Transforming into a Learning Health System: A Quality Improvement Initiative.

Background: The Institute of Medicine introduced the Learning Healthcare System concept in 2006. The system emphasizes quality, safety, and value to improve patient outcomes. The Bellevue Clinic and Surgical Center is an ambulatory surgical center that embraces continuous quality improvement to provide exceptional patient-centered care to the pediatric surgical population. Methods: We used statistical process control charts to study the hospital's electronic health record data. Over the past 7 years, we have focused on the following areas: efficiency (surgical block time use), effectiveness (providing adequate analgesia after transitioning to an opioid-sparing protocol), efficacy (creating a pediatric enhanced recovery program), equity (evaluating for racial disparities in surgical readmission rates), and finally, environmental safety (tracking and reducing our facility's greenhouse gas emissions from inhaled anesthetics). Results: We have seen improvement in urology surgery efficiency, resulting in a 37% increase in monthly surgical volume, continued adaptation to our opioid-sparing protocol to further reduce postanesthesia care unit opioid administration for tonsillectomy and adenoidectomy cases, successful implementation of an enhanced recovery program, continued work to ensure equitable healthcare for our patients, and more than 85% reduction in our facility's greenhouse gas emissions from inhaled anesthetics. Conclusions: The Bellevue Clinic and Surgical Center facility is a living example of a learning health system, which has evolved over the years through continued patient-centered QI work. Our areas of emphasis, including efficiency, effectiveness, efficacy, equity, and environmental safety, will continue to impact the community we serve positively.

Enhanced recovery program in ambulatory pediatric urology: A quality improvement initiative.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) was established in 2001 for adult patients undergoing complex procedures. ERAS in adult ambulatory surgery later followed with similar positive outcomes. For the pediatric population, ERAS implementation has shown promising results in complex surgeries such as bladder reconstruction. Its application in pediatric ambulatory surgery has only recently been reported. We hereby report a Quality Improvement initiative in implementing an Enhanced Recovery Protocol (ERP) for pediatric urology in an ambulatory surgery center. METHODS: A project was launched to evaluate and implement enhanced recovery elements into an institutional Enhanced Recovery Protocol (ERP). These included reliance on peripheral nerve blocks for all inguinal and genital cases and reduction of opioids intraoperatively and postoperatively. Improvements were placed into a project plan broken into one preparation phase to collect baseline data and three implementation phases to enhance existing and implement new elements. The implementation phase went through iterative Plan-Do-Study-Act (PDSA) cycles for all sub-projects. Team countermeasures were based on available evidence. A consensus process was used to resolve disagreement. Monthly meetings were held to share real-time data, gather new feedback, and modify plans as needed. The primary outcome measures selected were percent intraoperative opioid use, percent opioid prescribing, mean PACU length of stay, and average number of opioid doses prescribed. Secondary outcome measures were mean maximum pain score in PACU, PACU rescue rate for PONV, and patient/family satisfaction scores. Post-implementation data for 18 months was included for evaluation. Statistical process control methodology was used. RESULTS: The total number of participants was 3306: 561 (baseline), 220 (Phase 1) 356 (Phase 2) and 527 (Phase 3), 1642 (post-implementation). Intraoperative opioid use was eliminated in >99% of cases. Post-operative opioid prescribing was reduced from 30% to 15% of patients. The number of opioid doses was also reduced from an average of 7.6 to 6.1 doses. There was no change for the mean maximum pain score in the recovery room despite elimination of opioids. Patient/family satisfaction scores were high and sustained throughout the period of study (9.8/10). Balancing measures such as return to the operating room within 30 days and return to the emergency department within 7 days were unchanged. CONCLUSIONS: This QI project demonstrated the feasibility of a pediatric enhanced recovery protocol in a urology ambulatory surgery setting. With implementation of this protocol, intraoperative opioid use was virtually eliminated, and opioid prescribing was reduced without affecting pain scores or post-operative complications.

