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Author(s): G C Minetti [1, 9]; C Colussi [2, 9]; R Adami [3, 9]; C Serra [1, 4]; C Mozzetta [1]; V Parente [3]; S Fortuni [1]; S Straino [2]; [...]

Studies the electronic structure of tris(8-hydroxyquinoline) aluminum thin films in the pristine and reduced states. Results of a joint theoretical and experimental investigation; Combination of x-ray and ultraviolet photoelectron spectroscopies with quantum-chemical calculations.

Health-care workers (HCWs) on the frontlines of the 2019 Coronavirus Disease 2019 (COVID-19) have a high risk of acquiring and dying from the disease. Brazil is a country with high morbimortality and ranks highest in general mortality from COVID-19. A large proportion of medical doctors (MDs) is dying, impacting in the workforce. As part of the research by Fiocruz on working conditions among HCWs, we have conducted this study of death among MDs. We analyzed data from Federal Council of Medicine, the only national platform with details about deaths in MDs. A broad search of other sources, including the Ministry of Health, was done, but unfortunately, the data does not exist. A total of 622 MDs died from March 2020 to March 2021: 87.6% male and 75% over age 60. The Southeast had the highest percentage (34.7%), followed by the Northeast (27.2%), and rankings by state showed Rio de Janeiro (15.8%), followed by São Paulo, Pará, Paraná and Paraíba, totalizing 50.1%. The specialties with highest mortality were gynecology (12.2%), pediatrics (10.0%), internal medicine (9.3%), general surgery (7.8%) and cardiology (7.6%). May 2020 was the month of worst mortality (16.9%) followed by July and June. A slow decline was observed until October, when Brazil begun to experience the ‘‘second wave’’. The vaccination of MDs began at the end of January 2021 and has not been sufficient time to evaluate the impact on morbimortality. The results of a study of 50 professional categories are under analysis and will be published soon as well as a study of ‘‘invisible’’ HCWs, who do not have specific training but are essential to supporting health care system, from primary care units to high-complexity hospitals. We hope that the results of these studies will improve links among managers, those who define public policies, and union leaders, achieving better workplace and living conditions, minimizing health and socioeconomic disparities. Key messages: This study is about death by COVID-19 among medical doctors in Brazil, as part of a large one on professional categories, essentials to supporting health care system, conducted by FIOCRUZ. This stdy is part of a large one on professional categories, essentials to supporting health care system, conducted by FIOCRUZ. [ABSTRACT FROM AUTHOR]

We analyze the interaction at the surface of a three-dimensional (3D) topological insulator among 2D electron states belonging to the Dirac cone close to the point of the Brillouin zone and the Rayleigh surface phonon mode. The model deals with an elastic continuum in the long-wavelength limit, in Random Phase Approximation (RPA). Screening of the electronic polarization is quite effective at small wave vectors. On the other hand, the absence of backscattering for the Dirac electrons at the Fermi surface is partly responsible for the reduced influence of the electron-phonon interaction in renormalizing the phonon dispersion at finite wave vectors. We infer that softening of the Rayleigh mode appears as unlikely, at least for the case of a clean and defect-free surface to which our approximate treatment applies. The dielectric response to virtual excitation of the Rayleigh phonon could drive the electron-electron interaction attractive at low frequencies, but the average weak coupling pairing interaction is found to be too small to induce a surface superconducting instability. [ABSTRACT FROM AUTHOR]

We study the surface resistivity of a three-dimensional topological insulator when the boundaries exhibit a non trivial curvature. We obtain an analytical solution for a spherical topological insulator, and we show that a non trivial quantum spin connection emerges from the three dimensional band structure. We analyze the effect of the spin connection on the scattering by a bump on a flat surface. Quantum effects induced by the geometry lead to resonances when the electron wavelength is comparable to the size of the bump. [ABSTRACT FROM AUTHOR]

The analysis of the electronic properties of strained or lattice deformed graphene combines ideas from classical condensed matter physics, soft matter, and geometrical aspects of quantum field theory (QFT) in curved spaces. Recent theoretical and experimental work shows the influence of strains in many properties of graphene not considered before, such as electronic transport, spin–orbit coupling, the formation of Moiré patterns and optics. There is also significant evidence of anharmonic effects, which can modify the structural properties of graphene. These phenomena are not restricted to graphene, and they are being intensively studied in other two dimensional materials, such as the transition metal dichalcogenides. We review here recent developments related to the role of strains in the structural and electronic properties of graphene and other two dimensional compounds. [ABSTRACT FROM AUTHOR]

Objective: To determine whether differences exist in antibiotic prescribing for respiratory infections in pediatric urgent cares (PUCs) by patient race/ethnicity, insurance, and language., Design: Multi-center cohort study., Setting: Nine organizations (92 locations) from 22 states and Washington, DC., Participants: Patients ages 6 months-18 years evaluated April 2022-April 2023, with acute viral respiratory infections, otitis media with effusion (OME), acute otitis media (AOM), pharyngitis, community-acquired pneumonia (CAP), and sinusitis., Methods: We compared the use of first-line (FL) therapy as defined by published guidelines. We used race/ethnicity, insurance, and language as exposures. Multivariable logistic regression models estimated the odds of FL therapy by group., Results: We evaluated 396,340 ARI encounters. Among all encounters, 351,930 (88.8%) received FL therapy (98% for viral respiratory infections, 85.4% for AOM, 96.0% for streptococcal pharyngitis, 83.6% for sinusitis). OME and CAP had the lowest rates of FL therapy (49.9% and 60.7%, respectively). Adjusted odds of receiving FL therapy were higher in Black Non-Hispanic (NH) (adjusted odds ratio [aOR] 1.53 [1.47, 1.59]), Asian NH (aOR 1.46 [1.40, 1.53], and Hispanic children (aOR 1.37 [1.33, 1.41]), compared to White NH. Additionally, odds of receiving FL therapy were higher in children with Medicaid/Medicare (aOR 1.21 [1.18-1.24]) and self-pay (aOR 1.18 [1.1-1.27]) compared to those with commercial insurance., Conclusions: This multicenter collaborative showed lower rates of FL therapy for children of the White NH race and those with commercial insurance compared to other groups. Exploring these differences through a health equity lens is important for developing mitigating strategies.

