Clinical pathway development to standardize pharmacological medication management of agitation in pediatric inpatient settings.

Objective: Acute agitation in pediatrics is commonly encountered in hospital settings, can contribute to significant physical and psychological distress, and management is highly varied in practice. As such, the development of a standardized pharmacologic guideline is paramount. We aimed to develop a novel clinical pathway (CP) for management of acute agitation for all hospitalized pediatric patients in Canada. Methods: Healthcare professionals in Canada with expertise in treating and managing pediatric agitation formed a working group and developed a CP through conducting a literature review, engaging key partners, and obtaining interdisciplinary consensus (iterative real-time discussions with content experts). Once developed, the preliminary CP was presented to additional internal and external partners via multiple grand rounds and a webinar; feedback from participants guided final CP revisions. Results: The working group created a pediatric inpatient CP to guide pharmacologic management of agitation and serve as an easy-to-use clinical and educational resource with three complementary sections including: 1) a treatment algorithm, 2) a quick reference medication chart, and 3) two supporting documents, which provide a general overview of non-pharmacologic strategies prior to CP implementation and an illustrative scenario to accompany the medication chart to ensure effective utilization. Conclusions: This is the first CP to standardize pharmacological treatment and management of acute agitation in children in inpatient settings in Canada. Although further research is warranted to assess implementation and support process improvement, the CP can be adapted by individual institutions to assist in prompt pharmacological management of pediatric agitation to potentially improve outcomes for patients, families, and healthcare professionals.

Objectif: L'agitation aiguë en pédiatrie survient couramment en milieu hospitalier, elle peut contribuer à une détresse physique et psychologique significative, et la prise en charge en est très variée dans la pratique. Ainsi, l'élaboration de lignes directrices pharmacologiques standardisées est essentielle. Nous cherchions à développer un nouveau parcours clinique (PC) de la prise en charge de l'agitation aiguë pour tous les patients pédiatriques hospitalisés au Canada. Méthodes: Les professionnels de la santé au Canada qui ont l'expertise du traitement et de la prise en charge de l'agitation pédiatrique ont formé un groupe de travail et développé un PC en menant une revue littéraire, en embauchant des partenaires cibles, et en obtenant un consensus interdisciplinaire (discussions itératives en temps réel avec des experts en contenu). Une fois développé, le PC préliminaire a été présenté à des partenaires internes et externes additionnels lors de multiples grandes rondes et à un webinaire; les commentaires des participants ont guidé les révisions finales du PC. Résultats: Le groupe de travail a créé un PC pour patient psychiatrique hospitalisé afin de guider la prise en charge pharmacologique de l'agitation et de servir de ressource clinique et éducative facile à utiliser munie de trois sections complémentaires notamment : 1) un algorithme de traitement, 2) un tableau des médicaments de référence, et 3) deux documents de soutien, qui offrent un aperçu général de stratégies non-pharmacologiques avant la mise en œuvre du PC et un scénario illustré pour accompagner le tableau des médicaments afin d'assurer une utilisation efficace. Conclusions: C'est le premier PC qui normalise le traitement pharmacologique et la prise en charge de l'agitation aiguë chez les enfants en milieu hospitalier au Canada. Bien que plus de recherche soit justifiée afin d'évaluer la mise en œuvre et de soutenir l'amélioration du processus, le PC peut être adapté par les institutions individuelles afin d'aider à une gestion pharmacologique rapide de l'agitation pédiatrique et de potentiellement aider à la gestion pharmacologique de l'agitation pédiatrique pour les patients, les familles et les professionnels de la santé.

Postsurgical Pain Risk Stratification to Enhance Pain Management Workflow in Adult Patients: Design, Implementation, and Pilot Evaluation.