Reducing Pediatric Posttonsillectomy Opioid Prescribing: A Quality Improvement Initiative.

OBJECTIVE: Postoperative pain is the most common morbidity associated with tonsillectomy. Opioids are frequently used in multimodal posttonsillectomy analgesia regimens; however, concerns regarding respiratory depression, drug-drug interactions, and medication misuse necessitate responsible opioid stewardship among prescribing surgeons. It is unclear if intentionally reducing opioid prescription doses negatively affects the patient experience. METHODS: A quality improvement team reviewed all posttonsillectomy opioid prescriptions at a pediatric ambulatory surgery center between January and June 2021 (preintervention, 163 patients). Following this review, we performed an opioid education session for surgeons and studied opioid prescribing habits between July and December 2021 (Plan-Do-Study-Act [PDSA] 1, 152 patients). We then implemented a standardized prescription protocol of 7 doses of oxycodone per patient and again reviewed prescriptions between January and June 2022 (PDSA 2, 178 patients). The following measures were evaluated: initial number of opioid doses prescribed, need for refills, 7-day emergency department (ED) visits, and readmissions. RESULTS: Each intervention reduced the average number of initial oxycodone doses per patient (12.2 vs 9.2 vs 6.9 doses, P < .001). There were no changes in the rate of refill requests, 7-day ED visits, and readmissions, by descriptive or Statistical Process Control analyses. DISCUSSION: In 2 PDSA cycles, we achieved a 43% reduction in the number of doses of oxycodone prescribed following tonsillectomy. We did not observe any increased rates in balancing measures, which are surrogates for unintentional effects of PDSA changes, including refills, ED presentations, and readmission rates. IMPLICATIONS FOR PRACTICE: Directed provider education and standardized posttonsillectomy prescription protocols can safely decrease postoperative opioid prescribing. Further PDSA cycles are required to consider even fewer opioid prescription doses.

Outcomes for 41 260 pediatric surgical patients with opioid-free anesthesia: One center's experience.

BACKGROUND: Opioid use is common and associated with side effects and risks. Consequently, analgesic strategies to reduce opioid utilization have been developed. Regional anesthesia and multimodal strategies are central tenets of enhanced recovery pathways and facilitate reduced perioperative opioid use. Opioid-free anesthesia (OFA) protocols eliminate all intraoperative opioids, reserving opioids for postoperative rescue treatment. Systematic reviews show variable results for OFA. METHODS: In a series of Quality Improvement (QI) projects, multidisciplinary teams developed interventions to test and spread OFA first in our ambulatory surgery center (ASC) and then in our hospital. Outcome measures were tracked using statistical process control charts to increase the adoption of OFA. RESULTS: Between January 1, 2016, and September 30, 2022, 19 872 of 28 574 ASC patients received OFA, increasing from 30% to 98%. Post Anesthesia Care Unit (PACU) maximum pain score, opioid-rescue rate, and postoperative nausea and vomiting (PONV) treatment all decreased concomitantly. The use of OFA now represents our ambulatory standard practice. Over the same timeframe, the spread of this practice to our hospital led to 21 388 of 64 859 patients undergoing select procedures with OFA, increasing from 15% to 60%. Opioid rescue rate and PONV treatment in PACU decreased while hospital maximum pain scores and length of stay were stable. Two procedural examples with OFA benefits were identified. The use of OFA allowed relaxation of adenotonsillectomy admission criteria, resulting in 52 hospital patient days saved. Transition to OFA for laparoscopic appendectomy occurred concomitantly with a decrease in the mean hospital length of stay from 2.9 to 1.4 days, representing a savings of >500 hospital patient days/year. CONCLUSIONS: These QI projects demonstrated that most pediatric ambulatory and select inpatient surgeries are amenable to OFA techniques which may reduce PONV without worsening pain.

Germline de novo mutations in families with Mendelian cancer syndromes caused by defects in DNA repair.

