Prospective Multicenter Case-control Study Research Articles

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Risk factors for candidemia: a prospective matched case-control study

BackgroundCandidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs.MethodsThis prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia.ResultsOne hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia.DiscussionWhile this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU).ConclusionThis study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients’ management strategies and fungal epidemiology.

Abstract WP408: Risk of Lobar Intracerebral Hemorrhage From Hypertension is Greatest at an Early Age

Background: The risk of intracerebral hemorrhage (ICH) with hypertension (HTN) is well documented, with prior studies showing that HTN is the most important risk factor associated with ICH. Prior studies have shown that while the prevalence of HTN increases with age, the odds ratio (OR) of HTN for non-lobar ICH is greater earlier in life. We have previously found a lack of Apolipoprotein E allele association with lobar ICH in minority populations. Here we seek to determine if, similar to non-lobar ICH, the odds ratio of HTN for lobar ICH is greater at an earlier age. Methods: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Cases were enrolled from 42 sites. Controls matched to cases 1:1 by age (±5 years), sex, ethnicity/race, and metropolitan area were identified by random-digit dialing. Participants were interviewed to determine history of HTN. Participants were divided into age groups based on ethnicity-specific quartiles. Cases in each ethnic/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). ORs were calculated to show the risk of lobar ICH associated with HTN by quartile. Results: Overall, 917 lobar ICH cases and 932 controls were included. The Table shows the multivariable OR. ORs were highest in the youngest age quartile across all races (6.47 for blacks, 5.72 for Hispanics and 2.74 for whites). HTN produced a significant increase in risk for the youngest two quartiles in blacks and Hispanics, but only the youngest quartile in whites. However, the age of the lowest quartile in whites was equivalent to the bottom two quartiles in minorities. Discussion: Similar to non-lobar ICH, HTN earlier in life bears a greater risk of lobar ICH than later in life and this risk is across a greater range in disproportionately affected minorities. Research into how new onset or early life HTN leads to disproportionate risk compared to late life is needed.

OP34 Whole blood profiling of T-cell-derived miRNA allows the development of prognostic models in inflammatory bowel disease

Abstract Background There is an unmet need for blood-based biomarkers that help predict disease and its course at inception to allow tailoring of treatments, achieve early mucosal healing and improve clinical outcomes. In our study, we explore the clinical utility of miRNAs in Inflammatory bowel disease (IBD). Methods A 2-stage prospective multi-centre case–control study was performed. Small RNA sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes (90 CD4+ and CD8+ T-lymphocytes and CD14+ monocytes) from 32 patients (9 CD, 14 UC, 8 healthy controls) to identify differentially expressed cell-specific miRNAs.Top miRNAs were then validated in whole blood in 294 treatment naïve newly diagnosed IBD and non-IBD patients (97 UC, 98 CD, 98 non-IBD) using RT-qPCR, recruited across 5 centres in UK and Europe. Phenotype and outcome data were collected and Cox proportional hazards were derived to assess the contribution of each miRNA to outcomes; defined as the need for 2 or more immunosuppressants and/or surgery after initial disease remission. RT-qPCR target miRNA relative quantification was calculated using 2−ΔΔCq method. Results Each leucocyte subset (30 CD4+ T cells, 28 CD8+ T cells and 32 CD14+ monocytes) was analysed between disease and controls, adjusting for age, gender and batch effects. A total of three miRNAs differentiated IBD from controls in CD4+ T cells including miR-1307-3p (FDR p = 0.01), miR-3615 (p = 0.02) and miR-4792 (p = 0.01); these signals being UC specific. In CD8 T cells, miR-200b-3p was the only differentially expressed miRNA and no CD14+ signals were seen.Three miRNAs were validated in whole blood in an independent multi-centre cohort of 294 patients using RT-qPCR. miR-1307-3p predicted IBD (1.55 fold change (fc),IQR: 1.00–1.87; p = 2.77 × 10–5),in particular UC (1.69 fc, IQR: 1.01–2.00; p = 1.56 × 10–6). Similarly, miR-3615 and miR-4792 were up-regulated in UC compared with controls (1.21fc, IQR:0.91–1.48; p = 8.26 × 10−4and 1.91 fc, IQR: 0.81–2.56; p = 9.21 × 10–3, respectively).There was no correlation with conventional inflammatory markers. Follow-up data were available on 195 IBD patients of which 80 patients required treatment escalation over a median time of 371 days (IQR: 140–711). miR-1307-3p was able to predict disease course in IBD (HR 1.98, IQR: 1.20–3.27; log-rank p = 1.80 × 10−3), in particular CD (HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4). In UC, both miR-3615 (HR 3.34, CI: 1.43–7.78, p = 0.01) and miR-4792 (HR 3.96, CI: 1.65–9.52; p = 2.11 × 10–3) predicted treatment escalation. Conclusion We have identified unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These blood-based miRNAs are able to predict treatment escalation at disease inception and have the potential for clinical translation.

