Resident perspectives on the impact of program leadership communication on well-being during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced a myriad of changes that negatively impacted resident physicians' well-being. Communication from program leadership may mitigate resident stress during times of crisis, yet literature supporting this premise is scant, and best communication practices remain uncertain. This qualitative study aimed to identify stressors to residents and explore the influence of residency program leadership's communication on emotional stress during the COVID-19 pandemic. METHODS: Informed by Kotter's 8-step management model to support resident well-being, this qualitative study used grounded theory methods to interview 25 residents from three training programs (Pediatrics, Internal Medicine, and Medicine-Pediatrics) on a single academic medical campus from May-September 2020. Four investigators coded the data using the constant comparative analysis. Sampling continued until reaching thematic saturation. Codes were built using an iterative approach and organized into themes. Discrepancies were resolved by consensus discussion among investigators. RESULTS: Residents described increased stress levels, the all-consuming nature of COVID-19, mixed emotions about their role as healthcare providers, new coping mechanisms, and changes to their education and work environment that impacted stress. Communication from leadership to residents during the pandemic varied. Effective communication helped mitigate stress; perceived suboptimal communication exacerbated stress. Who was communicating, methods of communication, and content of communication influenced resident stress. CONCLUSIONS: The COVID-19 pandemic introduced new stressors and challenges to residents. The perception of leadership communication played a critical role in mitigating or exacerbating resident stress. We propose a communication framework ("Who? What? Where? When? How?") that residency leadership can utilize during times of crisis.

Intrauterine Smoke Exposure, microRNA Expression during Human Lung Development, and Childhood Asthma.

Intrauterine smoke (IUS) exposure during early childhood has been associated with a number of negative health consequences, including reduced lung function and asthma susceptibility. The biological mechanisms underlying these associations have not been established. MicroRNAs regulate the expression of numerous genes involved in lung development. Thus, investigation of the impact of IUS on miRNA expression during human lung development may elucidate the impact of IUS on post-natal respiratory outcomes. We sought to investigate the effect of IUS exposure on miRNA expression during early lung development. We hypothesized that miRNA-mRNA networks are dysregulated by IUS during human lung development and that these miRNAs may be associated with future risk of asthma and allergy. Human fetal lung samples from a prenatal tissue retrieval program were tested for differential miRNA expression with IUS exposure (measured using placental cotinine concentration). RNA was extracted and miRNA-sequencing was performed. We performed differential expression using IUS exposure, with covariate adjustment. We also considered the above model with an additional sex-by-IUS interaction term, allowing IUS effects to differ by male and female samples. Using paired gene expression profiles, we created sex-stratified miRNA-mRNA correlation networks predictive of IUS using DIABLO. We additionally evaluated whether miRNAs were associated with asthma and allergy outcomes in a cohort of childhood asthma. We profiled pseudoglandular lung miRNA in n = 298 samples, 139 (47%) of which had evidence of IUS exposure. Of 515 miRNAs, 25 were significantly associated with intrauterine smoke exposure (q-value < 0.10). The IUS associated miRNAs were correlated with well-known asthma genes (e.g., ORM1-Like Protein 3, ORDML3) and enriched in disease-relevant pathways (oxidative stress). Eleven IUS-miRNAs were also correlated with clinical measures (e.g., Immunoglobulin E andlungfunction) in children with asthma, further supporting their likely disease relevance. Lastly, we found substantial differences in IUS effects by sex, finding 95 significant IUS-miRNAs in male samples, but only four miRNAs in female samples. The miRNA-mRNA correlation networks were predictive of IUS (AUC = 0.78 in males and 0.86 in females) and suggested that IUS-miRNAs are involved in regulation of disease-relevant genes (e.g., A disintegrin and metalloproteinase domain 19 (ADAM19), LBH regulator of WNT signaling (LBH)) and sex hormone signaling (Coactivator associated methyltransferase 1(CARM1)). Our study demonstrated differential expression of miRNAs by IUS during early prenatal human lung development, which may be modified by sex. Based on their gene targets and correlation to clinical asthma and atopy outcomes, these IUS-miRNAs may be relevant for subsequent allergy and asthma risk. Our study provides insight into the impact of IUS in human fetal lung transcriptional networks and on the developmental origins of asthma and allergic disorders.

Sleep in Hospitalized Children With Cancer: A Cross-Sectional Study.

OBJECTIVES: Many children with cancer have repeated and prolonged hospitalizations, and in-hospital sleep disruption may negatively affect outcomes. Our objective for this study was to characterize sleep quality and quantity in hospitalized children with cancer by using parental surveys and actigraphy, to evaluate the association between subjective and objective sleep measures, and to describe hospital-associated risk factors related to poor sleep. METHODS: Cross-sectional study of children aged 0 to 18 years old admitted to a pediatric oncology ward. Parents completed a baseline sleep questionnaire describing their child's sleep at home before hospitalization, followed by daily questionnaires describing their child's sleep for up to 3 nights while in the hospital. A subgroup of children aged 5 to 18 years wore actigraphs during the same time period. Demographic and clinical data were extracted from the electronic medical record. The primary outcome was inadequate sleep, defined by the total sleep duration adjusted for age. RESULTS: Among 56 participants over 135 hospital nights, 66% (n = 37) reported inadequate sleep. Actigraphy was completed on 39 nights (29%), with a median total sleep time of 477 (interquartile range 407-557) minutes. There was a strong correlation between subjective questionnaire measures and actigraphic measures (r = 0.76). No patient-specific demographic factors were related to inadequate sleep. A multivariable model indicated the following hospital-related factors were associated with inadequate sleep: noise (adjusted odds ratio [aOR] 3.0; confidence interval [CI] 1.2-7.7), alarms (aOR 3.1; CI 1.2-8.3), child's worries (aOR 2.8; CI 1.1-7.2), and receipt of benzodiazepines (aOR 2.9; CI 1.2-7.5). CONCLUSIONS: A majority of children experienced inadequate sleep during hospitalization. Subjective report of sleep duration correlated well with objective measures of sleep by actigraphy. Several potentially modifiable factors were independently associated with poor sleep. Further interventional studies are required to test approaches to optimize sleep in hospitalized children with cancer.