DNA repair defects underlie many cancer syndromes. We tested whether de novo germline mutations (DNMs) are increased in families with germline defects in polymerase proofreading or base excision repair. A parent with a single germline POLE or POLD1 mutation, or biallelic MUTYH mutations, had 3-4 fold increased DNMs over sex-matched controls. POLE had the largest effect. The DNMs carried mutational signatures of the appropriate DNA repair deficiency. No DNM increase occurred in offspring of MUTYH heterozygous parents. Parental DNA repair defects caused about 20-150 DNMs per child, additional to the ~60 found in controls, but almost all extra DNMs occurred in non-coding regions. No increase in post-zygotic mutations was detected, excepting a child with bi-allelic MUTYH mutations who was excluded from the main analysis; she had received chemotherapy and may have undergone oligoclonal haematopoiesis. Inherited DNA repair defects associated with base pair-level mutations increase DNMs, but phenotypic consequences appear unlikely.

Circulating IgG antibodies to periodontal bacteria and lung cancer risk in the CLUE cohorts.

BACKGROUND: Oral health is a key indicator of overall health, well-being, and quality of life. Several studies have provided new evidence about the role of oral diseases, specifically periodontitis, in generating risk for various forms of cancers, including lung, colorectal, and pancreatic cancers. METHODS: Incident lung cancer cases (n = 192) and matched controls (n = 192) were selected from participants of the CLUE I and CLUE II cohorts. Archived serum samples collected from participants in 1974 (in CLUE I) were analyzed using immunoblotting for immunoglobulin G (IgG) antibody levels to 13 bacteria of the periodontium. Associations between antibody levels and lung cancer were estimated using conditional logistic regression. RESULTS: Most of the periodontal bacterial antibodies measured were inversely associated with lung cancer risk; of these, 3 were statistically significant (Prevotellaintermedia, Actinomyces naeslundii, and Veillonella parvula). A statistically significant positive association was observed for one of the Porphyromonas gingivalis strains after adjusting for P. intermedia. The sum of the logarithm of antibodies against the 13 measured bacteria was inversely associated with risk of lung cancer when the analysis was restricted to a longer follow-up (31-44 years after blood collection, highest vs lowest quartile: odds ratio = 0.26, 95% confidence interval = 0.08 to 0.84). CONCLUSIONS: Findings from this study highlight the complexity of using serum IgG antibodies to periodontal bacteria to identify associations between oral pathogens and risk of lung cancer. The inverse associations observed for antibodies to periodontal bacteria suggest that these may represent markers of immunity that provide some advantage in reducing the development of lung cancer.

Antibodies to oral pathobionts and colon cancer risk in the CLUE I cohort study.

Periodontitis has been associated with an increased risk for gastrointestinal cancers. The objective of our study was to investigate the association of antibodies to oral bacteria and the risk of colon cancer in a cohort setting. Using the CLUE I cohort, a prospective cohort initiated in 1974 in Washington County, Maryland, we conducted a nested case-control study to examine the association of levels of IgG antibodies to 11 oral bacterial species (13 total strains) with risk of colon cancer diagnosed a median of 16 years later (range: 1-26 years). Antibody response was measured using checkerboard immunoblotting assays. We included 200 colon cancer cases and 200 controls matched on age, sex, cigarette smoking status, time of blood draw and pipe or cigar smoking status. Controls were selected using incidence density sampling. Conditional logistic regression models were used to assess the association between antibody levels and colon cancer risk. In the overall analysis, we observed significant inverse associations for 6 of the 13 antibodies measured (P-trends <.05) and one positive association for antibody levels to Aggregatibacter actinomycetemcomitans (ATCC 29523; P-trend = .04). While we cannot rule out a role for periodontal disease in colon cancer risk, findings from our study suggest that a strong adaptive immune response may be associated with a lower risk of colon cancer. More studies will need to examine whether the positive associations we observed with antibodies to A. actinomycetemcomitans reflect a true causal association for this bacterium.

