Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4‐/‐ mice

The role of CC chemokine receptor 4 (CCR4) during the development and maintenance of Th2type allergic airway disease is controversial. In this study, we examined the role of CCR4 in the chronic allergic airway response to live Aspergillus fumigatus spores, or conidia, in A. fumigatussensitized mice. After the conidia challenge, mice lacking CCR4 (CCR4‐/‐ mice) exhibited significantly increased numbers of airway neutrophils and macrophages, and conidia were more rapidly eliminated from these mice compared with control CCR4 wild‐type (CCR4+/+) mice. Significant airway hyperresponsiveness to intravenous methacholine was observed at day 3 in CCR4‐/‐ mice, whereas at days 7 and 30, airway hyperresponsiveness was attenuated in these mice compared with control mice. A major reduction in peribronchial and airway eosinophilia was observed in CCR4‐/‐ mice at all times after conidia challenge in contrast to CCR4+/+ mice. Further, whole lung levels of interleukin (IL) 4 and IL‐5 were significantly increased in CCR4‐/‐ mice at day 3, whereas these Th2 cytokines and IL‐13 were significantly decreased at day 30 in CCR4‐/‐ mice compared with their wild‐type counterparts. Peribronchial fibrosis and goblet cell hyperplasia were similar in both groups of mice throughout the course of this model. In summary, CCR4 modulates both innate and acquired immune responses associated with chronic fungal asthma.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154441/1/fsb2fasebj16100193-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154441/2/fsb2fasebj16100193.pd

Using electronic patient records to assess the effect of a complex antenatal intervention in a cluster randomised controlled trial-data management experience from the DESiGN Trial team.

BACKGROUND: The use of electronic patient records for assessing outcomes in clinical trials is a methodological strategy intended to drive faster and more cost-efficient acquisition of results. The aim of this manuscript was to outline the data collection and management considerations of a maternity and perinatal clinical trial using data from electronic patient records, exemplifying the DESiGN Trial as a case study. METHODS: The DESiGN Trial is a cluster randomised control trial assessing the effect of a complex intervention versus standard care for identifying small for gestational age foetuses. Data on maternal/perinatal characteristics and outcomes including infants admitted to neonatal care, parameters from foetal ultrasound and details of hospital activity for health-economic evaluation were collected at two time points from four types of electronic patient records held in 22 different electronic record systems at the 13 research clusters. Data were pseudonymised on site using a bespoke Microsoft Excel macro and securely transferred to the central data store. Data quality checks were undertaken. Rules for data harmonisation of the raw data were developed and a data dictionary produced, along with rules and assumptions for data linkage of the datasets. The dictionary included descriptions of the rationale and assumptions for data harmonisation and quality checks. RESULTS: Data were collected on 182,052 babies from 178,350 pregnancies in 165,397 unique women. Data availability and completeness varied across research sites; each of eight variables which were key to calculation of the primary outcome were completely missing in median 3 (range 1-4) clusters at the time of the first data download. This improved by the second data download following clarification of instructions to the research sites (each of the eight key variables were completely missing in median 1 (range 0-1) cluster at the second time point). Common data management challenges were harmonising a single variable from multiple sources and categorising free-text data, solutions were developed for this trial. CONCLUSIONS: Conduct of clinical trials which use electronic patient records for the assessment of outcomes can be time and cost-effective but still requires appropriate time and resources to maximise data quality. A difficulty for pregnancy and perinatal research in the UK is the wide variety of different systems used to collect patient data across maternity units. In this manuscript, we describe how we managed this and provide a detailed data dictionary covering the harmonisation of variable names and values that will be helpful for other researchers working with these data. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 02/11/16

Socioeconomic conditions and number of pain sites in women

<p>Abstract</p> <p>Background</p> <p>Women in deprived socioeconomic situations run a high pain risk. Although number of pain sites (NPS) is considered highly relevant in pain assessment, little is known regarding the relationship between socioeconomic conditions and NPS.</p> <p>Methods</p> <p>The study population comprised 653 women; 160 recurrence-free long-term gynecological cancer survivors, and 493 women selected at random from the general population. Demographic characteristics and co-morbidity over the past 12 months were assessed. Socioeconomic conditions were measured by Socioeconomic Condition Index (SCI), comprising education, employment status, income, ability to pay bills, self-perceived health, and satisfaction with number of close friends. Main outcome measure NPS was recorded using a body outline diagram indicating where the respondents had experienced pain during the past week. Chi-square test and forward stepwise logistic regression were applied.</p> <p>Results and Conclusion</p> <p>There were only minor differences in SCI scores between women with 0, 1-2 or 3 NPS. Four or more NPS was associated with younger age, higher BMI and low SCI. After adjustment for age, BMI and co-morbidity, we found a strong association between low SCI scores and four or more NPS, indicating that there is a threshold in the NPS count for when socioeconomic determinants are associated to NPS in women.</p

