bluuebunny/crossref_metadata_2025 huggingface dataset:
Double-Stranded RNA Induces Biphasic STAT1 Phosphorylation by both Type I Interferon (IFN)-Dependent and Type I IFN-Independent Pathways
Authors: Dempoya Junichi , Matsumiya Tomoh , Imaizumi Tadaatsu , Hayakari Ryo , Xing Fei , Yoshida Hidemi , Okumura Ken , Satoh Kei
Published: September 2012

Upon viral infection, pattern recognition receptors sense viral nucleic acids, leading to the production of type I interferons (IFNs), which initiate antiviral activities. Type I IFNs bind to their cognate receptor, IFNAR, resulting in the activation of signal-transducing activators of transcription 1 (STAT1). Thus, it has long been thought that double-stranded RNA (dsRNA)-induced STAT1 phosphorylation is mediated by the transactivation of type I IFN signaling. Foreign RNA, such as viral RNA, in cells is sensed by the cytoplasmic sensors retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5). In this study, we explored the molecular mechanism responsible for STAT1 phosphorylation in response to the sensing of dsRNA by cytosolic RNA sensors. Polyinosinic-poly(C) [poly(I:C)], a synthetic dsRNA that is sensed by both RIG-I and MDA-5, induces STAT1 phosphorylation. We found that the poly(I:C)-induced initial phosphorylation of STAT1 is dependent on the RIG-I pathway and that MDA-5 is not involved in STAT1 phosphorylation. Furthermore, pretreatment of the cells with neutralizing antibody targeting the IFN receptor suppressed the initial STAT1 phosphorylation in response to poly(I:C), suggesting that this initial phosphorylation event is predominantly type I IFN dependent. In contrast, neither the known RIG-I pathway nor type I IFN is involved in the late phosphorylation of STAT1. In addition, poly(I:C) stimulated STAT1 phosphorylation in type I IFN receptor-deficient U5A cells with delayed kinetics. Collectively, our study provides evidence of a comprehensive regulatory mechanism in which dsRNA induces STAT1 phosphorylation, indicating the importance of STAT1 in maintaining very tight regulation of the innate immune system.
Structure of Hepatitis C Virus Envelope Glycoprotein E2 Antigenic Site 412 to 423 in Complex with Antibody AP33
Authors: Kong Leopold , Giang Erick , Nieusma Travis , Robbins Justin B. , Deller Marc C. , Stanfield Robyn L. , Wilson Ian A. , Law Mansun
Published: September 2012

We have determined the crystal structure of the broadly neutralizing antibody (bnAb) AP33, bound to a peptide corresponding to hepatitis C virus (HCV) E2 envelope glycoprotein antigenic site 412 to 423. Comparison with bnAb HCV1 bound to the same epitope reveals a different angle of approach to the antigen by bnAb AP33 and slight variation in its β-hairpin conformation of the epitope. These structures establish two different modes of binding to E2 that antibodies adopt to neutralize diverse HCV.
A Species-Specific Amino Acid Difference in the Macaque CD4 Receptor Restricts Replication by Global Circulating HIV-1 Variants Representing Viruses from Recent Infection
Authors: Humes Daryl , Emery Sandra , Laws Elizabeth , Overbaugh Julie
Published: September 2012

HIV-1 replicates poorly in macaque cells, and this had hindered the advancement of relevant nonhuman primate model systems for HIV-1 infection and pathogenesis. Several host restriction factors have been identified that contribute to this species-specific restriction to HIV-1 replication, but these do not fully explain the poor replication of most strains of HIV-1 in macaque cells. Only select HIV-1 envelope variants, typically those derived from viruses that have been adapted in cell culture, result in infectious chimeric SIVs encoding HIV-1 envelope (SHIVs). Here we demonstrate that most circulating HIV-1 variants obtained directly from infected individuals soon after virus acquisition do not efficiently mediate entry using the macaque CD4 receptor. The infectivity of these viruses is ca. 20- to 50-fold lower with the rhesus and pig-tailed macaque versus the human CD4 receptor. In contrast, culture-derived HIV-1 envelope variants that facilitate efficient replication in macaques showed similar infectivity with macaque and human CD4 receptors (within ∼2-fold). The ability of an envelope to mediate entry using macaque CD4 correlated with its ability to mediate entry of cells expressing low levels of the human CD4 receptor and with soluble CD4 sensitivity. Species-specific differences in the functional capacity of the CD4 receptor to mediate entry mapped to a single amino acid difference at position 39 that is under strong positive selection, suggesting that the evolution of CD4 may have been influenced by its function as a viral receptor. These results also suggest that N39 in human CD4 may be a critical residue for interaction of transmitted HIV-1 variants. These studies provide important insights into virus-host cell interactions that have hindered the development of relevant nonhuman primate models for HIV-1 infection and provide possible markers, such as sCD4 sensitivity, to identify potential HIV-1 variants that could be exploited for development of better SHIV/macaque model systems.
Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past
Authors: Taubenberger Jeffery K. , Baltimore David , Doherty Peter C. , Markel Howard , Morens David M. , Webster Robert G. , Wilson Ian A.
Published: September 2012

