Childhood Asthma Control Test and spirometry values in school-age children.

OBJECTIVE: To determine the relationship between child and parent reports of asthma control using the Childhood Asthma Control Test (C-ACT) and spirometry. METHODS: This descriptive study included 648 children ages 5-11 years from a school-based asthma program. Not well-controlled asthma was defined as forced expiratory volume in 1 s (FEV1) and by FEV1/forced vital capacity (FVC) of 80% predicted or lower. Sensitivity and specificity of C-ACT scores for low FEV1 and FEV1/FVC levels were calculated. Logistic regression was used to obtain the area under the receiver operating characteristic curve (AUC) for C-ACT score categories by FEV1 level. RESULTS: Mean child age was 8.2 years, mean C-ACT score was 20.3 (SD = 3.96), mean FEV1 was 94.3% (SD = 17.1), and mean FEV1/FVC was 81.3 (SD = 8.5). Children with an FEV1 of 80% or less had significantly lower C-ACT scores than those with an FEV1 > 80% (p = .023, t = -2.015, df = 167); 95% CI [. -1.79 to -0.018]). The sensitivity and specificity of a C-ACT score of 19 or less for an FEV1 of 80% predicted or lower were 44.9 and 66.4%. With a C-ACT score of 22 or less, sensitivity and specificity for low FEV1 were 67.7 and 30.9%. The AUC for a C-ACT score of 19 or less and FEV1 of 80% or lower was .444 while the AUC was higher at .507 for a CACT score of 22 or less. CONCLUSION: The C-ACT is a useful screen but spirometry should be performed in children with persistent symptoms to assess current asthma control.

Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation.

Integrin adhesion complexes (IACs) are integrin-based plasma-membrane-associated compartments where cells sense environmental cues. The physical mechanisms and molecular interactions that mediate initial IAC formation are unclear. We found that both p130Cas ('Cas') and Focal adhesion kinase ('FAK') undergo liquid-liquid phase separation in vitro under physiologic conditions. Cas- and FAK- driven phase separation is sufficient to reconstitute kindlin-dependent integrin clustering in vitro with recombinant mammalian proteins. In vitro condensates and IACs in mouse embryonic fibroblasts (MEFs) exhibit similar sensitivities to environmental perturbations including changes in temperature and pH. Furthermore, mutations that inhibit or enhance phase separation in vitro reduce or increase the number of IACs in MEFs, respectively. Finally, we find that the Cas and FAK pathways act synergistically to promote phase separation, integrin clustering, IAC formation and partitioning of key components in vitro and in cells. We propose that Cas- and FAK-driven phase separation provides an intracellular trigger for integrin clustering and nascent IAC formation.

The Feasibility of a School Nurse-Led Mindfulness Program.

The purpose of this study was to evaluate the feasibility of a school nurse-led mindfulness program in a public school. Elementary students in an urban public school system are exposed to many stressors including poverty, family disturbances, and mental health conflicts. Previous research suggests that mindfulness interventions given by teachers promote prosocial behavior and stress reduction; however, there are no studies that have determined whether the school nurse could lead the program. A pre- to posttest design was employed using school-aged children enrolled in the fourth grade who were administered a mindfulness program. The participants were assessed for emotional states before and after the intervention. A total of 12 students completed the intervention. Students found the mindfulness program to be helpful, and the school nurse may be able to successfully complete the intervention. With appropriate planning, school nurses may be able to successfully implement the mindfulness curriculum in an urban public school.

Organization of Chromatin by Intrinsic and Regulated Phase Separation.

Eukaryotic chromatin is highly condensed but dynamically accessible to regulation and organized into subdomains. We demonstrate that reconstituted chromatin undergoes histone tail-driven liquid-liquid phase separation (LLPS) in physiologic salt and when microinjected into cell nuclei, producing dense and dynamic droplets. Linker histone H1 and internucleosome linker lengths shared across eukaryotes promote phase separation of chromatin, tune droplet properties, and coordinate to form condensates of consistent density in manners that parallel chromatin behavior in cells. Histone acetylation by p300 antagonizes chromatin phase separation, dissolving droplets in vitro and decreasing droplet formation in nuclei. In the presence of multi-bromodomain proteins, such as BRD4, highly acetylated chromatin forms a new phase-separated state with droplets of distinct physical properties, which can be immiscible with unmodified chromatin droplets, mimicking nuclear chromatin subdomains. Our data suggest a framework, based on intrinsic phase separation of the chromatin polymer, for understanding the organization and regulation of eukaryotic genomes.

