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Krista M Schroeder,1 Steve Gelwicks,1 April N Naegeli,1 Pamela C Heaton2 1Global Patient Outcomes – Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 2James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USACorrespondence: Krista M SchroederEli Lilly and Company, Indianapolis, IN 46285, USATel +1 317 276 3039Email schroeder_krista_marie@lilly.comBackground: Establishing disease-related cost and/or healthcare resource utilization (HCRU) is an important aspect of health outcomes research, particularly when considering the cost offset of novel treatments. However, few studies have compared methodologies used to assess disease-related cost/HCRU.Methods: Data from the United States IBM® MarketScan® Research Databases were used to compare four different methods of calculating disease-related cost and HCRU in patients with rheumatoid arthritis (RA). The analysis was repeated, in part, for patients with ulcerative colitis (UC) to explore the generalizability of findings to a second autoimmune disease. Four methods of disease-related cost/HCRU attribution were selected following a literature search for potential methods: Method 1, claim-wide cost/HCRU attribution based on claim-listed diagnosis codes and a predetermined disease-related medication list (pharmacy claims only); Method 2, line-item cost/HCRU attribution based on procedures/medications more likely to occur in disease cases than in matched controls at two likelihood ratio cutoffs (1.5× and 3.5×); Method 3, disease-related cost/HCRU calculated as the difference in total average cost/HCRU between cases and matched controls; Method 4, line-item cost/HCRU attribution based on clinician manual determination of procedures/medications related to the disease.Results and conclusion: Overall, 24,373 patients with RA and 9665 with UC were included. Average total cost during 2015 was $US28,750 per patient with RA and $US20,480 per patient with UC. Disease-related cost and HCRU for RA calculated using Method 4 were most closely approximated by Methods 1 and 2 (3.5×), with Method 2 (3.5×) the closest approximation. However, in certain research scenarios, the simplest method compared in this analysis, Method 1, may provide an adequate approximation of disease-related cost and HCRU. Although Method 4 was not executed in the UC analysis because of its labor-intensive nature, similar patterns of disease-related cost and HCRU were observed for Methods 1–3 in patients with UC and RA.Keywords: health outcomes research, methods, disease-related cost, administrative claims databases, autoimmune diseases

Corey Amlong, Moltu Guy, Kristopher M Schroeder, Melanie J Donnelly Department of Anesthesiology, University of Wisconsin Hospital and Clinics, Madison, WI, USA Purpose: Paravertebral blocks (PVBs) are a method of limiting postoperative pain for patients undergoing video-assisted thoracoscopic surgery (VATS). We began providing ultrasound-guided PVBs for patients undergoing VATS in the spring of 2011, using an out-of-plane approach. The aim of this study was to evaluate this practice change. Methods: Following institutional review board approval, we reviewed the charts of 114 patients undergoing VATS by one surgeon at our institution between January 2011 and July 2012. Of the 78 eligible patients, 49 patients received a PVB prior to surgery. We evaluated opioids administered in the perioperative period, pain scores, and side effects from pain medications. Results: Patients who received a preoperative PVB required fewer narcotics intraoperatively and during their hospital stay (P=0.001 and 0.011, respectively). Pain scores on initial assessment and in recovery were lower in patients who received a PVB (P=0.005), as were dynamic and resting pain scores at 24 hours after surgery (P=0.003 and P

Purpose: Femoral nerve catheter (FNC) insertion is commonly performed for postoperative analgesia following total knee arthroplasty (TKA). A wide range of rates has been reported relating to the bacterial colonization of catheters complicating FNC insertion. The BIOPATCH® is a chlorhexidine (CHG) impregnated patch designed to inhibit bacterial growth for days. The BIOPATCH has proven to be effective at decreasing bacterial colonization in epidural and vascular catheters. We hypothesized that the BIOPATCH would be effective at decreasing the rates of FNC bacterial colonization.Methods: Following Institutional Review Board approval and written informed consent, 100 patients scheduled for TKA were prospectively enrolled in the study. Patients at elevated risk for infection were excluded from analysis. Femoral nerve catheters were inserted and tunneled under sterile conditions using ultrasound guidance following CHG skin cleansing. Participants were then randomized either to have the BIOPATCH applied to the catheter exit site or not to have the patch applied. All patients received pre/postoperative antibiotic therapy. The FNC tip and catheter exit site were cultured for bacterial growth at the conclusion of therapy.Results: No differences were observed between groups in regards to catheter exit site. Catheter colonization was observed in three of 48 (6.3%) BIOPATCH patients and two of 47 (4.3%) non-BIOPATCH patients (risk ratio [RR] = 1.5; 95% confidence interval [CI] 0.3 to 8.4; P = 1.0). Colonization of the catheter exit site was observed in 12 BIOPATCH and 14 non-BIOPATCH patients (RR = 0.8; 95% CI 0.4 to 1.6; P = 0.65). Local skin inflammation (non-BIOPATCH 10.6% vs BIOPATCH 2.1%) and colonization of the FNC exit site by more than one type of bacteria trended towards increased values in the non-BIOPATCH group.Conclusions: The baseline rate of bacterial colonization of FNCs is quite low in the setting of short-term use, CHG skin decontamination, ultrasound guidance, subcutaneous tunneling, and perioperative antibiotic therapy. No benefit was shown by using the BIOPATCH in this patient population. (ClinicalTrials.gov number: NCT01411891). [ABSTRACT FROM AUTHOR]