The influenza pandemic of 1918–1919 killed approximately 50 million people. The unusually severe morbidity and mortality associated with the pandemic spurred physicians and scientists to isolate the etiologic agent, but the virus was not isolated in 1918. In 1996, it became possible to recover and sequence highly degraded fragments of influenza viral RNA retained in preserved tissues from several 1918 victims. These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics.
“Listening In” on How a Bacterium Takes Over the Plant Vascular System
Authors: Vinatzer Boris A.
Published: September 2012

Bacteria that infect the plant vascular system are among the most destructive kind of plant pathogens because pathogen proliferation in the vascular system will sooner or later shut down the plant’s water and nutrient supply and necessarily lead to wilting and, in the worst case, death of the entire plant. How bacterial plant pathogens adapted to life in the plant vascular system is still poorly understood. As described in a recent article, Caitilyn Allen and her group studied the archetypical vascular pathogen
Ralstonia solanacearum
, the causative agent of bacterial wilt disease in almost 200 crop and ornamental plant species, and they have described the results of a microarray analysis that allowed them to “listen in” on the pathogen’s sabotaging activity inside the plant [J. M. Jacobs et al.,

mBio
3(4):e00114-12, 2012

]. Besides gaining for the first time an almost complete picture of
R. solanacearum
gene expression during infection, this approach allowed revision of a wrong assumption about the activity of the pathogen’s type III secretion system during infection and uncovered the importance of sucrose as an energy source for vascular pathogens like
R. solanacearum
.
Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice
Authors: Li Guomin , Zhang Xuezhu , Cheng Haiyan , Shang Xuemei , Xie Hui , Zhang Xin , Yu Jianchun , Han Jingxian
Published: September 2012

Objectives

To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing.

Methods

Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique.

Results

The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group.

Conclusions

Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.
Nitrofurantoin-induced microangiopathic haemolytic anaemia and thrombocytopaenia in a patient with systemic lupus erythematosus
Authors: López-López Linnette , Rivera-Rodríguez Noridza , Vilá Luis M
Published: September 2012

Patients with systemic lupus erythematosus (SLE) may develop thrombotic thrombocytopaenic purpura (TTP) or TTP-like illness manifested by microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction between active SLE and TTP is difficult because these entities share similar clinical features. Drug-induced TTP caused by an immune-mediated reaction have been documented for several drugs. Herein, we report a middle-aged Hispanic woman with long-standing SLE, who developed a TTP-like illness characterised by MAHA and thrombocytopaenia after exposure to nitrofurantoin. The patient responded well to plasmapheresis and immunosuppressive therapy and has remained clinically stable after 18 months of follow-up. To our knowledge, this is the first case that reports the association between nitrofurantoin and a TTP-like presentation.
Cyclosporine-induced haemolytic anaemia in a child with juvenile dermatomyositis: Table 1
Authors: Queirós Gustavo , Romeira Ana Margarida , Brito Maria João , Conde Marta
Published: September 2012

Cyclosporine-induced haemolysis is a very rare adverse reaction. The few published cases in the literature are described in the context of haemolytic-uraemic syndrome in transplanted patients. We report a case of cyclosporine-induced haemolytic anaemia in a 9-year-old girl being treated for severe dermatomyositis.
Do helmets worn for hurling fail to protect the ear? Identification of an emerging injury pattern
Authors: Martin-Smith James D , Chan Jeffery C Y , Power Kieran T , Crowley Paddy J , Clover Anthony James P
Published: September 2012

Hurling is an Irish national game of stick and ball known for its ferocity, played by 190 000 players. Facial injuries were common but have been significantly reduced by legislation enforcing compulsory helmet wearing. Current standard helmets worn by hurlers do not offer protection to the external ear. Here we describe an emerging pattern of ear injuries and demonstrate the risk of external ear injuries in hurlers complying with current helmet safety standards. A 6-month retrospective analysis was carried out of patients attending Cork University Hospital (CUH) with ear lacerations sustained while hurling. Patient notes were reviewed and helmet manufacturers were interviewed. Seven patients were identified, all of whom sustained complex through ear lacerations while wearing helmets complying with current safety standards. Current helmet design fails to protect the external ear placing it at an increased risk of injury, a potential solution is to include ear protection in the helmet design.
Cohort study of the association of hypnotic use with mortality in postmenopausal women
Authors: Hartz Arthur , Ross John Jacob
Published: September 2012

Objective

Previous studies found an association between hypnotic use and mortality risk. The prospective outcome data and the many baseline risk factors included in the Women's Health Initiative (WHI) provide an opportunity to better understand the reasons for this association.

Setting

The WHI is a long-term national health study that focused on strategies for preventing disease in postmenopausal women. Participants were enrolled from 1993 to 1998.