Measuring socio-demographic differences in volunteers with a value-based index: illustration in a mega event

The phenomenon of volunteering can be analysed as a consumer experience through the concept of value as a trade-off between benefits and costs. In event volunteering, both the expected value (pre-experienced) and the perceived value (post-experienced) of volunteering can be assessed. With this purpose, an online quantitative survey is conducted with a sample of 711 volunteers in a religious mega event, with questions related to five dimensions of their experience: efficiency, social value, play, spirituality and time spent. These five scales, properly tested are used for building a multidimensional index of both the expected and perceived value of the volunteer experience. ANOVAs test show significant differences on the index in both moments upon the socio-demographic profiles: negative expectations/experience balance by age, contrasted results by sex, and more experienced volunteers being more critical with the value experienced. Implications for event managers are proposed, in line with the motivation of volunteers

The emergence of health inequalities in early adulthood: evidence on timing and mechanisms from a West of Scotland cohort

Background Evidence is inconsistent as to whether or not there are health inequalities in adolescence according to socio-economic position (SEP) and whether or when they emerge in early adulthood. Despite the large health inequalities literature, few studies have simultaneously compared the relative importance of ?health selection? versus ?social causation? at this life-stage. This study followed a cohort through the youth-adult transition to: (1) determine whether, and if so, when, health inequalities became evident according to both class of origin and current SEP; (2) compare the importance of health selection and social causation mechanisms; and (3) investigate whether these phenomena vary by gender. Methods Data are from a West-of-Scotland cohort, surveyed five times between age 15 (in 1987, N=1,515, response=85%) and 36. Self-reported physical and mental health were obtained at each survey. SEP was based on parental occupational class at 15, a combination of own education or occupational status at 18 and own occupational class (with an additional non-employment category) at older ages. In respect of when inequalities emerged, we used the relative index of inequality to examine associations between both parental and own current SEP and health at each age. In respect of mechanisms, path models, including SEP and health at each age, investigated both inter and intra-generational paths from SEP to health (?causation?) and from health to SEP (?selection?). Analyses were conducted separately for physical and mental health, and stratified by gender. Results Associations between both physical and mental health and parental SEP were non-significant at every age. Inequalities according to own SEP emerged for physical health at 24 and for mental health at 30. There was no evidence of selection based on physical health, but some evidence of associations between mental health in early adulthood and later SEP (intra-generational selection). Paths indicated intra-generational (males) and inter-generational (females) social causation of physical health inequalities, and intra-generational (males and females) and inter-generational (females) social causation of mental health inequalities. Conclusions The results suggest complex and reciprocal relationships between SEP and health and highlight adolescence and early adulthood as a sensitive period for this process, impacting on future life-chances and health

Mastery, perceived stress and health-related behaviour in northeast Arnhem Land: a cross-sectional study

