Optimizing Implementation of the Neonatal Enhanced Recovery After Surgery Guideline.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS®) protocols require multidisciplinary team engagement from healthcare professionals (HCPs), where limited studies exist on neonatal ERAS®protocols. Therefore, we aimed to capture perceptions of HCPs on facilitation and implementation of the neonatal ERAS®guideline. METHODS: 10 neonates were recruited. 13 HCPs involved in these patient's care were interviewed and 8 surveyed consisting of pediatric anesthesiologists, neonatologists, neonatal intensive care unit (NICU) registered nurses (RNs), and pediatric surgeons. Using a multi-methods design, recruitment, semi-structured interviews and surveys were conducted from May 17, 2021 to November 1, 2022. Data was coded using The Promoting Action on Research Implementation in Health Studies and then thematically analyzed. RESULTS: Interviews were conducted with 4 pediatric anesthesiologists, 4 neonatologists, 2 NICU RNs, and 3 pediatric surgeons and surveys with 1 pediatric anesthesiologist, 2 neonatologists, 3 NICU RNs, and 2 pediatric surgeons. From interviews, the top 3 facilitation strategies were utilization of: (1) multidisciplinary guideline champions, (2) reminders and education, and (3) results to facilitate adherence. Incorporation of these strategies resulted in perceived: (1) stronger buy-in and engagement and (2) improved team communication, job satisfaction, care quality, and parental involvement. CONCLUSION: HCPs stressed the importance of guideline champions, reminders and education, and results distribution. Given implementation during the COVID-19 pandemic, awareness and education were mixed. Nonetheless, HCPs perceived improved buy-in and engagement, communication, job satisfaction, quality of care, and parental involvement. Incorporation of these strategies can promote successful ERAS® guideline facilitation and implementation and should be considered for future ERAS® projects. LEVEL OF EVIDENCE: IV.

The Androgen Receptor Does Not Directly Regulate the Transcription of DNA Damage Response Genes.

The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes in nascent RNA transcription in response to IR, the AR antagonist enzalutamide, or the combination of the two, we find that enzalutamide treatment significantly decreased expression of canonical AR target genes but had no effect on DDR gene sets in prostate cancer cells. Surprisingly, we also found that the AR is not a primary regulator of DDR genes either in response to IR or at a steady state in asynchronously growing prostate cancer cells. IMPLICATIONS: Our data indicate that the clinical benefit of combining ADT with RT is not due to direct AR regulation of DDR gene transcription, and that the field needs to consider alternative mechanisms for this clinical benefit.

Enabling genomic island prediction and comparison in multiple genomes to investigate bacterial evolution and outbreaks.

Outbreaks of virulent and/or drug-resistant bacteria have a significant impact on human health and major economic consequences. Genomic islands (GIs; defined as clusters of genes of probable horizontal origin) are of high interest because they disproportionately encode virulence factors, some antimicrobial-resistance (AMR) genes, and other adaptations of medical or environmental interest. While microbial genome sequencing has become rapid and inexpensive, current computational methods for GI analysis are not amenable for rapid, accurate, user-friendly and scalable comparative analysis of sets of related genomes. To help fill this gap, we have developed IslandCompare, an open-source computational pipeline for GI prediction and comparison across several to hundreds of bacterial genomes. A dynamic and interactive visualization strategy displays a bacterial core-genome phylogeny, with bacterial genomes linearly displayed at the phylogenetic tree leaves. Genomes are overlaid with GI predictions and AMR determinants from the Comprehensive Antibiotic Resistance Database (CARD), and regions of similarity between the genomes are also displayed. GI predictions are performed using Sigi-HMM and IslandPath-DIMOB, the two most precise GI prediction tools based on nucleotide composition biases, as well as a novel blast-based consistency step to improve cross-genome prediction consistency. GIs across genomes sharing sequence similarity are grouped into clusters, further aiding comparative analysis and visualization of acquisition and loss of mobile GIs in specific sub-clades. IslandCompare is an open-source software that is containerized for local use, plus available via a user-friendly, web-based interface to allow direct use by bioinformaticians, biologists and clinicians (at https://islandcompare.ca).

Canadian surveillance study of complex regional pain syndrome in children.

ABSTRACT: This study describes the minimum incidence of pediatric complex regional pain syndrome (CRPS), clinical features, and treatments recommended by pediatricians and pain clinics in Canada. Participants in the Canadian Paediatric Surveillance Program reported new cases of CRPS aged 2 to 18 years monthly and completed a detailed case reporting questionnaire from September 2017 to August 2019. Descriptive analysis was completed, and the annual incidence of CRPS by sex and age groupings was estimated. A total of 198 cases were reported to the Canadian Paediatric Surveillance Program, and 168 (84.8%) met the case definition. The minimum Canadian incidence of CRPS is estimated at 1.14/100,000 (95% confidence interval 0.93-1.35/100,000) children per year. Incidence was highest among girls 12 years and older (3.10, 95% confidence interval 2.76-3.44/100,000). The mean age of CRPS diagnosis was 12.2 years (SD = 2.4), with the mean time from symptom onset to diagnosis of 5.6 months (SD = 9.9) and no known inciting event for 19.6% of cases. Most cases had lower limb involvement (79.8%). Nonsteroidal anti-inflammatory drugs (82.7%) and acetaminophen (66.0%) were prescribed more commonly than antiepileptic drugs (52.3%) and antidepressants (32.0%). Referrals most commonly included physical therapy (83.3%) and multidisciplinary pain clinics (72.6%); a small number of patients withdrew from treatment because of pain exacerbation (5.3%). Pain education was recommended for only 65.6% of cases. Treatment variability highlights the need for empiric data to support treatment of pediatric CRPS and development of treatment consensus guidelines.