We performed a prospective, open-label, randomised controlled trial comparing the air-Q(®) against the LMA-ProSeal™ in adults undergoing general anaesthesia. One hundred subjects (American Society of Anesthesiologists physical status 1-3) presenting for elective, outpatient surgery were randomly assigned to 52 air-Q(®) and 48 ProSeal devices. The primary study endpoint was airway seal pressure. Oropharyngolaryngeal morbidity was assessed secondarily. Mean (SD) airway seal pressures for the air-Q(®) and ProSeal were 30 (7) cmH (2) O and 30 (6) cmH(2) O, respectively (p = 0.47). Postoperative sore throat was more common with the air-Q(®) (46% vs 38%, p = 0.03) as was pain on swallowing (30% vs 5%, p = 0.01). In conclusion, the air-Q(®) performs well as a primary airway during the maintenance of general anaesthesia with an airway seal pressure similar to that of the ProSeal, but with a higher incidence of postoperative oropharyngolaryngeal complaints. [ABSTRACT FROM AUTHOR]

Gender nonconforming (GNC) boys often elicit negative reactions from peers and adults. However, it is unclear which aspects of nonconformity evoke negative social consequences. Are appearance characteristics, activity interests, or traits most impactful for peers' evaluations? Sixty-seven 6- to 11-year-old children and their parents interacted with a magnetic paper doll of a GNC boy who was displayed with feminine appearance characteristics, activity interests, and traits. Participants were allowed to physically remove feminine attributes and/or add masculine and neutral attributes to help the GNC boy make friends with boys. Participants were (1) more likely to change appearance and activities and less likely to change traits and (2) more likely to remove feminine attributes than add masculine and neutral attributes. Interactions between attribute type and gender differed across parents and children. Results suggest that interventions to reduce discrimination towards GNC boys should focus on reducing prejudice towards appearance- and activity-based nonconformity., (© 2024 British Psychological Society.)

Background: Medicare claims data enables broad characterization of United States (US) patients with Alzheimer's disease and related dementias (ADRD). Resulting insights can be used as a reference to describe this population and as a benchmark for generalizability of patients with ADRD enrolled in clinical trials., Objective: To characterize demographics, comorbidities, comedications, and healthcare resource utilization in US patients with newly diagnosed ADRD, focusing on differences across Medicare fee-for-service (FFS) and Medicare Advantage enrollees., Methods: This observational cohort study used complete (100%) Medicare claims data inclusive of both FFS and Medicare Advantage insurance types. Study patients were ≥65-years-old with ≥12 months of continuous pre-index enrollment and Medicare Part D coverage. Two cohorts of patients were selected in calendar year 2019; those newly diagnosed with ADRD and those with a new acetylcholinesterase inhibitor (AChEI) claim., Results: The newly diagnosed ADRD and new AChEI users cohorts included 861,727 and 395,319 patients, respectively. Demographics and comedications were generally similar across the two cohorts, supporting internal validity of the study results. Circulatory system-related comorbidities and mood disorders were common in both cohorts. Differences in race, inpatient claims and long-term care claims were observed between insurance types., Conclusions: The study results provide a reference for describing the ADRD population in the US and emphasize the importance of evaluating new Alzheimer's disease drugs in broad patient populations with comorbidities and concomitant medication use.

Early-life experiences with signals used in communication are instrumental in shaping an animal's social interactions. In songbirds, which use vocalizations for guiding social interactions and mate choice, recent studies show that sensory effects on development occur earlier than previously expected, even in embryos and nestlings. Here, we explored the neural dynamics underlying experience-dependent song categorization in young birds prior to the traditionally studied sensitive period of vocal learning that begins around 3 weeks post-hatch. We raised zebra finches either with their biological parents, cross-fostered by Bengalese finches beginning at embryonic day 9, or with only the non-singing mother from 2 days post-hatch. Then, 1-5 days after fledging, we conducted behavioral experiments and extracellular recordings in the auditory forebrain to test responses to zebra finch and Bengalese finch songs. Auditory forebrain neurons in cross-fostered and isolated birds showed increases in firing rate and decreases in responsiveness and selectivity. In cross-fostered birds, decreases in responsiveness and selectivity relative to white noise were specific to conspecific song stimuli, which paralleled behavioral attentiveness to conspecific songs in those same birds. This study shows that auditory and social experience can already impact song 'type' processing in the brains of nestlings, and that brain changes at this age can portend the effects of natal experience in adults., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The theory of ecological speciation posits that adaptive divergence among incipient species raises incidental barriers to reproduction, thus catalyzing the emergence of new species. In this study, we conducted an experimental test of this theory in Galápagos finches, a clade in which beaks and mating songs are mechanistically linked. We forecasted the acoustic structure of songs for a set of possible evolutionary futures (successive droughts spurring increasingly large beaks) and, in a field assay, presented resulting song simulations to territorial males. We found that responses to songs dropped off after six simulated drought events, to degrees roughly comparable to drops in response to songs that diverged through cultural drift and acoustic adaptation. Our results support, in Darwin's finches, the feasibility and mechanistic bases of an ecological speciation hypothesis.

Competing Interests: Conflicts of Interest, Funding: See DISCLOSURES at the end of this article.