Clinical Findings and Electrodiagnostic Testing in Ulnar Neuropathy at the Elbow and Differences According to Site and Type of Nerve Damage.

The aim of the study was to evaluate the clinical and electrodiagnostic testing in ulnar neuropathy at the elbow and differences according to site (humeroulnar arcade vs. retroepicondylar groove) and injury physiopathology (axonal vs. demyelinating), through prospective multicenter case-control study. Cases and controls were matched by age and sex. Ulnar neuropathy at the elbow diagnosis was made on symptoms. Statistical analysis was performed using Mann-Whitney, χ, and analysis of variance tests. One hundred forty-four cases and 144 controls were enrolled. Sensory loss in the fifth finger had the highest sensitivity (70.8%) compared with clinical findings. Motor conduction velocity across elbow reached the highest sensitivity (84.7%) in localizing ulnar neuropathy at the elbow recording from at least one of the two hand muscles (first dorsal interosseous and abductor digiti minimi). Abnormal sensory action potential amplitude from the fifth finger occurred more frequently in axonal than in demyelinating forms. Differences between retroepicondylar groove and humeroulnar arcade regarded conduction block and job type. Clinical findings have less usefulness than electrodiagnostic testing in ulnar neuropathy at the elbow diagnosis. Motor conduction velocity across elbow recorded from both abductor digiti minimi and first dorsal interosseous increases diagnostic accuracy. Axonal forms have greater clinical and electrodiagnostic testing severity than demyelinating forms, which are more frequent in retroepicondylar groove. Manual workers prevailed in humeroulnar arcade. These findings may be helpful in prognostic and therapeutic approaches.

Palivizumab Prophylaxis in Preterm Infants and Subsequent Recurrent Wheezing. Six-Year Follow-up Study.

Respiratory syncytial virus (RSV) induces not only infantile recurrent wheezing but also potentially atopic asthma. To test the effect of RSV infection on development of subsequent atopic asthma, we evaluated whether palivizumab, an anti-RSV monoclonal antibody, by preventing severe RSV disease in the first year of life, could impact subsequent recurrent wheezing and atopic asthma at 6 years of age. During the 2007 to 2008 RSV season, the decision to administer palivizumab was made based on standard medical practice and an observational prospective multicenter (n = 52) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed from 0 to 3 years (preceding Committee on Recurrent Wheezing study). The 52 investigators at hospitals then followed these subjects until 6 years of age, reported here (Effects of Preventive Treatment for Respiratory Syncytial [RS] Virus Infection During Infancy on Later Atopic Asthma in Preterm Infants; Scientific Committee for Elucidation of Infantile Asthma). Parents of study subjects reported the infants' physicians' assessment of recurrent wheezing, using a report card and a novel mobile phone-based reporting system using the Internet. The primary endpoint was the incidence of atopic asthma. Of 444 preterm infants enrolled, 349 received palivizumab during the first year of life. At 6 years, atopic asthma was not different in the groups: 15.3 and 18.2% of infants in the treated and untreated groups, respectively (P = 0.57). On the other hand, physician-diagnosed recurrent wheezing was observed in 15.3 and 31.6% in the treated and untreated groups, respectively (P = 0.003). Palivizumab prophylaxis administered to preterm infants did not suppress the onset of atopic asthma but resulted in a significantly lower incidence of recurrent wheezing during the first 6 years. Clinical trial registered with www.clinicaltrials.gov (NCT 01545245).

Analysis of Immunogenetic Factors in Idiosyncratic Drug-induced Liver Injury in the Pediatric Population.