Importance: Poor-quality handoffs can lead to medical errors when transitioning patient care. Biased language within handoffs may contribute to errors and lead to disparities in health care delivery., Objective: To compare clinical information recall accuracy and attitudes toward patients among trainees in paired cases of biased vs neutral language in simulated handoffs., Design, Setting, and Participants: Surveys administered from April 29 to June 15 and from July 20 to October 10, 2023, included 3 simulated verbal handoffs, randomized between biased and neutral, and measured clinical information recall, attitudes toward patients, and key takeaways after each handoff. Participants included residents in internal medicine, pediatrics, and internal medicine-pediatrics and senior medical students at 2 academic medical centers in different geographic regions of the US. Data were analyzed from November 2023 to June 2024., Exposures: Each participant received 3 handoffs that were based on real handoffs about Black patients at 1 academic center. These handoffs were each randomized to either a biased or neutral version. Biased handoffs had 1 of 3 types of bias: stereotype, blame, or doubt. The order of handoff presentation was also randomized. Internal medicine and pediatrics residents received slightly different surveys, tailored for their specialty. Internal medicine-pediatrics residents received the pediatric survey. Medical students were randomly assigned the survey type., Main Outcomes and Measures: Each handoff was followed by a clinical information recall question, an adapted version of the Provider Attitudes Toward Sickle Cell Patients Scale (PASS), and 3 free-response takeaways., Results: Of 748 trainees contacted, 169 participants (142 residents and 27 medical students) completed the survey (23% overall response rate), distributed across institutions, residency programs, and years of training (95 female [56%]; mean [SD] age, 28.6 [2.3] years). Participants who received handoffs with blame-based bias had less accurate information recall than those who received neutral handoffs (77% vs 93%; P = .005). Those who reported bias as a key takeaway of the handoff had lower clinical information recall accuracy than those who did not (85% vs 93%; P = .01). Participants had less positive attitudes toward patients per PASS scores after receiving biased compared with neutral handoffs (mean scores, 22.9 [3.3] vs 25.2 [2.7]; P < .001). More positive attitudes toward patients were associated with higher clinical information recall accuracy (odds ratio, 1.12; 95% CI, 1.02-1.22)., Conclusions and Relevance: In this survey study of residents and medical students, biased handoffs impeded accurate transfer of key clinical information and decreased empathy, potentially endangering patients and worsening health disparities. Handoff standardization is critical to addressing racial bias and improving patient safety.

Health equity is the point at which all individuals have an equal opportunity to experience optimal health and thriving. The current state of health care is far from this ideal as numerous populations experience health disparities: differences in health or health outcomes that negatively impact groups who experience systemic disadvantage. All research has the potential to widen, maintain, or close health disparities. This article focuses on key opportunities for hospitalists of all levels of research experience to conduct research that promotes health equity from project planning to disseminating results. During the planning phase, learning health equity research concepts, developing study designs in partnership with communities, and recognizing the limitations of secondary analyses are key strategies that promote health equity. Developing strategies for recruiting populations underrepresented in research helps ensure that disparities in health outcomes are identified. Rather than conducting descriptive research to identify disparities, research which aims to improve health outcomes for groups that have been marginalized is urgently needed. Study analyses should consider intersectionality and patient-centered outcomes. Finally, dissemination to both academic and community audiences, with careful attention to words and figures, can catalyze future directions, mitigate bias, and help ensure that marginalized communities benefit equitably from research findings., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Context: Congenital heart disease (CHD) is a common condition with high morbidity and mortality and is subject to racial and ethnic health disparities., Objective: To conduct a systematic review of the literature to identify differences in mortality in pediatric patients with CHD based on race and ethnicity., Data Sources: Legacy PubMed (MEDLINE), Embase (Elsevier), and Scopus (Elsevier) STUDY SELECTION: English language articles conducted in the USA focused on mortality based on race and ethnicity in pediatric patients with CHD., Data Extraction: Two independent reviewers assessed studies for inclusion and performed data extraction and quality assessment. Data extraction included mortality based on patient race and ethnicity., Results: There were 5094 articles identified. After de-duplication, 2971 were screened for title and abstract content, and 45 were selected for full-text assessment. Thirty studies were included for data extraction. An additional 8 articles were identified on reference review and included in data extraction for a total of 38 included studies. Eighteen of 26 studies showed increased risk of mortality in non-Hispanic Black patients. Results were heterogenous in Hispanic patients with eleven studies of 24 showing an increased risk of mortality. Results for other races demonstrated mixed outcomes., Limitations: Study cohorts and definitions of race and ethnicity were heterogenous, and there was some overlap in national datasets used., Conclusion: Overall, racial and ethnic disparities existed in the mortality of pediatric patients with CHD across a variety of mortality types, CHD lesions, and pediatric age ranges. Children of races and ethnicities other than non-Hispanic White generally had increased risk of mortality, with non-Hispanic Black children most consistently having the highest risk of mortality. Further investigation is needed into the underlying mechanisms of these disparities so interventions to reduce inequities in CHD outcomes can be implemented., (© 2023. W. Montague Cobb-NMA Health Institute.)