Design

Baseline hypnotic use was evaluated for an association with subsequent mortality or disease after adjusting for baseline risk.

Subjects

148 938 postmenopausal women between the ages of 50 and 79 throughout the USA. The median follow-up was 8 years.

Main outcome measures

Mortality. Secondary outcomes included myocardial infarction, stroke, diabetes and seven types of cancer.

Results

For persons who use hypnotic medications almost daily the age-adjusted hazard ratio (HR) for mortality was 1.62 (95% CI 1.50 to 1.74). Greater hypnotic use was associated with less healthy levels of physical function, general health and smoking at baseline. After adjustment for these factors the HR for almost daily hypnotic use was 1.14 (1.06 to 1.23) for mortality and 1.53 (1.18 to 1.99) for melanoma; it was not significantly associated with increased incidence of other diseases tested. Less frequent hypnotic use and several types of sleeping difficulties were not associated with mortality, but sleeping more than 10 h a night had a risk-adjusted HR for mortality of 1.28 (1.01 to 1.61).

Conclusions

The association of hypnotic use with mortality and incident disease was greatly reduced after adjusting for baseline risk factors. These findings do not support a strong independent association of hypnotic use with most health outcomes.
OP19 Social Networks and Depressive Symptoms in Russia, Poland and the Czech Republic: Evidence from the Hapiee Study
Authors: Franchi M , Pikhart H , Bobak M , Kubinova R , Malyutina S , Croezen S
Published: September 2012

Background

In countries of Central and Eastern Europe, prevalence rates of depressive symptoms are as high as 20% in men and 40% in women. Inclusion in social networks has been found to be a strong predictor of depressive symptoms in other countries, but little research on this association has been carried out in Central and Eastern Europe. This study aims to examine this association in the adult urban population in Russia, Poland and the Czech Republic.

Methods

Cross-sectional analysis was performed on baseline data (2002–2005) from the Health Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study, involving men and women aged 45–69 from the adult urban population of the three countries of interest (Total N=25,674). Depressive symptoms were measured by the Centre for Epidemiological Studies Depression (CESD–20) scale. Inclusion in social networks was measured in terms of trust in informal or formal networks, and frequency of contacts with friends and distant relatives.

Results

In Russia and the Czech Republic, odds of depressive symptoms were higher for men (Russia, OR 3.94, 95%CI 2.37–6.54; Czech Republic OR 2.04, 95%CI 1.18–3.52) and women (Russia, OR 2.19, 95%CI 1.47–2.99; Czech Republic OR 1.87, 95%CI 1.10–3.16) who had nobody to rely upon, compared with those who relied on friends or family. The pattern of association between frequency of contact with distant relatives or friends and depressive symptoms varied according to gender and country of origin of participants. Not having relatives outside the household was predictive of depressive symptoms among Polish men (OR 1.54, 95% C.I. 1.10–2.15) and women (OR 2.01, 95% C.I. 1.36–2.97); and not having any friends was associated with higher odds of depressives symptoms among Russian women (OR 1.54, 95% C.I. 1.09–2.19), and Polish men (OR 1.60, 95% C.I. 1.15–2.22).

Conclusion

The results presented here suggest that exclusion from social networks is a strong predictor of depressive symptoms and that there is a country specific pattern of variation in how frequency of contact with social networks affects the risk of depressive symptoms. We argue that this variation could be due to differences in economic development and social capital of Russia, Poland and the Czech Republic.
OP41 Birth Size and Mortality in Breast Cancer Patients
Authors: Sovio U , Jones R , Koupil I
Published: September 2012

Background

Previous studies suggest that larger birth size is associated with a higher breast cancer incidence, but the few studies of birth measures and mortality in breast cancer cases have been inconclusive. The aim of this study was to investigate survival of women after breast cancer diagnosis (N=436) in the Uppsala Birth Cohort born in 1915–1929, who had detailed obstetric records available.

Methods

Cox regression was used to calculate hazard ratios (HR) and their 95% confidence intervals (CIs) for death from any cause after a breast cancer diagnosis until the end of 2010. Cancer register diagnoses were available from 1958. The main exposures were birth measures: gestational age (GA), birth length (BL), and birth weight (BW) for GA. They were converted to standard deviation (SD) scores to ensure comparability of the effect sizes. Analyses were performed with and without adjustment for own adult socio-economic position (SEP) measured by education, occupation and income. Analyses were additionally adjusted for age at breast cancer diagnosis, decade of diagnosis, and age at first birth. Adjustment for family SEP at birth was considered but omitted since it did not affect the estimates and was not related to mortality after adjustment for other confounders.

Results

In adjusted analyses, one SD increase in GA was associated with 7% (95% CI 2–12%) lower mortality and this association did not change after additional adjustments for BL or BW. There was no association between BL and mortality (adjusted HR=1.02 (0.91–1.16)). One SD increase in BW for GA was associated with 14% (1–29%) and 26% (9–46%) higher mortality without and with an additional adjustment for BL, respectively. Adjustment for SEP or other confounders did not substantially alter the estimates.