Effect of a school-based asthma clinic on asthma outcomes.

Background: The St. Louis Children's Hospital Healthy Kids Express Asthma (HKEA) program was developed to improve asthma control in children who attend schools with the highest asthma prevalence in the metropolitan area. The HKEA program differs from other programs because unscheduled visits occur at school without parents present. Objective: To assess the effectiveness of the HKEA program via a retrospective quality assurance study. Methods: A chart review was performed to evaluate the change in health-care utilization, absenteeism, staff and student education, inhaler technique checks, and parent satisfaction surveys before and after participation in the program. The Wilcoxon signed rank test, two-way analysis of variance, and descriptive statistics were used to analyze the data. Results: The HKEA program recruited 1076 participants ages 5-15 years during 3 school years, from 2008 to 2011. The participants showed a reduction in emergency department visits (36.9% to 14.2%) and hospitalizations (7.1% to 5.0%) from the year before beginning the program to the third year of the program. Absenteeism was significantly improved, from 59.1% to 27.1%. Staff and student knowledge of asthma improved significantly after completing asthma education programs. More than 90% of participants completed three technique checks of their inhaler and spacer technique and showed significant improvement in their tech check (an inhaler/aero chamber technique check) scores. Parent satisfaction with the HKEA program was rated excellent or very good by 96.9% of the parents. Conclusion: The HKEA program is a novel school-based asthma clinic that is well accepted by parents, and results in less health-care utilization and school absences as well as improved asthma knowledge in participants and the school staff.

Pertussis outbreak in an Amish Community: Kent County, Delaware, 2018.

The Amish lead a very simplistic lifestyle free of modern conveniences. They have unique perceptions and beliefs regarding health and illness and generally do not adhere to conventional preventive measures such as immunizations, which can result in un- or under-immunized populations. Populations with low vaccination coverage are at greater risk of outbreaks compared to vaccinated populations as a result of low herd immunity. Over the past two decades, the Delaware Division of Public Health (DPH) has recorded three distinct outbreaks of pertussis in Delaware's Amish community. The third, and most recent, outbreak was detected in May 2018. DPH conducted an outbreak investigation in the Amish community to identify cases, estimate the burden of disease in the community, and implement control measures including vaccination, treatment, and post-exposure prophylaxis. Through the conduct of active surveillance activities, DPH interviewed 134 families and identified 181 confirmed and probable cases of pertussis. The majority of pertussis cases (77%) occurred among children ≤10 years of age, of which 87% were unvaccinated. DPH engaged the Amish community in meetings, distributed educational materials, and provided medication and vaccines in the community to encourage prevention and implement control measures. DPH officially closed the outbreak investigation on December 20, 2018 following three full incubation periods (63 days) without any new pertussis cases identified in the community.

Cognitive functioning following stabilisation from first episode mania.

BACKGROUND: The purpose of this study was to examine cognitive functioning in people following first-episode mania relative to a demographically similar healthy control group. METHODS: Forty-one patients, who had recently stabilised from a first manic episode, and twenty-one healthy controls, were compared in an extensive cognitive assessment. RESULTS: First-episode mania participants had significantly lower Full-Scale IQ (FSIQ) relative to healthy controls; however, this finding could be driven by premorbid differences in intellectual functioning. There were no significant differences between groups in Verbal IQ (VIQ) and Performance IQ (PIQ). First-episode mania participants performed significantly poorer than healthy controls in processing speed, verbal learning and memory, working memory, and cognitive flexibility with medium-to-large effects. There were no group differences in other measures of cognition. CONCLUSIONS: Participants following first-episode mania have poorer global intelligence than healthy controls, and have cognitive difficulties in some, but not all areas of cognitive functioning. This highlights the importance of early intervention and cognitive assessment in the early course of the disorder.

Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

Quetiapine v. lithium in the maintenance phase following a first episode of mania: randomised controlled trial.

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.

Timeliness of Breast Cancer Treatment in Delaware.

