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An infection-resistant, immediately available conduit for trauma and urgent vascular reconstruction remains a critical need for successful limb salvage. While autologous vein remains the gold standard, vein-limited patients and size mismatch are common issues. The Human Acellular Vessel (HAV) (Humacyte, Inc., Durham, NC) is a bioengineered conduit with off-the-shelf availability and resistance to infection, ideal characteristics for patients with challenging revascularization scenarios. This report describes HAV implantation in patients with complex limb-threatening ischemia and limited conduit options who may have otherwise faced limb loss.The Food and Drug Administration (FDA) expanded-access program was used to allow urgent implantation of the HAV for arterial reconstruction. Electronic medical records were reviewed with extraction of relevant data including patient demographics, surgical implantation, patency, infectious complications, and mortality.The HAV was implanted in 8 patients requiring vascular reconstruction. Graft or soft tissue infection was present in 2 patients. One patient with severe penetrating pelvic injury had 4 HAV placed to repair bilateral external iliac artery and vein injuries. There was 1 technical failure due to poor outflow, 2 patients died unrelated to HAV use, and 5 lower extremity bypasses maintained patency at an average of 11.4 months (range: 4-20 months). No HAV infectious complications were identified.This report is the first United States series describing early outcomes using the HAV under the FDA expanded-access program for urgent vascular reconstruction. The HAV demonstrates resistance to infection, reliable patency, and offers surgeons an immediate option when confronted with complex revascularization scenarios. Assessment of long-term outcomes will be important for future studies.

Insertion of cerebrospinal fluid (CSF) shunts in patients with idiopathic intracranial hypertension (IIH) is challenging mainly due to the small ventricles and phenotypical body habitus. In this report the authors present their surgical protocol for insertion of a ventriculoperitoneal shunt (VPS) in patients with IIH and the associated revision rates.The protocol comprises the following: shunt surgery by neurosurgeons with expertise in CSF disorders; a frontal VPS usually right sided but left sided if the left ventricle is bigger; use of the proGAV 2.0 valve with gravitational unit, set at 10 and the M.scio telemetric sensor; cannulation of the ventricle with StealthStation EM navigation system; and laparoscopic insertion of the peritoneal catheter. The authors describe the protocol and rationale and evidence behind each component and present the results of a prospective analysis on revision rates.The protocol has been implemented since 1 July, 2019, and by 28 February, 2022, sixty-two patients with IIH had undergone primary VPS insertion. The 30-day revision rate was 6.5%, and overall 11.3% of patients underwent revision during the study period, which compares favorably with the literature. The etiology for early failures was related to the surgical technique.The components of the Birmingham standardized IIH shunt protocol are evidence based and address the technical challenges of CSF diversion in patients with IIH. This protocol is associated with a low revision rate, and the authors recommend standardization for CSF shunting in IIH.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of daily life, including dietary intake; however, few studies have reported its impacts on dietary behaviors and food security across multiple countries.We examined self-reported impacts of COVID-19 on food behaviors, food security, and overall diet healthfulness in 5 countries.Adults aged 18-100 years (n = 20,554) in Australia, Canada, Mexico, the United Kingdom, and the United States completed an online survey in November and December 2020 as part of the International Food Policy Study, an annual, repeat cross-sectional survey. Survey measures assessed perceived impacts of the COVID-19 pandemic on eating food prepared away from home, having food delivered from a restaurant, and buying groceries online, as well as perceived food security and overall diet healthfulness. Regression models examined associations between each outcome and sociodemographic correlates.Across all countries, 62% of respondents reported eating less food prepared away from home due to the pandemic, while 11% reported eating more. Some participants reported having less food delivered from a restaurant (35%) and buying fewer groceries online (17%), while other respondents reported more of each (19% and 25%, respectively). An average of 39% reported impacts on their food security, and 27% reported healthful changes to their overall diet. The largest changes for all outcomes were observed in Mexico. Participants who were younger, ethnic minorities, or had lower income adequacy tended to be more likely to report food-related changes in either direction; however, these relationships were often less pronounced among respondents in Mexico.Respondents reported important changes in how they sourced their food during the pandemic, with trends suggesting shifts towards less food prepared away from home and more healthful diets overall. However, changes in diet and food behaviors occurred in both healthful and less healthful directions, suggesting that dietary responses to the pandemic were highly variable.