Introduction: Artificial intelligence and large language models (LLMs) have emerged as potentially disruptive technologies in healthcare. In this study GPT-3.5, an accessible LLM, was assessed for its accuracy and reliability in performing guideline-based evaluation of neuraxial bleeding risk in hypothetical patients on anticoagulation medication. The study also explored the impact of structured prompt guidance on the LLM's performance., Methods: A dataset of 10 hypothetical patient stems and 26 anticoagulation profiles (260 unique combinations) was developed based on American Society of Regional Anesthesia and Pain Medicine guidelines. Five prompts were created for the LLM, ranging from minimal guidance to explicit instructions. The model's responses were compared with a "truth table" based on the guidelines. Performance metrics, including accuracy and area under the receiver operating curve (AUC), were used., Results: Baseline performance of GPT-3.5 was slightly above chance. With detailed prompts and explicit guidelines, performance improved significantly (AUC 0.70, 95% CI (0.64 to 0.77)). Performance varied among medication classes., Discussion: LLMs show potential for assisting in clinical decision making but rely on accurate and relevant prompts. Integration of LLMs should consider safety and privacy concerns. Further research is needed to optimize LLM performance and address complex scenarios. The tested LLM demonstrates potential in assessing neuraxial bleeding risk but relies on precise prompts. LLM integration should be approached cautiously, considering limitations. Future research should focus on optimization and understanding LLM capabilities and limitations in healthcare., Competing Interests: Competing interests: RKG is responsible for the creation and maintenance of the ASRA-PM Coags app, is a Member of the ASRA-PM Board of Directors and is an Associate Editor for Regional Anesthesia and Pain Medicine., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Artificial intelligence (AI) has demonstrated a disruptive ability to enhance and transform clinical medicine. While the dexterous nature of anesthesiology work offers some protections from AI clinical assimilation, this technology will ultimately impact the practice and augment the ability to provide an enhanced level of safe and data-driven care. Whether predicting difficulties with airway management, providing perioperative or critical care risk assessments, clinical-decision enhancement, or image interpretation, the indications for AI technologies will continue to grow and are limited only by our collective imagination on how best to deploy this technology.An essential mission of academia is education, and challenges are frequently encountered when working to develop and implement comprehensive and effectively targeted curriculum appropriate for the diverse set of learners assigned to teaching faculty. Curriculum development in this context frequently requires substantial efforts to identify baseline knowledge, learning needs, content requirement, and education strategies. Large language models offer the promise of targeted and nimble curriculum and content development that can be individualized to a variety of learners at various stages of training. This technology has not yet been widely evaluated in the context of education deployment, but it is imperative that consideration be given to the role of AI in curriculum development and how best to deploy and monitor this technology to ensure optimal implementation., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Large language models (LLMs) excel at answering knowledge-based questions. Many aspects of blood banking and transfusion medicine involve no direct patient care and require only knowledge and judgment. We hypothesized that public LLMs could perform such tasks with accuracy and precision., Study Design and Methods: We presented three sets of tasks to three publicly-available LLMs (Bard, GPT-3.5, and GPT-4). The first was to review short case presentations and then decide if a red blood cell transfusion was indicated. The second task was to answer a set of consultation questions common in clinical transfusion practice. The third task was to take a multiple-choice test experimentally validated to assess internal medicine postgraduate knowledge of transfusion practice (the BEST-TEST)., Results: In the first task, the area under the receiver operating characteristic curve for correct transfusion decisions was 0.65, 0.90, and 0.92, respectively for Bard, GPT-3.5 and GPT-4. All three models had a modest rate of acceptable responses to the consultation questions. Average scores on the BEST-TEST were 55%, 40%, and 87%, respectively., Conclusion: When presented with transfusion medicine tasks in natural language, publicly available LLMs demonstrated a range of ability, but GPT-4 consistently scored very well in all tasks. Research is needed to assess the utility of LLMs in transfusion medicine practice. Transfusion Medicine physicians should consider their role alongside such technologies, and how they might be used for the benefit and safety of patients., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: The pediatric patient-reported outcomes version of the common terminology criteria for adverse event measure was developed and validated for use in pediatric cancer clinical trials to better capture the symptom experiences through direct self-report. The study aim was to develop and validate a Swahili language version of the patient-reported outcomes version of the common terminology criteria for adverse event measure., Methods: The pediatric version of 15 core symptom adverse events, and the corresponding questions, were selected from the patient-reported outcomes version of the common terminology criteria for adverse event library, then forward and back translated into Swahili by bilingual translators. The translated items were further refined using concurrent cognitive interviewing. Each round of interviews included five children, ages 8-17 years-old, receiving cancer therapy at Bugando Medical Centre, the cancer referral hospital for Northwest Tanzania, and continued until at least 80% of participants understood the question., Results: Three rounds of cognitive interviews were completed involving 13 patients and 5 caregivers. Among patients, 50% of questions (19/38) were fully comprehended after the first interview round. Two Adverse Events (anxiety and peripheral neuropathy) were the most difficult for participants to understand, associated with education level and experience. Goal comprehension was achieved after three rounds of interviews with no further revisions required. All parents in the first cognitive interview group comprehended the survey, with no additional revisions., Conclusion: A Swahili patient-reported outcomes version of the common terminology criteria for adverse event was effective in eliciting patient-reported Adverse Events related to cancer treatment, with good comprehension for children aged 8-17 years. This survey is important to incorporate patient self-reporting of symptomatic toxicities and is an effective tool to increase capacity for pediatric cancer clinical trials throughout East Africa, further reducing global disparities in cancer care., (© 2023. The Author(s).)