Objective: Many have found racial differences in clinician-patient communication using validated codebooks that represent effective communication. No codebooks used for examining racial differences, however, have included patient input. In this paper, we describe creating codebook with Black patient advocates to determine if we could reliably code discriminatory/valuing communication and assess racial differences in these behaviors., Methods: We created a codebook for discriminatory/valuing communication behaviors with the input of Black patient advocates. We used the codebook to analyze data from 101 audio recorded encounters between White cardiologists and Black and White patients. We examined the differences in the prevalence of behaviors in cardiology encounters., Results: In comparison to White patients, cardiologists made fewer tailoring statements to their Black patients (68% vs. 49%, p = 0.07). Coders found 4 instances of stereotyping behaviors and only Black patients (p = 0.12). We found no significant associations between any of the other outcomes and patient race. Black patients had a lower incidence of tailoring statements (p = 0.13), lower incidence of interrupting statements (p = 0.16), and higher rushed global score (p = 0.14)., Conclusion and Practice Implications: We found that coders can reliably identify discriminatory/valuing behaviors in cardiology encounters. Future work should apply these codes to other datasets to assess their validity and generalizability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene resulting in reduced levels of the SMN protein. Nusinersen, the first antisense oligonucleotide (ASO) approved for SMA treatment, binds to the SMN2 gene, paralogue to SMN1, and mediates the translation of a functional SMN protein. Here, we used longitudinal high-resolution mass spectrometry (MS) to assess both global proteome and metabolome in cerebrospinal fluid (CSF) from ten SMA type 3 patients, with the aim of identifying novel readouts of pharmacodynamic/response to treatment and predictive markers of treatment response. Patients had a median age of 33.5 [29.5; 38.25] years, and 80% of them were ambulant at time of the enrolment, with a median HFMSE score of 37.5 [25.75; 50.75]. Untargeted CSF proteome and metabolome were measured using high-resolution MS (nLC-HRMS) on CSF samples obtained before treatment (T0) and after 2 years of follow-up (T22). A total of 26 proteins were found to be differentially expressed between T0 and T22 upon VSN normalization and LIMMA differential analysis, accounting for paired replica. Notably, key markers of the insulin-growth factor signaling pathway were upregulated after treatment together with selective modulation of key transcription regulators. Using CombiROC multimarker signature analysis, we suggest that detecting a reduction of SEMA6A and an increase of COL1A2 and GRIA4 might reflect therapeutic efficacy of nusinersen. Longitudinal metabolome profiling, analyzed with paired t-Test, showed a significant shift for some aminoacid utilization induced by treatment, whereas other metabolites were largely unchanged. Together, these data suggest perturbation upon nusinersen treatment still sustained after 22 months of follow-up and confirm the utility of CSF multi-omic profiling as pharmacodynamic biomarker for SMA type 3. Nonetheless, validation studies are needed to confirm this evidence in a larger sample size and to further dissect combined markers of response to treatment., (© 2023. The Author(s).)

Introduction: Current sociopolitical events coupled with requirement modifications by the Liaison Committee on Medical Education have reinvigorated a need for training in cultural awareness and health disparities in undergraduate medical education. Many institutions, however, have not established longitudinal courses designed to address this content. Additionally, little is known about the change in learners' awareness of cultural determinants of health and health disparities after enrollment in such curricula. In 2016, the authors developed a yearlong required course entitled Cultural Determinants of Health and Health Disparities for first year medical students at a large university medical school in the United States. The course launched in the 2017 academic year., Methods: Two cohorts participated in twelve 2.5 to 3-hour multi-modal sessions focused on various aspects of healthcare delivery for marginalized populations and factors that contribute to health disparities. The Multicultural Assessment Questionnaire was used pre and post course to assess students' self-evaluated changes in knowledge, skills, and awareness related to cultural competency in healthcare., Results: Students' self-reported knowledge, skills, and awareness scores regarding cultural competence in health care increased from pre to post-course assessment. On the knowledge scale, students' mean score increased from 2.63 to 2.97 (P < .001), with 16% reporting a decreased score, 30% reporting no change, and 54% reporting growth. On the skills scale, students' mean score increased from 2.64 to 3.38 (P < .001), with 11% reporting a decreased score, 17% reporting no change, and 72% reporting growth. On the awareness scale, students' overall score increased from 3.76 to 3.97 (P < .05), with 16% reporting a decreased score, 50% reporting no change, and 34% reporting growth. There were no changes in KSA scores across cohorts pre and post course., Conclusion: Perceived knowledge, skills, and awareness related to the importance of cultural competence in healthcare delivery increased at the end of the academic year. This type of longitudinal course model could be broadly adopted at other institutions to enhance patient, peer, and future provider awareness regarding cultural impacts on care and health disparities among vulnerable populations., Competing Interests: Declaration of Competing Interest Victoria Parente reports support from the NICHD and the Duke Center for Research to Advance Healthcare Equity (REACH Equity); consulting fees for PCORI, and honoraria from the PEW Charitable Trust. No other authors report conflicts of interest., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations or deletions in SMN1 that lead to progressive death of alpha motor neurons, ultimately leading to severe muscle weakness and atrophy, as well as premature death in the absence of treatment. Recent approval of SMN-increasing medications as SMA therapy has altered the natural course of the disease. Thus, accurate biomarkers are needed to predict SMA severity, prognosis, drug response, and overall treatment efficacy. This article reviews novel non-targeted omics strategies that could become useful clinical tools for patients with SMA. Proteomics and metabolomics can provide insights into molecular events underlying disease progression and treatment response. High-throughput omics data have shown that untreated SMA patients have different profiles than controls. In addition, patients who clinically improved after treatment have a different profile than those who did not. These results provide a glimpse on potential markers that could assist in identifying therapy responders, in tracing the course of the disease, and in predicting its outcome. These studies have been restricted by the limited number of patients, but the approaches are feasible and can unravel severity-specific neuro-proteomic and metabolic SMA signatures.