BACKGROUND: Food marketing increases product appeal, purchasing, and consumption, using diverse strategies and locations to reach consumers. OBJECTIVES: The aim of this study was to examine differences in adults’ self-reported exposure to various marketing strategies (brand and licensed characters, celebrities, and sponsorship of sports and cultural events) and locations (television, radio, and digital media) across 5 countries: Australia, Canada, Mexico, the United Kingdom, and the United States. METHODS: We analyzed cross-sectional survey data on self-reported exposure to food marketing strategies and locations collected in 2018 by the International Food Policy Study. Participants (n = 21,678) aged ≥18 years completed an online survey. Exposures to unhealthy food marketing strategies and locations in the prior 30 days were self-reported. Regression models examined differences in marketing exposure and locations across countries. RESULTS: The average number of unhealthy food marketing strategies to which participants reported being exposed ranged from 0.5 in the United Kingdom to 2.3 in Mexico. Self-reported exposure to strategies across all countries was highest for brand characters (32%), followed by licensed characters (22%). In total, the reported mean exposure of marketing locations was 1.6 in the prior month. Television was the most prevalent location (44%), followed by digital marketing (32%). Adjusted models indicated that the odds of reporting exposure to marketing strategies and marketing locations were higher for Mexico compared to the rest of the countries. CONCLUSIONS: Adults report a variety of exposures to unhealthy food marketing in all countries, but exposure was highest in Mexico. Special attention should be paid to regulating marketing strategies, such as brand characters and licensed characters, and locations, such as television and digital marketing.

To evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility.Hospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated.Shortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million.Early initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.

Family history of alcohol use disorder (AUD) is frequently endorsed by persons with chronic pain. Although individuals with a family history of AUD have demonstrated enhanced sensitivity to painful stimulation, previous research has not examined endogenous pain modulation in this population. The goal of this study was to test family history of AUD as a predictor of conditioned pain modulation, offset analgesia, and temporal summation among a sample of moderate and heavy drinkers. Adults with no current pain (N = 235; 58.3% male; M(age) = 34.3; 91.9% non-Hispanic; 60% white) were evaluated for family history of AUD at baseline and pain modulatory outcomes were assessed via quantitative sensory testing. Participants with a family history of AUD (relative to those without) evinced a pro-nociceptive pain modulation profile in response to experimental pain. Specifically, family history of AUD was associated with deficits in pain-inhibitory processes. Approximately 4% of the variance in endogenous pain modulation was accounted for by family history, and exploratory analyses suggested these effects may be driven by paternal AUD.

This review discusses the literature on Video-Based Coaching (VBC) and explores the barriers to widespread implementation.A search was performed on Scopus and PubMed for the terms "operation," "operating room," "surgery," "resident," "house staff," "graduate medical education," "teaching," "coaching," "assessment," "reflection," "camera," and "video" on July 27, 2021, in English. This yielded 828 results. A single author reviewed the titles and abstracts and eliminated any results that did not pertain to operative VBC or assessment. All bibliographies were reviewed, and appropriate manuscripts were included in this study. This resulted in a total of 52 manuscripts included in this review.Original, peer-reviewed studies focused on VBC or assessment.VBC has been both subjectively and objectively found to be a valuable educational tool. Nearly every study of video recording in the operating room found that subjects, including surgical residents and seasoned surgeons alike, overwhelmingly considered it a useful, non-redundant adjunct to their training. Most studies that evaluated skill acquisition via standardized assessment tools found that surgical residents who underwent a VBC program had significant improvements compared to their counterparts who did not undergo video review. Despite this evidence of effectiveness, fewer than 5% of residency programs employ video recording in the operating room. Barriers to implementation include significant time commitments for proposed coaching curricula and difficulty with integration of video cameras into the operating room.VBC has significant educational benefits, but a scalable curriculum has not been developed. An optimal solution would ensure technical ease and expediency, simple, high-quality cameras, immediate review, and overcoming entrenched surgical norms and culture.