Completion of an Enhanced Recovery Program in a Pediatric Ambulatory Surgery Center: A Quality Improvement Initiative.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) was first established in 2001 focusing on recovery from complex surgical procedures in adults and recently expanded to ambulatory surgery. The evidence for ERAS in children is limited. In 2018, recognized experts began developing needed pediatric evidence. Center-wide efforts involving all ambulatory surgical patients and procedures have not previously been described. METHODS: A comprehensive assessment and gap analysis of ERAS elements in our ambulatory center identified 11 of 19 existing elements. The leadership committed to implementing an Enhanced Recovery Program (ERP) to improve existing elements and close as many remaining gaps as possible. A quality improvement (QI) team was launched to improve 5 existing ERP elements and to introduce 6 new elements (target 17/19 ERP elements). The project plan was broken into 1 preparation phase to collect baseline data and 3 implementation phases to enhance existing and implement new elements. Statistical process control methodology was used. Team countermeasures were based on available evidence. A consensus process was used to resolve disagreement. Monthly meetings were held to share real-time data, gather new feedback, and modify countermeasure plans as needed. The primary outcome measure selected was mean postanesthesia care unit (PACU) length of stay (LOS). Secondary outcomes measures were mean maximum pain score in PACU and patient/family satisfaction scores. RESULTS: The team had expanded the pool of active ERP elements from 11 to 16 of 19. The mean PACU LOS demonstrated significant reduction (early in phase 1 and again in phase 3). No change was seen for the mean maximum pain score in PACU or surgical complication rates. Patient/family satisfaction scores were high and sustained throughout the period of study (91.1% ± 5.7%). Patient/family and provider engagement/compliance were high. CONCLUSIONS: This QI project demonstrated the feasibility of pediatric ERP in an ambulatory surgical setting. Furthermore, a center-wide approach was shown to be possible. Additional studies are needed to determine the relevance of this project to other institutions.

Recovering from COVID - Improving operating room capacity.

INTRODUCTION: COVID-19 pandemic required that health systems made great efforts to mitigate the impact of high demands of patients requiring treatment. Triaging surgical cases reduced operating room capacity. Immunizations, massive testing, and personal protective equipment enabled re-activation of operating rooms. Delayed and newly added cases has placed stress on the system. We hypothesize that standardization in practice for tasks performed between anesthesia ready and surgery start time, also known as "prepping time", can reduce operative time, improve efficiency and increase capacity. The aim of our project was to create and implement a best practice standardized prepping protocol, to explore its impact on operating room capacity. METHODS: Once local policies allowed re-opening of the operating rooms, our multidisciplinary group developed a working plan following Adaptive Clinical Management (ACM) principles to optimize surgical prepping time. Using electronic medical record (EMR) data, surgeons with the lowest surgical prepping times were identified (positive deviants). Their surgical prepping time workflows were reviewed. A clinical standard work (CSW) protocol was created by the team leader. New CSW protocol was defined and implemented by the leader and then by the rest of the surgeons. Baseline data was automatically extracted from EMR and analyzed by statistical process control (SPC) charts using AdaptX. Balancing measures included "last case end time" and rates of surgical site infections. RESULTS: A total of 2506 patients were included for analysis with 1333 prior to intervention and 1173 after. Team leader implementated the new CSW prepping protocol showing a special cause variation with an average time improvement from 14.6 min to 11.6 min and for all surgeons from 13.8 to 12.0 min. Total cases per month increased from 70 to 90 cases per month. Baseline 'Last Case End Time' was 15.7 min later than the scheduled. New CSW improve end time with an average of 20.8 min before the schedule. Baseline surgical site infection was 0.1% for the study population. No difference was seen after implementation. DISCUSSION: Variations in performance can be quantified using funnel plots showing individual practices allowing best practice to be identified, tested and scaled. Implementation of our surgical prepping time protocol showed a sustainable increase in efficiency without affecting quality, safety or workload. This additional increase is estimated to represent approximately $2-2.5M additional revenue per year. CONCLUSION: Adaptive clinical management is a practical solution to increase OR capacity by improving efficiency to reduce extra burden presented during COVID19 pandemic.

