduction (1 h 8 min improvement, p = 0.001) and RJH achieved a 62.5 % reduction (2 h 11 min improvement, p < 0.001). Secondary outcomes indicated patients may receive analgesia faster when the opioid protocol was nurse initiated (median 43 minutes) vs physician initiated (median 1 h 1 min) at VGH. Pain score documentation at triage improved from <10 % in 2019 to >50 % in 2020 at both sites. Approximately 95 % of EP and nursing staff thought nurse-initiated opioids are safe, effective, and should be supported by regulatory boards. CONCLUSION: Implementing a new triage protocol to expedite initiation of an analgesic protocol was associated with significantly reduced time to analgesia for patients with moderate to severe pain. Time reductions may be greater with nurse-initiated analgesia before physician assessment.

Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis.

The heterogeneous course, severity, and treatment responses among patients with atopic dermatitis (AD; eczema) highlight the complexity of this multifactorial disease. Prior studies have used traditional typing methods on cultivated isolates or sequenced a bacterial marker gene to study the skin microbial communities of AD patients. Shotgun metagenomic sequence analysis provides much greater resolution, elucidating multiple levels of microbial community assembly ranging from kingdom to species and strain-level diversification. We analyzed microbial temporal dynamics from a cohort of pediatric AD patients sampled throughout the disease course. Species-level investigation of AD flares showed greater Staphylococcus aureus predominance in patients with more severe disease and Staphylococcus epidermidis predominance in patients with less severe disease. At the strain level, metagenomic sequencing analyses demonstrated clonal S. aureus strains in more severe patients and heterogeneous S. epidermidis strain communities in all patients. To investigate strain-level biological effects of S. aureus, we topically colonized mice with human strains isolated from AD patients and controls. This cutaneous colonization model demonstrated S. aureus strain-specific differences in eliciting skin inflammation and immune signatures characteristic of AD patients. Specifically, S. aureus isolates from AD patients with more severe flares induced epidermal thickening and expansion of cutaneous T helper 2 (TH2) and TH17 cells. Integrating high-resolution sequencing, culturing, and animal models demonstrated how functional differences of staphylococcal strains may contribute to the complexity of AD disease.

Programmatic Efforts at the National Institutes of Health to Promote and Support the Careers of Women in Biomedical Science.

Although women have reached parity at the training level in the biological sciences and medicine, they are still significantly underrepresented in the professoriate and in mid- and senior-level life science positions. Considerable effort has been devoted by individuals and organizations across science sectors to understanding this disparity and to developing interventions in support of women's career development. The National Institutes of Health (NIH) formed the Office of Research on Women's Health (ORWH) in 1990 with the goals of supporting initiatives to improve women's health and providing opportunities and support for the recruitment, retention, reentry, and sustained advancement of women in biomedical careers. Here, the authors review several accomplishments and flagship activities initiated by the NIH and ORWH in support of women's career development during this time. These include programming to support researchers returning to the workforce after a period away (Research Supplements to Promote Reentry into Biomedical and Behavioral Research Careers), career development awards made through the Building Interdisciplinary Research Careers in Women's Health program, and trans-NIH involvement and activities stemming from the NIH Working Group on Women in Biomedical Careers. These innovative programs have contributed to advancement of women by supporting the professional and personal needs of women in science. The authors discuss the unique opportunities that accompany NIH partnerships with the scientific community, and conclude with a summary of the impact of these programs on women in science.

Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders.

Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

Classification and treatment of Class II subdivision malocclusions.