Donabedian's framework offers a model to evaluate the relationship between patient outcomes, influenced by clinical care delivery structures and processes. Applying this model proposes that adequate and appropriate structures and processes within organizations are necessary to realize optimal outcomes; it is imperative that leadership focuses on those structures and processes to reduce the risk of burnout. Current research cannot determine whether burnout causes decreased quality or working in a setting with decreased quality causes burnout. The follow-up question is whether curtailing burnout will improve quality or whether improving quality of care will reduce provider burnout?

The levels of burnout nurses experience continue to increase with resultant negative impacts on the nursing work environment, patient outcomes, and the retention of qualified nurses. Nurse leaders are essential in developing and fostering positive work environments that retain an empowered and motivated workforce. Research indicates that positive and relational leadership styles can improve nurses' job satisfaction, organizational commitment, and retention while concurrently reducing emotional exhaustion and burnout.

Nurses experience high levels of burnout, and this has become a major factor in recruitment and retention of nurses. Several factors have been associated with burnout, but it is not clear which factors are the most significant predictors. Understanding the most prevalent factors that are associated with burnout will allow for the development and implementation of interventions to ameliorate and/or reduce burnout in the nursing workforce.

Health system response to COVID-19 required drastic care delivery changes, but also a substantially altered environment in which to observe implementation of more standard quality improvement efforts. Implementation assessment during disrupted operational norms (“business not as usual”) distills challenges solved by prioritization from those requiring solutions that address more fundamental barriers to change. This commentary retrospectively analyzes health system implementation of a clinical practice guideline intended to support COVID-19 treatment. We use the QUERI roadmap to reflect upon implementation strategy within the context of a nascent LHS framework. In doing so, we identify aspects of implementation that were facilitated by the COVID-19-altered environment, enduring implementation challenges with respect to fidelity and sustainability, and key areas of necessary continued investment to strengthen a responsive system for learning and improvement. Moving forward, COVID-19 response highlighted key investments that bridge learning health system structures to implementation practices. This includes structures that (1) accelerate ideas that emerge from the front lines, (2) promote “living” care guidelines that are supported by continuous review of emergent evidence, and (3) enhance analytic capacity that supports organizational learning. COVID-19 response has offered opportunities for “new norm” thinking around what’s possible to build out a learning health system. Strategic application of implementation frameworks to learning health system infrastructure has highlighted necessary investments that build and sustain a more responsive, improvement-oriented organization.