Publication bias and the decreased publication of trials with negative or non-significant results is a well-recognized problem in human and veterinary medical publications. These biases may present an incomplete picture of evidence-based clinical care and negatively impact medical practices. The purpose of this study was to utilize a novel sentiment analysis tool as a quantitative measure for assessing clinical trial reporting trends in human and veterinary medical literature. Abstracts from 177,617 clinical trials in human medical journals and 8684 in veterinary medical journals published in the PubMed database from 1995 to 2020. Abstracts were analyzed using the GAN-BioBERT sentiment classifier for both general trends and percentage of neutral/negative publications. Sentiment was defined on a - 1 (highly negative) to 1 (highly positive) scale. Human-based clinical trial publications were less likely to feature positive findings (OR 0.87, P < 0.001) and more likely to include neutral findings (OR 1.18, P < 0.001) relative to veterinary clinical trials. No difference was found in reporting of negative sentiment trials (OR 1.007, P = 0.83). In both groups, the published sentiment of clinical trials increased over time. Using sentiment analysis to evaluate large publication datasets and compare publication trends within and between groups, this study is significant in its detection of significant publication differences between human and veterinary medicine clinical trials and a continued unbalanced positive sentiment in the published literature. The implications of this unbiased reporting have important clinical and research implications that require consideration., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is a disease of lymphoid progenitor cells with an often aggressive course and is commonly caused by the BCR-ABL fusion gene t(9;22) in adults. This fusion gene encodes a constitutively active tyrosine kinase that can be effectively inhibited by tyrosine kinase inhibitors (TKIs), with imatinib being the paradigmatic agent of this class. However, BCR-ABL+ ALL cells rapidly develop mutations against many of the available TKIs, and consecutive disease relapse still results in an overall unfavorable prognosis for patients with this disease. To date, allogeneic stem cell transplantation is the only known curative therapeutic option for the mostly elderly patients with BCR-ABL+ ALL. The discrepancy between the limited therapeutic armamentarium and the growing therapeutic need in an aging population is therefore a reason to test drug combinations against BCR-ABL+ ALL. In this study, we demonstrate that the combination of TKIs with proteasome inhibitors efficiently and under certain conditions synergistically exerts cytotoxic effects in BCR-ABL+ ALL cells in vitro with respect to the induction of apoptosis. Both sole and combined treatment of BCR-ABL+ ALL with the proteasome inhibitors bortezomib and ixazomib, respectively, and TKI causes a significantly greater reduction in cell viability than TKI treatment alone in both BCR-ABL+ cell lines TOM-1 and BV-173. In BV-173 cells, we observed a significant reduction in cell viability to only 1.26%±0.46% with bortezomib treatment and 1.57±0.7% with combination treatment, whereas cells treated with dasatinib alone still had a viable percentage of 40.58±2.6%. Similar results were obtained when ixazomib was applied to both cell lines, and apoptosis was induced in both cases (93.36%±2.7% apoptotic BV-173 cells when treated with ixazomib and TKI). The combination of TKI and proteasome inhibitor is efficient in vitro, potentially expanding the spectrum of therapeutic options for patients with BCR-ABL+ ALL., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: IA received funding from Novartis® and Takeda Pharmaceuticals®. This as well as the adapted competing interests statement does not alter authors’ adherence to PLOS ONE policies on sharing data and materials.

Changes in the biosphere carbon (C) sink are of utmost importance given rising atmospheric CO 2 levels. Concurrent global changes, such as increasing nitrogen (N) deposition, are affecting how much C can be stored in terrestrial ecosystems. Understanding the extent of these impacts will help in predicting the fate of the biosphere C sink. However, most N addition experiments add N in rates that greatly exceed ambient rates of N deposition, making inference from current knowledge difficult. Here, we leveraged data from a 13-year N addition gradient experiment with addition rates spanning realistic rates of N deposition (0, 1, 5, and 10 g N m -2  year -1 ) to assess the rates of N addition at which C uptake and storage were stimulated in a temperate grassland. Very low rates of N addition stimulated gross primary productivity and plant biomass, but also stimulated ecosystem respiration such that there was no net change in C uptake or storage. Furthermore, we found consistent, nonlinear relationships between N addition rate and plant responses such that intermediate rates of N addition induced the greatest ecosystem responses. Soil pH and microbial biomass and respiration all declined with increasing N addition indicating that negative consequences of N addition have direct effects on belowground processes, which could then affect whole ecosystem C uptake and storage. Our work demonstrates that experiments that add large amounts of N may be underestimating the effect of low to intermediate rates of N deposition on grassland C cycling. Furthermore, we show that plant biomass does not reliably indicate rates of C uptake or soil C storage, and that measuring rates of C loss (i.e., ecosystem and soil respiration) in conjunction with rates of C uptake and C pools are crucial for accurately understanding grassland C storage., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Background: The therapeutic armamentarium in multiple myeloma has been significantly broadened by proteasome inhibitors, highly efficient means in controlling of multiple myeloma. Despite the developments of therapeutic regimen in treatment of multiple myeloma, still the complete remission requires a novel therapeutic strategy with significant difference in outcomes. Proteasome inhibitors induce autophagy and ER stress, both pivotal pathways for protein homeostasis. Recent studies showed that the IRE1α-XBP1 axis of the unfolded protein response (UPR) is up-regulated in multiple myeloma patients. In addition, XBP1 is crucial for the maintenance of viability of acute lymphoblastic leukemia (ALL)., Results: We analyzed the efficacy of targeting IRE1α-XBP1 axis and autophagy in combination with proteasome inhibitor, ixazomib in treatment of multiple myeloma. In this present study, we first show that targeting the IRE1α-XBP1 axis with small molecule inhibitors (STF-083010, A106) together with the ixazomib induces cell cycle arrest with an additive cytotoxic effect in multiple myeloma. Further, we examined the efficacy of autophagy inhibitors (bafilomycin A, BAF and chloroquine, CQ) together with ixazomib in multiple myeloma and observed that this combination treatment synergistically reduced cell viability in multiple myeloma cell lines (viable cells Ixa: 51.8 ± 3.3, Ixa + BAF: 18.3 ± 7.2, Ixa + CQ: 38.4 ± 3.7) and patient-derived multiple myeloma cells (Ixa: 59.6 ± 4.4, Ixa + CQ: 7.0 ± 2.1). We observed, however, that this combined strategy leads to activation of stress-induced c-Jun N-terminal kinase (JNK). Cytotoxicity mediated by combined proteasome and autophagy inhibition was reversed by addition of the specific JNK inhibitor JNK-In-8 (viable cells: Ixa + BAF: 11.6 ± 7.0, Ixa + BAF + JNK-In-8: 30.9 ± 6.1)., Conclusion: In this study we showed that combined inhibition of autophagy and the proteasome synergistically induces cell death in multiple myeloma. Hence, we consider the implication of pharmaceutical inhibition of autophagy together with proteasome inhibition and UPR-directed therapy as promising novel in vitro treatment strategy against multiple myeloma., (© 2022. The Author(s).)