Understanding the Extent of Polypharmacy and its Association With Health Service Utilization Among Persons With Cancer and Multimorbidity: A Population-Based Retrospective Cohort Study in Ontario, Canada.

BACKGROUND: Cancer often co-occurs with other chronic conditions, which may result in polypharmacy. Polypharmacy is associated with adverse outcomes, including increased health service utilization. OBJECTIVES: This study examines the overall prevalence of polypharmacy (5 or more medications) among adults with cancer and multimorbidity, as well as the association of both minor polypharmacy (5-9 medications) and hyper-polypharmacy (10 or more medications) on high use of emergency room visits and hospitalizations, while controlling for age, sex, and type and stage of cancer. METHODS: This retrospective longitudinal study used linked health administrative databases and included persons 18 years and older diagnosed with cancer between April 2010 and March 2013 in Ontario, Canada. Data on the number of health service utilizations at or above the 90th percentile (high users), was collected up to March 2014 and multivariate logistic regression was used to determine the impact of polypharmacy. RESULTS: The prevalence of polypharmacy was 46% prior to cancer diagnosis, and 57% one year after diagnosis. Polypharmacy prior to and after cancer diagnosis increased with the level of multimorbidity, increasing age, but did not differ by sex. It was also highest in persons with lung cancer (52.4%) and those diagnosed with stage 4 cancer (51.3%). Minor polypharmacy increased the odds of being a high user of emergency rooms (1.16; 99% CI: 1.09-1.24) and hospitalizations (1.03; 0.98-1.09) and the odds of high use was greater with hyper-polypharmacy (1.41; 1.33-1.51) and (1.23; 1.17-1.29) respectively. CONCLUSION: Polypharmacy is highly prevalent and is associated with high health service utilization among adults with cancer and multimorbidity.

Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo.

Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-ß signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome.

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5'-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management.

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.

Pathogenic germline exonuclease domain (ED) variants of POLE and POLD1 cause the Mendelian dominant condition polymerase proof-reading associated polyposis (PPAP). We aimed to describe the clinical features of all PPAP patients with probably pathogenic variants. We identified patients with a variants mapping to the EDs of POLE or POLD1 from cancer genetics clinics, a colorectal cancer (CRC) clinical trial, and systematic review of the literature. We used multiple evidence sources to separate ED variants into those with strong evidence of pathogenicity and those of uncertain importance. We performed quantitative analysis of the risk of CRC, colorectal adenomas, endometrial cancer or any cancer in the former group. 132 individuals carried a probably pathogenic ED variant (105 POLE, 27 POLD1). The earliest malignancy was colorectal cancer at 14. The most common tumour types were colorectal, followed by endometrial in POLD1 heterozygotes and duodenal in POLE heterozygotes. POLD1-mutant cases were at a significantly higher risk of endometrial cancer than POLE heterozygotes. Five individuals with a POLE pathogenic variant, but none with a POLD1 pathogenic variant, developed ovarian cancer. Nine patients with POLE pathogenic variants and one with a POLD1 pathogenic variant developed brain tumours. Our data provide important evidence for PPAP management. Colonoscopic surveillance is recommended from age 14 and upper-gastrointestinal surveillance from age 25. The management of other tumour risks remains uncertain, but surveillance should be considered. In the absence of strong genotype-phenotype associations, these recommendations should apply to all PPAP patients.

Recovery of platelet reactivity following cessation of either aspirin or ticagrelor in patients treated with dual antiplatelet therapy following percutaneous coronary intervention: a GLOBAL LEADERS substudy.