Learning to read primary scientific literature (PSL) is an important part of developing scientific literacy skills. First-year students entering college often have little previous exposure to PSL and therefore face initial barriers in learning how to engage with PSL. Annotations have been shown to be a useful tool in undergraduate education and have potential for guiding students in developing higher-level reading strategies. In this study, we collected both qualitative and quantitative data to test the hypothesis of whether annotated PSL aids in the development of reading strategies for novice students learning to read PSL. Our qualitative results showed that annotations help students (i) break down PSL into manageable pieces, (ii) summarize the text, (iii) identify key information, and (iv) distinguish between different sections of PSL. Quantitatively, we saw no significant influence of annotations on the development of reading strategies for students learning to read PSL. Overall, our study provides a window into better understanding of specific strategies that students employ in reading PSL. Collectively, we suggest incorporating annotated PSL with some scaffolding social activities as an effective strategy to bring novice readers up the on-ramp of scientific literacy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Lee et al.)

Objectives: Examine the association of coder ratings of cardiologist behaviors and global scores of cardiologist communication style with patient participation in clinic encounters., Methods: We coded transcripts of clinic encounters for patient participatory behaviors: asking questions, assertive statements, and expressing negative emotions; clinician behavior counts: reflective statements, open-ended questions, empathic statements, and eliciting questions. We used general linear regression models to examine associations of mean number of patient participatory behaviors with clinician behaviors., Results: Our sample included 161 patients of 40 cardiologists. Patient female gender was associated with on average 2.1 (CI: 0.06, 4.1; p = 0.04) more patient participatory behaviors. In an adjusted model, clinician reflective statements were associated with on average 0.3 (CI: 0.04, 0.4; p = 0.02) more patient participatory behaviors. A clinician making at least one empathic statement was associated with on average 3.7 (CI: 0.2, 7.1; p = 0.04) more patient participatory behaviors., Conclusions: These results demonstrate that some individual clinician behaviors are associated with higher patient participation in cardiology encounters., Practice Implications: Clinician reflective and empathic statements may be important targets in communication training to increase patient participation., Section: Communication Studies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Becker muscular dystrophy (BMD) is an X-linked neuromuscular disorder due to mutation in the DMD gene, encoding dystrophin. Despite a wide clinical variability, BMD is characterized by progressive muscle degeneration and proximal muscle weakness. Interestingly, a dysregulated expression of muscle-specific microRNAs (miRNAs), called myomirs, has been found in patients affected with muscular dystrophies, although few studies have been conducted in BMD. We analysed the serum expression levels of a subset of myomirs in a cohort of 29 ambulant individuals affected by BMD and further classified according to the degree of alterations at muscle biopsy and in 11 age-matched healthy controls. We found a significant upregulation of serum miR-1, miR-133a, miR-133b and miR-206 in our cohort of BMD patients, supporting the role of these miRNAs in the pathophysiology of the disease, and we identified serum cut-off levels discriminating patients from healthy controls, confiming the potential of circulating miRNAs as promising noninvasive biomarkers. Moreover, serum levels of miR-133b were found to be associated with fibrosis at muscle biopsy and with patients' motor performances, suggesting that miR-133b might be a useful prognostic marker for BMD patients. Taken together, our data showed that these serum myomirs may represent an effective tool that may support stratification of BMD patients, providing the opportunity of both monitoring disease progression and assessing the treatment efficacy in the context of clinical trials., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Extracorporeal membrane oxygenation (ECMO) is a lifesaving support for respiratory and cardiovascular failure. However, ECMO induces a systemic inflammatory response syndrome that can lead to various complications, including endothelial dysfunction in the cerebral circulation. We aimed to investigate whether ECMO-associated endothelial dysfunction also affected coronary circulation. Ten-day-old piglets were randomized to undergo either 8 h of veno-arterial ECMO (n = 5) or no treatment (Control, n = 5). Hearts were harvested and coronary arteries were dissected and mounted as 3 mm rings in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U46619, concentration−response curves to the endothelium-dependent vasodilator bradykinin (BK) and the nitric oxide (NO) donor (endothelium-independent vasodilator) sodium nitroprusside (SNP) were performed. Relaxation to BK was studied in the absence or presence of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME). U46619-induced contraction and SNP-induced relaxation were similar in control and ECMO coronary arteries. However, BK-induced relaxation was significantly impaired in the ECMO group (30.4 ± 2.2% vs. 59.2 ± 2.1%; p < 0.0001). When L-NAME was present, no differences in BK-mediated relaxation were observed between the control and ECMO groups. Taken together, our data suggest that ECMO exposure impairs endothelium-derived NO-mediated coronary relaxation. However, there is a NO-independent component in BK-induced relaxation that remains unaffected by ECMO. In addition, the smooth muscle cell response to exogenous NO is not altered by ECMO exposure.