In this 14-day study, we tested whether Latinx adolescents' (M age  = 12.76 years, 52% female; 52% U.S. born; N = 21) and parents' (95% female; 24% U.S. born) daily discrimination experiences were associated with their own and other's daily affective states. Results indicated that on days when adolescents reported discrimination, they reported higher negative affect and marginally lower positive affect and, interestingly, parents reported higher positive affect. On average (i.e., across the 2-week period), adolescents' discrimination was associated with higher adolescent negative affect and lower parent positive affect. Together, findings suggest that Latinx adolescents' discrimination experiences are linked to their own affective states and their parents'. Results underscore how discrimination is linked to the affective states present in family contexts., (© 2022 The Authors. Journal of Research on Adolescence published by Wiley Periodicals LLC on behalf of Society for Research on Adolescence.)

Background: The aim of this study was to validate a three-class sentiment classification model for clinical trial abstracts combining adversarial learning and the BioBERT language processing model as a tool to assess trends in biomedical literature in a clearly reproducible manner. We then assessed the model's performance for this application and compared it to previous models used for this task., Methods: Using 108 expert-annotated clinical trial abstracts and 2,000 unlabeled abstracts this study develops a three-class sentiment classification algorithm for clinical trial abstracts. The model uses a semi-supervised model based on the Bidirectional Encoder Representation from Transformers (BERT) model, a much more advanced and accurate method compared to previously used models based upon traditional machine learning methods. The prediction performance was compared to those previous studies., Results: The algorithm was found to have a classification accuracy of 91.3%, with a macro F1-Score of 0.92, significantly outperforming previous studies used to classify sentiment in clinical trial literature, while also making the sentiment classification finer grained with greater reproducibility., Conclusion: We demonstrate an easily applied sentiment classification model for clinical trial abstracts that significantly outperforms previous models with greater reproducibility and applicability to large-scale study of reporting trends., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Myszewski, Klossowski, Meyer, Bevil, Klesius and Schroeder.)

