International Multicenter Cohort Study Research Articles

Exploration and Confirmation of Factors Associated With Uncomplicated Pregnancy in Nulliparous Women

Objective To identify factors at 15 and 20 weeks’ gestation associated with a subsequent uncomplicated pregnancy. Design Prospective international multicentre observational cohort study. Setting Auckland, New Zealand and Adelaide, Australia (exploration and local replication dataset) and Manchester, Leeds, and London, United Kingdom, and Cork, Republic of Ireland (external confirmation dataset). Participants 5628 healthy nulliparous women with a singleton pregnancy. Main outcome measure Uncomplicated pregnancy, defined as a normotensive pregnancy delivered at >37 weeks’ gestation, resulting in a liveborn baby not small for gestational age, and the absence of any other significant pregnancy complications. In a stepwise logistic regression the comparison group was women with a complicated pregnancy. Results Of the 5628 women, 3452 (61.3%) had an uncomplicated pregnancy. Factors that reduced the likelihood of an uncomplicated pregnancy included increased body mass index (relative risk 0.74, 95% confidence intervals 0.65 to 0.84), misuse of drugs in the first trimester (0.90, 0.84 to 0.97), mean diastolic blood pressure (for each 5 mm Hg increase 0.92, 0.91 to 0.94), and mean systolic blood pressure (for each 5 mm Hg increase 0.95, 0.94 to 0.96). Beneficial factors were prepregnancy fruit intake at least three times daily (1.09, 1.01 to 1.18) and being in paid employment (per eight hours’ increase 1.02, 1.01 to 1.04). Detrimental factors not amenable to alteration were a history of hypertension while using oral contraception, socioeconomic index, family history of any hypertensive complications in pregnancy, vaginal bleeding during pregnancy, and increasing uterine artery resistance index. Smoking in pregnancy was noted to be a detrimental factor in the initial two datasets but did not remain in the final model. Conclusions This study identified factors associated with normal pregnancy through adoption of a novel hypothesis generating approach, which has shifted the emphasis away from adverse outcomes towards uncomplicated pregnancies. Although confirmation in other cohorts is necessary, this study implies that individually targeted lifestyle interventions (normalising maternal weight, increasing prepregnancy fruit intake, reducing blood pressure, stopping misuse of drugs) may increase the likelihood of normal pregnancy outcomes. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000551493.

Abstract 19787: Transcatheter Aortic Valve Implantation in Patients With Bicuspid Aortic Valve: a Patient Level Multi-center Analysis

Objective: The purpose of the study was to determine the safety and efficacy of TAVI in patients with stenotic bicuspid aortic valve (BAV). Background: To date, patients with BAV have been excluded from major TAVI studies due to a theoretical increased risk of paravalvular leak (PVL). Data on the clinical performance of TAVI in these patients is limited. Methodology: We conducted a retrospective international multicenter cohort study of patients with BAV undergoing TAVI. The primary outcome of the study was the combined early safety endpoint - a composite of 30 day mortality, stroke, life-threatening bleeding, acute kidney injury, coronary artery obstruction, major vascular complication and valve related dysfunction. Secondary endpoints included the individual components of the primary endpoint as well as post TAVI paravalvular leak (PVL), rehospitalization, new pacemaker insertion and device success rates at 30 days and 1 year. Results: A total of 107 patients with BAV were identified in 21 centers in Canada, Spain, Italy, Poland and Singapore who underwent TAVI between January 2005 and March 2014. The composite primary outcome occurred in one third of patients (28.6%) - mainly driven by re-intervention for valve malposition (12.3%). The 30-day and 1 year mortality rate was 9.7% and 17.2% respectively with AR ≥ 3+ occurring in 8.8% of patients. Device success was achieved in 85% of cases with pacemaker insertion in 17.9%. While PVL was not associated with an increased risk of 30 day or 1 year mortality - Type I BAV anatomy with left and right cusp fusion had significantly better outcomes than other variants. Conclusion: In selected patients with BAV and severe aortic stenosis TAVI appears both safe and feasible with acceptable clinical outcomes. A randomized comparison of TAVI versus surgical aortic valve replacement in this patient population is warranted.

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Exploration and confirmation of factors associated with uncomplicated pregnancy in nulliparous women: prospective cohort study

Objective To identify factors at 15 and 20 weeks’ gestation associated with a subsequent uncomplicated pregnancy. Design Prospective international multicentre observational cohort study. Setting Auckland, New Zealand and Adelaide, Australia...

The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation

Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan-Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31-1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.