Idiosyncratic drug-induced liver injury is a multifactorial complex disease, in which the toxic potential of the drug, together with genetic and acquired factors and deficiencies in adaptive processes, which limit the extent of damage, can determine susceptibility, and make individuals unique in their development of hepatotoxicity. The aim of the present study is to analyse the genetic factors (human leukocyte antigen [HLA], cytokine polymorphisms, and killer cell immunoglobulin-like receptor [KIR] genotype) of children who experience an episode of drug-induced liver injury. Prospective multicentre case-control study. The subjects included in the study were 30 paediatric patients-infants and children ages between 0 and 15 years and who presented possible liver disease associated with the intake of medicines, herbal products, drugs, or toxins. As a control group, 62 subjects were selected. Although HLAC0401 and HLADQB0603 may provide a hepatoprotective mechanism in the paediatric population, HLADQA0102 and HLA-DR12 are more commonly found in sick children and their presence may be related to liver damage. The KIR inhibitor KIR3DL1 was not present in any child in the control group. Polymorphisms that are low producers of interleukin-10 occur more frequently in children who have experienced hepatotoxicity.

Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design.

Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case-control study enrolling patients aged 18-49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient-control pairs enrolled by the end of 2018. SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Changes In Leptin Level After Different Bariatric Procedures: Gastric Balloon And Sleeve Gastrectomy, And Its Relation To The Effectiveness Of Weight Loss.

Background: Obesity can affect the neuroendocrine system in various ways, either by hormonal elevation as in ghrelin and growth hormone or by depression as in the case of leptin and insulin. Leptin has been previously researched in its relation t o the energy homeostasis in obesity, however the effect of various surgical procedures are far from being fully understood. Methods: A prospective multicenter case control study was done including twenty non morbidly obese ( ≤ 40 kg/m 2 ) and morbidly obese (> 40 kg/m 2 )patients treated with IGB (control) or SG with base line and follow up after six months leptin level determination and weight loss assessment. Results: Leptin showed a highly significant (P<0.001) decrease six months after the insertion of the balloon. The mean decline of leptin hormone level was 8 ug/l (+/- 5.06). In the group of sleeve gastrectomy (SG), leptin showed a significant (P<0.05) decrease six months after the operation. The mean decline of leptin hormone level was 17.6 ug/l (+/ - 17.06). There was a statistically significant differe nce between the two groups as regard the weight loss (P<0.05). Conclusion: The effect of different intervention procedures on the neuroendocrine system can give us an important clue to the future of individualized therapy either in the further selection of patients to undertake the most beneficial cost effective procedure or to add adjuvant hormonal therapy to the treatment.

The International Endometriosis Evaluation Program (IEEP Study) - A Systematic Study for Physicians, Researchers and Patients.

Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.

Genetic systems for a new approach to risk of progression of diabetic retinopathy

ObjectiveTo evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). Material and methodsA prospective multicentre case–control study of 132 participants was distributed into: T2D with (+DR) or without (−DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY™ ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG−DR=6; CG=6) by performing next-generation sequencing (NGS). SPSS 15.0 statistical program was used to perform data analysis. ResultsThe mean age was 67±12 years in the T2DG vs. 55±21 years in the CG. Distribution men/women: 25/30 in T2DG vs. 51/28 in CG. A family history of DM, diet compliance, smoking, drinking and exercise, showed significant differences between groups (p<0.001). A 20–25μL sample of tears contained a mean of 9.42±3.30ng/mL of purified ARN, with significant differences between T2DG/CG (p=0.002) and T2DG+RD/CG (p=0.004). Tear expression of miARNs in T2DG directly correlated with age/obesity/T2D duration (p<0.05), and indirectly with visual acuity (p<0.05). A total of 14 miRNAs related to the presence, pathogenic mechanisms and risk factors for the progression of diabetic retinopathy, were identified. ConclusionsWe propose to use tears as a source of genetic information for DM. Specific miRNAs involved in DR development and/or progression can be used as molecular biomarkers, and based on these, for developing future biotherapies.