BACKGROUND: Exposure to opioids after surgery is the initial contact for some people who develop chronic opioid use disorder. Hence, effective postoperative pain management, with less reliance on opioids, is critical. The Perioperative Opioid Quality Improvement (POQI) program developed (1) a digital health platform leveraging patient-survey-reported risk factors and (2) a postsurgical pain risk stratification algorithm to personalize perioperative care by integrating several commercially available digital health solutions into a combined platform. Development was reduced in scope by the COVID-19 pandemic. OBJECTIVE: This pilot study aims to assess the screening performance of the risk algorithm, quantify the use of the POQI platform, and evaluate clinicians' and patients' perceptions of its utility and benefit. METHODS: A POQI platform prototype was implemented in a quality improvement initiative at a Canadian tertiary care center and evaluated from January to September 2022. After surgical booking, a preliminary risk stratification algorithm was applied to health history questionnaire responses. The estimated risk guided the patient assignment to a care pathway based on low or high risk for persistent pain and opioid use. Demographic, procedural, and medication administration data were extracted retrospectively from the electronic medical record. Postoperative inpatient opioid use of >90 morphine milligram equivalents per day was the outcome used to assess algorithm performance. Data were summarized and compared between the low- and high-risk groups. POQI use was assessed by completed surveys on postoperative days 7, 14, 30, 60, 90, and 120. Semistructured patient and clinician interviews provided qualitative feedback on the platform. RESULTS: Overall, 276 eligible patients were admitted for colorectal procedures. The risk algorithm stratified 203 (73.6%) as the low-risk group and 73 (26.4%) as the high-risk group. Among the 214 (77.5%) patients with available data, high-risk patients were younger than low-risk patients (age: median 53, IQR 40-65 years, vs median 59, IQR 49-69 years, median difference five years, 95% CI 1-9; P=.02) and were more often female patients (45/73, 62% vs 80/203, 39.4%; odds ratio 2.5, 95% CI 1.4-4.5; P=.002). The risk stratification was reasonably specific (true negative rate=144/200, 72%) but not sensitive (true positive rate=10/31, 32%). Only 39.7% (85/214) patients completed any postoperative quality of recovery questionnaires (only 14, 6.5% patients beyond 60 days after surgery), and 22.9% (49/214) completed a postdischarge medication survey. Interviewed participants welcomed the initiative but noted usability issues and poor platform education. CONCLUSIONS: An initial POQI platform prototype was deployed operationally; the risk algorithm had reasonable specificity but poor sensitivity. There was a significant loss to follow-up in postdischarge survey completion. Clinicians and patients appreciated the potential impact of preemptively addressing opioid exposure but expressed shortcomings in the platform's design and implementation. Iterative platform redesign with additional features and reevaluation are required before broader implementation.

Treatment of Francisella philomiragia bacteremia in a dog.

To describe the diagnosis and successful treatment of systemic francisellosis in a dog. An 11-year-old female spayed Labrador retriever presented for progressive lethargy, hyporexia, and cough. The dog was febrile with a neutrophilia, nonregenerative anemia, thrombocytopenia, and had increased activity in serum of liver-derived enzymes. Francisella philomiragia was isolated from aerobic blood culture. The dog was treated for 6 weeks with enrofloxacin orally. Repeated aerobic blood cultures after 2 and 6 weeks of antibiotic therapy were negative. The dog was clinically normal 7 months after diagnosis with no evidence of relapse.

Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.

Oral cinacalcet administration decreases serum ionized calcium and parathyroid hormone concentrations in healthy dogs.

Cinacalcet is an oral calcimimetic that has potential to non-invasively treat primary hyperparathyroidism in dogs (Canis lupis familiaris). There is minimal data assessing its efficacy in dogs. This study aimed to determine whether a single dose of cinacalcet decreases serum ionized calcium (iCa), total calcium (tCa), and parathyroid hormone (PTH) concentrations. Twelve dogs received a median dose of 0.49 mg/kg (range 0.30-0.69 mg/kg) cinacalcet per os. Venous blood samples were collected at time 0 (before cinacalcet administration), 3, 8, and 24 h following cinacalcet administration. PTH, iCa, and tCa concentrations were measured at each time point and compared to 0 hour concentrations. A significant (50%) decrease in serum PTH occurred at 3 h with a median PTH of 4.6 pmol/L (range 2.7-10.8) at baseline and 1.65 pmol/L (range 0.5-14.7) at 3 h; p = .005. A significant, but not clinically relevant, decrease in serum iCa from a median baseline of 1.340 mmol/L (range 1.32-1.41) to a 3 h median of 1.325 mmol/L (range 1.26-1.39), p = .043, was also observed. tCa concentrations were not different. This study showed that a single dose of cinacalcet leads to transient decreases in iCa and PTH concentrations in healthy dogs.