Objective To examine the disposition outcomes and disposition intentions of elective egg freezers (EEFs) toward their surplus frozen oocytes and the psychosocial determinants underlying these. Design A systematic review and meta-analysis. Setting Not applicable. Patient(s) Actual EEFs (women with oocytes in storage), potential EEFs (women investigating elective oocyte cryopreservation or about to freeze their oocytes), and women of reproductive age (women in the community aged ≥18 years). Intervention(s) A systematic review was undertaken and electronically searched MEDLINE, Embase, and PsycINFO on the Ovid platform for conference abstracts and peer-reviewed articles, published in English after January 1, 2010. A search strategy combined synonyms for oocyte, cryopreservation, donation, disposition, elective, and attitude. Eligible studies assessed disposition outcomes (how an oocyte was disposed of) and disposition intentions (how women intend to dispose of an oocyte) and/or the psychosocial determinants underlying disposition outcomes and intentions. The Joanna Briggs Institute Prevalence Tool was used to assess the risk of bias. A meta-analysis using random effects was applied to pool proportions of women with similar disposition intentions toward their oocytes. Main Outcome Measure(s) Disposition outcomes and intentions toward surplus frozen oocytes: donate to research; donate to others; discard; unsure. Psychosocial determinants (beliefs, attitudes, barriers, and facilitators) of disposition outcomes and intentions. Result(s) A total of 3,560 records were identified, of which 22 (17 studies) met the inclusion criteria (8 studies from Europe, 7 from North America, and 2 from Asia). No studies reported on past oocyte disposition outcomes. Seventeen studies reported on the future disposition intentions of 5,446 women. Only 2 of the 17 studies reported on the psychosocial determinants of oocyte disposition intentions. There was substantial heterogeneity in the pooled results, which was likely a result of the significant variation in methodology. Actual EEFs were included in eight studies (n = 873), of whom 53% (95% confidence interval [CI], 44–63; I2, 87%) would donate surplus oocytes to research, 31% (95% CI, 23–40; I2, 72%) were unsure, 26% (95% CI, 17–38; I2, 92%) would donate to others, and 12% (95% CI, 6–21; I2, 88%) would discard their eggs. Psychosocial determinants: One study reported that 50% of these women were aware of friends and/or family having difficulty conceiving, which may have contributed to their willingness to donate to others. Potential EEFs were included in 4 studies (n = 645), of whom 38% (95% CI, 28–50; I2, 84%) would donate to research, 32% (95% CI, 17–51; I2, 91%) would donate to others, 29% (95% CI, 17–44; I2, 89%) would discard, and 7% (95% CI, 1–27; I2, 77%) were unsure. Psychosocial determinants: No studies. Women of reproductive age were included in 5 studies (n = 3,933), of whom 59% (95% CI, 48–70; I2, 97%) would donate to research and 46% (95% CI, 35–57; I2, 98%) would donate to others. “Unsure” and “discard” were not provided as response options. Psychosocial determinants: One study reported that the facilitators for donation to others included a family member or friend in need, to help others create a family, financial gain, to further science, and control or input over the selection of recipients. Barriers for donation included fear of having a biological child they do not know or who is raised by someone they know. Conclusion(s) No studies reported on the disposition outcomes of past EEFs. Disposition intentions varied across the three groups; however, “donating to research” was the most common disposition preference. Notably, the second disposition preference for one-third of actual EEFs was “unsure” and for one-third of potential EEFs was “donate to others.” There were limited studies for actual and potential EEFs, and only two studies that explored the psychosocial determinants of oocyte disposition intentions. Additionally, these data suggest that disposition decisions change as women progress on their egg freezing journey, highlighting the importance of ongoing contact with the fertility team as intentions may change over time. More research is needed to understand the psychosocial determinants of oocyte disposition decisions so fertility clinics can provide EEFs with the support and information they need to make informed decisions about their stored eggs and reduce the level of uncertainty reported among EEFs and the potential risk of psychological distress and regret. Clinical Trial Registration Number PROSPERO 2020: CRD42020202733

Introduction Virtual patients (VPs) are a safe and standardised method of simulating clinical environments but few studies have explored health care professional's experiences of learning via a VP. This study explored how users experienced and used a VP that aimed to teach the user to deliver non-vitamin K oral anticoagulant patient education. Methods The study used semi-structured interviews with pharmacists and pre-registration trainees from a wider research study. Interview topics were based on key areas concerning VP use. Interviews were audio-recorded and transcribed verbatim before being analysed using the framework approach to thematic analysis. Ethical approval was granted by Keele University. Results There was variation in the type and nature of use of the VP and in the reported learning, which included reinforcement of knowledge, an opportunity to promote reflection, and acquisition and application of knowledge to clinical, patient-facing interactions. The VP was seen as an adjunct to other education and training. The majority of users indicated that they used the VP more than once. Some users seemed to have gamified their learning with a drive to achieve perfect feedback rather than true engagement with the learning, whereas for others the learning appeared to be deep with a reflective focus. Conclusions The VP offered an educational use as experiential learning, although the users experienced the VP differently; commonly the VP facilitated learning via reinforcement of pre-existing knowledge. The users reported that the VP had value as an adjunct to other education and training resources.