Background and Objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia., Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement., Results: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29., Conclusion: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: Adenocarcinoma (AC) is the number one pathological entity of lung cancer with approximately 30-40% of cases. It is known to be heterogeneous and has 5 histopathological growth patterns. We evaluated the long-term survival rates of patients with predominant subtypes., Methods: 290 patients with AC underwent pulmonary resection between 2012 and 2017 at our institution. We excluded all patients with lymph node involvement and distant metastases. Hence, 163 patients were included for further analysis. Predominant growth pattern was defined if more than 10% of cells showed a growth pattern. 1, 3, and 5-year survival rates were evaluated. Survival was assessed by Kaplan-Meier curves and the Cox proportional hazards model was used to identify prognostic factors for overall survival., Results: Predominant growth patterns >10% were compared to <10% growth patterns of the same subtype. 1-year, 3-year, and 5-year overall survival rates of patients with predominant solid tumor growth >10% differed significantly from patients with <10% (88.4% vs. 97.6%, p = 0.04; 65.8% vs. 87.4% p = 0.001, 36.4% vs. 65.9% p = 0.01). Survival rates did not differ between >10% papillary and acinar growth compared to <10%. Kaplan-Meier curves showed reduced overall survival for patients with solid tumor growth >10% (log-rank 0.002). Solid tumor growth >10% was an independent prognostic factor for worse long-term survival (Hazard ratio: 3.05, p = 0.01)., Conclusion: Our study demonstrates that the presence of a predominant solid pattern in pulmonary adenocarcinoma is a factor for an unfavorable prognosis. This should be kept in mind in daily clinical practice., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Sentiment analysis, by evaluating written wording and its context, is a growing tool used in computer science that can determine the level of support expressed in a body of text using artificial intelligence methodologies. The application of sentiment analysis to biomedical literature is a growing field and offers the potential to rapidly and economically explore large amounts of published research and characterize treatment efficacy., Methods: We compared the results of sentiment analysis of 115 article abstracts analyzed in a recently published meta-analysis of peripheral nerve block usage in primary hip and knee arthroplasty to the conclusions drawn by the authors of the original meta-analysis., Results: A moderately positive outlook supporting the utilization of regional anesthesia for hip and knee arthroplasty was found in the 115 articles that were included for analysis, with 46% expressing positive sentiment, 35% expressing neutral sentiment, and 19% of abstracts expressing negative sentiment. This was well aligned with the conclusions reached by a previous meta-analysis of the same articles., Discussion: Sentiment analysis applied to the medical literature can rapidly evaluate large collections of published data and generate an impression of overall findings that are aligned with the findings of a traditional meta-analysis., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The US Health and Human Services Pain Management Best Practices Inter-Agency Task Force initiated a public-private partnership which led to the publication of its report in 2019. The report emphasized the need for individualized, multimodal, and multidisciplinary approaches to pain management that decrease the over-reliance on opioids, increase access to care, and promote widespread education on pain and substance use disorders. The Task Force specifically called on specialty organizations to work together to develop evidence-based guidelines. In response to this report's recommendations, a consortium of 14 professional healthcare societies committed to a 2-year project to advance pain management for the surgical patient and improve opioid safety. The modified Delphi process included two rounds of electronic voting and culminated in a live virtual event in February 2021, during which seven common guiding principles were established for acute perioperative pain management. These principles should help to inform local action and future development of clinical practice recommendations., Competing Interests: Competing interests: JMS declares salary support from Blue Cross Blue Shield of Michigan; research funding from Neuros Medical (Willoughby, OH, USA), Setpoint Medical (Valencia, CA, USA), and Medtronic (Dublin, Ireland; legal consulting for Yates, McLamb and Weyher, LLP (Raleigh, NC, USA). KKKH is a consultant for True Digital Surgery (Goleta, CA, USA). GS is an advisory board member for Dorsal Health (New York, NY, USA) and consultant for Pacira Biosciences (Parsippany-Troy Hills, NJ, USA). SS is a consultant for Masimo (Irvine, CA, USA), Allergan (Dublin, Ireland), and SPR Therapeutics (Cleveland, OH, USA). These companies had absolutely no input into any aspect of the project design, Pain Summit, or manuscript preparation. None of the other authors has any financial interests to declare., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The analysis of dinosaur ecology hinges on the appropriate reconstruction and analysis of dinosaur biodiversity. Benson et al . question the data used in our analysis and our subsequent interpretation of the results. We address these concerns and show that their reanalysis is flawed. Indeed, when occurrences are filtered to include only valid taxa, their revised dataset strengthens our earlier conclusions.

Background: Limited English proficiency (LEP) is associated with adverse clinical outcomes. The clinical impact of LEP in hematopoietic stem cell transplant (HSCT) has not been studied. The objectives of this study were to compare HSCT outcomes and health care utilization of Hispanic pediatric patients with and without parental LEP., Methods: We conducted a retrospective review of Hispanic/Latino pediatric patients receiving HSCT at a single institution. Families were identified as LEP or English proficient (EP) based on clinicians' notes, social work documentation, or the signature of a Spanish interpreter on treatment consents., Results: A total of 83 Hispanic/Latino patients were identified with 53 (65.1%) having parental LEP. More patients in the LEP group had a documented financial burden at pretransplant psychosocial evaluation (72.2% vs. 41.4%, p = .009). LEP patients were more likely to have health insurance coverage through government-sponsored Medicaid (76.9% vs. 27.6%, p < .001). LEP patients were hospitalized on average 13 days longer than EP patients, and LEP patients were more likely to have pretransplant cytomegalovirus (CMV) reactivity (67.3%) than EP patients (p = .001). Overall survival was lower in LEP than EP, but was not statistically significant (p = .193). Multivariable Cox modeling suggested a potentially higher risk of death in LEP versus EP (hazard ratio = 1.56, 95% CI: 0.38, 6.23)., Conclusions: Parental LEP in HSCT is associated with prolonged hospitalization and pretransplant CMV reactivity. These factors are associated with posttransplant complications and death. Our results suggest parental LEP is a risk factor for poor HSCT outcomes. Further study is warranted in a larger cohort., (© 2021 Wiley Periodicals LLC.)