Dispositional mindfulness moderates the links between potentially morally injurious event exposure and symptoms of anxiety and depression but not suicidal ideation.

Exposure to potentially morally injurious events (PMIEs) is a pervasive threat for military service members and may be associated with symptoms of anxiety, depression, and suicidal ideation. However, coping mechanisms, such as mindfulness, may ameliorate symptoms and improve recovery. Two studies were conducted to test dispositional mindfulness as a moderator of the links between PMIEs, as assessed using the Moral Injury Events Scale (i.e., total score and Self-Transgression, Other-Transgression, and Betrayal subscale scores), and symptoms of anxiety, depression, and suicidal ideation among different samples of active-duty soldiers in garrison. In Sample 1 (N = 310), mindfulness buffered the links between PMIE exposure and symptoms of both anxiety, ∆R2 = .02, and depression, ∆R2 = .03. In Sample 2 (N = 669), mindfulness moderated the link between the MIES Betrayal subscale and anxiety symptoms, ∆R2 = .01. The results suggest that dispositional mindfulness may be a protective factor against some of the negative impacts of PMIE exposure. Further implications are discussed.

Serine Supports Epithelial and Immune Cell Function in Colitis.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, and mucosal healing is critical for remission. Serine is a nonessential amino acid that supports epithelial and immune cell metabolism and proliferation; however, whether these roles affect IBD pathogenesis is not well understood. Herein, the study showed that serine synthesis increased selectively in the epithelial cells of colons from patients with IBD and murine models of colitis. Inhibiting serine synthesis impaired colonic mucosal healing and increased susceptibility to acute injury in mice, effects associated with diminished epithelial cell proliferation. Dietary removal of serine similarly sensitized mice to acute chemically induced colitis but ameliorated inflammation in chronic colitis models. The anti-inflammatory effect of exogenous serine depletion in chronic colitis was associated with mitochondrial dysfunction of macrophages, resulting in impaired nucleotide production and proliferation. Collectively, these results suggest that serine plays an important role in both epithelial and immune cell biology in the colon and that modulating its availability could impact IBD pathogenesis.

Ubiquitous acceleration in Greenland Ice Sheet calving from 1985 to 2022.

Nearly every glacier in Greenland has thinned or retreated over the past few decades1-4, leading to glacier acceleration, increased rates of sea-level rise and climate impacts around the globe5-9. To understand how calving-front retreat has affected the ice-mass balance of Greenland, we combine 236,328 manually derived and AI-derived observations of glacier terminus positions collected from 1985 to 2022 and generate a 120-m-resolution mask defining the ice-sheet extent every month for nearly four decades. Here we show that, since 1985, the Greenland Ice Sheet (GrIS) has lost 5,091 ± 72 km2 of area, corresponding to 1,034 ± 120 Gt of ice lost to retreat. Our results indicate that, by neglecting calving-front retreat, current consensus estimates of ice-sheet mass balance4,9 have underestimated recent mass loss from Greenland by as much as 20%. The mass loss we report has had minimal direct impact on global sea level but is sufficient to affect ocean circulation and the distribution of heat energy around the globe10-12. On seasonal timescales, Greenland loses 193 ± 25 km2 (63 ± 6 Gt) of ice to retreat each year from a maximum extent in May to a minimum between September and October. We find that multidecadal retreat is highly correlated with the magnitude of seasonal advance and retreat of each glacier, meaning that terminus-position variability on seasonal timescales can serve as an indicator of glacier sensitivity to longer-term climate change.

Cerebral autoregulation-based mean arterial pressure targets and delirium in critically ill adults without brain injury: a retrospective cohort study.