Background The COVID-19 pandemic exposed racism as a public health crisis embedded in structural processes. Editors of surgical research journals pledged their commitment to improve structure and process through increasing diversity in the peer review and editorial process; however, little benchmarking data are available. Methods A survey of editorial board members from high impact surgical research journals captured self-identified demographics. Analysis of manuscript submissions from 2016 to 2020 compared acceptance for diversity, equity, and inclusion (DEI)-focused manuscripts to overall rates. Results 25.6% of respondents were female, 2.9% Black, and 3.3% Hispanic. There was variation in the diversity among journals and in the proportion of DEI submissions they attract, but no clear correlation between DEI acceptance rates and board diversity. Conclusions Diversity among board members reflects underrepresentation of minorities seen among surgeons nationally. Recruitment and retention of younger individuals, representing more diverse backgrounds, may be a strategy for change. DEI publication rates may benefit from calls for increasing DEI scholarship more so than changes to the peer review process.

Worldwide, smartphone use is a major contributing factor to road crash among young drivers. While young drivers may be aware of their heightened crash risk and the legal penalties associated with this behaviour, young drivers continue to engage with their smartphones. The development of novel interventions targeting this behaviour is therefore crucial. The current 2 × 2 between groups experimental study (N = 153, 107F, 43 M, 1 other) investigated the concept of cognitive dissonance in relation to smartphone use among young drivers aged 17–25 years (Mage = 20.66 SD = 2.26). Specifically, it applied the induced hypocrisy paradigm to this context. The induced hypocrisy paradigm elicits cognitive dissonance by asking participants to both advocate for the desired behaviour and identify their engagement in the undesired behaviour. Participants are then motivated to change their behaviour to reduce the feelings of dissonance. The current study investigated the efficacy of both the traditional in-person methodology with a new online methodology. Analyses (e.g., ANCOVA) found that the online conditions were more effective than the in-person groups at eliciting dissonance and that the intervention conditions were more effective in reducing both intention and change in behaviour (from pre- to post-intervention) than the control groups. The intervention groups were also more likely to take/request a flyer about driver distraction. While more research is needed to corroborate these findings, these initial results suggest that cognitive dissonance occurs when young drivers use their smartphones and that the induced hypocrisy paradigm may be an effective intervention. In particular, this study’s findings suggest that an online version of the induced hypocrisy paradigm has merit and may form part of future cost-effective, mass interventions.

Background Readmission after percutaneous coronary intervention is common in the early postdischarge period, often linked to limited opportunity for education and preparation for self-care. Attending a nurse-led clinic within 30 d after discharge has the potential to enhance health outcomes. Objective The aim of the study was to synthesise the available literature on the effectiveness of nurse-led clinics, during early discharge (up to 30 d), for patients who have undergone percutaneous coronary intervention. Review method used A systematic review of randomised and quasi-randomised controlled trials was undertaken. Data sources The databases included PubMed, OVID, CINAHL, EMBASE, the Cochrane Library, SCOPUS, and ProQuest. Review methods Databases were searched up to November 2018. Two independent reviewers assessed studies using the Cochrane risk-of-bias tool. Results Of 2970 articles screened, only four studies, representing 244 participants, met the review inclusion criteria. Three of these studies had low to moderate risk of bias, with the other study unclear. Interventions comprised physical assessments and individualised education. Reported outcomes included quality of life, medication adherence, cardiac rehabilitation attendance, and psychological symptoms. Statistical pooling was not feasible owing to heterogeneity across interventions, outcome measures, and study reporting. Small improvements in quality of life and some self-management behaviours were reported, but these changes were not sustained over time. Conclusions This review has identified an important gap in the research examining the effectiveness of early postdischarge nurse-led support after percutaneous coronary intervention on outcomes for patients and health services. More robust research with sufficiently powered sample sizes and clearly defined interventions, comparison groups, and outcomes is recommended to determine effectiveness of nurse-led clinics in the early discharge period.

Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.