Poor Outcomes after Whole Brain Radiotherapy in Patients with Brain Metastases: Results from an International Multicentre Cohort Study

AimsTo describe the characteristics and outcomes of cancer patients receiving Whole Brain Radiotherapy (WBRT) and delineate poor outcome groups after WBRT. Materials and methodsFrom 1991 to 2007, 3459 patients receiving WBRT for brain metastases at three centres (in Australia and the Netherlands) were retrospectively reviewed. The effect of clinicodemographic factors, including age, gender, primary cancer, time to WBRT from primary cancer diagnosis and WBRT timing relative to other radiotherapy courses on overall survival, survival from WBRT commencement (WBRT-SV) and death within 6 weeks were analysed. ResultsWBRT was the first radiotherapy course in 2161/3459 (63%) and the last in 2932/3459 (85%). The most common primary cancer sites with brain metastases were lung (n = 1800; 52%), breast (n = 568; 16%), melanoma (n = 350; 10%) and colorectal (n = 209; 6%). The median time to WBRT from primary cancer diagnosis was 34 weeks, overall survival 1.42 years (0.04–28.70) and WBRT-SV 0.33 years (0–8.60). Older age, male gender and a shorter time from the primary cancer diagnosis to WBRT predicted worse overall survival and WBRT-SV. Seventeen per cent survived less than 6 weeks. Older patients with a shorter time from the primary cancer diagnosis to WBRT and a lower WBRT episode number were more likely to die less than 6 weeks after WBRT. ConclusionsCancer patients with brain metastases have poor overall outcomes. High mortality within 6 weeks of starting WBRT suggests patient selection remains challenging.

Prospective food diaries demonstrate breastfeeding characteristics in a UK birth cohort.

Breastfeeding duration and exclusive breastfeeding rates are universally below those recommended by World Health Organization. Due to limitations and challenges associated with researching breastfeeding characteristics, the times when exclusivity is likely to be lost and when women are most likely to discontinue breastfeeding have not yet been identified. Prospective food diaries allow reliable description of the dynamics of breastfeeding to be made to help identify these key time periods. Food diaries detailing intake from birth until the cessation of breastfeeding were analysed for 718 infants recruited into a national arm of an international multicentre birth cohort study (EuroPrevall). Analyses included linear regression analysis and Kaplan-Meier time course analysis. Breastfeeding and exclusive breastfeeding cessation rates for younger mothers (<25 years) are high in the first few weeks after delivery but slow markedly in the period 10-12 weeks after delivery. Cessation rates are consistent from 0 to 26 weeks in older mothers. This difference in feeding patterns led to significant differences between the two different age groups at 26 weeks for breastfeeding (P = 0.006) and exclusive breastfeeding at 8 weeks (P = 0.009). Forty-nine per cent of younger mothers (<25 years) stopped breastfeeding before their infant was 3 weeks old. To increase breastfeeding duration, further work is required to investigate the attitudes and perceptions associated with such high breastfeeding cessation rates in younger mothers during these very early post-natal weeks.

Maintenance Therapy with Opium Tincture for Injecting Drug Users; Implications for Prevention from Viral Infections

Maintenance Therapy with Opium Tincture for Injecting Drug Users; Implications for Prevention from Viral Infections

Cardiovascular Risk among Stable Individuals Suspected of Having Coronary Artery Disease with No Modifiable Risk Factors: Results from an International Multicenter Study of 5262 Patients

To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥ 50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality.

Cancer risk in systemic lupus: An updated international multi-centre cohort study

ObjectiveTo update estimates of cancer risk in SLE relative to the general population. MethodsA multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. ResultsAcross 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person–years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61–0.88), endometrial (SIR 0.44, 95% CI 0.23–0.77), and possibly ovarian cancers (0.64, 95% CI 0.34–1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). ConclusionThese data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study

IntroductionHyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients.MethodsThis is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes.ResultsAmong patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands >140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV >20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes.ConclusionsAlthough hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.See related commentary by Krinsley, http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot, http://ccforum.com/content/17/2/134

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

IntroductionData are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients.MethodsWe performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality.ResultsOf the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0 ± 40.1 ml/kg for underweight, 43.2 ± 33.4 for normal BMI, 37.1 ± 30.8 for obese and 27.7 ± 22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese).ConclusionsThe obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome.

Analytic comments of the initial results of the VISION (Vascular events In noncardiac Surgery patIents cOhort evaluatioN): Association between troponin T and mortality at 30 days in noncardiac surgery patients

The initial results of the VISION study (Vascular events In noncardiac Surgery patIents cOhort evaluatioN) have recently been published in JAMA. VISION was proposed, designed, and directed by the team of Dr. Devereaux (McMaster University, Ontario, Canada), a cardiologist--epidemiologist who runs a perioperative ischemia research program. VISION is a prospective international multicenter cohort study, with more than 20,000 patients recruited to date. The two participating centers in Spain, with over 3700 patients included, are, respectively, Hospital Sant Pau in Barcelona, and Hospital Gregorio Maranon, in Madrid. The study initially intended

Abstract 9643: Effect of Partial Fatty Acids Oxidation Inhibition With Trimetazidine on Survival in Heart Failure: Results From an International Multicentre Retrospective Cohort Study