PURPOSE: Cerebral autoregulation (CA) is a mechanism that acts to maintain consistent cerebral perfusion across a range of blood pressures, and impaired CA is associated with delirium. Individualized CA-derived blood pressure targets are poorly characterized in critically ill patients and the association with intensive care unit (ICU) delirium is unknown. Our objectives were to characterize optimal mean arterial pressure (MAPopt) ranges in critically ill adults without brain injury and determine whether deviations from these targets contribute to ICU delirium. METHODS: We performed a retrospective cohort analysis of patients with shock of any etiology and/or respiratory failure requiring invasive mechanical ventilation, without a neurologic admitting diagnosis. Patients were screened daily for delirium. Cerebral oximetry and mean arterial pressure data were captured for the first 24 hr from enrolment. RESULTS: Forty-two patients with invasive blood pressure monitoring data were analyzed. Optimal mean arterial pressure targets ranged from 55 to 100 mm Hg. Optimal mean arterial pressure values were not significantly different based on history of hypertension or delirium status, and delirium was not associated with deviations from MAPopt. Nevertheless, the majority (69%) of blood pressure targets exceeded the current 65 mm Hg Surviving Sepsis guidelines. CONCLUSION: We observed that MAPopt targets across patients were highly variable, but did not observe an association with the incidence of delirium. Studies designed to evaluate the impact on neurologic outcomes are needed to understand the association with individualized mean arterial pressure targets in the ICU. STUDY REGISTRATION: ClinicalTrials.gov (NCT02344043); first submitted 22 January 2015.

RéSUMé: OBJECTIF: L'autorégulation cérébrale (AC) est un mécanisme qui agit pour maintenir une perfusion cérébrale constante pour une gamme de tensions artérielles, et une altération de l'AC est associée au delirium. Les cibles de tension artérielle individualisées dérivées de l'AC sont mal caractérisées chez les patient·es gravement malades et l'association avec le delirium à l'unité de soins intensifs (USI) est inconnue. Nos objectifs étaient de caractériser la tension artérielle moyenne optimale (TAMopt) chez les adultes gravement malades sans lésion cérébrale et de déterminer si les écarts par rapport à ces cibles contribuaient au delirium à l'USI. MéTHODE: Nous avons réalisé une analyse de cohorte rétrospective de patient·es présentant un choc de toute étiologie et/ou une insuffisance respiratoire nécessitant une ventilation mécanique invasive, et n'ayant pas reçu de diagnostic d'atteinte neurologique à l'admission. Les patients ont été dépistés quotidiennement pour le delirium. Les données d'oxymétrie cérébrale et de tension artérielle moyenne ont été saisies pendant les 24 premières heures suivant le recrutement. RéSULTATS: Quarante-deux patient·es pour qui des données de monitorage invasif de la tension artérielle étaient disponibles ont été analysé·es. Les cibles optimales de tension artérielle moyenne variaient de 55 à 100 mm Hg. Les valeurs optimales de tension artérielle moyenne n'étaient pas significativement différentes en fonction des antécédents d'hypertension ou de delirium, et le delirium n'était pas associé à des écarts par rapport à la TAMopt. Néanmoins, la majorité (69 %) des cibles de tension artérielle dépassaient celle de 65 mm Hg préconisée par les lignes directrices Surviving Sepsis. CONCLUSION: Nous avons observé que les cibles de TAMopt étaient très variables chez les patient·es, mais nous n'avons pas observé d'association avec l'incidence de delirium. Des études conçues pour évaluer l'impact sur les issues neurologiques sont nécessaires pour comprendre l'association avec les cibles de tension artérielle moyenne individualisées à l'USI. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02344043); soumis pour la première fois le 22 janvier 2015.

Pediatric Delirium Educational Tool Development With Intensive Care Unit Clinicians and Caregivers in Canada: Focus Group Study.

Background: Pediatric intensive care unit (PICU)-associated delirium contributes to a decline in postdischarge quality of life, with worse outcomes for individuals with delayed identification. As delirium screening rates remain low within PICUs, caregivers may be able to assist with early detection, for which they need more education, as awareness of pediatric delirium among caregivers remains limited. Objective: This study aimed to develop an educational tool for caregivers to identify potential delirium symptoms during their child's PICU stay, educate them on how to best support their child if they experience delirium, and guide them to relevant family resources. Methods: Web-based focus groups were conducted at a tertiary pediatric hospital with expected end users of the tool (ie, PICU health care professionals and caregivers of children with an expected PICU length of stay of over 48 h) to identify potential educational information for inclusion in a family resource guide and to identify strategies for effective implementation. Data were analyzed thematically to generate requirements to inform prototype development. Participants then provided critical feedback on the initial prototype, which guided the final design. Results: In all, 24 participants (18 health care professionals and 6 caregivers) attended 7 focus groups. Participants identified five informational sections for inclusion: (1) delirium definition, (2) key features of delirium (signs and symptoms), (3) postdischarge outcomes associated with delirium, (4) tips to inform family-centered care, and (5) education or supportive resources. Participants identified seven design requirements: information should (1) be presented in an order that resembles the structure of the clinical discussion around delirium; (2) increase accessibility, recall, and preparedness by providing multiple formats; (3) aim to reduce stress by implementing positive framing; (4) minimize cognitive load to ensure adequate information processing; (5) provide supplemental electronic resources via QR codes; (6) emphasize collaboration between caregivers and the health care team; and (7) use prompting questions to act as a call to action for caregivers. Conclusions: Key design requirements derived from end-user feedback were established and guided the development of a novel pediatric delirium education tool. Implementing this tool into regular practice has the potential to reduce distress and assist in the early recognition and treatment of delirium in the PICU domain. Future evaluation of its clinical utility is necessary.

