Factors Associated with Medical Students' Attitudes About Cost-Conscious Care: A Mixed-Methods Multi-school Study.

BACKGROUND: Because physician practices contribute to national healthcare expenditures, initiatives aimed at educating physicians about high-value cost-conscious care (HVCCC) are important. Prior studies suggest that the training environment influences physician attitudes and behaviors towards HVCCC. OBJECTIVE: To explore the relationship between medical student experiences and HVCCC attitudes. DESIGN: Quantitative and qualitative analysis of a multi-institutional survey. PARTICIPANTS: Medical students from nine US medical schools. APPROACH: A 44-item survey that included the Maastricht HVCCC Attitudes Questionnaire, a validated tool for assessing HVCCC attitudes, was administered electronically. Attitudinal domains of high-value care (HVC), cost incorporation (CI), and perceived drawbacks (PD) were compared using one-way ANOVA among students with a range of exposures. Open text responses inviting participants to reflect on their attitudes were analyzed using classical content analysis. KEY RESULTS: A total of 740 students completed the survey (response rate 15%). Students pursuing a "continuity-oriented" specialty held more favorable attitudes towards HVCCC than those pursuing "technique-oriented" specialties (HVC sub-score = 3.20 vs. 3.06; p = 0.005, CI sub-score = 2.83 vs. 2.74; p < 0.001). Qualitative analyses revealed personal, educational, and professional experiences shape students' HVCCC attitudes, with similar experiences interpreted differently leading to both more and less favorable attitudes. CONCLUSION: Students pursuing specialties with longitudinal patient contact may be more enthusiastic about practicing high-value care. Life experiences before and during medical school shape these attitudes, and complex interactions between these forces drive student perceptions of HVCCC.

Virtual Molecular and Precision Medicine Clinic to Improve Access to Clinical Trials for Patients With Metastatic Breast Cancer: An Academic/Community Collaboration.

PURPOSE: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic. METHODS: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise. Providers contacted vMAP regarding patients with MBC, and on receipt of referral, the vMAP team engaged in discussion to identify if further diagnostics were needed (including genomic testing) and to identify potential clinical trials or standard treatment options. Recommendations were then sent to the referring provider within 72 hours. Pre-/postsurveys were issued to network physicians to assess for barriers, clinical trial access, and vMAP referral experience. Program implementation was evaluated with the Squire 2.0 reporting guidelines for quality improvement in health care as a framework. RESULTS: Eighty-one cases from 22 providers were referred to vMAP over a 26-month period. The average response time to the referring provider with a finalized recommendation was 1.90 ± 1.82 days. A total of 86.4% of cases had clinical trial options on vMAP prescreen, with 40.7% initiating formal screening assessments and 27 patients (33.3%) ultimately enrolling on trials. On resurvey, 92% of survey responses across community oncology referring providers said that they were very likely to use vMAP again. CONCLUSION: In the initial 2-year period, vMAP demonstrated an efficient means to offer real-time interpretation of genomic testing and identification of clinical trials for patients with MBC, with effective clinical trial enrollment and high rates of referring provider satisfaction.

CT Use Reduction In Ostensive Ureteral Stone (CURIOUS).

INTRODUCTION: Computed tomography (CT) is performed in over 90% of patients diagnosed with ureteral stones, but only 10% of patients presenting to the emergency department (ED) with acute flank pain are hospitalized for a clinically important stone or non-stone diagnosis. Hydronephrosis can be accurately detected using point-of-care ultrasound and is a key predictor of ureteral stone and risk of subsequent complications. The absence of hydronephrosis is insufficient to exclude a stone. We created a sensitive clinical decision rule to predict clinically important ureteral stones. We hypothesized that this rule could identify patients at low risk for this outcome. METHODS: We conducted a retrospective cohort study in a random sample of 4000 adults who presented to one of 21 Kaiser Permanente Northern California EDs and underwent a CT for suspected ureteral stone from 1/1/2016 to 12/31/2020. The primary outcome was clinically important stone, defined as stone resulting in hospitalization or urologic procedure within 60 days. We used recursive partition analysis to generate a clinical decision rule predicting the outcome. We estimated the C-statistic (area under the curve), plotted the receiver operating characteristic (ROC) curve for the model, and calculated sensitivity, specificity, and predictive values of the model based on a risk threshold of 2%. RESULTS: Among 4000 patients, 354 (8.9%) had a clinically important stone. Our partition model resulted in four terminal nodes with risks ranging from 0.4% to 21.8%. The area under the ROC curve was 0.81 (95% CI 0.80, 0.83). Using a 2% risk cut point, a clinical decision tree including hydronephrosis, hematuria, and a history of prior stones predicted complicated stones with sensitivity 95.5% (95% CI 92.8%-97.4%), specificity 59.9% (95% CI 58.3%-61.5%), positive predictive value 18.8% (95% CI 18.1%-19.5%), and negative predictive value 99.3% (95% CI 98.8%-99.6%). CONCLUSIONS: Application of this clinical decision rule to imaging decisions would have led to 63% fewer CT scans with a miss rate of 0.4%. A limitation was the application of our decision rule only to patients who underwent CT for suspected ureteral stone. Thus, this rule would not apply to patients who were thought to have ureteral colic but did not receive a CT because ultrasound or history were sufficient for diagnosis. These results could inform future prospective validation studies.