BACKGROUND: Indigenous peoples in Australia are disadvantaged on all markers of health and social status across the life course. Psychosocial factors are implicated in the aetiology of chronic diseases and in pathways underpinning social health disparities. Minimal research has investigated psychosocial factors and health in Indigenous peoples. This study evaluated associations between mastery, perceived stress, and health-related behaviour for a remote Indigenous population in Australia. METHODS: Complete data on mastery (the degree to which individuals feel in control of their lives), perceived stress, physical activity, and fruit and vegetable consumption were obtained for 177 participants in a community-based chronic disease risk factor survey. Psychosocial questionnaires were completed as an option during community screening (response rate = 61.9%). Extensive consultation facilitated the cross-cultural adaptation of measures. RESULTS: Mastery was inversely correlated with perceived stress measures (p < 0.009): recent stress, r = -0.47; chronic stress, r = -0.41; and youth stress, r = -0.30. Relationships between mastery and behaviour varied according to age group (<25 or ≥25 years) for physical activity (p = 0.001) and vegetable consumption (p = 0.005). Individuals aged ≥25 years engaging in ≤2 bouts of physical activity/week had lower mastery than individuals engaging in ≥3 bouts/week, with means (95% CI) of 14.8 (13.7–15.8) and 17.1 (15.3–19.0), respectively (p = 0.026). Individuals aged ≥25 years eating vegetables ≤3 times/week had lower mastery than those eating vegetables ≥4 times/week (p = 0.009) [means 14.7 (13.8–15.5) and 17.3 (15.5–19.1), respectively]. Individuals <25 years engaging in ≤2 bouts of physical activity/week had greater mastery than individuals engaging in ≥3 bouts/week (p = 0.022) [means 17.2 (15.2–19.2) and 13.8 (11.9–15.7), respectively]. For men ≥25 years and women ≥15 years, mastery was inversely related to age (p < 0.002). Men <25 years had less mastery than women of equivalent age (p = 0.001) [means 13.4 (12.1–14.7) and 17.5 (15.3–19.8), respectively]. CONCLUSION: Consistent with previous research, this study provides additional support for a link between mastery and health-related behaviour, and extends evidence of this association to a remote Indigenous population. Mastery's association with perceived stress, its age-specific association with health behaviour, and findings of low mastery amongst young men, highlights a need for life course research accounting for contextual factors affecting Indigenous peoples

Migrant health in French Guiana: Are undocumented immigrants more vulnerable?

<p>Abstract</p> <p>Background</p> <p>Few data exist on the health status of the immigrant population in French Guiana. The main objective of this article was to identify differences in its health status in relation to that of the native-born population.</p> <p>Methods</p> <p>A representative, population-based, cross-sectional survey was conducted in 2009 among 1027 adults living in Cayenne and St-Laurent du Maroni. Health status was assessed in terms of self-perceived health, chronic diseases and functional limitations. The migration variables were immigration status, the duration of residence in French Guiana and the country of birth. Logistic regression models were conducted.</p> <p>Results</p> <p>Immigrants account for 40.5% and 57.8% of the adult population of Cayenne and St-Laurent du Maroni, respectively. Most of them (60.7% and 77.5%, respectively) had been living in French Guiana for more than 10 years. A large proportion were still undocumented or had a precarious legal status. The undocumented immigrants reported the worst health status (OR = 3.18 [1.21-7.84] for self-perceived health, OR = 2.79 [1.22-6.34] for a chronic disease, and OR = 2.17 [1.00-4.70] for a functional limitation). These differences are partially explained by socioeconomic status and psychosocial factors. The country of birth and the duration of residence also had an impact on health indicators.</p> <p>Conclusion</p> <p>Data on immigrant health are scarce in France, and more generally, immigrant health problems have been largely ignored in public health policies. Immigrant health status is of crucial interest to health policy planners, and it is especially relevant in French Guiana, considering the size of the foreign-born population in that region.</p

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474

Identifying the quality of life effects of urinary incontinence with depression in an Australian population

Background: To explore the additive effect of urinary incontinence, in people with comorbid depression, on health related quality of life. Methods: Males and females, 15 to 95 years (n = 3010, response rate 70.2%) were interviewed face to face in the 1998 Autumn South Australian Health Omnibus Survey. Results: Self-reported urinary incontinence was found in 20.3% (n=610), and depression as defined by the PRIME-MD in 15.2% (n=459) of the survey population. Urinary incontinence with comorbid depression was found in 4.3% of the overall population. Univariate analysis showed that respondents with urinary incontinence and comorbid depression were more likely to be aged between 15 and 34 years and never married when compared to those with incontinence only. Multivariate analysis demonstrated that in people with incontinence, the risk of having comorbid depression was increased by an overall health status of Fair or Poor, or the perception that their incontinence was moderately or very serious. Respondents reporting that they experienced incontinence with comorbid depression scored significantly lower than those experiencing incontinence without depression on all dimensions of the SF-36. The interaction of the presence of incontinence and the presence of depression was significantly associated with the dimensions of physical functioning. Conclusions: Depression and incontinence both reduce QOL. When they occur together there appears to be an additive effect which affects both physical and mental health, perhaps by increasing a person’s negative perceptions of their illness. Clinicians should identify and manage comorbid depression when treating patients who have incontinence to improve their overall QOL.Jodie C Avery, Nigel P Stocks, Paul Duggan, Annette J Braunack-Mayer, Anne W Taylor, Robert D Goldney and Alastair H MacLenna