INTRODUCTION: Patients with Class II subdivision malocclusions are a challenge for clinicians because reestablishing symmetry in 1 arch or both arches is often a treatment goal. In patients with mandibular skeletal asymmetry, surgery is often a treatment option. However, patients may be unwilling to undergo surgery, and other options might have to be considered. The aim of this study was to evaluate the etiologies and outcomes of Class II subdivision patients treated at the University of Washington graduate orthodontic clinic in Seattle from 1995 through 2011. METHODS: A search of patients treated between 1995 and 2011 resulted in the identification of 110 consecutively treated Class II subdivision subjects with complete records. Ninety-eight subjects could be classified into 1 of 3 groups, based on midline position and dental or skeletal etiology. Initial and final models were used to measure the peer assessment rating scores, midlines, overjet, overbite, and molar positions. Initial and final cephalograms were traced and measured. Charts were reviewed for information regarding treatment. RESULTS: Twenty-five percent of the 98 subjects had their maxillary and mandibular midlines coincident with the facial midline; their asymmetries were due to a maxillary posterior dental asymmetry. Another 15% had maxillary midlines deviated from their facial midlines, caused by maxillary anterior and posterior dental asymmetry. About 50% of the subjects had mandibular midlines that were not coincident with their facial midlines, and most of them exhibited some degree of mandibular skeletal asymmetry. Over the past 15 years, treatment strategies used at the University of Washington indicated trends toward less surgery, fewer extractions, less use of headgear, and more reliance on fixed functional appliances. Ideal correction of midlines was not always achieved, especially in patients with mandibular skeletal asymmetry, with undercorrection occurring more commonly than overcorrection. Final peer assessment rating scores were comparable, regardless of the origin of the asymmetry or the extractions status. Mandibular incisor proclination was increased when fixed functional appliances were used, as well as when a Class I molar relationship was the target for the Class II side. CONCLUSIONS: Class II subdivision malocclusions were grouped into 3 main categories; the largest category was mandibular asymmetry. Interesting trends were noted with regard to treatment strategies, midline and molar corrections, and mandibular incisor proclination.

More than a pore: the cellular response to cholesterol-dependent cytolysins.

Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell.

Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response.

The cysteine protease caspase-7 has an established role in the execution of apoptotic cell death, but recent findings also suggest involvement of caspase-7 during the host response to microbial infection. Caspase-7 can be cleaved by the inflammatory caspase, caspase-1, and has been implicated in processing and activation of microbial virulence factors. Thus, caspase-7 function during microbial infection may be complex, and its role in infection and immunity has yet to be fully elucidated. Here we demonstrate that caspase-7 is cleaved during cytosolic infection with the intracellular bacterial pathogen, Listeria monocytogenes. Cleavage of caspase-7 during L. monocytogenes infection did not require caspase-1 or key adaptors of the primary pathways of innate immune signaling in this infection, ASC, RIP2 and MyD88. Caspase-7 protected infected macrophages against plasma membrane damage attributable to the bacterial pore-forming toxin Listeriolysin O (LLO). LLO-mediated membrane damage could itself trigger caspase-7 cleavage, independently of infection or overt cell death. We also detected caspase-7 cleavage upon treatment with other bacterial pore-forming toxins, but not in response to detergents. Taken together, our results support a model where cleavage of caspase-7 is a consequence of toxin-mediated membrane damage, a common occurrence during infection. We propose that host activation of caspase-7 in response to pore formation represents an adaptive mechanism by which host cells can protect membrane integrity during infection.

Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection.

BACKGROUND: New therapeutic targets for antibiotic-resistant bacterial pathogens are desperately needed. The bacterial surface polysaccharide poly-ß-(1-6)-N-acetyl-glucosamine (PNAG) mediates biofilm formation by some bacterial species, and antibodies to PNAG can confer protective immunity. By analyzing sequenced genomes, we found that potentially multidrug-resistant bacterial species such as Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia, and the Burkholderia cepacia complex (BCC) may be able to produce PNAG. Among patients with cystic fibrosis patients, highly antibiotic-resistant bacteria in the BCC have emerged as problematic pathogens, providing an impetus to study the potential of PNAG to be targeted for immunotherapy against pan-resistant bacterial pathogens. METHODS: The presence of PNAG on BCC was assessed using a combination of bacterial genetics, microscopy, and immunochemical approaches. Antibodies to PNAG were tested using opsonophagocytic assays and for protective efficacy against lethal peritonitis in mice. RESULTS: PNAG is expressed in vitro and in vivo by the BCC, and cystic fibrosis patients infected by the BCC species B. dolosa mounted a PNAG-specific opsonophagocytic antibody response. Antisera to PNAG mediated opsonophagocytic killing of BCC and were protective against lethal BCC peritonitis even during coinfection with methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Our findings raise potential new therapeutic options against PNAG-producing bacteria, including even pan-resistant pathogens.