Objective: The purpose of this study was to investigate the efficacy of hyperangulated video laryngoscopy (HAVL) versus standard geometry video laryngoscopy (SGVL) in the simulated prehospital environment using a manikin. There is consensus that video laryngoscopy (VL) can be very useful in the emergency department when difficult intubations are predicted. Emergency medical service (EMS) providers are also often faced with difficult, rapidly deteriorating airway management situations that not only involve patient and operator factors but also include challenging unique environmental factors, such as nonoptimized positions in transport vehicles (eg, helicopters and ambulances) or at ground level or entrapped positions. To our knowledge, there has never been a study purposefully investigating the efficacy of hyperangulated geometry versus standard geometry VL techniques in the prehospital environment., Methods: A single-center, randomized controlled crossover trial was performed using attending physician helicopter EMS providers. Physicians were randomized to perform 5 HAVL or SGVL intubations followed by the subsequent technique. Intubations were performed on ground level and then repeated in the helicopter with the first location also randomized. A manikin airway management trainer was used to simulate intubation in each environment. The time to intubation (primary outcome) as well as first-pass success and the Cormack-Lehane view were recorded for each attempt. Qualitative data were also obtained for physician preference and perceived difficulty., Results: There was no statistically significant difference in the time to intubation with HAVL versus SGVL (ground: 15.02 vs. 14.88 seconds, P = .86; helicopter: 16.11 vs. 16.14 seconds, P = .93). First-pass success was 100% for both techniques in both scenarios. More Grade 1 views were obtained with HAVL (147/150 vs. 134/150). Moreover, most physicians preferred HAVL overall and felt that HAVL required less force (9/15 grounded manikin and 10/15 helicopter manikin) and led to the best chance for first-pass success (11/15 grounded manikin and 10/15 helicopter manikin)., Conclusion: The results of this study are limited because of the static and highly favorable anatomy of a manikin versus the variability and often difficult anatomy of individual patients. Our results suggest that both techniques are efficacious when the patient is both on the ground or in the helicopter, although provider preference does seem to vary., (Published by Elsevier Inc.)

Background: This retrospective study harnessed an institutional cancer registry to construct a childhood cancer survivorship cohort, integrate electronic health record (EHR) and geospatial data to stratify survivors based on late-effect risk, analyze follow-up care patterns, and determine factors associated with suboptimal follow-up care., Procedure: The survivorship cohort included patients ≤18 years of age reported to the institutional cancer registry between January 1, 1994 and November 30, 2012. International Classification of Diseases for Oncology, third revision (ICD-O-3) coding and treatment exposures facilitated risk stratification of survivors. The EHR was linked to the cancer registry based on medical record number (MRN) to extract clinic visits., Results: Five hundred and ninety pediatric hematology-oncology (PHO) and 275 pediatric neuro-oncology (PNO) survivors were included in the final analytic cohort. Two hundred and eight-two survivors (32.6%) were not seen in any oncology-related subspecialty clinic at Duke 5-7 years after initial diagnosis. Factors associated with follow-up included age (p = .008), diagnosis (p < .001), race/ethnicity (p = .010), late-effect risk strata (p = .001), distance to treatment center (p < .0001), and area deprivation index (ADI) (p = .011). Multivariable logistic modeling attenuated the association for high-risk (OR 1.72; 95% CI 0.805, 3.66) and intermediate-risk (OR 1.23, 95% CI 0.644, 2.36) survivors compared to survivors at low risk of late effects among the PHO cohort. PNO survivors at high risk for late effects were more likely to follow up (adjusted OR 3.66; 95% CI 1.76, 7.61)., Conclusions: Nearly a third of survivors received suboptimal follow-up care. This study provides a reproducible model to integrate cancer registry and EHR data to construct risk-stratified survivorship cohorts to assess follow-up care., (© 2021 Wiley Periodicals LLC.)

Encoding of conspecific signals during development can reinforce species barriers as well as set the stage for learning and production of species-typical vocalizations. In altricial songbirds, the development of the auditory system is not complete at hatching, so it is unknown the degree to which recently hatched young can process auditory signals like birdsong. We measured in vivo extracellular responses to song stimuli in a zebra finch (Taeniopygia guttata) secondary auditory forebrain region, the caudomedial nidopallium (NCM). We recorded from three age groups between 13 days post-hatch and adult to identify possible shifts in stimulus encoding that occur before the opening of the sensitive period of song motor learning. We did not find differences in putative cell type composition, firing rate, response strength, and selectivity across ages. Across ages narrow-spiking units had higher firing rates, response strength, accuracy, and trial-by-trial reliability along with lower selectivity than broad-spiking units. In addition, we showed that stimulus-specific adaptation, a characteristic of adult NCM, was also present in nestlings and fledglings. These results indicate that most features of secondary auditory processing are already adult-like shortly after hatching. Furthermore, we showed that selectivity for species-specific stimuli is similar across all ages, with the greatest fidelity in temporal coding in response to conspecific song and domesticated Bengalese finch song, and reduced fidelity in response to owl finch song, a more ecologically relevant heterospecific, and white noise. Our study provides the first evidence that the electrophysiological properties of higher-order auditory neurons are already mature in nestling songbirds., (© 2021 Wiley Periodicals, LLC.)

