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Childhood vaccine hesitancy has been studied extensively before the COVID-19 pandemic. The pandemic presented new barriers to pediatric vaccinations. Furthermore, the development of COVID-19 vaccines has complicated factors underlying vaccine hesitancy. We performed a cross-sectional mobile phone-based survey at Children’s Hospital Los Angeles querying parents regarding perspectives on vaccines before and during the pandemic. Our primary aim was to understand the impact of the pandemic on routine childhood vaccine hesitancy. Secondarily, we examined intent to vaccinate, COVID-19 vaccine hesitancy, and key contributing demographic factors. Among 252 participants, we found overall increased childhood vaccine hesitancy (p = 0.006), increased risk perception (p = 0.006), and unchanged vaccine confidence during the COVID-19 pandemic. Increased hesitancy did not translate into decreased intent to vaccinate with routine childhood vaccines or influenza vaccines. During the pandemic, households with higher income (50–99 K, > 100 K) correlated with decreased routine childhood vaccine hesitancy, while Hispanic ethnicity and African American race had increased risk perception. For COVID-19 vaccine hesitancy, households with higher income (> 100 K) correlated with decreased hesitancy, while non-White ethnicity and race had increased risk perception. We found that routine childhood vaccine hesitancy increased during the COVID-19 pandemic, mainly due to increased risk perception. Key contributing demographic factors behind both childhood vaccine hesitancy and COVID-19 vaccine hesitancy included household income and race. Understanding factors behind routine childhood vaccine hesitancy is crucial to maintaining pediatric vaccination rates and promoting vaccine confidence during and after the COVID-19 pandemic.

Key Points The clinical definition of perimenopause focuses on functional changes in the reproductive system; however, the symptoms of the perimenopause are largely neurological in nature Most women transition through perimenopause without long-term adverse effects; however, a substantial proportion of women emerge from this transition with an increased risk of neurological decline Estrogen functions as a master regulator to ensure the brain responds appropriately to coordinate signalling and transcriptional pathways that regulate energy metabolism The estrogen receptor network becomes uncoupled from the bioenergetic system during the perimenopausal transition and a hypometabolic state associated with neurological dysfunction emerges In neurological transition states, indicators of dysfunction at the limits of those normally seen can signal tipping points for neurological diseases The presence, variability, intensity and duration of neurological perimenopausal symptoms could be warning signs for increased risk of neurodegenerative diseases later in life All women, regardless of ethnicity, geographic location or culture will transition through perimenopause. Many of the neurological symptoms that emerge during this transition are the result of estrogen depletion in the brain. In this Review, the authors discuss the neurological symptoms associated with perimenopause in the context of estrogen-mediated processes in the brain. Perimenopause is a midlife transition state experienced by women that occurs in the context of a fully functioning neurological system and results in reproductive senescence. Although primarily viewed as a reproductive transition, the symptoms of perimenopause are largely neurological in nature. Neurological symptoms that emerge during perimenopause are indicative of disruption in multiple estrogen-regulated systems (including thermoregulation, sleep, circadian rhythms and sensory processing) and affect multiple domains of cognitive function. Estrogen is a master regulator that functions through a network of estrogen receptors to ensure that the brain effectively responds at rapid, intermediate and long timescales to regulate energy metabolism in the brain via coordinated signalling and transcriptional pathways. The estrogen receptor network becomes uncoupled from the bioenergetic system during the perimenopausal transition and, as a corollary, a hypometabolic state associated with neurological dysfunction can develop. For some women, this hypometabolic state might increase the risk of developing neurodegenerative diseases later in life. The perimenopausal transition might also represent a window of opportunity to prevent age-related neurological diseases. This Review considers the importance of neurological symptoms in perimenopause in the context of their relationship to the network of estrogen receptors that control metabolism in the brain.

Abstract Background Persistent Staphylococcus aureus bacteremia (SAB) is defined based on varying duration in literature. The primary objective was to determine the risk of poor outcomes in relation to bacteremia duration. Methods Multicenter, prospective, observational study of adult hospitalized patients with SAB. Medical records were reviewed for pertinent data. Patients were grouped by bacteremia duration: short (1–2 days), intermediate (3–6 days), and prolonged (≥7 days) and compared for risk factors and outcomes. Results Of 884 patients, 63% had short, 28% intermediate, and 9% prolonged bacteremia. Overall mean age was 57 years, and 70% were male. The prolonged group had the highest proportion of methicillin-resistant SAB (P < .0001). Choice of antibiotic therapy did not significantly affect bacteremia duration; however, time to source-control procedure was delayed in the prolonged and intermediate groups compared with the short group (3.5 vs 3 vs 1 day, P < .0001). Metastatic complications, length of stay, and 30-day mortality were progressively worse as bacteremia duration increased (P < .0001). Every continued day of bacteremia was associated with a relative risk of death of 1.16 (95% confidence interval, 1.10–1.22; P < .0001), with a significant increase in risk starting at 3 days as determined by receiver operating characteristic analysis. Conclusions Optimal management of SAB should target bacterial clearance as soon as possible to minimize incremental risk of mortality with each day of positive blood culture. Delay in source control but not type of antistaphylococcal therapy was significantly associated with prolonged bacteremia and worse outcomes. Every continued day of persistent Staphylococcus aureus bacteremia is associated with a 16% increased risk of death. Bacteremia duration of 3 days was found to best distinguish patients who died versus those who survived.

