Lack of insurance coverage and urgent care use for asthma: A retrospective cohort study

BACKGROUND: Asthma is a common chronic disease with profound impacts upon individuals and the US health care system. Inadequate health care coverage has been associated with more frequent and severe exacerbations of the disease. We examined the relationship between adequacy of health care coverage and use of emergent care of adults with asthma. METHODS: The 2001 Behavioral Risk Factor Surveillance System was the source of data on adults with current asthma. Bivariate and multiple logistic regression analysis modeled identifiable factors in predicting urgent or emergent care. RESULTS: Key variables included demographics and information on self-reported gaps in health care coverage. The primary outcome was emergency room or urgent care visits for worsening of asthma symptoms. Of 16,234 subjects nationally with current asthma, 2,195 from eight states had valid responses to a supplemental module asking about emergency room use or urgent care visits because of asthma. Thirty four percent of these individuals required such care in the previous year. Having an interruption in health care coverage in the past year was associated with an increased risk of needed urgent or emergent care (crude Odds Ratio [OR] 1.48, 95% confidence intervals [CI]1.03, 2.1). The association was not statistically significant in the adjusted multivariate model including race/ethnicity, employment status, gender, age, education and the ability to identify a primary physician (adjusted OR 1.2, 95% CI 0.8, 1.8). CONCLUSION: This study provides population-level, generalizable evidence of increased risk of exacerbations of asthma in adults and (1) their demographic characteristics, and (2) continuous adequate health care coverage

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain

Assessment of knowledge about childhood autism among paediatric and psychiatric nurses in Ebonyi state, Nigeria

<p>Abstract</p> <p>Background</p> <p>There is increasing public and professional awareness of autism spectrum disorders with early recognition, diagnosis and interventions that are known to improve prognosis. Poor knowledge about childhood autism among paediatric and psychiatric nurses who are members of multidisciplinary teams that care for such children may be a major barrier to early interventions that could improve quality of life and prognosis in childhood autism. Factors that influence knowledge about childhood autism among these nurses are not known. This study assessed knowledge about childhood autism among paediatric and psychiatric nurses in Ebonyi state, Nigeria and determined the factors that could be influencing such knowledge.</p> <p>Methods</p> <p>Forty specialist paediatric and forty psychiatric nurses, making a total sample of eighty, were randomly selected from all the health care facilities in Ebonyi state, Nigeria. A socio-demographic questionnaire and knowledge about childhood autism among health workers (KCAHW) questionnaire were administered to them and the study was a point survey.</p> <p>Results</p> <p>The total mean score on the KCAHW questionnaire among the nurses that participated in the study was 12.56 ± 3.23 out of a total of 19 possible. The mean score for the paediatric nurses was 11.78 ± 3.64 while psychiatric nurses had mean score of 13.35 ± 2.58. The mean scores in Domain 1 were 6.17 ± 1.75 for the paediatric nurses and 6.52 ± 1.43 for the psychiatric nurses. The mean scores in Domain 2 were 0.65 ± 0.48 for the paediatric nurses and 0.80 ± 0.41 for the psychiatric nurses. Domain 3 showed mean scores of 1.97 ± 1.25 for the paediatric nurses while psychiatric nurses scored 2.62 ± 1.23. Domain 4 yielded the mean scores of 2.97 ± 1.54 and 3.42 ± 0.98 for the paediatric and psychiatric nurses respectively.</p> <p>There was significant relationship between the total mean score on the KCAHW questionnaire for the two groups and the area of specialisation of the nurses (t = -2.23, df = 78, p = 0.03) and there was also significant relationship between previous involvement in managing children with childhood autism as a specialist paediatric or psychiatric nurse and the total mean score on the KCAHW questionnaire (t = 6.90, df = 78, p = 0.00).</p> <p>Conclusion</p> <p>The scores reflect deficits in knowledge about childhood autism among the study cohorts. Paediatric and psychiatric nurses as members of multidisciplinary teams that care for children with childhood autism are expected to provide holistic care and adequate counselling to the families of these children. Unfortunately in this environment, they are not fully equipped with enough knowledge about childhood autism. Education on childhood autism is therefore needed and can be provided through continuing medical education and emphasizing childhood autism in their training curriculum. This will enhance early identification and diagnosis of childhood autism with early interventions that are known to improve prognosis.</p