Importance: Patients with language barriers have a higher risk of experiencing hospital safety events. This study hypothesized that language barriers would be associated with poorer perceptions of hospital safety climate relating to communication openness., Objective: To examine disparities in reported hospital safety climate by language proficiency in a cohort of hospitalized children and their families., Design, Setting, and Participants: This cohort study conducted from April 29, 2019, through March 1, 2020, included pediatric patients and parents or caregivers of hospitalized children at general and subspecialty units at 21 US hospitals. Randomly selected Arabic-, Chinese-, English-, and Spanish-speaking hospitalized patients and families were approached before hospital discharge and were included in the analysis if they provided both language proficiency and health literacy data. Participants self-rated language proficiency via surveys. Limited English proficiency was defined as an answer of anything other than "very well" to the question "how well do you speak English?", Main Outcomes and Measures: Primary outcomes were top-box (top most; eg, strongly agree) 5-point Likert scale ratings for 3 Children's Hospital Safety Climate Questionnaire communication openness items: (1) freely speaking up if you see something that may negatively affect care (top-box response: strongly agree), (2) questioning decisions or actions of health care providers (top-box response: strongly agree), and (3) being afraid to ask questions when something does not seem right (top-box response: strongly disagree [reverse-coded item]). Covariates included health literacy and sociodemographic characteristics. Logistic regression was used with generalized estimating equations to control for clustering by site to model associations between openness items and language proficiency, adjusting for health literacy and sociodemographic characteristics., Results: Of 813 patients, parents, and caregivers who were approached to participate in the study, 608 completed surveys (74.8% response rate). A total of 87.7% (533 of 608) of participants (434 [82.0%] female individuals) completed language proficiency and health literacy items and were included in the analyses; of these, 14.1% (75) had limited English proficiency. Participants with limited English proficiency had lower odds of freely speaking up if they see something that may negatively affect care (adjusted odds ratio [aOR], 0.26; 95% CI, 0.15-0.43), questioning decisions or actions of health care providers (aOR, 0.19; 95% CI, 0.09-0.41), and being unafraid to ask questions when something does not seem right (aOR, 0.44; 95% CI, 0.27-0.71). Individuals with limited health literacy (aOR, 0.66; 95% CI, 0.48-0.91) and a lower level of educational attainment (aOR, 0.59; 95% CI, 0.36-0.95) were also less likely to question decisions or actions., Conclusions and Relevance: This cohort study found that limited English proficiency was associated with lower odds of speaking up, questioning decisions or actions of providers, and being unafraid to ask questions when something does not seem right. This disparity may contribute to higher hospital safety risk for patients with limited English proficiency. Dedicated efforts to improve communication with patients and families with limited English proficiency are necessary to improve hospital safety and reduce disparities.

Objective: Despite widespread adoption of family-centered rounds, few have investigated differences in the experience of family-centered rounds by family race and ethnicity. The purpose of this study was to explore racial and ethnic differences in caregiver perception of inclusion and empowerment during family-centered rounds., Methods: We identified eligible caregivers of children admitted to the general pediatrics team through the electronic health record. Surveys were completed by 99 caregivers (47 non-Latinx White and 52 Black, Latinx, or other caregivers of color). To compare agreement with statements of inclusivity and empowerment, we used the Wilcoxon rank sum test in unadjusted analyses and linear regression for the adjusted analyses., Results: Most (91%) caregivers were satisfied or extremely satisfied with family-centered rounds. We found no differences by race or ethnicity in statements of satisfaction or understanding family-centered rounds content. However, in both unadjusted and adjusted analyses, we found that White caregivers more strongly agreed with the statements "I felt comfortable participating in rounds," "I had adequate time to ask questions during rounds," and "I felt a valued member of the team during rounds" compared with Black, Latinx, and other caregivers of color., Conclusions: Congruent with studies of communication in other settings, caregivers of color may experience barriers to inclusion in family-centered rounds, such as medical team bias, less empathic communication, and shorter encounters. Future studies are needed to better understand family-centered rounds disparities and develop interventions that promote inclusive rounds., Competing Interests: POTNTIAL CONFLICT OF INTEREST DISCLOSURE: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Objectives: The aim of the study was to evaluate the impact of a resident-led patient safety council. This study measured change in resident perceptions and knowledge of safety issues for 3 years, as well as behavioral choices to participate in patient safety activities during and after residency., Methods: Pediatric residents formed a resident-led safety council to engage their peers in patient safety activities. Surveys were distributed annually from 2013 to 2015 to measure residents' perception and knowledge surrounding patient safety. The number of patient safety reports submitted by residents was tracked for the same period. In addition, recent graduates were surveyed to assess the influence of the council on postresidency involvement in patient safety., Results: Resident perception of the institutional culture of safety improved and knowledge of basic patient safety concepts increased. The number of resident-submitted safety reports increased from 6.2 to 15.2 reports per month in the 2013 and 2015 academic years, respectively. Surveys of recent graduates suggest that involvement with the safety council during residency fostered future engagement in patient safety., Conclusions: This resident-led council models successful involvement of trainees in system-based patient safety. Such involvement can help shape the safety culture within a training program and encourages continued participation in patient safety after residency completion., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Graduate medical education (GME) trainees have a unique perspective from which to identify and report patient safety concerns. However, it is not known how safety reports submitted by GME trainees differ from those submitted by other clinical staff. We hypothesized that GME trainees were more likely to submit safety reports regarding transitions of care, delays in care, and lapses in communication, and reports of higher severity compared with other frontline staff such as nurses, pharmacists, and other providers., Methods: Patient safety reports submitted by clinical staff for 1 year at an academic tertiary care children's hospital were retrospectively reviewed and categorized by reporter type. Severity level and event type were analyzed by reporter type, and repeat χ2 tests were used to compare the percentage of reports at each severity level and in each event type submitted by GME trainees compared with each other reporter type., Results: Graduate medical education trainees submitted reports of greater severity (level E/F/G) compared with nurses (10% versus 5%, P = 0.021) and pharmacists (10% versus 2%, P = 0.001). A greater percent of GME trainees' reports were categorized as errors in transitions of care, diagnosis, ordering, laboratory collection, and care delays compared with several other reporter types., Conclusions: Graduate medical education trainees identify system vulnerabilities not detected by other personnel, supporting efforts to increase safety reporting by GME trainees., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Muscular dystrophies are a heterogeneous group of inherited diseases characterized by the progressive degeneration and weakness of skeletal muscles, leading to disability and, often, premature death. To date, no effective therapies are available to halt or reverse the pathogenic process, and meaningful treatments are urgently needed. From this perspective, it is particularly important to establish reliable in vitro models of human muscle that allow the recapitulation of disease features as well as the screening of genetic and pharmacological therapies. We herein review and discuss advances in the development of in vitro muscle models obtained from human induced pluripotent stem cells, which appear to be capable of reproducing the lack of myofiber proteins as well as other specific pathological hallmarks, such as inflammation, fibrosis, and reduced muscle regenerative potential. In addition, these platforms have been used to assess genetic correction strategies such as gene silencing, gene transfer and genome editing with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), as well as to evaluate novel small molecules aimed at ameliorating muscle degeneration. Furthermore, we discuss the challenges related to in vitro drug testing and provide a critical view of potential therapeutic developments to foster the future clinical translation of preclinical muscular dystrophy studies.