Systematic tissue collection during clinical breast biopsy is feasible, safe and enables high-content translational analyses.

Systematic collection of fresh tissues for research at the time of diagnostic image-guided breast biopsy has the potential to fuel a wide variety of innovative studies. Here we report the initial experience, including safety, feasibility, and laboratory proof-of-principle, with the collection and analysis of research specimens obtained via breast core needle biopsy immediately following routine clinical biopsy at a single institution over a 14-month period. Patients underwent one or two additional core biopsies following collection of all necessary clinical specimens. In total, 395 patients were approached and 270 consented to the research study, yielding a 68.4% consent rate. Among consenting patients, 238 lesions were biopsied for research, resulting in 446 research specimens collected. No immediate complications were observed. Representative research core specimens showed high diagnostic concordance with clinical core biopsies. Flow cytometry demonstrated consistent recovery of hundreds to thousands of viable cells per research core. Among a group of HER2 + tumor research specimens, HER2 assessment by flow cytometry correlated highly with immunohistochemistry (IHC) staining, and in addition revealed extensive inter- and intra-tumoral variation in HER2 levels of potential clinical relevance. Suitability for single-cell transcriptomic analysis was demonstrated for a triple-negative tumor core biopsy, revealing substantial cellular diversity in the tumor immune microenvironment, including a prognostically relevant T cell subpopulation. Thus, collection of fresh tissues for research purposes at the time of diagnostic breast biopsy is safe, feasible and efficient, and may provide a high-yield mechanism to generate a rich tissue repository for a wide variety of cross-disciplinary research.

A Retrospective Study of Neurological Complications in Pediatric Patients With Moyamoya Disease Undergoing General Anesthesia.

BACKGROUND: Moyamoya disease is a condition with potentially devastating and permanent neurological sequelae. Adequate volume status and blood pressure, tight control of carbon dioxide to achieve normocarbia, and providing postoperative analgesia to prevent hyperventilation are typical goals that are used during anesthetic care in these patients. The purpose of this study was to assess postanesthesia neurological complications in moyamoya patients undergoing general anesthesia for imaging studies and surgical procedures excluding neurosurgical revascularization. METHODS: We performed a retrospective cohort study examining moyamoya patients who received general anesthesia for imaging studies and nonneurosurgical-revascularization procedures between January 1, 2001 and December 1, 2016 at our quaternary care pediatric hospital. A general anesthetic encounter was excluded if it occurred within 30 days after a revascularization surgery. The electronic medical records of study patients were analyzed for perioperative management, and neurological outcomes within 30 days of an anesthetic were assessed. RESULTS: A total of 58 patients undergoing 351 anesthesia exposures were included in the study. Three patients experienced neurological complications, which included focal neurological weakness, seizure, and altered mental status. The incidence of complications during anesthesia encounters was 0.85% (3/351) with a 95% confidence interval of 0.28-2.62. CONCLUSIONS: Over a 16-year period at our hospital, 3 children with moyamoya disease who underwent anesthesia for nonneurosurgical-revascularization purposes demonstrated postanesthesia neurological symptoms. The symptoms were consistent with transient ischemic attacks and all resolved without long-term sequelae.

Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival.

Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projection neurons (SPNs) of the striatum. HD is widely accepted to be caused by a toxic gain-of-function of mutant HTT. However, whether loss of HTT function, because of dominant-negative effects of the mutant protein, plays a role in HD and whether HTT is required for SPN health and function are not known. Here, we delete Htt from specific subpopulations of SPNs using the Cre-Lox system and find that SPNs require HTT for motor regulation, synaptic development, cell health, and survival during aging. Our results suggest that loss of HTT function in SPNs could play a critical role in HD pathogenesis.

3D-Printed Structure Boosts the Kinetics and Intrinsic Capacitance of Pseudocapacitive Graphene Aerogels.