Studies have shown timely screening, diagnosis, and treatment of breast cancer reduces mortality rates. The objective of this study is to evaluate the overall timeliness of breast cancer diagnosis and treatment for Delawarean women using the Centers for Disease Control and Prevention's (CDC) National Breast and Cervical Cancer Early Detection Program's (NBCCEDP) recommendations of 60 days maximum for screening to diagnosis and 60 days maximum for diagnosis to treatment. This study analyzed Delaware Cancer Registry (DCR) data for female Delawarean breast cancer patients diagnosed in 2010 who had valid screening, diagnosis, and treatment dates. Calculations of three time intervals were performed: screening to diagnosis (Time A), diagnosis to treatment (Time B), and screening to treatment (Time C). The mean and median for Time Intervals A (21.2 days, 17.0 days), B (27.8 days, 25.0 days), and C (49.0 days, 42.0 days) met CDC recommendations. Our results show most Delawarean women who had valid screening, diagnosis, and treatment dates received a diagnosis within 60 days of screening and first course of treatment occurred within 60 days of diagnosis and therefore met the NBCCEDP recommendations.

Asthma control and obesity in urban African American children.

OBJECTIVE: To examine the relationship between body mass index (BMI), gender, age, controller medication use, household smoke exposure, season, and allergic rhinitis status with asthma control in a group of lower income, African American children. We hypothesized that non-obese children would have better asthma control. METHODS: Baseline data from a longitudinal study of children in a school-based asthma program in a Midwest urban area were analyzed. 360 children, ages 4-15 years, who were enrolled in either the 2012-2013 or 2013-2014 program were included. Asthma control was classified using criteria from the 2007 National Asthma Education and Prevention Program. Multiple ordinal regression was performed. RESULTS: The median age was 9 years, 61% had well-controlled asthma, and 29% were obese. The model included all main effects plus two interaction terms and was significant (χ2(7) = 22.17, p =.002). Females who were normal weight (OR, 2.78; 95% CI, 1.38-5.60, p =.004) or overweight (OR, 3.12; 95% CI, 1.26-7.72, p =.014) had better asthma control than obese females. For males, there were no differences by BMI category but males without allergic rhinitis had significantly better asthma control (OR, 2.23; 95% CI, 1.25-3.97, p =.006) than those with allergic rhinitis. CONCLUSIONS: Non-obese girls and non-allergic males had better asthma control. Promotion of healthy activity and nutrition as well as management of allergic rhinitis should be part of the asthma plan in school-based programs in low income urban areas. Innovative approaches to address asthma care in low income populations are essential.

Timeliness of Breast Cancer Treatment in Delaware.

Studies have shown timely screening, diagnosis, and treatment of breast cancer reduces mortality rates. The objective of this study was to evaluate the overall timeliness of breast cancer diagnosis and treatment for Delawarean women using the Centers for Disease Control and Prevention (CDC)'s National Breast and Cervical Cancer Early Detection Program (NBCCEDP)'s recommendations of 60 days maximum for screening to diagnosis and 60 days maximum for diagnosis to treatment. This study analyzed Delaware Cancer Registry data for female Delawarean breast cancer patients diagnosed in 2010 who had valid screening, diagnosis, and treatment dates. Calculations of 3 time intervals were performed: screening to diagnosis (time interval A), diagnosis to treatment (time interval B), and screening to treatment (time interval C). The mean and median for time intervals A (21.2 days, 17.0 days), B (27.8 days, 25.0 days), and C (49.0 days, 42.0 days) met CDC recommendations. Our results show most Delawarean women who had valid screening, diagnosis, and treatment dates received a diagnosis within 60 days of screening and first course of treatment occurred within 60 days of diagnosis and therefore met the NBCCEDP recommendations.

Nutritional support in children and young people with cancer undergoing chemotherapy.