BACKGROUND: Nonmedical formulary switches (NMFS) routinely occur in managed health care plans and involve changing preferred medications for reasons outside of clinical considerations. The cost implications of NMFS are infrequently published and the clinical outcomes rarely assessed. OBJECTIVE: To assess the real-world clinical and cost implications of an NMFS involving sitagliptin and linagliptin. METHODS: An NMFS was made to the Geisinger Health Plan (GHP) commercial, health care reform, and Medicaid formularies on February 1, 2018, involving a change in preferred medication from sitagliptin to linagliptin. Claims data from GHP and clinical information from electronic health records of the Geisinger Health System were used to evaluate the cost and clinical impact of this change. Patients aged 18 years or older who were continuously enrolled in a GHP commercial, health care reform, or Medicaid plan throughout the entire study period and had at least 1 fill for sitagliptin during the preswitch phase were included in the study. We investigated the differences in various clinical and economic outcomes from pre- to postswitch among those who switched and remained adherent to the new preferred therapy throughout the 12-month postperiod ("linagliptin switch" group) and patients who did not ("other switch" group). Clinical outcomes included all-cause hospitalization, diabetes-related hospitalization, and glycosylated hemoglobin (HbA1c), while economic measures included changes in per member per month (PMPM) spending. The negative binomial regression model was used to estimate utilization counts. A generalized linear model with a log link and gamma distribution was used to analyze cost data. RESULTS: 1,203 patients met the inclusion criteria. Of these, 501 (41.6%) individuals switched to and remained at least 80% adherent to linagliptin in the postperiod, while 702 (58.4%) did not. No difference between groups was found when comparing the pre- to postswitch change in all-cause hospitalization (incidence rate ratio (IRR) = 1.46, 95% CI = 0.66-3.23, P = 0.3436) or diabetes-related hospitalization (IRR = 1.39, 95% CI = 0.62-3.10, P = 0.4203). Additionally, no difference was found between groups regarding the change in HbA1c 12-month postswitch compared with baseline (difference between groups = -0.10%, 95% CI = -0.39%-0.19%, P = 0.4962). Total PMPM spending was 43% higher in the other switch group compared with the linagliptin switch group (IRR = 1.43, 95% CI = 1.25-1.63, P < 0.0001). This trend was driven by 92% higher medical PMPM spending in the other switch group compared with the linagliptin switch group (IRR = 1.92, 95% CI = 1.58-2.33, P < 0.0001) but was offset by 12% lower pharmacy PMPM spending in the other switch group (IRR = 0.88, 95% CI = 0.82-0.95, P = 0.0009). CONCLUSIONS: An NMFS from sitagliptin to linagliptin resulted in overall health plan savings with no significant changes in health outcomes. DISCLOSURES: Funding for this study was provided by Geisinger Health System, which had no role in the study outside of a final review of the submitted manuscript. Johns and Gionfriddo are Geisinger employees. The authors report no financial conflicts of interest.