We investigate the deterrence effect of experience with regulatory enforcement on fraud in a unique natural setting. Using ride-level data on New York City taxicab drivers, we identify drivers who fraudulently overcharge customers and pair them with the outcomes of drivers’ experience with regulatory enforcement (taxi court). We examine whether drivers’ experience with the taxi court, specifically whether the taxi court found them guilty or not guilty of fraud, affects their subsequent fraud. Interestingly, we find that the effect of experience with the regulatory enforcement on the likelihood of future fraud depends on the verdict received. Consistent with an impact bias in drivers’ affective forecasting, drivers who are found guilty (not guilty) are more (less) likely to commit fraud than similar drivers without recent taxi court experience. Our results have implications for academics and policymakers by showing that sometimes the threat of enforcement can be more effective at deterring future fraud than the actual enforcement itself.

Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.

OBJECTIVE To characterize the normal progression of quantitative CT parameters in normal children from birth to adulthood. MATERIALS AND METHODS Patients aged 0-18 years with non-contrast-enhanced chest CT and evidence of normal lung parenchyma were included. Patients with respiratory symptoms, incomplete anthropometric measurements, or sub-optimal imaging technique were excluded. Segmentation was performed using an open-source software with an automated threshold segmentation. The following parameters were obtained: mean lung density, kurtosis, skewness, lung volume, and mass. Linear and exponential regression models were calculated with age and height as independent variables. A p-value of

To evaluate the mean aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) observed during open cardiac massage (OCM) versus those obtained with selective aortic arch perfusion (SAAP) in post-mortem hypovolemic swine.Post-mortum, male swine, utilized in prior studies of hemorrhage, were included in the study. Animals were bled ∼25-50% of circulating volume prior to death. Animals either underwent clamshell thoracotomy and OCM immediately after death was confirmed (n = 6) or underwent SAAP within 5-15 min of death (n = 6). Aortic root and right atrial pressures were recorded continuously during each method of resuscitation using solid state blood pressure catheters. Representative five beat samples were extracted; short, similarly timed segments of SAAP were also extracted. Mean AoP-RAP gradient and CPPs were calculated and compared.Mean AoP-RAP gradient and CPP were significantly higher in SAAP animals compared to OCM animals (mean ± SD; 29.1 ± 8.4 vs. 24.5 ± 5.0, p 0.001; 28.9 ± 8.5 vs. 9.9 ± 6.0, p 0.001). Mean CPP was not significantly different from mean AoP-RAP gradient in SAAP animals (p = 0.92); mean CPP was significantly lower than mean AoP-RAP gradient in OCM animals (p 0.001). While 97% of SAAP segments had a CPP 15 mmHg, only 17% of OCM segments had a CPP 15 mmHg (p 0.001).SAAP appears to create a more favorable and efficient hemodynamic profile for obtaining ROSC when compared to OCM in this preclinical porcine study.

Solar Energetic Particles (SEP) events are interesting from a scientific perspective as they are the product of a broad set of physical processes from the corona out through the extent of the heliosphere, and provide insight into processes of particle acceleration and transport that are widely applicable in astrophysics. From the operations perspective, SEP events pose a radiation hazard for aviation, electronics in space, and human space exploration, in particular for missions outside of the Earth’s protective magnetosphere including to the Moon and Mars. Thus, it is critical to imific understanding of SEP events and use this understanding to develop and improve SEP forecasting capabilities to support operations. Many SEP models exist or are in development using a wide variety of approaches and with differing goals. These include computationally intensive physics-based models, fast and light empirical models, machine learning-based models, and mixed-model approaches. The aim of this paper is to summarize all of the SEP models currently developed in the scientific community, including a description of model approach, inputs and outputs, free parameters, and any published validations or comparisons with data.

OBJECTIVES: We aimed to identify when and how integration should take place within evaluations of complex population health interventions (PHIs). STUDY DESIGN: Descriptive analytical approach. METHODS: We draw on conceptual insights that emerged through (1) a working group on integration and (2) a diverse range of literature on case studies, small-n evaluations and mixed methods evaluation studies. RESULTS: We initially sought techniques to integrate analyses at the end of a complex PHI evaluation. However, this conceptualization of integration proved limiting. Instead, we found value in conceptualizing integration as a process that commences at the beginning of an evaluation and continues throughout. Many methods can be used for this type of integration, including process tracing, realist evaluation, congruence analysis, general elimination methodology/modus operandi, pattern matching and contribution analysis. Clearly signposting when integrative methods should commence within an evaluation should be of value to the PHI evaluation community, as well as to funders and related stakeholders. CONCLUSIONS: Rather than being a tool used at the end of an evaluation, we propose that integration is more usefully conceived as a process that commences at the start of an evaluation and continues throughout. To emphasize the importance of this timing, integration can be described as comprising 'Work Package Zero' within evaluations of complex PHIs.