BACKGROUND: It is well documented that malnutrition is a common complication of paediatric malignancy and its treatment. Malnutrition can often be a consequence of cancer itself or a result of chemotherapy. Nutritional support aims to reverse malnutrition seen at diagnosis, prevent malnutrition associated with treatment and promote weight gain and growth. The most effective and safe forms of nutritional support in children and young people with cancer are not known. OBJECTIVES: To determine the effects of any form of parenteral (PN) or enteral (EN) nutritional support, excluding vitamin supplementation and micronutrient supplementation, in children and young people with cancer undergoing chemotherapy and to determine the effect of the nutritional content of PN and EN. This is an update of a previous Cochrane review. SEARCH METHODS: We searched the following databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the National Research Register (2007) and Dissertations & Theses (2007). Experts in the field were also contacted for information on relevant trials. For this update, we searched the same electronic databases from 2006 to September 2013. We also scrutinised the reference lists of included articles to identify additional trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any form of nutritional support with another, or control, in children or young people with cancer undergoing chemotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials. At least two authors independently assessed quality and extracted data. We contacted trialists for missing information. MAIN RESULTS: The current review included the eight trials from the initial review and six new trials which randomised 595 participants (< 21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The trials were all of low quality with the exception of two of the trials looking at glutamine supplementation. One small trial found that compared to EN, PN significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33), serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00, 95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One trial comparing peripheral PN and EN with central PN found that mean daily weight gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI -26.81 to -3.19) were significantly less for the peripheral PN and EN group, whereas mean change in serum albumin was significantly greater for that group (MD 0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found an increase in mean energy intake (% recommended daily amount) in children fed an energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to 39%). Three studies looked at glutamine supplementation. The evidence suggesting that glutamine reduces severity of mucositis was not statistically significant in two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and differences in reduction of infection rates were also not significant in two studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one study compared olive oil based PN to standard lipid containing PN. Despite similar calorie contents in both feeds, the standard lipid formula lead to greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study compared standard EN with fructooligosaccharide containing EN. There was no difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to 0.33), with adverse effects (nausea) occurring equally between the groups (RR 0.92, 95% CI 0.48 to 1.74). AUTHORS' CONCLUSIONS: There is limited evidence from individual trials to suggest that PN is more effective than EN in well-nourished children and young people with cancer undergoing chemotherapy. The evidence for other methods of nutritional support remains unclear. Limited evidence suggests an energy dense feed increases mean daily energy intake and has a positive effect on weight gain. Evidence suggesting glutamine supplementation reduces incidence and severity of mucositis, infection rates and length of hospital stay is not statistically significant. Further research, incorporating larger sample sizes and rigorous methodology utilising valid and reliable outcome measures, is essential.

A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation. SUBJECTS AND METHODS: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility. Clinical status was evaluated at 1 day, 7-10 days, and 2 weeks after ablation. CE-MRI was performed 25-40 days after ablation, followed by surgical resection within 5 days. RESULTS: Ultrasound-guided cryoablation was uniformly technically successful, and postablation clinical status was good to excellent in all participants. Cryoablation was not clinically successful in 15% (three of 20 patients). Three participants had residual cancer at the periphery of the cryoablation site. Two participants had viable nonmalignant tissue within the central zone of cryoablation-induced necrosis. Postablation CE-MRI had a sensitivity of 0% (0/3) and specificity of 88% (15/17). The predictive value of negative findings on CE-MRI was 83% (15/18). Correlations between cancer characteristics, cryoablation procedural variables, postablation CE-MRI findings, and surgical specimen features were not statistically significant. There were also no significant differences in participants with or without residual cancer. CONCLUSION: In our pilot experience, ultrasound-guided cryoablation of invasive ductal carcinomas up to 15 mm has a clinical failure rate of 15% but is technically feasible and well tolerated by patients. The majority of cryoablation failures are manifest as DCIS outside the cryoablation field. Postablation CE-MRI does not reliably predict cryoablation outcome.

Medical anthropology and the physician assistant profession.

Medical anthropology is a subfield of anthropology that investigates how culture influences people's ideas and behaviors regarding health and illness. Medical anthropology contributes to the understanding of how and why health systems operate the way they do, how different people understand and interact with these systems and cultural practices, and what assets people use and challenges they may encounter when constructing perceptions of their own health conditions. The goal of this article is to highlight the methodological tools and analytical insights that medical anthropology offers to the study of physician assistants (PAs). The article discusses the field of medical anthropology; the advantages of ethnographic and qualitative research; and how medical anthropology can explain how PAs fit into improved health delivery services by exploring three studies of PAs by medical anthropologists.