Mrs Joanna Latter

Background: Most trials of electronic alcohol screening and brief intervention (e-SBI) have been conducted in young people. The aim of this study was to evaluate the effect of e-SBI in adults with hazardous or harmful drinking. Methods: This individually randomized, parallel, two-group, double-blind controlled trial was conducted in the outpatient department of a large public hospital in Australia. Consenting adults who scored 5¿9 on the AUDIT-C (837/3225; 26%) were randomized in a 1:1 ratio by computer to screening alone (442/837; 53%) or to 10 min of assessment and personalized feedback on their alcohol consumption (comparisons with medical guidelines and age and sex-specific norms), peak blood alcohol concentration, expenditure on alcohol, and risk of alcohol dependence (395/837; 47%). The two primary outcomes, assessed six months after randomization, were the number of standard drinks (10 g ethanol) consumed by participants in the last seven days and their AUDIT score. Results: 693/837 (83%) and 635/837 (76%) participants were followed-up at 6 and 12 months, respectively. There was no statistically significant difference between the groups in the median number of standard drinks consumed in the last seven days (intervention: 12; control: 10.5; rate ratio, 1.12 [95% confidence interval, 0.96¿1.31]; P =.17) or in their median AUDIT score (intervention: 7; control: 7; mean difference, 0.28 [-0.42 to 0.98]; P =.44). Conclusion: These results do not support the implementation of an e-SBI program comprising personalized feedback and normative feedback for adults with hazardous or harmful drinking in the hospital outpatient setting.

Objective: There have been no trials in healthcare settings of genetic susceptibility feedback in relation to alcohol consumption. The purpose of this study was to determine the feasibility and acceptability of conducting a full-scale randomised trial estimating the effect of personalised genetic susceptibility feedback on alcohol consumption in hospital outpatients with risky drinking. Methods: Outpatients =18 years of age who reported drinking more than 14 standard drinks in the past week or in a typical week were asked to provide a saliva sample for genetic testing. Genetic susceptibility feedback was posted to participants 6 months after recruitment. The co-primary outcomes were the proportion of participants who (i) provided a saliva sample that could be genotyped, and (ii) spoke with a genetic counsellor. Secondary outcomes included changes in patients' weekly alcohol consumption; scores on scales measuring readiness to change, importance of changing and confidence in ability to change drinking habits; knowledge about which cancers are alcohol-attributable; and acceptability of the saliva collection procedure and the genetic-feedback intervention. McNemar's test and paired t-tests were used to test for differences between baseline and follow-up in proportions and means, respectively. Results: Of 100 participants who provided a saliva sample, 93 had adequate DNA for at least one genotyping assay. Three participants spoke to a genetic counsellor. Patients' readiness to change their drinking, their views on the importance of changing and their stated confidence in their ability to change increased between baseline and follow-up. There was no increase in patients' knowledge about alcohol-attributable cancers nor any reduction in how much alcohol they drank 4 months after receiving the feedback. Most participants (80%) were somewhat comfortable or very comfortable with the process used to collect saliva, 84% understood the genetic feedback, 54% found it useful, 10% had sought support to reduce their drinking after receiving the feedback, and 37% reported that the feedback would affect how much they drink in the future. Conclusion: Results of this study suggest it would be feasible to conduct a methodologically robust trial estimating the effect of genetic susceptibility feedback on alcohol consumption in hospital outpatients with risky drinking.

Background:Microvascular dysregulation following preterm birth is associated with increased illness severity and hypotension, particularly in males. Sympathetic nervous vascular regulation is evident in females. We hypothesized that sympathetic dysfunction in male preterm infants may contribute to a failure of peripheral microvascular vasoconstriction.Methods:Microvascular blood flow of infants 24-43 wk gestational age was assessed at 6, 24, and 72 h of age by laser Doppler. Blood flow Fourier transformed frequency distribution spectra (low frequency/high frequency ratio) were used to assess the influence of sympathetic tone on microvascular regulation. Total sympathetic output was assessed as urinary normetanephrine.Results:Microvascular sympathetic activity at 24 h postnatal age decreased in early preterm males, but not females. Peripheral sympathetic activity increased with advancing postnatal age in females, but decreased in males. In early preterm infants, total normetanephrine outputs increase significantly with postnatal age, in both sexes.Conclusion:Sympathetic activation following preterm birth is sexually dimorphic, with preterm males having reduced sympathetic tone and reduced upregulation of sympathetic tone following birth. There is evidence of a disconnect between central sympathetic activity and local peripheral microcirculatory sympathetic drive. This may relate to autonomic nervous immaturity and highlights the need to understand how preterm birth may affect autonomic function.