Cross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT). We examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area. Spatial models and land-use data were used to estimate the home outdoor mean concentration of particulate matter up to 2.5 micrometer in diameter (PM2.5), and to classify residence by proximity to traffic-related pollution (within 100 m of highways). PM2.5 and traffic proximity were positively associated with CIMT progression. Adjusted coefficients were larger than crude associations, not sensitive to modelling specifications, and statistically significant for highway proximity while of borderline significance for PM2.5 (P = 0.08). Annual CIMT progression among those living within 100 m of a highway was accelerated (5.5 micrometers/yr [95%CI: 0.13-10.79; p = 0.04]) or more than twice the population mean progression. For PM2.5, coefficients were positive as well, reaching statistical significance in the socially disadvantaged; in subjects reporting lipid lowering treatment at baseline; among participants receiving on-trial treatments; and among the pool of four out of the five trials. Consistent with cross-sectional findings and animal studies, this is the first study to report an association between exposure to air pollution and the progression of atherosclerosis--indicated with CIMT change--in humans. Ostensibly, our results suggest that air pollution may contribute to the acceleration of cardiovascular disease development--the main causes of morbidity and mortality in many countries. However, the heterogeneity of the volunteering populations across the five trials, the limited sample size within trials and other relevant subgroups, and the fact that some key findings reached statistical significance in subgroups rather than the sample precludes generalizations to the general population.

ObjectiveTo 1) define the number and characteristics of NICUs in the United States (US) and 2) identify hospital and population characteristics related to US NICUs.Study designCohort study of US NICUs.ResultsThere were 1424 NICUs identified in the US. Higher number of NICU beds was positively associated with higher NICU level (p < 0.0001). Higher acuity level and number of NICU beds related to being in a children’s hospital (p < 0.0001;p < 0.0001), part of an academic center (p = 0.006;p = 0.001), and in a state with Certificate of Need legislation (p = 0.023;p = 0.046). Higher acuity level related to higher population density (p < 0.0001), and higher number of beds related to increasing proportions of minorities in the population up until 50% minorities. There was also significant variation in NICU level by region.ConclusionsThis study contributes new knowledge by describing an updated registry of NICUs in the US in 2021 that can be used for comparisons and benchmarking.

In this trial, which was stratified by time since menopause (<6 or ≥10 years), 17β-estradiol treatment was associated with less progression of atherosclerosis than was placebo when therapy was initiated early after menopause but not when initiated late after menopause. After dozens of observational studies consistently showed inverse associations between postmenopausal hormone therapy and the risk of coronary heart disease and death from any cause, it was difficult to understand the null or adverse effects of the therapy on coronary heart disease that were reported from randomized, controlled trials. One explanation is that in observational studies, women were younger (approximately 50 years of age) and closer to menopause (typically within 2 years) when they initiated hormone therapy than were the women included in randomized trials (mean age in the 60s, typically >10 years past menopause). This so-called timing hypothesis posits . . .

Background Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. Methods Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO 2 max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). Results Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO 2 max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group ( p  = 0.94) while there was a significant decrease in VO 2 max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks ( p  = 0.001). Conclusions HIIT is a feasible exercise intervention to maintain VO 2 max in breast cancer patients receiving anthracycline-based chemotherapy. Trial registration The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).

Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM. This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter ) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: ) FA, ) nPM, ) , and ) . Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. The joint group exhibited synergistic effects on white matter injury (2.3× the additive nPM and scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the cohort demonstrated impaired working memory when compared to the group. Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.

Background Disparities in life-saving interventions for low-income patients with cirrhosis necessitate innovative models of care. Aim To implement a novel generalist-led FLuid ASPiration (FLASP) clinic to reduce emergency department (ED) care for refractory ascites. Setting A large safety net hospital in Los Angeles. Participants MediCal patients with paracentesis in the ED from 6/1/2020 to 1/31/2021 or in FLASP clinic or the ED from 3/1/2021 to 4/30/2022. Program Description According to RE-AIM, adoption obtained administrative endorsement and oriented ED staff. Reach engaged ED staff and eligible patients with timely access to FLASP. Implementation trained FLASP clinicians in safer, guideline-based paracentesis, facilitated timely access, and offered patient education and support. Program Evaluation After FLASP clinic opened, significantly fewer ED visits were made by patients discharged after paracentesis [rate ratio (RR) of 0.33 (95% CI 0.28, 0.40, p  < 0.0001)] but not if subsequently hospitalized (RR = 0.88, 95% CI 0.70, 1.11). Among 2685 paracenteses in 225 FLASP patients, complications were infrequent: 39 (1.5%) spontaneous bacterial peritonitis, 265 (9.9%) acute kidney injury, and 2 (< 0.001%) hypotension. FLASP patients rated satisfaction highly on a Likert-type question. Discussion Patients with refractory ascites in large safety net hospitals may benefit from an outpatient procedure clinic instead of ED care.