Conclusion

Our results suggest that both low GA and high BW for GA predict a higher mortality in breast cancer cases. This study strengthens the current evidence that size at birth is related to breast cancer mortality as well as incidence. It also brings in new evidence of the inverse relationship between GA and breast cancer mortality that has not been reported before. The observed associations persisted after an adjustment for SEP, although breast cancer cases from lower SEP are known to have a poorer survival and also birth measures are socially patterned. Further studies are needed to investigate how the observed associations are mediated.
OP42 Lifecourse Socioeconomic Position and Cognitive Function in Later Life in Central and Eastern Europe: Preliminary Findings from the Hapiee Study
Authors: Horvat P , Richards M , Bobak M
Published: September 2012

Background

Socioeconomic position (SEP) across the lifecourse is positively associated with cognitive function in later life in studies of Western populations, with later SEP likely mediating the effect of early life factors. However, it remains to be seen whether similar associations are observed in settings with markedly different social histories with apparently smaller income inequalities. This study aims to investigate the association between measures of SEP reflective of the lifecourse and cognitive function in mid and later life in three Central and Eastern European populations.

Methods

Cross-sectional analysis of 7,990 men and women aged 45–69 years in 2002 from the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study recruited in Novosibirsk (Russia), Krakow (Poland), and six Czech towns using random probability sampling. Measures of lifecourse SEP included self-reported childhood socioeconomic conditions (parental education, ownership of household amenities at age 10), own education and current material circumstances. Linear regression was used to estimate the associations between lifecourse SEP measures and three cognitive tests: verbal memory (recall of 10 words), verbal fluency (naming animals) and letter search speed. Fully adjusted models included health and lifestyle covariates (medical history, depression, alcohol, physical activity).

Results

Broadly similar patterns of associations were observed across countries. Indicators of SEP across the lifecourse made independent contributions to cognition, with stronger contributions from education and current asset ownership (an indicator of contemporary material circumstances), than from childhood socioeconomic conditions. Socioeconomic advantage was associated with higher levels of cognitive functioning. For example, in fully adjusted models, university education was associated with 3.9 (SE 0.7) word recall advantage in memory performance in Czech men and 2.2 (SE 0.5) and 2.7 (SE 0.3) word advantage in Russian and Polish men; in women these figures were 3.7 (SE 0.4), 3.0 (SE 0.5) and 3.2 (SE 0.3), respectively. The effect of childhood socioeconomic conditions on cognition was largely attenuated after adjustment for education and current material circumstances, suggesting mediation by later SEP measures.

Conclusion

Socioeconomic position across the lifecourse is an important predictor of cognition in mid and later life in these Eastern European populations. The attenuation of the effects of childhood SEP after adjustment for own education and current material circumstances supports the model where this association is, at least partly, mediated through later life measures of SEP. Future research should focus on lifecourse influences on cognitive aging trajectories as long-term follow-up of this cohort and other studies in Eastern European populations become available.
OP45 Caesarean Section and Subsequent Fetal Death: Systematic Review and Meta-Analysis
Authors: Neill SM O , Kearney PM , Kenny LC , Khashan AS , Henriksen TB , Lutomski JE , Greene RA
Published: September 2012

Background

Spontaneous miscarriage (the death of a fetus before 20 weeks of pregnancy), occurs in 10–15% of recognised pregnancies. Stillbirth (the death of a fetus after 24 weeks of pregnancy), occurs in approximately one in every 200 deliveries. The cause of miscarriage and stillbirth is frequently unknown. However, there is some evidence to suggest that previous Caesarean delivery may be a risk factor.

Objective: to compare the risk of fetal death in subsequent pregnancy by mode of delivery.

Methods

This was a systematic review of relevant studies identified through CINAHL, the Cochrane library, Embase, Medline, PubMed, SCOPUS and Web of Knowledge (1945 - November 2011), using a comprehensive search strategy, and cross-checking of reference lists. Study selection: cohort and case-control studies reporting on Caesarean delivery and spontaneous miscarriage or stillbirth. Two reviewers independently assessed titles, abstracts, and full articles to identify eligible studies, using a standardised data collection form.

Results

Miscarriage:From 6,857 titles identified, eight articles were included, totalling 147,017 women and 12,682 events. Odds ratios (ORs) were combined using a fixed-effect model to estimate the overall association using Review Manager Software. From the meta-analysis, the pooled OR estimate of miscarriage among women who previously delivered by Caesarean versus vaginally, was 1.11 [95% CI 1.06,1.17]. The OR of miscarriage was 1.26 [95% CI 0.54,2.92] for one case-control study, 1.11 [95% CI 1.06,1.17] for seven cohort studies and 1.11 [95% CI 1.06,1.17] for primiparous women (eight studies).