The performance of pseudocapacitive electrodes at fast charging rates are typically limited by the slow kinetics of Faradaic reactions and sluggish ion diffusion in the bulk structure. This is particularly problematic for thick electrodes and electrodes highly loaded with active materials. Here, a surface-functionalized 3D-printed graphene aerogel (SF-3D GA) is presented that achieves not only a benchmark areal capacitance of 2195 mF cm-2 at a high current density of 100 mA cm-2 but also an ultrahigh intrinsic capacitance of 309.1 µF cm-2 even at a high mass loading of 12.8 mg cm-2 . Importantly, the kinetic analysis reveals that the capacitance of SF-3D GA electrode is primarily (93.3%) contributed from fast kinetic processes. This is because the 3D-printed electrode has an open structure that ensures excellent coverage of functional groups on carbon surface and facilitates the ion accessibility of these surface functional groups even at high current densities and large mass loading/electrode thickness. An asymmetric device assembled with SF-3D GA as anode and 3D-printed GA decorated with MnO2 as cathode achieves a remarkable energy density of 0.65 mWh cm-2 at an ultrahigh power density of 164.5 mW cm-2 , outperforming carbon-based supercapacitors operated at the same power density.

Screening for perinatal anxiety disorders: Room to grow.

BACKGROUND: The anxiety and their related disorders (AD) are the most prevalent of all mental health conditions, disproportionately affecting women. The value of perinatal AD screening is well established but there is very limited evidence to support the applicability of existing anxiety screening instruments. To our knowledge, no previous studies have evaluated an AD screening instrument in a perinatal population using full gold standard methodology. OBJECTIVE: To assess the accuracy of the most commonly used and/or recommended screening tools for perinatal AD (i.e., the Edinburgh Postnatal Depression Scale (EPDS) and its anxiety subscale (EPDS-3A), and the Generalized Anxiety Disorder 7 and 2-item Scales (GAD-7 and GAD-2) alongside a clinically derived alternative; the Anxiety Disorder - 13 (AD-13). METHODS: 310 Canadian women completed mood and anxiety questionnaires at approximately 3-months postpartum. Those scoring at/above cut-off on one or more questionnaire completed a diagnostic interview for depression and all AD (n = 115). The accuracy of each scale was assessed via ROC analyses. RESULTS: Only the AD-13 met the standard of a clinically useful screening measure, with an area under the curve (AUC) above 0.8. This was achieved with and without the inclusion of the related disorders. No other measure demonstrated an AUC above 0.8, either including or excluding the related disorders. CONCLUSIONS: Neither the EPDS/EPDS 3-A, nor the GAD-7/GAD-2 can be recommended for widespread use as a perinatal AD screening tool. The high performance of the AD-13 is a good indication that an effective alternative is well within reach.

Prepartum and Postpartum Mothers' and Fathers' Unwanted, Intrusive Thoughts in Response to Infant Crying.

BACKGROUND: Unwanted intrusive thoughts of intentionally harming one's infant (intrusive harm thoughts) are common distressing experiences among postpartum mothers and fathers. AIM: To understand infant crying as a stimulus for intrusive harm thoughts and associated emotional responses in prepartum and postpartum mothers and fathers in response to infant cry. METHOD: Following completion of self-report measures of negative mood and anger, prepartum (n = 48) and postpartum (n = 44) samples of mother and father pairs completed 10 minutes of listening to audio-recorded infant crying. Post-test questionnaires assessed harm thoughts, negative emotions, urges to comfort and flee, and thoughts of shaking as a soothing or coping strategy. RESULTS: One quarter of prepartum and 44% of postpartum parents reported intrusive infant-related harm thoughts following crying. Mothers and fathers did not differ in the likelihood of reporting harm thoughts, nor in the number of thoughts reported. Women reported more internalizing emotions compared with men. Hostile emotions were stronger among postpartum parents, and parents reporting harm thoughts. All parents reported strong urges to comfort the infant. Urges to flee were stronger among parents who reported harm thoughts. The likelihood of using infant shaking as a soothing or coping strategy was minimally endorsed, albeit more strongly by fathers and parents who also reported harm thoughts. CONCLUSIONS: In response to crying, harm thoughts are common and are associated with hostile emotions, urges to flee, and increased thoughts of using infant shaking. Reassuringly, the number of participants considering infant shaking as a strategy for soothing or for coping with a crying infant was low.

One Laryngospasm, 2 Realities: A Case Report Highlighting the Impact of Data Granularity on Post Hoc Analysis of Perioperative Events.

We present the case of a laryngospasm event in a 21-month-old child in which the changes in pulse oximetry and end-tidal carbon dioxide were recorded by both our Anesthesia Information Management System and middleware medical device integration platform. When this case was analyzed retrospectively, we noted that the 2 systems recorded the event very differently with respect to pulse oximetry. This case report illustrates the impact of data sampling rates on post hoc analysis of perioperative events and highlights the importance of understanding data collection processes when using electronically recorded data.