Objectives: For pediatric complex care programs to target enhanced care coordination services to the highest-risk patients, it is critical to accurately identify children with medical complexity (CMC); however, no gold standard definition exists. The aim of this study is to describe a point-of-care screening algorithm to identify CMC with high health care use, a group that may benefit the most from improved care coordination., Methods: From July 1, 2015, to June 30, 2016 (fiscal year 2016 [FY16]), a medical complexity screening algorithm was implemented by a pediatric complex care program at a single tertiary care center for hospitalized patients at the time of admission. Using the screening algorithm, we categorized inpatients into 1 of 3 groups: CMC, children with special health care needs (CSHCN), or previously healthy (PH) children. Inpatient resource use for FY16 and FY17 encounters was extracted for children screened in FY16., Results: We categorized 2187 inpatients in FY16 into the 3 complexity groups (CMC = 77; CSHCN = 1437; PH children = 673). CMC had more complex chronic conditions (median = 6; interquartile range [IQR] 4-11) than CSHCN (median = 1; IQR 0-2) and PH children (median = 0; IQR 0-0). CMC had greater per-patient and per-encounter hospital use than CSHCN and PH children. CMC and children with ≥4 complex chronic conditions had comparable levels of resource use., Conclusions: By implementation of a point-of-care screening algorithm, we identified CMC with high health care use. By using this algorithm, it was feasible to identify hospitalized CMC that could benefit from care coordination by a pediatric complex care program., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Incidental azygos vein cannulation has been reported in a few cases of neonatal extracorporeal membrane oxygenation (ECMO). This complication is described in the literature mainly in pathological conditions wherein increased central venous pressure dilates the superior vena cava (SVC), i.e., right congenital diaphragmatic hernia (CDH) or pulmonary hypertension. Azygos vein cannulation should always be suspected in cases of impaired venous return and circuit failure. Although rare, it hinders proper venous aspiration of the ECMO circuit and generally requires repositioning or replacement of the venous cannula or conversion to central cannulation. In this report, we describe a newborn with severe right CDH who required ECMO assistance, wherein incidental cannulation of the azygos vein resulted in successful functioning of the circuit because of the concomitant presence of isolated interruption of the inferior vena cava and azygos continuation. To the best of our knowledge, this is the first report of successful neonatal ECMO despite azygos vein cannulation in a patient with such rare physiology., (Copyright © 2019 Mayer, Raffaeli, Schena, Parente, Sorrentino, Macchini, Colli, Mauri, Neri, Borzani, Leva, Mosca and Cavallaro.)

Health care disparities exist along the continuum of care for children admitted to the hospital; they start before admission, impact hospital course, and continue after discharge. During an acute illness, risk of admission, length of stay, hospital costs, communication during family-centered rounds, and risk of readmission have all been shown to vary by socioeconomic status, race, and ethnicity. Understanding factors beyond the acute illness that increase a child's risk of admission, increase hospital course complications, and lower discharge quality is imperative for the new generation of pediatric hospitalists focused on improving health for a population of children. In this article, we describe a framework to conceptualize socioeconomic, racial, and ethnic health disparities for the hospitalized child. Additionally, we offer actions pediatric hospitalists can take to address disparities within their practices., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: The Accreditation Council for Graduate Medical Education (ACGME) Clinical Learning Environment Review (CLER) program focuses on aspects of the graduate medical education learning environment, such as patient safety. Data from CLER site visits reveal that many resident physicians do not receive adequate training on patient safety., Objective: We evaluated a pediatric resident-led safety council as a method to meet CLER Pathways to Excellence patient safety objectives., Methods: The Duke Pediatric Residency Safety Council (PRSC) created an infrastructure for residents to participate in department safety efforts, review safety events, and act as leaders for safety initiatives. Annual surveys were distributed to graduate medical education trainees through the institution's patient safety center and the PRSC. Survey results of safety attitudes were compared over time within the pediatrics program and between pediatrics and nonpediatrics trainees at the institution. Resident-submitted safety reports were tracked through an institutional safety event repository., Results: From 2013 to 2017, the percentage of residents who strongly agreed that they could submit a safety report doubled (from 35% [6 of 17] to 73% [22 of 30], P = .011). The average number of safety reports submitted by a pediatrics resident per year did not significantly change during this period (from 3.0 to 3.8, P = .11). In 2017, 90% of pediatrics residents (27 of 30) agreed or strongly agreed that their concerns would be addressed if they entered a safety report., Conclusions: The council addressed 5 of the 7 CLER Pathways to Excellence in patient safety., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Care plans can reduce care fragmentation for children with medical complexity (CMC); however, implementation is challenging. Mobile health innovations could improve implementation. This mixed methods study's objectives were to (1) evaluate feasibility of mobile complex care plans (MCCPs) for CMC enrolled in a complex care program and (2) study MCCPs' impact on parent engagement, parent experience, and care coordination. MCCPs were individualized, updated quarterly, integrated within the electronic health record, and visible on parents' mobile devices via an online portal. In 1 year (September 1, 2016, to August 31, 2017), 94% of eligible patients (n = 47) received 162 MCCPs. Seventy-four percent of parents (n = 35) reviewed MCCPs online. Forty-six percent of these parents (n = 16) sent a follow-up message, and the care team responded within 8 hours (median time = 7.2 hours). In interviews, parents identified MCCPs as an important reference and communication tool. MCCPs for CMC in a complex care program were feasible, facilitated parental engagement, and delivered timely communication.