Stillbirth:From 6,857 studies identified, seven articles were included, totalling 1,661,335 pregnancies and 5,741 events. ORs were combined using a random effect model (due to the heterogeneity of included studies) to estimate the overall association. From the meta-analysis, the pooled OR estimate of stillbirth among women who previously delivered by Caesarean versus vaginally, was 1.32 [95% CI 1.11,1.57]. The OR of stillbirth was 1.30 [95% CI 1.03,1.64] for primiparous women (five studies), 1.40 [95% CI 1.24,1.59] for multiparous women (two studies), 1.80 [95% CI 1.27,2.55] for studies including all stillbirths (five studies) and, 1.20 [95% CI 1.02,1.42] for studies including only unexplained antepartum stillbirths (three studies).

Conclusion

Caesarean delivery compared to vaginal delivery is associated with an increased risk of spontaneous miscarriage by 11% and stillbirth by 32% in subsequent pregnancies. In light of the recently published National Institute for Health and Clinical Excellence (NICE) guidelines, which support a woman’s right to request a Caesarean delivery without medical reason, there is an urgent need to establish whether mode of delivery has a causal effect on risk of fetal death.
OP48 Increased Mortality Associated with Weekend Admission; A Result of Higher Severity of Illness at the Time of Admission?
Authors: Paudyal P , Shepheard-Walwyn T , Gericke C
Published: September 2012

Background

A number of studies have shown that weekend admissions to hospital are associated with significantly higher mortality compared with weekday admissions. Previous studies have suggested that the observed variability in weekend-weekday mortality is a consequence of the quality of care provided in hospital. However, little information exists on whether the increased mortality associated with weekend admission is explained by the relative severity of illness at the time of admission.

Methods

We performed a retrospective analysis of all emergency acute care admissions in England between April 2009 and March 2010 using Hospital Episode Statistics data. In-hospital mortality among patients who were admitted as emergency admission on weekends as compared to weekdays was analysed using the following measures: (1) overall deaths in hospital; (2) deaths in hospital within and after 3 days of admission (3) deaths in hospital among patients with ‘higher risk’ conditions and ‘lower risk’ conditions. The ‘higher risk’ conditions consisted of 103 Primary Diagnosis codes (ICD–10), which accounted for the 74% of in-hospital deaths in the UK. The remaining Primary Diagnosis codes were categorised as ‘lower risk’ conditions.

Results

There were 10,221,500 emergency hospital admissions during the two-year study period; 23.8% of the patients were admitted on weekends. A total of 391,938 patients died in hospital; a quarter of these died within 3 days of admission. Admission on weekends was associated with significantly higher in-hospital deaths as compared to weekday admission (Odds Ratio 1.11, 95% CI 1.10–1.12). Mortality within 3 days of admission (early deaths) was also higher for patients admitted on weekends (OR 1.16, 95%CI (1.14–1.17) and this difference persisted for both ‘higher risk’ and ‘lower risk’ conditions. However, when early deaths were excluded from the analysis, mortality was not affected by weekend admission.

Conclusion

Higher mortality was seen among patients admitted on weekends compared to those admitted on weekdays. However, as the odds ratio for deaths after 3 days of admission was not affected by day of admission, it is probable that the weekend admission effect on mortality is at least in part due to higher severity of illness at the time of admission rather than purely being a consequence of poorer quality of in hospital care at the weekend, and this warrants further investigation.
OP50 Alcohol Intake, Drinking Behaviour and Drinking Patterns as Predictors Of Employment Status in Working-Age Men in Izhevsk, Russia
Authors: Cook S A , Leon D A
Published: September 2012

Background

Hazardous alcohol consumption and unemployment are both associated with high mortality in Russia. Unemployment adversely affects mental and physical health. The relationship between alcohol and employment is complex as alcohol consumption may lead to unemployment but unemployment may also increase hazardous consumption. Very few longitudinal studies have investigated the effects of alcohol use on employment status. The objectives of this study were to investigate alcohol intake, drinking behaviour and drinking patterns as predictors of employment status in a longitudinal study of working-age men in Izhevsk, Russia.

Methods

Participants were 1217 men aged 25–54 resident in Izhevsk, Russia in regular paid employment at baseline (2003–6) who were followed up and re-interviewed (2008–9). Alcohol use was measured by total volume of ethanol consumed from beverage alcohol, drinking behaviour (abstainers, beverage alcohol drinkers with no problem drinking behaviour, beverage alcohol drinkers with problem drinking behaviour and non-beverage alcohol drinkers (e.g. eau de cologne)), and three aspects of drinking pattern (drinking spirits without food, drinking alone and drinking before noon). Problem drinking was defined as twice weekly or more frequency of hangover, excessive drunkenness, sleeping in clothes because of drunkenness or one or more episodes of zapoi in the past year (defined as continuous drunkenness of two or more days during which participants were withdrawn from normal life). Logistic regression was used to investigate whether alcohol use at baseline predicted employment status at follow up after adjusting for socio-demographic variables.