Summary There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.

In 2017 the ACGME enacted new regulations requiring sponsoring institutions to ensure "safe transportation options for residents who may be too fatigued to safely return home." We investigate here the impact of a pilot "Safe Ride" program designed to mitigate the risks of fatigued driving.During a 2-month pilot period at a single university-affiliated general surgery residency with four urban clinical sites, all residents (n = 72) were encouraged to hire a rideshare (e.g., Uber, Lyft) to and from 24-h clinical shifts if they felt too fatigued to drive safely. The cost of the rideshare was fully reimbursed to the resident. The impact of this intervention was evaluated using utilization data and a post-intervention resident survey.A total of 16.6% of trainees utilized a rideshare at least one time. Sixty-three post-call rides were taken, predominantly by junior residents (92.4%) and for commutes greater than 15 miles (91%). The cost for the 60-day pilot was $3030. Comparing pre-intervention to post-intervention data, there was a significant improvement in the reported frequency of falling asleep or nearly asleep while driving (P 0.001). Trainees nearly unanimously (98%) supported efforts to make the program permanent.Driving while fatigued is common among surgical residents, with increased risk among junior residents, during longer commutes and following longer shifts. A reimbursed rideshare program effectively targets these risk factors and was associated with a significant decrease in rates of self-reported fatigued driving. Future efforts should focus on strategies to promote use of reimbursed rideshare programs while remaining cost efficient.

Objective The use of temporary intravascular shunts (TIVSs) allow for restoration of distal perfusion and reduce ischemic time in the setting of arterial injury. As a damage control method, adjunct shunts restore perfusion during treatment of life-threatening injuries, or when patients require evacuation to a higher level of care. Single-center reports and case series have demonstrate that TIVS use can extend the opportunity for limb salvage. However, few multi-institutional studies on the topic have been reported. The objective of the present study was to characterize TIVS use through a multi-institutional registry and define its effects on early limb salvage. Methods Data from the Prospective Observation Vascular Injury Treatment registry was analyzed. Civilian patients aged ≥18 years who had sustained an extremity vascular injury from September 2012 to November 2018 were included. Patients who had a TIVS used in the management of vascular injury were included in the TIVS group and those who had received treatment without a TIVS served as the control group. An unadjusted comparison of the groups was conducted to evaluate the differences in the baseline and outcome characteristics. Double robust estimation combining logistic regression with propensity score matching was used to evaluate the effect of TIVS usage on the primary end point of limb salvage. Results TIVS use was identified in 78 patients from 24 trauma centers. The control group included 613 patients. Unmatched analysis demonstrated that the TIVS group was more severely injured (mean ± standard deviation injury severity score, 18.83 ± 11.76 for TIVS vs 14.93 ± 10.46 for control; P = .002) and had more severely mangled extremities (mean ± standard deviation abbreviated injury scale, extremity, score 3.23 ± 0.80 for TIVS vs 2.95 ± 0.87 for control; P = .008). Logistic regression demonstrated that propensity-matched control patients had a three times greater likelihood of amputation compared with the TIVS patients (odds ratio, 3.6; 95% confidence interval, 1.2-11.1; P = .026). Concomitant nerve injury and orthopedic fracture were associated with a greater risk of amputation. The median follow-up for the TIVS group was 12 days (interquartile range, 4-25 days) compared with 9 days (interquartile range, 4-18 days) for the control group. Conclusions To the best of our knowledge, the present study is the first multicenter, matched-cohort study to characterize early limb salvage as a function of TIVS use in the setting of extremity vascular injury. Shunts expedite limb perfusion and resulted in lower rates of amputation during the early phase of care. The use of TIVS should be one part of a more aggressive approach to restore perfusion in the most injured patients and ischemic limbs.