Modelling sound particle motion in shallow watera).

Fish species and aquatic invertebrates are sensitive to underwater sound particle motion. Studies on the impact of sound on marine life would benefit from sound particle motion models. Benchmark cases and solutions are proposed for the selection and verification of appropriate models. These include a range-independent environment, with and without shear in the sediment, and a range-dependent environment, without sediment shear. Analysis of the acoustic impedance illustrates that sound particle velocity can be directly estimated from the sound pressure field in shallow water scenarios, except at distances within one wavelength of the source, or a few water depths at frequencies where the wavelength exceeds the water depth.

Pilot Lipidomics Study of Copepods: Investigation of Potential Lipid-Based Biomarkers for the Early Detection and Quantification of the Biological Effects of Climate Change on the Oceanic Food Chain.

Maintenance of the health of our oceans is critical for the survival of the oceanic food chain upon which humanity is dependent. Zooplanktonic copepods are among the most numerous multicellular organisms on earth. As the base of the primary consumer food web, they constitute a major biomass in oceans, being an important food source for fish and functioning in the carbon cycle. The potential impact of climate change on copepod populations is an area of intense study. Omics technologies offer the potential to detect early metabolic alterations induced by the stresses of climate change. One such omics approach is lipidomics, which can accurately quantify changes in lipid pools serving structural, signal transduction, and energy roles. We utilized high-resolution mass spectrometry (≤2 ppm mass error) to characterize the lipidome of three different species of copepods in an effort to identify lipid-based biomarkers of copepod health and viability which are more sensitive than observational tools. With the establishment of such a lipid database, we will have an analytical platform useful for prospectively monitoring the lipidome of copepods in a planned long-term five-year ecological study of climate change on this oceanic sentinel species. The copepods examined in this pilot study included a North Atlantic species (Calanus finmarchicus) and two species from the Gulf of Mexico, one a filter feeder (Acartia tonsa) and one a hunter (Labidocerca aestiva). Our findings clearly indicate that the lipidomes of copepod species can vary greatly, supporting the need to obtain a broad snapshot of each unique lipidome in a long-term multigeneration prospective study of climate change. This is critical, since there may well be species-specific responses to the stressors of climate change and co-stressors such as pollution. While lipid nomenclature and biochemistry are extremely complex, it is not essential for all readers interested in climate change to understand all of the various lipid classes presented in this study. The clear message from this research is that we can monitor key copepod lipid families with high accuracy, and therefore potentially monitor lipid families that respond to environmental perturbations evoked by climate change.

An Individualized Postoperative Pain Risk Communication Tool for Use in Pediatric Surgery: Co-Design and Usability Evaluation.