Sistemas genéticos para un nuevo abordaje del riesgo de progresión de la retinopatía diabética

ObjectiveTo evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). Material and methodsA prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (−DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ™ ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG−DR=6; CG=6) by performing next-generation sequencing (NGS). SPSS 15.0 statistical program was used to perform data analysis. ResultsThe mean age was 67±12 years in the T2DG vs. 55±21 years in the CG. Distribution men/women: 25/30 in T2DG vs. 51/28 in CG. A family history of DM, diet compliance, smoking, drinking and exercise, showed significant differences between groups (P<.001). A 20-25 microlitre sample of tears contained a mean of 9.42±3.30 ng/mL of purified ARN, with significant differences between T2DG/CG (P=.002) and T2DG+RD/CG (P=.004). Tear expression of miARNs in T2DG directly correlated with age/obesity/T2D duration (P<.05), and indirectly with visual acuity (P<.05). A total of 14 miRNAs related to the presence, pathogenic mechanisms and risk factors for the progression of diabetic retinopathy, were identified. ConclusionsWe propose to use tears as a source of genetic information for DM. Specific miRNAs involved in DR development and/or progression can be used as molecular biomarkers, and based on these, for developing future biotherapies.

Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome

In patients with preterm premature rupture of membranes, intrauterine inflammation and/or infection is frequently present, can lead to fetal inflammatory response syndrome, and is associated with adverse neonatal outcome. Clinical decision making requires balancing the potential benefits of pregnancy prolongation against the risk of intrauterine infection. Diagnostic tests in maternal serum are of moderate prediction value and amniocentesis is an invasive procedure. Therefore, markers obtained noninvasively would be helpful in patients with expectant management. To determine the predictive values of amniotic fluid interleukin-6 and tumor necrosis factor-α in vaginal secretions for fetal inflammatory response syndrome and/or histologic funisitis and for adverse neonatal outcome in patients with preterm premature rupture of membranes. In this prospective multicenter case-control study, vaginal secretions were sampled daily with a noninvasive method from 99 women with preterm premature rupture of membranes and expectant management. Amniotic fluid interleukin-6 and tumor necrosis factor-α were measured by 2 different immunoassays (an automated chemiluminescent enzyme immunoassay and a lateral flow immunoassay). After delivery, patients were divided into a control or a fetal inflammatory response syndrome group according to neonatal interleukin-6 in cord plasma and/or the presence of funisitis. Univariate and multivariate regression analyses were performed and prediction models were developed by calculating receiver operating characteristic curves. Gestational age at delivery was lower and latency period was longer in the fetal inflammatory response syndrome group compared to the control group. The strongest risk factor for composite adverse neonatal outcome was fetal inflammatory response syndrome (odds ratio, 2.48; confidence interval, 1.40-4.38). The median concentrations of amnioticfluid interleukin-6 and tumor necrosis factor-α in vaginal secretions were significantly higher in the fetal inflammatory response groupcompared to the control group in both immunoassays (P < .001). The area under the curve of the clinical reference model (including common clinical parameters) was 0.66. Adding interleukin-6 and tumor necrosis factor-α into the model improved the area under the curve to 0.92 (in both assays, interleukin-6 IMMULITE and QuickLine); 0.87 (tumor necrosis factor-α IMMULITE) and 0.94 (tumor necrosis factor-α QuickLine), respectively. The strongest risk factor for worse neonatal outcome (composite neonatal outcome) was fetal inflammatory response syndrome. Amniotic fluid interleukin-6 and tumor necrosis factor-α seem to be good predictors for fetal inflammatory response syndrome and for histologic funisitis and may improve the clinical management of patients with preterm premature rupture of membranes. The noninvasive technique of sampling amniotic fluid from vaginal secretions facilitates daily measurements and bedside assessment of cytokines and is in this respect preferable to invasive amniocentesis.