Cessation of one component of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has been associated with increased risk of ischemic events but it is uncertain whether discontinuation of aspirin is preferable to discontinuation of the oral P2Y12 inhibitor. The GLOBAL LEADERS study compared two antiplatelet strategies following PCI, cessation of aspirin at 1 month with continued ticagrelor monotherapy for 23 months versus standard DAPT for 12 months followed by aspirin monotherapy for a further 12 months. We assessed recovery of platelet reactivity after withdrawal of either aspirin or ticagrelor at 1 month and 12 months, respectively, in this study. Platelet aggregation (PA) was assessed before cessation of DAPT ('baseline') and after 2, 7, and 14 days post-cessation using Multiplate whole-blood aggregometry with collagen, thrombin-receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. Following cessation of aspirin at 1 month, there was marked recovery of PA induced by AA (baseline [mean ± SD]: 11.1 ± 7.4 U vs. 14 days: 64.9 ± 19.6 U, p < .0001) and collagen (37.4 ± 22.9 U vs. 79.8 ± 13.8 U, p < .0001), whereas PA induced by ADP (18.6 ± 6.6 vs. 69.1 ± 20.5, p < .0001) and collagen (34.4 ± 18.7 U vs. 43.0 ± 21.0, p = .0018) recovered following cessation of ticagrelor at 12 months. There were no significant changes in TRAP-induced PA in either group. In conclusion, cessation of either component of DAPT leads to substantial increase in platelet reactivity with differential effects on different pathways of platelet activation when aspirin or the P2Y12 inhibitor is stopped. Further work is required to determine which patients receive net benefit from long-term continuation of DAPT.

Increased somatic mutation burdens in normal human cells due to defective DNA polymerases.

Mutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.

An Opioid-free Anesthesia Protocol for Pediatric Strabismus Surgery: A Quality Improvement Project.

INTRODUCTION: This quality improvement (QI) project tracks a series of 2 Plan-Do-Study-Act (PDSA) cycles as we standardized and refined an ambulatory pediatric anesthesia strabismus protocol. We aimed to provide effective pain relief, reduce postoperative nausea and vomiting (PONV) rates, and be cost-efficient while minimizing perioperative opioids over 5 years. METHODS: We used statistical process control (SPC) charts to analyze real-world data captured from the medical record. We chose the following outcome and process measures to evaluate effectiveness: postoperative morphine rescue rate, maximum pain score in the postanesthesia care unit (PACU), and PONV rescue rate. We also used 2 balancing measures: postoperative length of stay (LOS) and total anesthesia time. We standardized our anesthesia protocol for our first PDSA cycle (April 2017) by removing intraoperative intravenous acetaminophen and utilizing fentanyl only. For the second PDSA cycle (January 2019), we replaced intraoperative fentanyl with dexmedetomidine. RESULTS: There was a total of 325 pediatric strabismus repair surgeries performed between April 2015 and July 2020. There was no special cause variation detected in the SPC charts for the family of measures chosen to measure effectiveness: postoperative morphine rescue rate, maximum pain score in the PACU, or the PONV rescue rate. The PONV rescue rate was 0 with the removal of opioids. Also, there was no special cause variation for the balancing measures: postoperative LOS or total anesthesia time. CONCLUSIONS: Throughout 2 PDSA cycles, this QI project enabled our team to standardize an opioid-free and cost-efficient anesthesia protocol for pediatric strabismus surgery over 5 years.

Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate.