BACKGROUND: Risk identification and communication tools have the potential to improve health care by supporting clinician-patient or family discussion of treatment risks and benefits and helping patients make more informed decisions; however, they have yet to be tailored to pediatric surgery. User-centered design principles can help to ensure the successful development and uptake of health care tools. OBJECTIVE: We aimed to develop and evaluate the usability of an easy-to-use tool to communicate a child's risk of postoperative pain to improve informed and collaborative preoperative decision-making between clinicians and families. METHODS: With research ethics board approval, we conducted web-based co-design sessions with clinicians and family participants (people with lived surgical experience and parents of children who had recently undergone a surgical or medical procedure) at a tertiary pediatric hospital. Qualitative data from these sessions were analyzed thematically using NVivo (Lumivero) to identify design requirements to inform the iterative redesign of an existing prototype. We then evaluated the usability of our final prototype in one-to-one sessions with a new group of participants, in which we measured mental workload with the National Aeronautics and Space Administration (NASA) Task Load Index (TLX) and user satisfaction with the Post-Study System Usability Questionnaire (PSSUQ). RESULTS: A total of 12 participants (8 clinicians and 4 family participants) attended 5 co-design sessions. The 5 requirements were identified: (A) present risk severity descriptively and visually; (B) ensure appearance and navigation are user-friendly; (C) frame risk identification and mitigation strategies in positive terms; (D) categorize and describe risks clearly; and (E) emphasize collaboration and effective communication. A total of 12 new participants (7 clinicians and 5 family participants) completed a usability evaluation. Tasks were completed quickly (range 5-17 s) and accurately (range 11/12, 92% to 12/12, 100%), needing only 2 requests for assistance. The median (IQR) NASA TLX performance score of 78 (66-89) indicated that participants felt able to perform the required tasks, and an overall PSSUQ score of 2.1 (IQR 1.5-2.7) suggested acceptable user satisfaction with the tool. CONCLUSIONS: The key design requirements were identified, and that guided the prototype redesign, which was positively evaluated during usability testing. Implementing a personalized risk communication tool into pediatric surgery can enhance the care process and improve informed and collaborative presurgical preparation and decision-making between clinicians and families of pediatric patients.

Enhanced recovery support for people with eating disorders during the COVID-19 pandemic: quality improvement using a web-based, stepped-care programme in Canada.

BACKGROUND: Throughout the COVID-19 pandemic, the number of individuals struggling with eating disorders (EDs) increased substantially. Body Brave (a not-for-profit) created and implemented a web-based stepped-care Recovery Support Programme (RSP) to improve access to community-based ED services. This quality improvement study describes the RSP and assesses its ability to deliver timely access to treatment and platform engagement. METHODS: We conducted a retrospective cohort study comparing access to, and use of Body Brave services 6 months before and 12 months after implementation of the RSP platform (using 6-month increments for two postimplementation periods). Primary programme quality measures included registration requests, number of participants onboarded and time to access services; secondary measures included use of RSP action plans, attendance for recovery sessions and workshops, number of participants accessing treatment and text-based patient experience data. RESULTS: A substantial increase in registration requests was observed during the first postimplementation period compared with the preimplementation period (176.5 vs 85.5; p=0.028). When compared with the preimplementation period, the second postimplementation observed a significantly larger percentage of successfully onboarded participants (76.6 vs 37.9; p<0.01) and a reduction in the number of days to access services (2 days vs 31 days; p<0.01). Although participant feedback rates were low, many users found the RSP helpful, easy to access, user-friendly and were satisfied overall. Users provided suggestions for improvement (eg, a platform instructional video, offer multiple times of day for live sessions and drop-in hours). CONCLUSIONS: Although clinical benefit needs to be assessed, our findings demonstrate that the RSP enabled participants to quickly onboard and access initial services and have informed subsequent improvements. Understanding initial programme effects and usage will help assess the feasibility of adapting and expanding the RSP across Canada to address the urgent need for low-barrier, patient-centred ED care.

Association of program-specific variation in bariatric surgery volume for Medicaid patients and access to care: a tale of inequality?