Sedation strategies in children with pediatric acute respiratory distress syndrome (PARDS).

In this review, we discuss the changing landscape of sedation in mechanically ventilated children with pediatric acute respiratory distress syndrome (PARDS). While previous approaches advocated for early and deep sedation with benzodiazepines, emerging literature has highlighted the benefits of light sedation and use of non-benzodiazepine sedating agents, such as dexmedetomidine. Recent studies have emphasized the importance of monitoring multiple factors including, but not limited to, sedation depth, analgesia efficacy, opiate withdrawal, and development of delirium. Through this approach, we hope to improve PARDS outcomes. Overall, more research is needed to further our understanding of the best sedation strategies in children with PARDS.

Cortical developmental abnormalities in logopenic variant primary progressive aphasia with dyslexia.

An increased prevalence of dyslexia has been observed in individuals diagnosed with primary progressive aphasia, most notably the logopenic variant primary progressive aphasia. The underlying pathology most commonly associated with logopenic variant primary progressive aphasia is Alzheimer's disease. In this clinical case report series, we describe the neuropathological findings of three patients with logopenic variant primary progressive aphasia and developmental dyslexia, each demonstrating a pattern of cerebrocortical microdysgenesis, reminiscent of findings first reported in dyslexic individuals, alongside expected Alzheimer's disease pathology. Neurodevelopmental and most severe Alzheimer's disease pathological changes overlapped within perisylvian brain regions, areas associated with phonological deficits in both logopenic variant primary progressive aphasia and dyslexia. These three cases with pathological findings support the hypothesis that early-life neurodevelopmental changes might influence later-life susceptibility to neurodegenerative disease and could contribute to non-amnestic, early age-of-onset presentations of Alzheimer's disease. Larger studies investigating neurobiological vulnerability across the lifespan are needed.

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy.

Importance: Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. Objective: To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). Design, Setting, and Participants: This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. Main Outcomes and Measures: Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. Results: A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy. Conclusions and Relevance: Nonlanguage mathematical and visuospatial LDs were associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.

Delirium in Hospitalized Children with Cancer: Incidence and Associated Risk Factors.

OBJECTIVE: To assess the incidence of delirium and its risk factors in hospitalized children with cancer. STUDY DESIGN: In this cohort study, all consecutive admissions to a pediatric cancer service over a 3-month period were prospectively screened for delirium twice daily throughout their hospitalization. Demographic and treatment-related data were collected from the medical record after discharge. RESULTS: A total of 319 consecutive admissions, including 186 patients and 2731 hospital days, were included. Delirium was diagnosed in 35 patients, for an incidence of 18.8%. Risk factors independently associated with the development of delirium included age <5 years (OR = 2.6, P = .026), brain tumor (OR = 4.7, P = .026); postoperative status (OR = 3.3, P = .014), and receipt of benzodiazepines (OR = 3.7,P < .001). Delirium was associated with increased hospital length of stay, with median length of stay for delirious patients of 10 days compared with 5 days for patients who were not delirious during their hospitalization (P < .001). CONCLUSIONS: In this cohort, delirium was a frequent complication during admissions for childhood cancer, and was associated with increased hospital length of stay. Multi-institutional prospective studies are warranted to further characterize delirium in this high-risk population and identify modifiable risk factors to improve the care provided to hospitalized children with cancer.

Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies.

Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.

The Geriatric Emergency Department.

This article presents an overview of the complex needs of older patients presenting to the emergency department for care. Discussion points for hospital communities considering emergency services to accommodate the aging population are highlighted. The essential components of a geriatric emergency department, including transition of care strategies, are reviewed.

Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration.

IMPORTANCE: We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE: To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS: A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES: Clinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS: Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE: In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imaging may be useful for differentiating underlying PSP from CBD pathology during life.

Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production abilities, while left and right ventral anterior insula volumes correlated with ratings of aberrant eating behavior. These two FTD clinical variants show different patterns of insular sub-region atrophy in the left precentral dorsal anterior and bilateral ventral anterior regions, providing further evidence for the role of these sub-regions in speech production and social-emotional function.

Integrated model of palliative care in the emergency department.

An integrated model of palliative care in the emergency department (ED) of an inner city academic teaching center utilized existing hospital resources to reduce hospital length of stay (LOS) and reduce overall cost. Benefits related to resuscitation rates, intensity of care, and patient satisfaction are attributed to the ED-based palliative team's ability to provide real time consults, and utilize InterQual criteria to admit to a less costly level of care or transfer directly to home or hospice.