287 Homeless Patients in France: A National Case-Cohort Prospective Study

Homeless people represent a vulnerable population. Homelessness is associated with reduced life expectancy, increased risk of comorbidities, and increased incidence of psychiatric illness. Public hospitals and their emergency departments (EDs) are known to be used frequently by these patients. They can be seen as difficult to treat, and have an increased incidence of substance abuse and risk of violence in the ED. We aimed to analyse a large sample of homeless patients to determine the quality of care delivered to homeless people in French EDs. We tested the hypothesis that homeless patients experience suboptimal care by the provision of fewer health care resources. We conducted a prospective multicenter case-control study in 31 EDs in France. Our institutional review board authorized the study without the need for signed informed consent. We defined a homeless patient as a patient who currently lives on the street or in a shelter. During 72 hours from March 3, 2015, all homeless patients who visited the participating EDs were included in the study. One control patient was prospectively recruited after each case was included: the next patient who visited the ED with similar severity triage level (on a one to four scale), similar age (±ten years) and same sex. We retrieved demographic and social characteristics of included patients, along with their vital parameters, and characteristics of ED utilization. The primary outcome measures were length of stay, number of investigations per patient and treatment in the ED. A total of 212 homeless patients and 212 control patients were included in the study. Mean age was 44 (SD 13) years in both groups, and 87% were male. Homeless patients were more likely to have visited the ED in the past 28 days than other patients (47% vs 10%, P < .001). They presented with similar rates and types of comorbidities than control patients, except for a more frequent history of substance abuse. Heart rate, blood pressure, temperature, capillary blood glucose and Glasgow Coma Scale score were similar in both groups. Chief complaint was “housing demand” for 30 (14%) homeless patients. After excluding them, we found no difference in the type of chief complaint except for alcohol abuse, more frequent in homeless patients (20% vs 4%, P < .001). We found a similar median waiting time to physician assessment in the two groups (58 minutes for both), although mean length of stay was longer for homeless patients than for control patients (6.2 vs 3.9 hours, P < .001). We found no significant difference in the rate of radiological or biological investigations between the two groups. Similarly, we found no significant difference for the rate of oral or parenteral treatment administration, and admission rate was similar in the two groups (9% vs 7%, P = .6). Amongst the 182 analyzed homeless patients that visit the ED beside a housing demand, 53 (29%) were uninsured. We did not find a difference in the level of medical care delivered in French ED to homeless patients when compared to matched control. Resource consumption was similar for both groups, as was the admission rate. Nevertheless, homeless patients visit ED more often for an alcohol-related complaint, are often uninsured and have higher rates of return visit.

O30. Diet and preeclampsia: A prospective multicentre unmatched case control study in Ethiopia

Background Preeclampsia is one of the most commonly encountered hypertensive disorders of pregnancy that accounts for 20–80% of maternal mortality in developing countries, including Ethiopia. For many years diet have been suggested to play a role in preeclampsia. However, the hypotheses have been diverse and often revealed inconsistent results across studies, and this has not been studied in Ethiopia Objectives The objective of this study was to determine the effect of dietary habits on the incidence of preeclampsia Bahir Dar, Ethiopia Methods A prospective multicentre unmatched case- control study was conducted among 453 (151 cases and 302 controls) pregnant women attending antepartum or intrapartum care in public health facilities of Bahir Dar City Administration. Interviewer administered face to face interview, measurement of mid-arm circumference (MUAC) and document review were conducted using a standardized and pretested questionnaire. Data entry and cleaning was done by Epi.info version 3.5.3.The data were transported to SPSS version 20 for analysis. Both bivariate and multivariate logistic regression analyses were applied. Backward stepwise unconditional logistic regression analysis was employed to determine the putative association of predictive variables with the outcome variable and to control for the effect of confounding variables. A P -value 0.05 was considered to declare statistically significant throughout the study. Result For every 1-cm increase of MUAC, there was an increase in the incidence rate of preeclampsia by a factor of 1.35 ( AOR = 1.35, 95%CI:1.21, 1.51). A higher incidence of preeclampsia was found in women who reported to have consumed coffee daily during pregnancy ( AOR = 1.78, 95%CI: 1.20, 3.05). Similarly for women who had anemia during the first trimester the incidence of preeclampsia 2.5 times higher than their counterparts ( AOR = 2.47, 95%CI: 1.12,7.61). This study also revealed consumption of fruit or vegetables at least three times a week during pregnancy to be protective against preeclampsia ( AOR = 0.51, 95%CI: 0.29, 0.91; AOR = 0.46, 95%CI: 0.24, 0.90, respectively). In addition compliance with IFA during pregnancy has shown a significant independent effect on the prevention of preeclampsia in this study ( AOR = 0.16, 95%CI: 0.08, 0.29) Conclusion and recommendation Adequate vegetable and fruit consumption and compliance to folate intake during pregnancy are independent protective factors of preeclampsia. On the other hand, higher mid upper arm circumference, anemia and daily coffee intake during pregnancy are risk factors for the development of preeclampsia. Audience specific education and promotion for the use of the protective factors identified in this study should be strengthened. The risk factors identified can be used for prediction and early diagnoses of preeclampsia allowing timely interventions to be performed to minimize deaths associated with severe preeclampsia/eclampsia.