The aim of this study is to develop a new formula for age estimation in a longitudinal study of a sample from the radiological collection of wrist bones of growing infants, children, and adolescents recorded at the Burlington Growth Centre. A sample of 82 individuals (43 boys and 39 girls), aged between 3 and 16 years, were analyzed with a total of 623 X-rays of left hand-wrist bones by measuring the area of carpal bones and epiphyses of the ulna and radius (Bo) and carpal area (Ca). The intra-class correlation coefficient (ICC) and its 95% confidence interval were used to evaluate intra-observer agreement. Hierarchical Bayesian calibration has been adopted to exceed the bias deriving from the classical regression approach used for age estimation in forensic disciplines, since it tends to overestimate or underestimate the age of the individuals. Calibration distributions of the dataset obtained by the evaluation of BoCa (the ratio of Bo and Ca) suggested mean absolute errors (MAE) of 1.07 and 1.34 years in boys and girls, respectively. The mean interquartile range (MIQR) was 1.7 and 2.42 years in boys and girls, respectively. The respective bias of the estimates was β ERR  = - 0.025 and - 0.074. Furthermore, a correspondence between different BoCa values and estimated age with its standard deviation (SD) was calculated for boys and girls, respectively. In conclusion, the Bayesian calibration method appears to be suitable for assessing both age and its distribution in subadults, according to hand-wrist maturity. Furthermore, it can easily incorporate other age predictors, obtaining a distribution of the subjects with multivariate predictors.

Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by the progressive loss of cortical, bulbar, and spinal motor neurons (MNs). The cardinal manifestation of ALS is a progressive paralysis which leads to death within a time span of 3 to 5 years after disease onset. Despite similar final output of neuronal death, the underlying pathogenic causes are various and no common cause of neuronal damage has been identified to date. Inflammation-mediated neuronal injury is increasingly recognized as a major factor that promotes disease progression and amplifies the MN death-inducing processes. The neuroimmune activation is not only a physiological reaction to cell-autonomous death but is an active component of nonautonomous cell death. Such injury-perpetuating phenomenon is now proved to be a common mechanism in many human disorders characterized by progressive neurodegeneration. Therefore, it represents an interesting therapeutic target. To date, no single cell population has been proved to play a major role. The existing evidence points to a complex cross talk between resident immune cells and nonresident cells, like monocytes and T lymphocytes, and to a dysregulation in cytokine profile and in phenotype commitment. After a summary of the most important mechanisms involved in the inflammatory reaction in ALS, this review will focus on novel therapeutic tools that rely on tackling inflammation to improve motor function and survival. Herein, completed, ongoing, or planned clinical trials, which aim to modify the rapidly fatal course of this disease, are discussed. Anti-inflammatory compounds that are currently undergoing preclinical study and novel suitable molecular targets are also mentioned.

Spinal muscular atrophy (SMA) is a progressive, recessively inherited neuromuscular disease, characterized by the degeneration of lower motor neurons in the spinal cord and brainstem, which leads to weakness and muscle atrophy. SMA currently represents the most common genetic cause of infant death. SMA is caused by the lack of survival motor neuron (SMN) protein due to mutations, which are often deletions, in the SMN1 gene. In the absence of treatments able to modify the disease course, a considerable burden falls on patients and their families. Greater knowledge of the molecular basis of SMA pathogenesis has fuelled the development of potential therapeutic approaches, which are illustrated here. Nusinersen, a modified antisense oligonucleotide that modulates the splicing of the SMN2 mRNA transcript, is the first approved drug for all types of SMA. Moreover, the first gene therapy clinical trial using adeno-associated virus (AAV) vectors encoding SMN reported positive results in survival and motor milestones achievement. In addition, other strategies are in the pipeline, including modulation of SMN2 transcripts, neuroprotection, and targeting an increasing number of other peripheral targets, including the skeletal muscle. Based on this premise, it is reasonable to expect that therapeutic approaches aimed at treating SMA will soon be changed, and improved, in a meaningful way. We discuss the challenges with regard to the development of novel treatments for patients with SMA, and depict the current and future scenarios as the field enters into a new era of promising effective treatments., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Aptamers directed against human thrombin can selectively bind to two different exosites on the protein surface. The simultaneous use of two DNA aptamers, HD1 and HD22, directed to exosite I and exosite II respectively, is a very powerful approach to exploit their combined affinity. Indeed, strategies to link HD1 and HD22 together have been proposed in order to create a single bivalent molecule with an enhanced ability to control thrombin activity. In this work, the crystal structures of two ternary complexes, in which thrombin is sandwiched between two DNA aptamers, are presented and discussed. The structures shed light on the cross talk between the two exosites. The through-bond effects are particularly evident at exosite II, with net consequences on the HD22 structure. Moreover, thermodynamic data on the binding of the two aptamers are also reported and analyzed., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Controlling the bandgap through local-strain engineering is an exciting avenue for tailoring optoelectronic materials. Two-dimensional crystals are particularly suited for this purpose because they can withstand unprecedented nonhomogeneous deformations before rupture; one can literally bend them and fold them up almost like a piece of paper. Here, we study multilayer black phosphorus sheets subjected to periodic stress to modulate their optoelectronic properties. We find a remarkable shift of the optical absorption band-edge of up to ∼0.7 eV between the regions under tensile and compressive stress, greatly exceeding the strain tunability reported for transition metal dichalcogenides. This observation is supported by theoretical models that also predict that this periodic stress modulation can yield to quantum confinement of carriers at low temperatures. The possibility of generating large strain-induced variations in the local density of charge carriers opens the door for a variety of applications including photovoltaics, quantum optics, and two-dimensional optoelectronic devices.

Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)