Objectives: Telephone follow-up is not currently recommended as a strategy to improve retention in randomized trials. The aims of this study were to estimate the effect of telephone follow-up on retention, identify participant characteristics predictive of questionnaire completion during or after telephone follow-up, and estimate the effect of including participants who provided follow-up data during or after telephone follow-up on balance between randomly allocated groups in a trial estimating the effect of electronic alcohol screening and brief intervention on alcohol consumption in hospital outpatients with hazardous or harmful drinking. Method: Trial participants were followed up 6. months after randomization (June-December 2013) using e-mails containing a hyperlink to a web-based questionnaire when possible and by post otherwise. Telephone follow-up was attempted after two written reminders and participants were invited to complete the questionnaire by telephone when contact was made. Results: Retention before telephone follow-up was 62.1% (520/837) and 82.8% (693/837) afterward: an increase of 20.7% (173/837). Therefore, 55% (95% CI 49%-60%) of the 317 participants who had not responded after two written reminders responded during or after the follow-up telephone call. Age. <. 55. years, a higher AUDIT-C score and provision of a mobile/cell phone number were predictive of questionnaire completion during or after telephone follow-up. Balance between randomly allocated groups was present before and after inclusion of participants who completed the questionnaire during or after telephone follow-up. Conclusion: Telephone follow-up improved retention in this randomized trial without affecting balance between the randomly allocated groups.

Background & Aims: Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. Methods: 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. Results: No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. Conclusions: The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.

Problem: Susceptibility to Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. Method of study: ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithelial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Results: Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells. Genes upregulated in progesterone-treated and Chlamydia-infected cells only included multiple CC and CXC chemokines, IL-17C, IL-29, IL-32, TNF-a, DEFB4B, LCN2, S100A7-9, ITGAM, NOD2, JAK1, IL-6ST, type I and II interferon receptors, numerous interferon-stimulated genes and STAT6. CXCL10, CXCL11, CX3CL1 and IL-17C, which were also upregulated in infected secretory-stage primary cells, and there was a trend towards higher levels of immune mediators in infected secretory-phase compared with proliferative-phase cells. Conclusion: Progesterone treatment primes multiple innate immune pathways in hormone-responsive epithelial cells that could potentially increase resistance to chlamydial infection. © 2013 John Wiley & Sons Ltd.

Background: Few studies have examined the prevalence of unhealthy alcohol use in the hospital outpatient setting. Our aim was to estimate the prevalence of unhealthy alcohol use among patients attending a broad range of outpatient clinics at a large public hospital in Australia. Methods: Adult hospital outpatients were invited to complete the Alcohol Use Disorders Identification Test Consumption questions (AUDIT-C) using an iPad as part of a randomised trial testing the efficacy of alcohol electronic screening and brief intervention. Unhealthy alcohol use was defined as an AUDIT-C score =5 among men and =4 among women. Results: Sixty percent (3616/6070) of invited hospital outpatients consented, of whom 89% (3206/3616) provided information on their alcohol consumption (either reported they had not consumed any alcohol in the last 12 months or completed the AUDIT-C). The prevalence of unhealthy alcohol use was 34.7% (95% confidence interval [CI]: 33.0-36.3%). The prevalence among men aged 18-24 years, 25-39 years, 40-59 years and 60 years and older, was 74.4% (95% CI: 68.4-80.4%), 54.3% (95% CI: 48.7-59.8%), 44.1% (95% CI: 39.9-48.3%), and 27.0% (95% CI: 23.6-30.4%), respectively (43.1% overall; 95% CI: 40.8-45.5%). The prevalence among women aged 18-24 years, 25-39 years, 40-59 years, and 60 years and older, was 48.6% (95% CI: 39.2-58.1%), 36.9% (95% CI: 31.2-42.6%), 25.2% (95% CI: 21.5-29.0%) and 14.5% (95% CI: 11.7-17.3%), respectively (24.9% overall; 95% CI: 22.7-27.1%). Conclusion: A large number of hospital outpatients who are not currently seeking treatment for their drinking could benefit from effective intervention in this setting.