Diet and Pre-eclampsia: A Prospective Multicentre Case–Control Study in Ethiopia

IntroductionPre-eclampsia is one of the most commonly encountered hypertensive disorders of pregnancy that accounts for 20–80% of maternal mortality in developing countries, including Ethiopia. For many years, diet has been suggested to play a role in pre-eclampsia. However, the hypotheses have been diverse with inconsistent results across studies, and this has not been studied in Ethiopia. ObjectivesThe objective of this study was to determine the effect of dietary habits on the incidence of pre-eclampsia in Bahir Dar, Ethiopia MethodsA prospective multicentre unmatched case–control study was conducted among 453 (151 cases and 302 controls) pregnant women attending antepartum or intrapartum care in public health facilities of Bahir Dar City from June to September 2014. The interviewer conducted a face-to-face interview, measured the mid-upper arm circumference (MUAC) and collected the mid-pregnancy haemoglobin level from clinical notes using a standardized and pretested questionnaire. Epi Info 3.5.3 was used for data entry and cleaning, while IBM SPSS Statistics 20 was used for data analysis. Backward stepwise unconditional logistic regression analysis was employed to determine the strength of association of predictive variables with the outcome variable and to control for the effect of confounding variables. A P-value ≤0.05 was considered statistically significant. ResultFor every 1-cm increase of MUAC, there was an increase in the incidence rate of pre-eclampsia by a factor of 1.35 (adjusted odds ratio (AOR)=1.35, 95% confidence interval (CI): 1.21, 1.51). A higher incidence of pre-eclampsia was found in women who reported to have consumed coffee daily during pregnancy (AOR=1.78, 95% CI: 1.20, 3.05). Similarly, for women who had anaemia during the first trimester, the incidence of pre-eclampsia was 2.5 times higher than their counterparts (AOR=2.47, 95% CI: 1.12, 7.61). This study also revealed consumption of fruit or vegetables at least three times a week during pregnancy to be protective against pre-eclampsia (AOR=0.51, 95% CI: 0.29, 0.91; AOR=0.46, 95% CI: 0.24, 0.90, respectively). In addition, compliance with folate intake during pregnancy has shown a significant independent effect on the prevention of pre-eclampsia in this study (AOR=0.16, 95% CI: 0.08, 0.29). Conclusion and recommendationAdequate vegetable and fruit consumption and compliance with folate intake during pregnancy are independent protective factors against pre-eclampsia. On the other hand, higher MUAC, anaemia and daily coffee intake during pregnancy are risk factors for the development of pre-eclampsia. Audience-specific education and promotion of the use of the protective factors identified in this study should be prioritized. The risk factors identified can be used for prediction and early diagnoses of pre-eclampsia allowing timely interventions to be performed to minimize deaths associated with severe pre-eclampsia/eclampsia.

Birth experience of women conceiving with assisted reproduction: a prospective multicenter study.

To determine how infertility and subsequent assisted reproductive treatment (ART) affect a woman's childbirth experience. Prospective multicenter case-control study. We recruited women pregnant with a singleton fetus after either ART (n=324) or spontaneous conception (n=304) from five infertility clinics and one university maternity clinic in Finland. We studied their childbirth experience with the Delivery Satisfaction Scale. We compared how psychosocial and obstetric factors affected satisfaction and dissatisfaction with childbirth between and within the ART and the control group. Logistic regression was then used to analyse the most important contributors to the experienced dissatisfaction. Dissatisfaction with childbirth was as common in the ART group (11%) as in the control (10%) group. In the ART group, the women's education level, cesarean section (CS) and their partner's absence from the delivery were associated with dissatisfaction. In the control group, significant factors for dissatisfaction were nulliparity, severe pregnancy-related anxiety, emergency CS, recalled intense pain and the partner's absence from the delivery. According to adjusted logistic regression analysis of the whole sample, the independent risk factors were elective CS [odds ratio (OR) 5.7; 95% confidence interval (CI) 2.2-14.1] and emergency CS (OR 2.9; 95% CI 1.3-6.5), recalled intense pain (OR 6.8; 95% CI 3.3-16.2) and the partner's absence from the delivery (OR 2.7; 95% CI 1.1-7.3). ART is not a risk factor for dissatisfaction with childbirth by itself. However, the contributors to an unsatisfactory childbirth differ partly between women conceiving with ART and those conceiving spontaneously.

Natural Killer Lymphocytes Are Dysfunctional in Kidney Transplant Recipients On Diagnosis of Cancer.