Transplantation of Neural Progenitor Cells Expressing Glial Cell Line-Derived Neurotrophic Factor into the Motor Cortex as a Strategy to Treat Amyotrophic Lateral Sclerosis.

Early dysfunction of cortical motor neurons may underlie the initiation of amyotrophic lateral sclerosis (ALS). As such, the cortex represents a critical area of ALS research and a promising therapeutic target. In the current study, human cortical-derived neural progenitor cells engineered to secrete glial cell line-derived neurotrophic factor (GDNF) were transplanted into the SOD1G93A ALS rat cortex, where they migrated, matured into astrocytes, and released GDNF. This protected motor neurons, delayed disease pathology and extended survival of the animals. These same cells injected into the cortex of cynomolgus macaques survived and showed robust GDNF expression without adverse effects. Together this data suggests that introducing cortical astrocytes releasing GDNF represents a novel promising approach to treating ALS. Stem Cells 2018;36:1122-1131.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS: Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. RESULTS: All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. CONCLUSIONS: Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

A model of recurrent concussion that leads to long-term motor deficits, CTE-like tauopathy and exacerbation of an ALS phenotype.

BACKGROUND: Concussion injury is the most common form of traumatic brain injury (TBI). How recurrent concussions alter long-term outcomes is poorly understood, especially as related to the development of neurodegenerative disease. We evaluated the functional and pathological consequences of repeated TBI over time in wild type (WT) rats as well as rats harboring the human SOD1 mutation ("SOD1"), a model of familial amyotrophic lateral sclerosis (ALS). METHODS: A total of 42 rats, 26 WT and 16 SOD1, were examined over a study period of 25 weeks (or endpoint). At postnatal day 60, 20 WT and 7 SOD1 rats were exposed to mild, bilateral TBI once per week for either 2 weeks (2×TBI) or 5 weeks (5×TBI) using a controlled cortical impact device. Six WT and nine SOD1 rats underwent sham injury with anesthesia alone. Twenty WT rats were euthanized at 12 weeks after first injury and six WT rats were euthanized at 25 weeks after first injury. SOD1 rats were euthanized when they reached ALS disease endpoint. Weekly body weights and behavioral assessments were performed. Tauopathy in brain tissue was analyzed using immunohistochemistry. RESULTS: 2XTBI injured rats initially demonstrated recovery of motor function but failed to recover to baseline within the 12-week study period. Relative to both 2XTBI and sham controls, 5XTBI rats demonstrated significant deficits that persisted over the 12-week period. SOD1 5XTBI rats reached a peak body weight earlier than sham SOD1 rats, indicating earlier onset of the ALS phenotype. Histologic examination of brain tissue revealed that, in contrast with sham controls, SOD1 and WT TBI rats demonstrated cortical and corpus collosum thinning and tauopathy, which increased over time. CONCLUSIONS: Unlike previous models of repeat brain injury, which demonstrate only transient deficits in motor function, our concussion model of repeat, mild, bilateral TBI induced long-lasting deficits in motor function, decreased cortical thickness, shrinkage of the corpus callosum, increased brain tauopathy, and earlier onset of ALS symptoms in SOD1 rats. This model may allow for a greater understanding of the complex relationship between TBI and neurodegenerative diseases and provides a potential method for testing novel therapeutic strategies.

Heart rate in pediatric trauma: rethink your strategy.

BACKGROUND: The optimal heart rate (HR) for children after trauma is based on values derived at rest for a given age. As the stages of shock are based in part on HR, a better understanding of how HR varies after trauma is necessary. Admission HRs of pediatric trauma patients were analyzed to determine which ranges were associated with lowest mortality. MATERIALS AND METHODS: The National Trauma Data Bank was used to evaluate all injured patients ages 1-14 years admitted between 2007 and 2011. Patients were stratified into eight groups based on age. Clinical characteristics and outcomes were recorded, and regression analysis was used to determine mortality odds ratios (ORs) for HR ranges within each age group. RESULTS: A total of 214,254 pediatric trauma patients met inclusion criteria. The average admission HR and systolic blood pressure were 104.7 and 120.4, respectively. Overall mortality was 0.8%. The HR range associated with lowest mortality varied across age groups and, in children ages 7-14, was narrower than accepted resting HR ranges. The lowest risk of mortality for patients ages 5-14 was captured at HR 80-99. CONCLUSIONS: The HR associated with lowest mortality after pediatric trauma frequently differs from resting HR. Our data suggest that a 7y old with an HR of 115 bpm may be in stage III shock, whereas traditional HR ranges suggest that this is a normal rate for this child. Knowing when HR is critically high or low in the pediatric trauma population will better guide treatment.