Optimizing Outcomes After Cleft Palate Repair: Design and Implementation of a Perioperative Clinical Care Pathway.

OBJECTIVE: To evaluate the development process and clinical impact of implementing a standardized perioperative clinical care pathway for cleft palate repair. DESIGN: Medical records of patients undergoing primary cleft palate repair prior to pathway implementation were retrospectively reviewed as a historical control group (N = 40). The historical cohort was compared to a prospectively collected group of patients who were treated according to the pathway (N = 40). PATIENTS: Healthy, nonsyndromic infants undergoing primary cleft palate repair at a tertiary care pediatric hospital. INTERVENTIONS: A novel, standardized pathway was created through an iterative process, combining literature review with expert opinion and discussions with institutional stakeholders. The pathway integrated multimodal analgesia throughout the perioperative course and included intraoperative bilateral maxillary nerve blocks. Perioperative protocols for preoperative fasting, case timing, antiemetics, intravenous fluid management, and postoperative diet advancement were standardized. MAIN OUTCOME MEASURES: Primary outcomes include: (1) length of hospital stay, (2) cumulative opioid consumption, (3) oral intake postoperatively. RESULTS: Patients treated according to the pathway had shorter mean length of stay (31 vs 57 hours, P < .001), decreased cumulative morphine consumption (77 vs 727 µg/kg, P < .001), shorter time to initiate oral intake (9.3 vs 22 hours, P = .01), and greater volume of oral intake in first 24 hours postoperatively (379 vs 171 mL, P < .001). There were no differences in total anesthesia time, total surgical time, or complication rates between the control and treatment groups. CONCLUSIONS: Implementation of a standardized perioperative clinical care pathway for primary cleft palate repair is safe, feasible, and associated with reduced length of stay, reduced opioid consumption, and improved oral intake postoperatively.

Twin Peaks: Covid-19 and the labor market.

This paper develops a choice-theoretic equilibrium model of the labor market in the presence of a pandemic. It includes heterogeneity in productivity, age and the ability to work from home. Worker and firm behavior changes in the presence of the virus, which itself has equilibrium consequences for the infection rate. The model is calibrated to the UK and counterfactual lockdown measures are evaluated. We find a different response in both the evolution of the virus and the labor market with different lockdown policies. A laissez-faire approach results in lives lost and acts as negative shock to the economy. A lockdown policy, absent any other intervention, will reduce the lives lost but increase the economic burden. Consistent with recent evidence, we find that the economic costs from lockdown are most felt by those earning the least. Finally, we introduce a job retention scheme as implemented by the UK Government and find that it spreads the economic hardship more equitably.

IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK.

Head and neck cancer is the sixth most common cancer worldwide with a 5-year survival of only 65%. Targeting compensatory signaling pathways may improve therapeutic responses and combat resistance. Utilizing reverse phase protein arrays (RPPA) to assess the proteome and explore mechanisms of synergistic growth inhibition in HNSCC cell lines treated with IGF1R and Src inhibitors, BMS754807 and dasatinib, respectively, we identified focal adhesion signaling as a critical node. Focal Adhesion Kinase (FAK) and Paxillin phosphorylation were decreased as early as 15 min after treatment, and treatment with a FAK inhibitor, PF-562,271, was sufficient to decrease viability in vitro. Treatment of 3D spheroids demonstrated robust cytotoxicity suggesting that the combination of BMS754807 and dasatinib is effective in multiple experimental models. Furthermore, treatment with BMS754807 and dasatinib significantly decreased cell motility, migration, and invasion in multiple HNSCC cell lines. Most strikingly, treatment with BMS754807 and dasatinib, or a FAK inhibitor alone, significantly increased cleaved-PARP in human ex-vivo HNSCC patient tissues demonstrating a potential clinical utility for targeting FAK or the combined targeting of the IGF1R with Src. This ex-vivo result further confirms FAK as a vital signaling node of this combinatorial treatment and demonstrates therapeutic potential for targeting FAK in HNSCC patients.

Children's Pain During IV Induction: A Randomized-Controlled Trial With the MEDi® Robot.

OBJECTIVE: This study examined the impact of a humanoid robot (MEDi®) programmed to teach deep breathing as a coping strategy, on children's pain and fear as primary and secondary outcomes, respectively, during intravenous (IV) line placement. The completion of IV induction was also examined as an exploratory outcome. METHODS: In this randomized controlled, two-armed trial, 137 children (4-12 years) were recruited in Short Stay Surgery at a tertiary pediatric hospital. Patients were randomly assigned to standard care (SC) with Ametop© only (N = 60) or SC and robot-facilitated intervention (N = 59) before induction. Pain and fear before, during, and after IV insertion were rated by patients and observers. RESULTS: No significant differences were found between groups and there were no changes over time for pain or fear (ps > .05). Exploratory analyses show that patients in the MEDi® group were 5.04 times more likely to complete IV induction, compared to SC, Fisher's exact test: X2 (1) = 4.85, p = .04, φc = 0.22, odds ratio = 5.04, 95% CI [1.06, 24.00]. CONCLUSION: This study was the first to examine children's IV induction experience when provided MEDi® support. Reasons for nonsignificance, limitations, and research suggestions were made.