Depression after low-energy fracture in older women predicts future falls: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Falls are one of the main causes of fractures in elderly people and after a recent fracture, the risk of another fall is increased, resulting in subsequent fracture. Therefore, risk factors for future falls should be determined. We prospectively investigated the relationship between depression and the incidence of falls in post-menopausal women after a low-energy fracture.</p> <p>Methods</p> <p>At baseline, 181 women aged 60 years and older who presented with a recent low-energy fracture were evaluated at the fracture and osteoporosis outpatient clinics of two hospitals. As well as clinical evaluation and bone mineral density tests, the presence of depression (measured using the Edinburgh Depression Scale, EDS, depression cut-off > 11) and risk factors for falling were assessed. During two years of follow-up, the incidence of falls was registered annually by means of detailed questionnaires and interviews.</p> <p>Results</p> <p>Seventy-nine (44%) of the women sustained at least one fall during follow-up. Of these, 28% (<it>n </it>= 22) suffered from depression at baseline compared to 10% (<it>n </it>= 10) of the 102 women who did not sustain a fall during follow-up (<it>Χ</it>²= 8.76, df = 1, <it>p </it>= .003). Multiple logistic regression showed that the presence of depression and co-morbidity at baseline were independently related to falls (OR = 4.13, 95% CI = 1.58-10.80; OR = 2.25, 95% CI = 1.11-4.56, respectively) during follow-up.</p> <p>Conclusions</p> <p>The presence of depression in women aged 60 years and older with recent low-energy fractures is an important risk factor for future falls. We propose that clinicians treating patients with recent low-energy fractures should anticipate not only on skeletal-related risk factors for fractures, but also on fall-related risk factors including depression.</p

Differential activation of inflammatory pathways in A549 type II pneumocytes by Streptococcus pneumoniae strains with different adherence properties

BACKGROUND: Adherence of Streptococcus pneumoniae bacteria to lung cells is a first step in the progression from asymptomatic carriage to pneumonia. Adherence abilities vary widely among S. pneumoniae patient isolates. In this study, the binding properties of S. pneumoniae isolates and the effects of binding on activation of the Nuclear Factor-Kappa-B (NFκB) pathway and cytokine secretion by type II pneumocytes were measured. METHODS: Mechanisms of high- and low-binding S. pneumoniae adherence to A549 cells were investigated by blocking putative receptors on bacteria and host cells with antibody and by eluting choline-binding proteins off of bacterial surfaces. NFκB activation was measured by western blot and immunocytochemistry and cytokine secretion was detected by a protein array. RESULTS: This study shows that S. pneumoniae isolates from pneumonia patients (n = 298) can vary by as much as 1000-fold in their ability to bind to human lung epithelial cells. This difference resulted in differential activation of the NFκB pathway. High-, but not low-binding S. pneumoniae used Choline-binding protein A (CbpA) to bind to complement component C3 on epithelial cell surfaces. Interleukin-8 (IL-8) was the only cytokine secreted by cells treated with either low- or high-binding S. pneumoniae. CONCLUSION: These results indicate that S. pneumoniae clinical isolates are not homogeneous in their interaction with host epithelial cells. The differential activation of host cells by high- and low-binding S. pneumoniae strains could have implications for the treatment of pneumococcal pneumonia and for vaccine development

HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer Cells

BACKGROUND: The response rate to EGFR tyrosine kinase inhibitors (TKIs) may be poor and unpredictable in cancer patients with EGFR expression itself being an inadequate response indicator. There is limited understanding of the mechanisms underlying this resistance. Furthermore, although TKIs suppress the growth of HER2-overexpressing breast tumor cells, they do not fully inhibit HER2 oncogenic function at physiological doses. METHODOLOGY AND PRINCIPAL FINDINGS: Here we have provided a molecular mechanism of how HER2 oncogenic function escapes TKIs' inhibition via alternative HER receptor activation as a result of autocrine ligand release. Using both Förster Resonance Energy Transfer (FRET) which monitors in situ HER receptor phosphorylation as well as classical biochemical analysis, we have shown that the specific tyrosine kinase inhibitors (TKIs) of EGFR, AG1478 and Iressa (Gefitinib) decreased EGFR and HER3 phosphorylation through the inhibition of EGFR/HER3 dimerization. Consequent to this, we demonstrate that cleavage of HER4 and dimerization of HER4/HER2 occur together with reactivation of HER3 via HER2/HER3, leading to persistent HER2 phosphorylation in the now resistant, surviving cells. These drug treatment-induced processes were found to be mediated by the release of ligands including heregulin and betacellulin that activate HER3 and HER4 via HER2. Whereas an anti-betacellulin antibody in combination with Iressa increased the anti-proliferative effect in resistant cells, ligands such as heregulin and betacellulin rendered sensitive SKBR3 cells resistant to Iressa. CONCLUSIONS AND SIGNIFICANCE: These results demonstrate the role of drug-induced autocrine events leading to the activation of alternative HER receptors in maintaining HER2 phosphorylation and in mediating resistance to EGFR tyrosine kinase inhibitors (TKIs) in breast cancer cells, and hence specify treatment opportunities to overcome resistance in patients

Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants

The role of microbial colonization is indispensable for keeping a balanced immune response in life. However, the events that regulate the establishment of the microbiota, their timing, and the way in which they interact with the host are not yet fully understood. Factors such as gestational age, mode of delivery, environment, hygienic measures, and diet influence the establishment of microbiota in the perinatal period. Environmental microbes constitute the most important group of exogenous stimuli in this critical time frame. However, the settlement of a stable gut microbiota in preterm infants is delayed compared to term infants. Preterm infants have an immature gastrointestinal tract and immune system which predisposes to infectious morbidity. Neonatal microbial dynamics and alterations in early gut microbiota may precede and/or predispose to diseases such as necrotizing enterocolitis (NEC), late-onset sepsis or others. During this critical period, nutrition is the principal contributor for immunological and metabolic development, and microbiological programming. Breast milk is a known source of molecules that act synergistically to protect the gut barrier and enhance the maturation of the gut-related immune response. Host-microbe interactions in preterm infants and the protective role of diet focused on breast milk impact are beginning to be unveiled.M.C. acknowledges a “Rio Hortega” Research Fellowship Grant (CM13/0017) and M.V. acknowledges grants PI11/0313 and RD12/0026/0012 (Red SAMID) from the Instituto Carlos III (Spanish Ministry of Economy and Competitivity). M.C.C. and G.P-M. were supported by the grant AGL2013-47420-R from the Spanish Ministry of Science and Innovation.Peer reviewe

Behavioural activation by mental health nurses for late-life depression in primary care: a randomized controlled trial

Background: Depressive symptoms are common in older adults. The effectiveness of pharmacological treatments and the availability of psychological treatments in primary care are limited. A behavioural approach to depression treatment might be beneficial to many older adults but such care is still largely unavailable. Behavioural Activation (BA) protocols are less complicated and more easy to train than other psychological therapies, making them very suitable for delivery by less specialised therapists. The recent introduction of the mental health nurse in primary care centres in the Netherlands has created major opportunities for improving the accessibility of psychological treatments for late-life depression in primary care. BA may thus address the needs of older patients while improving treatment outcome and lowering costs.The primary objective of this study is to compare the effectiveness and cost-effectiveness of BA in comparison with treatment as usual (TAU) for late-life depression in Dutch primary care. A secondary goal is to explore several potential mechanisms of change, as well as predictors and moderators of treatment outcome of BA for late-life depression. Methods/design: Cluster-randomised controlled multicentre trial with two parallel groups: a) behavioural activation, and b) treatment as usual, conducted in primary care centres with a follow-up of 52 weeks. The main inclusion criterion is a PHQ-9 score > 9. Patients are excluded from the trial in case of severe mental illness that requires specialized treatment, high suicide risk, drug and/or alcohol abuse, prior psychotherapy, change in dosage or type of prescribed antidepressants in the previous 12 weeks, or moderate to severe cognitive impairment. The intervention consists of 8 weekly 30-min BA sessions delivered by a trained mental health nurse. Discussion: We expect BA to be an effective and cost-effective treatment for late-life depression compared to TAU. BA delivered by mental health nurses could increase the availability and accessibility of non-pharmacological treatments for late-life depression in primary care. Trial registration: This study is retrospectively registered in the Dutch Clinical Trial Register NTR6013on August 25th 2016. © 2017 The Author(s)

Outcomes for depression and anxiety in primary care and details of treatment: a naturalistic longitudinal study

<p>Abstract</p> <p>Background</p> <p>There is little evidence as to whether or not guideline concordant care in general practice results in better clinical outcomes for people with anxiety and depression. This study aims to determine possible associations between guideline concordant care and clinical outcomes in general practice patients with depression and anxiety, and identify patient and treatment characteristics associated with clinical improvement.</p> <p>Methods</p> <p>This study forms part of the Netherlands Study of Depression and Anxiety (NESDA).</p> <p>Adult patients, recruited in general practice (67 GPs), were interviewed to assess DSM-IV diagnoses during baseline assessment of NESDA, and also completed questionnaires measuring symptom severity, received care, socio-demographic variables and social support both at baseline and 12 months later. The definition of guideline adherence was based on an algorithm on care received. Information on guideline adherence was obtained from GP medical records.</p> <p>Results</p> <p>721 patients with a current (6-month recency) anxiety or depressive disorder participated. While patients who received guideline concordant care (N = 281) suffered from more severe symptoms than patients who received non-guideline concordant care (N = 440), both groups showed equal improvement in their depressive or anxiety symptoms after 12 months. Patients who (still) had moderate or severe symptoms at follow-up, were more often unemployed, had smaller personal networks and more severe depressive symptoms at baseline than patients with mild symptoms at follow-up. The particular type of treatment followed made no difference to clinical outcomes.</p> <p>Conclusion</p> <p>The added value of guideline concordant care could not be demonstrated in this study. Symptom severity, employment status, social support and comorbidity of anxiety and depression all play a role in poor clinical outcomes.</p