Pseudomonas aeruginosa causes life-threatening infections that are associated with antibiotic failure. Previously, we identified the antibiotic G2637, an analog of arylomycin, targeting bacterial type I signal peptidase, which has moderate potency against P. aeruginosa. We hypothesized that an antibody-antibiotic conjugate (AAC) could increase its activity by colocalizing P. aeruginosa bacteria with high local concentrations of G2637 antibiotic in the intracellular environment of phagocytes. Using a novel technology of screening for hybridomas recognizing intact bacteria, we identified monoclonal antibody 26F8, which binds to lipopolysaccharide O antigen on the surface of P. aeruginosa bacteria. This antibody was engineered to contain 6 cysteines and was conjugated to the G2637 antibiotic via a lysosomal cathepsin-cleavable linker, yielding a drug-to-antibody ratio of approximately 6. The resulting AAC delivered a high intracellular concentration of free G2637 upon phagocytosis of AAC-bound P. aeruginosa by macrophages, and potently cleared viable P. aeruginosa bacteria intracellularly. The molar concentration of AAC-associated G2637 antibiotic that resulted in elimination of bacteria inside macrophages was approximately 2 orders of magnitude lower than the concentration of free G2637 required to eliminate extracellular bacteria. This study demonstrates that an anti-P. aeruginosa AAC can locally concentrate antibiotic and kill P. aeruginosa inside phagocytes, providing additional therapeutic options for antibiotics that are moderately active or have an unfavorable pharmacokinetics or toxicity profile. IMPORTANCE Antibiotic treatment of life-threatening P. aeruginosa infections is associated with low clinical success, despite the availability of antibiotics that are active in standard microbiological in vitro assays, affirming the need for new therapeutic approaches. Antibiotics often fail in the preclinical stage due to insufficient efficacy against P. aeruginosa. One potential strategy is to enhance the local concentration of antibiotics with limited inherent anti-P. aeruginosa activity. This study presents proof of concept for an antibody-antibiotic conjugate, which releases a high local antibiotic concentration inside macrophages upon phagocytosis, resulting in potent intracellular killing of phagocytosed P. aeruginosa bacteria. This approach may provide new therapeutic options for antibiotics that are dose limited.

Impact of Eliminating Local Anesthesia on Immediate Postoperative Analgesia in Pediatric Ambulatory Adenotonsillectomy.

Our goal was to standardize intraoperative analgesic regimens for pediatric ambulatory tonsillectomy by eliminating local anesthetic use and to determine its impact on postoperative pain measures, while controlling for other factors. METHODS: We assembled a quality improvement team at an ambulatory surgery center. They introduced a standardized anesthetic protocol, involving American Society of Anesthesiologists Classification 1 and 2 patients undergoing adenotonsillectomy. Local anesthesia elimination was the project's single intervention. We collected pre-intervention data (79 cases) from July 5 to September 17, 2019 and post-intervention data (59 cases) from September 25 to December 17, 2019. The intervention requested that surgeons eliminate the use of local anesthetics. The following outcomes measures were evaluated using statistical process control charts and Shewhart's theory of variation: (1) maximum pain score in the post-anesthesia care unit, (2) total post-anesthesia care unit minutes, and (3) postoperative opioid rescue rate. RESULTS: No special cause variation signal was detected in any of the measures following the intervention. CONCLUSIONS: Our data suggest that eliminating intraoperative local anesthetic use does not worsen postoperative pain control at our facility. The intervention eliminated the added expenses and possible risks associated with local anesthetic use. This series is unique in its standardization of anesthetic regimen in a high-volume ambulatory surgery center with the exception of local anesthesia practices. The study results may impact the standardized clinical protocol for pediatric ambulatory adenotonsillectomy at our institution and may hold relevance for other centers.

Exodontia associated bacteremia in horses characterized by next generation sequencing.

Bacteremia resulting from dental surgery is increasingly recognized as a health risk, especially in older and immunocompromised patients. Dentistry-associated bacteremia can lead to remote infections, as exemplified by valvular endocarditis. Emerging evidence points to a novel role played by oral cavity commensals in the pathogenesis of diabetes, respiratory disease, cardiovascular disease, and adverse pregnancy outcomes. Whether dental extraction, a commonly undertaken procedure in old horses, causes bacteremia has not been reported extensively. In a prospective clinical study using next generation sequencing (based on bacterial 16S rRNA), the circulating blood microbiome was characterized before and at 1 h following extraction of incisor, canine or cheek teeth from 29 adult horses with dental disease. 16S rRNA gene sequencing results from the blood microbiome were compared with those from gingival swab samples obtained prior to extraction at the location of the diseased tooth. Bacteremia associated with translocated gingival commensals was demonstrated in horses undergoing exodontia and was, in some cases, still evident one hour post-operatively.