Results

Total volume of ethanol from beverage alcohol at baseline did not predict whether men were still in regular paid employment at follow-up (P value for linear trend=0.21). Problem drinkers (adjusted odds ratio 2.82 95% CI 1.23, 6.46) and non-beverage alcohol drinkers (adjusted odds ratio 2.42 (95% CI 1.18, 4.93) were more likely not to be in regular employment at follow-up than non-problem beverage alcohol drinkers. Among drinkers drinking spirits without food (adjusted odds ratio 2.13 95% CI 1.28, 3.54), drinking alone (adjusted odds ratio 1.65 95% CI 1.09, 2.50) and drinking before noon (adjusted odds ratio 2.49 95% CI 1.65, 3.78) all predicted employment status at follow-up.

Conclusion

Drinking behaviour and drinking patterns predicted future employment status in a sample of working-age men in Izhevsk Russia. However the volume of alcohol consumed per year did not, suggesting how alcohol is consumed and whether it leads to problem behaviour is more important than the overall amount consumed when considering the impact of alcohol on employment.
OP63 Associations of All-Cause and Cause-Specific Mortality with body Mass Index in a Large Norwegian Cohort: Use of Offspring Body Mass Index as an Instrumental Variable
Authors: Carslake DJ , Smith G Davey , Gunnell D , Nilsen TIL , Romundstad P
Published: September 2012

Background

People with high body mass index (BMI) suffer elevated rates of mortality from a variety of causes, particularly from cardiovascular disease (CVD). Some studies have also found elevated mortality at low BMI, but it is unclear whether this represents a causal association. Potential confounding by existing ill-health is of particular concern. To avoid this problem, we used the BMI of an offspring as an instrument for the parent’s BMI, as well as conducting conventional analyses of parental mortality against their own BMI.

Methods

We extracted 33,011 mother-offspring and 28,142 father-offspring pairs from HUNT, a large prospective cohort study conducted in Nord-Trøndelag county, Norway. Participants’ BMI was adjusted for age, sex, secular trends and smoking status. Associations of parental mortality rates with their own BMI were estimated as hazard ratios using Cox regression. Age was the time axis, and we adjusted for smoking, alcohol, exercise, education and employment. Additionally, adjusted causal hazard ratios between parental mortality and BMI were estimated using offspring BMI as an instrument for parental BMI and cubic splines were fitted to all associations to assess their linearity.

Results

There were 9,271 maternal and 9,889 paternal deaths within the follow-up period of 1984–2009. The associations of all-cause, CVD and cancer mortality with parents’ own BMI were substantially nonlinear, with elevated mortality at both extremes and minima at 21–25 kg m–2. Hazard ratios for all-cause mortality per standard deviation (4.1 kg m–2) of own BMI were 1.04 (95% CI: 1.02, 1.06) and 1.05 (1.02, 1.08) in mothers and fathers, respectively. In contrast, associations of mortality with offspring BMI were approximately linear and positive. Causal hazard ratios per standard deviation of BMI estimated from the instrumental variable analyses were 1.20 (1.11, 1.30) and 1.11 (1.02, 1.22) for all-cause mortality in mothers and fathers, respectively. For CVD they were 1.26 (1.13, 1.41) and 1.15 (1.01, 1.30), and for cancer they were 1.23 (1.05, 1.45) and 1.07 (0.90, 1.27).

Conclusion

These results confirm the elevated mortality from all causes, CVD and cancer in subjects with high or low BMI. The use of an offspring’s BMI as an instrument suggests that the elevated mortality at low BMI in this and other studies may be the result of confounding by existing ill-health, and that the causal relationship between BMI and mortality is positive and approximately linear.
OP67 Do Doctors Contribute to the Social Patterning of Disease? Contrasting Findings from an Epidemiologic Survey and a Decision Making Experiment
Authors: McKinlay J.B.
Published: September 2012

Background

That type 2 diabetes mellitus (T2DM) varies significantly by race and ethnicity is a widely accepted fact. It is often invoked as a base rate (a prioriprobability) during the process of clinical reasoning. Epidemiological studies repeatedly show undiagnosed T2DM varies more by socioeconomic status (SES), than by race/ethnicity. This study seeks to understand the discrepancy between the true prevalence of undiagnosed T2DM by SES and its continually reported prevalence by race/ethnicity.

Methods

Data from two different but complementary studies are employed: a) a large Boston Area Community Health (BACH) survey; and b) a factorial experiment conducted with primary care doctors to examine variations in clinical decision making. The BACH epidemiologic survey (n=5502) employed a stratified, multi-stage cluster sample design and used multivariable techniques including logistic regression. The factorial experiment concerning decision making employed clinically authentic videotaped scenarios presented to primary care doctors (n=192), and used ANCOVA analyses.

Results

Results from the epidemiologic survey show that both undiagnosed signs and symptoms and diagnosed T2DM vary similarly by socio-economic status (SES). This finding is independently corroborated by National Health and Nutrition Examination Survey (NHANES) data for diagnosed T2DM. Complementary data from the clinical decision making experiment show the diagnosis of T2DM varies significantly by a patients’ race/ethnicity, controlling for SES, age and gender in the design. While undiagnosed signs and symptoms of T2DM in the community vary significantly by SES, rather than race/ethnicity, following diagnosis by primary care doctors they vary more by race/ethnicity, rather than by SES.