Background: Cancer incidence is increased after kidney transplantation. Natural Killer (NK) cells are key effectors of the tumor immune response through activating receptors. In assessing immunological characteristics of T and NK cells from kidney transplant recipients (KTRs) who develop cancer, we found important deficiencies in NK cells. Patients and Methods: We conducted a prospective multicentre matched case-control study including 42 KTRs on diagnosis of cancer and 41 KTRs without cancer. Extensive phenotyping of T and NK cells populations was performed. Functional tests of NK cells were performed in a subset of patients. Results: KTRs with cancer had a significantly higher incidence of both acute rejection (P=0.02) and CMV infection (P=0.03) than matched controls. First, KTRs with cancer had more lymphopenia than control KTR (1020/mm3+/-32 vs 1218/mm3+/-34; P=0.001) including a significant CD4+ lymphopenia (P=0.01). Total CD3-/CD56+ NK cell counts were similar in KTRs with or without cancer. However, KTRs with cancer had a much lower frequency of the cytokine-enriched CD56bright NK cell subset (P=0.001), and consequently a higher CD56dim/bright ratio (P=0.005). The percentage of NK cells expressing NKp46 was decreased in KTRs with cancer both for all NK cells (44% vs 58%, P=0.01) and for CD56dim and CD56bright subsets. Furthermore, the NK cells showed functional deficiencies. The ability of NK cells to degranulate CD107a+ cytolytic vesicles was reduced in KTRs with cancer (11% vs 22% in control patients; P=0.01). In addition the percentage of NK cells secreting IFNg was decreased (7.5% in KTRs with cancer vs 28.8% in the control group; P=0.01). Conclusion: These results reveal an imbalance between NK cell subpopulations and functional NK defects in KTRs at the onset of malignancy. There was a decreased number of NK cells producing INFg. This study highlights the role of NKp46. Decreased expression of NKp46 may contribute to the initiation of malignancies. NKp46 could be considered as a potentially valuable marker during immunological follow-up of KTRss.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case–control study in the UK

ObjectiveSince 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the UK in men who have sex with men (MSM). Most cases present with proctitis, but there...

Abstract W P131: Light to Moderate Alcohol Intake and Lower Risk of Ischemic Stroke: A Matched Case-Control Study in Korean Population

Background: Heavy alcohol intake has consistently been identified as a risk factor for all type of stroke, whereas the effect of moderate drinking is less certain. Previous researches have limitation in declaring the dose-response relationship between alcohol intake and stroke because of the heterogeneity of stroke subtypes, the potential different effects across sex, race/ethnic group and the amounts of alcohol consumed. Objective: To determine the dose-response relationship between alcohol intake and risk of ischemic stroke in Korean population. Methods: We undertook a prospective multicenter matched case-control study in 9 hospitals between January 2011 and January 2012. Cases were patients hospitalized due to first-ever ischemic stroke within 7 days of onset, confirmed by diffusion-weighted MRI. Controls, obtained from the database of the 4th Korean National Health and Nutrition Examination Survey (KNHANES IV-V, between 2007-2010), had no history of stroke, and were matched with cases for age (± 3 years), sex and education level. All participants completed an interview using structured questionnaire about alcohol intake and past medical history. Results: During the study period, 1848 cases (mean age, 66.1 years; male, 58.9%) were enrolled and were matched to 3589 controls. Conditional logistic regression analysis found that light to moderate alcohol intake, up to 3-4 drinks (drink=10g ethanol) per day, was significantly protective for ischemic stroke after adjusting for hypertension, diabetes, hyperlipidemia, current smoking and body mass index (&lt;1 drink: OR 0.38, 95% CI 0.32-0.45; 1-2 drinks: OR 0.45, 95% CI 0.36-0.57; 3-4 drinks: OR 0.54 95% CI 0.39-0.74; ≥5 drinks OR 1.08 95% CI 0.84-1.40) in comparison to never drinking. These associations were not different among the subtypes of ischemic stroke. However, subgroup analysis according to sex revealed that the threshold of alcohol intake might differ by sex with respect to risk of ischemic stroke; decrease of risk up to &lt;1 drink in women vs. up to 3-4 drinks in men. Conclusion: Our findings suggest that light to moderate alcohol intake is associated with reduced risk of ischemic stroke and the margin of its protective effect may be different between men and women in the Korean population.