BACKGROUND: Although patients with lower socioeconomic status are at higher risk of obesity, bariatric surgery utilization among patients with Medicaid is low and may be due to program-specific variation in access. Our goal was to compare bariatric surgery programs by percentage of Medicaid cases and to determine if variation in distribution of patients with Medicaid could be linked to adverse outcomes. METHODS: Using a state-wide bariatric-specific data registry that included 43 programs performing 97,207 cases between 2006 and 2020, we identified all patients with Medicaid insurance (n = 4780, 4.9%). Bariatric surgery programs were stratified into quartiles according to the percentage of Medicaid cases performed and we compared program-specific characteristics as well as baseline patient characteristics, risk-adjusted complication rates and wait times between top and bottom quartiles. RESULTS: Program-specific distribution of Medicaid cases varied between 0.69 and 22.4%. Programs in the top quartile (n = 11) performed 18,885 cases in total, with a mean of 13% for Medicaid patients, while programs in the bottom quartile (n = 11) performed 32,447 cases in total, with a mean of 1%. Patients undergoing surgery at programs in the top quartile were more likely to be Black (20.2% vs 13.5%, p < 0.0001), have diabetes (35.1% vs 29.5%, p < 0.0001), hypertension (55.1% vs 49.6%, p < 0.0001) and hyperlipidemia (47.6% vs 45.2%, p < 0.0001). Top quartile programs also had higher complication rates (8.4% vs 6.6%, p < 0.0001), extended length of stay (5.6% vs 4.0%, p < 0.0001), Emergency Department visits (8.1% vs 6.5%, p < 0.0001) and readmissions (4.7% vs 3.9%, p < 0.0001). Median time from initial evaluation to surgery date was also significantly longer among top quartile programs (200 vs 122 days, p < 0.0001). CONCLUSIONS: Bariatric surgery programs that perform a higher proportion of Medicaid cases tend to care for patients with greater disease severity who experience delays in care and also require more resource utilization. Improving bariatric surgery utilization among patients with lower socioeconomic status may benefit from insurance standardization and program-centered incentives to improve access and equitable distribution of care.

Characterization of integrated Marek's disease virus genomes supports a model of integration by homology-directed recombination and telomere-loop-driven excision.

IMPORTANCE: Marek's disease virus (MDV) is a ubiquitous chicken pathogen that inflicts a large economic burden on the poultry industry, despite worldwide vaccination programs. MDV is only partially controlled by available vaccines, and the virus retains the ability to replicate and spread between vaccinated birds. Following an initial infection, MDV enters a latent state and integrates into host telomeres and this may be a prerequisite for malignant transformation, which is usually fatal. To understand the mechanism that underlies the dynamic relationship between integrated-latent and reactivated MDV, we have characterized integrated MDV (iMDV) genomes and their associated telomeres. This revealed a single orientation among iMDV genomes and the loss of some terminal sequences that is consistent with integration by homology-directed recombination and excision via a telomere-loop-mediated process.

Limitations of benefit finding as a coping mechanism for combat-related PTSD symptoms.

Benefit finding has been identified as a buffer of the combat exposure-PTSD symptom link in soldiers. However, benefit finding may have a limited buffering capacity on the combat-PTSD symptom link over the course of a soldier's post-deployment recovery period. In the present study, soldiers returning from Operation Iraqi Freedom (OIF) were surveyed at two different time periods post-deployment: Time 1 was 4 months post-deployment (n = 1,510), and Time 2 was at 9 months post-deployment (n = 783). The surveys assessed benefit finding, PTSD symptoms, and combat exposure. Benefit finding was a successful buffer of the cross-sectional relationship between combat exposure and PTSD reexperiencing symptoms at Time 1, but not at Time 2. In addition, the benefit finding by combat interaction at time 1 revealed that greater benefit finding was associated with higher symptoms under high combat exposure at Time 2 after controlling for PTSD arousal symptoms at Time 1. The results of the present study indicate that benefit finding may have a buffering capacity in the immediate months following a combat deployment, but also indicates that more time than is allotted during the post-deployment adjustment period is needed to enable recovery from PTSD. Theoretical implications are discussed.

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results.

Vα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB). The primary objectives were safety and determination of maximum tolerated dose (MTD). The anti-tumor activity of GD2-CAR.15 NKTs was assessed as a secondary objective. Immune response evaluation was an additional objective. No dose-limiting toxicities occurred; one patient experienced grade 2 cytokine release syndrome that was resolved by tocilizumab. The MTD was not reached. The objective response rate was 25% (3/12), including two partial responses and one complete response. The frequency of CD62L+NKTs in products correlated with CAR-NKT expansion in patients and was higher in responders (n = 5; objective response or stable disease with reduction in tumor burden) than non-responders (n = 7). BTG1 (BTG anti-proliferation factor 1) expression was upregulated in peripheral GD2-CAR.15 NKTs and is a key driver of hyporesponsiveness in exhausted NKT and T cells. GD2-CAR.15 NKTs with BTG1 knockdown eliminated metastatic NB in a mouse model. We conclude that GD2-CAR.15 NKTs are safe and can mediate objective responses in patients with NB. Additionally, their anti-tumor activity may be enhanced by targeting BTG1. ClinicalTrials.gov registration: NCT03294954 .