Conclusion

Race/ethnicity and SES in the US are almost totally confounded, such that measuring one is essentially also measuring the other. Consequently, doctors generally get the social patterning of T2DM right, but for entirely the wrong reason. Continued patterning of T2DM by race/ethnicity motivates the search for genetic and biophysiologic explanations and distracts attention from the more important and potentially modifiable contribution of SES circumstances to the prevalence of T2DM.
OP79 Youth Exposure to Television Alcohol Advertising in the UK
Authors: Patil S , Elliott M N , Winpenny E M , Rohr C , Nolte E
Published: September 2012

Background

Increasing evidence suggests that exposure to alcohol marketing increases the likelihood that adolescents will start to drink alcohol and that among those who already consume alcohol exposure to alcohol advertising is likely to increase its use. Existing research in Europe has tended to focus on the content of alcohol marketing and advertising but our understanding of the actual levels of exposure remains inadequate. This study aims to contribute to filling this gap by analysing youth exposure to television alcohol advertising in the UK.

Methods

We obtained data on viewership and on alcohol advertising volume for the top ten television channels with the highest number of viewers in the UK by age (4–9, 10–15, 16–24, 25 plus) for December 2010 to May 2011. Data were analysed descriptively to characterise youth viewership by channel, month and time of the day (‘daypart’) and alcohol advertising exposure. We then used a negative binomial regression model to measure incidental youth exposure to alcohol advertising relative to adults over 25 years of age. We applied sensitivity analyses to test robustness of the model.

Results

Viewership and alcohol advertising volume varied substantially across the 10 channels, months and dayparts. Children and adolescents (10–15 years) constituted about 4% of the total audience and young people (16–24 years) 8%, yet their exposure to alcohol commercials was 5% and 50%, respectively. Relative to adults 25 years of age and older, the regression analysis found advert intensity was higher where children and adolescents constituted a greater proportion of the viewership (incident rate ratio (IRR) 1.09, 95% CI 1.02, 1.17, p =0.013). This relationship was particularly strong for commercials of beer and cider (IRR =1.14, 95% CI 1.06, 1.23, p =0.000), super market brands (IRR =1.16, 95% CI 1.07, 1.28, p =0.000), and ready-mix drinks (IRR =1.51, 95% CI 1.27, 1.78, p =0.000). In contrast, although the IRR for those aged 16 to 24 years also differed significantly from that observed for older adults, the difference was small (1.02, 95% CI 1.01, 1.04, p =0.003 ). There were no statistically significant associations for wine and spirit advert incidence and viewership for any of the younger population groups.

Conclusion

Our findings suggest that young people in the UK have a disproportionately higher exposure to television alcohol (except wine and spirits) advertising than would be expected from general viewership patterns. Alcohol advertising practices should be modified to limit exposure of underage viewers.
OP82 An Evaluation of the Effect of the New School Food Policy on Children’s Nutritional Intake and Socio-Economic Consequences in North East England
Authors: Spence S , Shen J , Delve J , White M , Vale L , Adamson AJ
Published: September 2012

Background

After 20 years with no regulation of school food and a plethora of evidence on the state of children’s diets, new food and nutrient-based standards were re-introduced in 2006 to schools in England. As a major policy change receiving financial and legislative support from Government, our objectives were to evaluate the effect of this policy on children’s nutritional intake, and its wider consequences including the added costs.

Methods

A cross-sectional study was undertaken in primary (n=13) and middle (n=5) schools in North East England. Dietary, anthropometric and socio-economic data were collected from children aged 4–7y and 11–12y using identical quantitative methods pre, and post-implementation. In the 4–7y olds a four day food diary was completed using an observational method, the 11–12y olds completed 2x3 day food diaries followed by an interview. Economic analysis was conducted in the form of cost-consequence analysis, comparing the differences in costs with all of its possible consequences in a tabular format.

Results

The effect of lunch type (school or packed) and year had a significant effect on total dietary intake in the 4–7y olds (n=1,017). Children having school lunches post-implementation had a slightly higher mean daily intake of energy (93 kcals, p=0·004), but lower mean daily % energy from fat (3%, p<0·001) and saturated fat (1%, p<0·001). Mean daily intakes of micronutrients such as vitamin C, and iron were higher in children consuming school lunches. In contrast, there was limited evidence of the effect of lunch type post-implementation on the total diet in 11–12y olds (n=883). The exception was % energy from fat. In 1999–2000 children consuming a school lunch had a higher % energy from fat than those consuming a packed lunch, post-implementation this difference was no longer apparent. The cost per school meal following implementation of the school food policy is higher than pre-implementation, ranging from £29 to £55 per child per year depending on how differences in prices of food pre and post-implementation were adjusted for inflation. Wider social consequences, for example, a reduction in socio-economic inequality, educational benefits and change in health behaviour were also set against the increased cost.