Purpose: We sought to identify the immediate postoperative differences in opioid use, pain scores, and post-anesthesia care unit (PACU) length of stay (LOS) after hip arthroscopy related to the type of anesthesia used for the surgical procedure., Methods: Patients undergoing hip arthroscopy for femoroacetabular impingement syndrome with labral tears by a single surgeon at an academic center between October 2017 and July 2019 were reviewed retrospectively. The primary outcome was PACU opioid administration, measured by morphine equivalents. Secondary parameters included total LOS, postincision LOS, PACU LOS, and PACU arrival/discharge pain scores. Analyses conducted were t tests, Wilcoxon rank sum tests, or χ 2 tests., Results: A total of 129 patients met inclusion criteria for this study; 54 male and 75 female, with an average age of 28 (±10.1) years. In total, 52 (40.3%) had general anesthesia and 77 (59.7%) had neuraxial anesthesia, including spinal, epidural, and combined spinal-epidural anesthesia, which were intermixed throughout the study period. Intraoperative and PACU opioid administration demonstrated a significant difference in medians. Neuraxial methods required a lower morphine equivalents in both the operating room (30.0 vs 53.9, P = .001) and PACU (18.2 vs 31.2, P = 0.002). Neuraxial anesthesia had lower median PACU arrival and discharge pain scores (0.0 vs. 5.0, P = .001, 3.0 vs. 4.0, P = .013). There was no statistically significant difference in postincision LOS or traction time. General anesthesia was associated with a longer PACU phase 1 time (1.0 vs 1.3 hours, P = .005). No major adverse events such as death, disability, or prolonged hospitalization occurred in either group., Conclusions: Neuraxial anesthesia use in routine hip arthroscopy was associated with lower immediate postoperative pain scores, lower intraoperative and immediate postoperative opioid requirements, and may be associated with shorter anesthesia recovery time without any major adverse events when compared with general anesthesia., Level of Evidence: III, Retrospective Comparative Study., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Scoliosis, hip dysplasia, and other lower extremity deformities are common musculoskeletal pathology found in patients with cerebral palsy. Imaging studies allow for an improved identification of patients with these issues, help to understand the pathology, and aid in planning treatment strategies. Most of these deformities are visualized using plain radiographic techniques. Occasionally, as in the case of preoperative planning, advanced imaging, such as computerized topography and MRI, can be used for additional information. This article provides insight into the various imaging techniques for these musculoskeletal issues and aids in better care for patients with cerebral palsy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To describe the ultrasound-guided rectus sheath block technique and the anatomical spread of two volumes of methylene blue injection in dog cadavers., Study Design: Blinded, prospective, experimental cadaveric study., Animals: A total of eight dog cadavers weighing 8.9 ± 1.6 kg., Methods: Ultrasound-guided rectus sheath injections were performed bilaterally 1 cm cranial to the umbilicus using 0.25 mL kg -1 (low volume; LV) and 0.50 mL kg -1 (high volume; HV) of 0.5% methylene blue dye. A total of 16 hemiabdomens were injected. The ultrasound image quality of the muscular and fascial plane landmarks and needle visualization were scored using a standardized scale. Cadavers were dissected to determine the distribution of the dye and to assess staining of ventral branches of the spinal nerves., Results: Fewer ventral spinal nerve branches were stained in the LV group than in the HV group, at 2.00 ± 0 and 2.90 ± 0.83, respectively (p < 0.01). Ventral branches of thoracic (T) and lumbar (L) spinal nerves (T10, T11, T12, T13 and L1) were stained 25%, 100%, 75%, 25% and 0% of the time in LV group and 12.5%, 87.5%, 100.0%, 75.0% and 13.0% in HV group. A lesser extent of cranial-caudal dye distribution was observed in the LV group than in the HV group (7.1 ± 1.8 cm and 9.2 ± 1.8 cm, respectively; p = 0.03). There was no significant difference in medial-lateral spread of dye, number of test doses or ultrasound image quality scores between groups., Conclusions and Clinical Relevance: The results of this study suggest that, on an anatomical basis, this easily performed block has the potential to provide effective abdominal wall analgesia for the ventral midline. This study supports the potential of the rectus sheath block for abdominal procedures, and further investigations on its clinical efficacy are warranted., (Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The current study examined the trajectory of gender role attitudes of 471 Mexican-origin adolescents (236 girls, 235 boys) from 5th grade (Mage = 10.86 years) to 11th grade (Mage = 16.75 years), investigating how situating identities (i.e., gender, nativity, SES), ethnic identity (i.e., ethnic pride), and familial context (i.e., parents' attitudes) contributed to adolescents' gender role attitudes across time. Participant interviews were conducted every other year, resulting in 4 waves of data. Most parents (96%) were Mexico natives, with an average immigration age of 18.16 years for fathers and 14.01 years for mothers. Results revealed linear and quadratic trends in gender attitude traditionality for all adolescents, characterized by a linear decline through age 16 years that leveled off through age 18 years. Although both girls and boys trended toward egalitarian gender role attitudes across adolescence, girls endorsed more egalitarian attitudes than did boys. Adolescents from higher-SES backgrounds endorsed more egalitarian attitudes than those from lower-SES backgrounds. Significant within-person effects of ethnic pride surfaced, such that children with higher levels of ethnic pride at any given time also reported more traditional gender role attitudes. Significant between-person effects of mothers' and fathers' attitudes were found, such that parents with more traditional gender role attitudes tended to have children with relatively more traditional gender role attitudes. Overall, these findings highlight the importance of studying gender development in conjunction with situating identities, cultural identities, and the broader context, particularly when children are embedded in multiple cultures with contrasting gender role expectations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This article addresses the historical divide between gender development researchers and developmental researchers working with immigrant populations, advocating for the benefits gained by bridging research approaches and interests. For gender researchers, the immigrant context allows for the examination of how children embedded in multiple cultures navigate the potentially conflicting information about appropriate gendered behaviors and attitudes. Furthermore, research focusing on immigrant development can move beyond examining gender differences and benefit from understanding the ways in which gender differences develop. This bridging seems particularly relevant in middle childhood, given (a) the exposure to multiple contexts which increase the salience of cultural differences between home and outside-of-home environments and (b) greater awareness and internalization of collective identities (i.e., gender, ethnicity)., (© 2019 Society for Research in Child Development, Inc.)