Esophageal adenocarcinoma (EAC) is a lethal malignancy with poor prognosis. Pharmacologic inhibitors of inflammation, such as statins, have been shown to decrease the risk of development and progression of esophageal cancer, but the mechanism of this protection is unclear. The objective of this study was to elucidate the effect of statins on toll-like receptor 4-mediated-proliferation of human EAC cells and identify the mechanism responsible for these observed effects.Human EAC cells (OE33 and FLO1) were treated with simvastatin or atorvastatin for increasing doses and time periods. Toll-like receptor 4 (TLR4) expression was assessed. Cells were pretreated with statin followed by lipopolysaccharide (LPS). Cell proliferation and expression of signaling proteins were evaluated. FLO1 cells were injected into the flank of nude mice. Mice received intraperitoneal injections of simvastatin, atorvastatin, or control solution and tumor volume was measured.OE33 and FLO1 cells demonstrated decreased TLR4 expression after treatment with simvastatin or atorvastatin for 8 h (P 0.05). LPS increased proliferation, whereas pretreatment with statin abolished this response (P 0.05). Statins decreased expression and activation of LPS-induced signaling proteins, including MyD88, TRAF6, Akt, and NF-κB (P 0.05). Mice receiving daily statin injections demonstrated smaller tumors than control mice (P 0.001 at day 33).Treatment of EAC cells with simvastatin or atorvastatin decreases TLR4-mediated proliferation and in vivo tumor growth. Decreased TLR4 expression and subsequent reduction in MyD88-dependent signaling could be a mechanism by which statins act to reduce tumor growth rates.

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin −10−/− mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10−/− mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation. A preeclampsia-like phenotype was confirmed by blood pressure measurements; assessment of albuminuria; measurement of angiogenic factors; demonstration of foot process effacement and endotheliosis in kidney sections; and by accumulation of glycogen in placentas from IL-10−/− mice injected with sPE sera (IL-10−/−sPE). Vasomotor function of isolated aortas was assessed. The IL-10−/−sPE murine model demonstrated significantly augmented aortic contractions to phenylephrine and both impaired endothelium-dependent and, to a lesser extent, endothelium-independent relaxation compared to wild type normotensive mice. Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors. In contrast, indomethacin normalized relaxation of aortas derived from IL-10−/−sPE mice. Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10−/−sPE murine model of preeclampsia, and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.

Purpose To evaluate the feasibility of a new optical device that measures peripheral blood flow as a diagnostic and monitoring tool for patients with peripheral artery disease (PAD). Materials and Methods In this prospective study, 167 limbs of 90 patients (mean age, 76 y; 53% men) with suspected PAD were evaluated with the FlowMet device, which uses a new type of dynamic light-scattering technology to assess blood flow in real time. Measurements of magnitude and phasicity of blood flow were combined into a single-value flow–waveform score and compared vs ankle–brachial index (ABI), toe–brachial index (TBI), and clinical presentation of patients per Rutherford category (RC). Receiver operating characteristic curves were constructed to predict RC. Area under the curve (AUC), sensitivity, and specificity were compared among flow–waveform score, ABI, and TBI. Results Qualitatively, the FlowMet waveforms were analogous to Doppler velocity measurements, and degradation of waveform phasicity and amplitude were observed with increasing PAD severity. Quantitatively, the flow, waveform, and composite flow–waveform scores decreased significantly with decreasing TBI. In predicting RC ≥ 4, the flow–waveform score (AUC = 0.83) showed a linear decrease with worsening patient symptoms and power comparable to that of TBI (AUC = 0.82) and better than that of ABI (AUC = 0.71). Optimal sensitivity and specificity pairs were found to be 56%/83%, 72%/81%, and 89%/74% for ABI, TBI, and flow–waveform score, respectively. Conclusions The technology tested in this pilot study showed a high predictive value for diagnosis of critical limb ischemia. The device showed promise as a diagnostic tool capable of providing clinical feedback in real time.