Conclusion

These findings demonstrate that the introduction of the school food policy has the potential to have a positive impact not only on food eaten at school but also on children’s total diet. Economic analysis highlights the trade-offs between significant improvement of nutrient intakes of children and the increased cost.
OP91 Does Anonymity Increase the Reporting of Mental Health Symptoms?
Authors: Fear NT , Seddon R , Jones N , Greenberg N , Wessely S
Published: September 2012

Background

There is no doubt that the perceived stigma of having a mental disorder acts as a barrier to help seeking. It is possible that individuals may be reluctant to admit to symptoms suggestive of poor mental health when data can be linked to them, even if their personal details are only used to help them access care. This may be particularly relevant because individuals who have a mental health problem are more likely to experience barriers to care and hold stigmatising beliefs. If that is the case, then mental health screening programmes where personal details are required may not be effective in detecting those most in need of care. We aimed to compare mental health symptom reporting when using an anonymous versus identifiable questionnaire among UK military personnel on deployment in Iraq (early 2009).

Methods

This was a survey among UK military personnel using two questionnaires, one anonymous (n=315) and one identifiable (n=296). Questionnaires were distributed by alternative allocation. The questionnaire included the 12-item General Health Questionnaire (measuring symptoms of common mental disorder, CMD), the Post-Traumatic Stress Disorder (PTSD) Checklist Civilian Version (measuring probable PTSD) and 11 stigma statements relating to barriers of care and perceived social stigma.

Results

Of 612 personnel approached to take part, 99.8% completed the survey. The overall prevalence of probable PTSD was 3.3% and 20.5% for symptoms of CMD. No significant difference in the reporting of symptoms of CMD was found (18.1% identifiable vs. 22.9% anonymous, P=0.150). Personnel were more likely to report borderline and probable PTSD when completing questionnaires anonymously (borderline PTSD: 2.4% identifiable vs. 5.8% anonymous; probable PTSD: 1.7% identifiable vs. 4.8% anonymous, P=0.022). Of the 11 barriers to care and perceived social stigma statements considered, those completing the anonymous questionnaire were more likely to endorse: “leaders discourage the use of mental health services” (9.3% vs. 4.6%, P=0.029), “it would be too embarrassing” (41.6% vs. 32.5%, P=0.023) and “I would be seen as weak” (46.6% vs. 34.2%, P=0.003).

Conclusion

We found a significant effect on the reporting of PTSD and certain stigmatising beliefs (but not CMD) when using an anonymous compared to identifiable questionnaire. Our findings have implications for the current post-deployment screening policy used in the US militaryin which identifiable data are collected. These results suggest that researchers need to weigh up the balance between full anonymisation against the use of non-anonymised but confidential survey methods, which permit future follow up.
OP93 Orlistat and the Risk of Acute Liver Injury: A Self-Controlled Case-Series Study in United Kingdom General Practice Research Database
Authors: Langham J , Smeeth L , Brauer R , Bhaskaran K , Douglas I
Published: September 2012

Background

In 2009, based on spontaneous reports of serious liver injury the US Food and Drug Administration announced Orlistat may be linked to an increased risk of hepatic events. However, no causal association has been established. The aim of this study was to investigate the association between Orlistat and the incidence of acute liver injury.

Methods

This was a self-controlled case-series design using the United Kingdom General Practice Research Database (GPRD) and linked Hospital Episode statistics (HES). People were eligible if they had an incident occurrence of idiopathic acute liver injury with a diagnoses recorded (in GPRD or HES) and were exposed to Orlistat at any time in the observation period. If there was evidence of a known cause for liver disease, such as alcoholism, patients were excluded. Observation time for each patient was divided into strata determined by Orlistat exposure status (30 day strata) and current age. Within-person rate ratios (with 95% confidence intervals) for liver injury were estimated using conditional Poisson regression (Stata 12), comparing exposed with unexposed periods.

Results

In the GPRD, between 1999 and 2010, 94,695 people had received at least one prescription for Orlistat, of whom 1,741 had an eligible diagnosis recorded. Of these, 408 people fulfilled eligibility criteria for a definite event (including abnormal liver function test results and a referral). We found a higher incidence of events in the first 30 days of exposure, (compared to unexposed) RR 2.27 (95% CI 1.12 to 4.59) and in the 90 day pre-exposure period RR 1.96 (95% CI 1.35 to 2.85). There was no difference in the incidence of events between 90 days prior and 0–90 days post prescribing, RR 0.78 (95% CI 0.42 to 1.42).

Conclusion

This is the first study we are aware of to explore the risk of incident liver injury associated with Orlistat. We found an increased risk of liver events in the 90 days immediately prior to and post first Orlistat prescription, but no difference in risk between the pre and initial exposure periods. This suggests that Orlistat may be initiated during a period of time when adverse liver events are more likely due to poor underlying health, but does not suggest the risk increases with initiation of Orlistat.