Background: Trimetazidine (TMZ) shifts myocardial energy production from free fatty acids to glucose oxidation, a more efficient metabolic pathway. Previous small studies in patients with chronic heart failure (CHF) have shown that TMZ can improve contractile left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. Methods: In this international multicentre retrospective cohort study 669 patients (521 post-ischaemic) from the CHF clinics of our institutions were recruited. 362 patients (288 post-ischaemic) were on TMZ (20 mg tid or 35 mg bid) due to symptoms persistence (dyspnoea on exertion, fatigue, orthopnoea, oedema, alone or in combination) despite up titration of optimal CHF medical therapy, while the remaining patients continued conventional CHF therapy alone. Effects of TMZ administration were evaluated by Kaplan-Meier survival analysis and Cox-Regression survival analysis. Obtained results were corrected with propensity score (PS) in order to minimize selection bias. The protocol has been registered in the Italian Pharmaceutical Agency (AIFA) - Italian Ministry of Health, on the observational studies registry, ID number 458. Results: Kaplan-Meier analysis for global mortality showed 11•3% improved global survival (p=0•015) and 8•5% improved survival for death from cardiovascular disease (CVD) causes (p=0•050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a PS-corrected hazard ratio (HR)= 0•189 (confidence interval - CI 95%: 0•079-0•454; p=0•0002). TMZ also showed a good risk reduction profile for CVD death causes (PS-adjusted HR=0•072, CI 95%: 0•019-0•268, p=0•0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p &lt; 0•0005) with increased hospitalization-free survival of •8 months. Conclusions: TMZ is effective in reducing both global and cardiovascular mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long-term survival in CHF patients.

Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: Results from an international multicentre retrospective cohort study

ObjectivesThe aim of this cohort study was to retrospectively evaluate, in patients with chronic heart failure (CHF), the long term effect of trimetazidine (TMZ) on morbidity and mortality. BackgroundPrevious small studies in patients with CHF have shown that TMZ can improve left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. MethodsIn this international multicentre retrospective cohort study data from 669 patients were analyzed. 362 patients were on TMZ due to symptom persistence despite up-titration of optimal CHF therapy, while the remaining patients continued conventional CHF therapy alone. Propensity score analysis was performed in order to minimize selection bias between the two groups. ResultsKaplan–Meier analysis for global mortality showed 11.3% improved global survival (p=0.015) and 8.5% improved survival for cardiovascular (CVD) death (p=0.050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a hazard ratio (HR)=0.189 (confidence interval — CI 95%: 0.017–0.454; p=0.0002). TMZ also showed a good risk reduction profile for CVD death causes (HR=0.072, CI 95%: 0.019–0.268, p=0.0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5years (p<0.0005) with increased hospitalization-free survival of 7.8months. ConclusionTMZ is effective in reducing mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long term survival in CHF patients.

Nutritional practices and their relationship to clinical outcomes in critically ill children—An international multicenter cohort study*

To examine factors influencing the adequacy of energy and protein intake in the pediatric intensive care unit and to describe their relationship to clinical outcomes in mechanically ventilated children. We conducted an international prospective cohort study of consecutive children (ages 1 month to 18 yrs) requiring mechanical ventilation longer than 48 hrs in the pediatric intensive care unit. Nutritional practices were recorded during the pediatric intensive care unit stay for a maximum of 10 days, and patients were followed up for 60 days or until hospital discharge. Multivariate analysis, accounting for pediatric intensive care unit clustering and important confounding variables, was used to examine the impact of nutritional variables and pediatric intensive care unit characteristics on 60-day mortality and the prevalence of acquired infections. 31 pediatric intensive care units in academic hospitals in eight countries participated in this study. Five hundred patients with mean (SD) age 4.5 (5.1) yrs were enrolled and included in the analysis. Mortality at 60 days was 8.4%, and 107 of 500 (22%) patients acquired at least one infection during their pediatric intensive care unit stay. Over 30% of patients had severe malnutrition on admission, with body mass index z-score >2 (13.2%) or <-2 (17.1%) on admission. Mean prescribed goals for daily energy and protein intake were 64 kcals/kg and 1.7 g/kg respectively. Enteral nutrition was used in 67% of the patients and was initiated within 48 hrs of admission in the majority of patients. Enteral nutrition was subsequently interrupted on average for at least 2 days in 357 of 500 (71%) patients. Mean (SD) percentage daily nutritional intake (enteral nutrition) compared to prescribed goals was 38% for energy and 43% (44) for protein. A higher percentage of goal energy intake via enteral nutrition route was significantly associated with lower 60-day mortality (Odds ratio for increasing energy intake from 33.3% to 66.6% is 0.27 [0.11, 0.67], p = .002). Mortality was higher in patients who received parenteral nutrition (odds ratio 2.61 [1.3, 5.3], p = .008). Patients admitted to units that utilized a feeding protocol had a lower prevalence of acquired infections (odds ratio 0.18 [0.05, 0.64], p = .008), and this association was independent of the amount of energy or protein intake. Nutrition delivery is generally inadequate in mechanically ventilated children across the world. Intake of a higher percentage of prescribed dietary energy goal via enteral route was associated with improved 60-day survival; conversely, parenteral nutrition use was associated with higher mortality. Pediatric intensive care units that utilized protocols for the initiation and advancement of enteral nutrient intake had a lower prevalence of acquired infections. Optimizing nutrition therapy is a potential avenue for improving clinical outcomes in critically ill children.

The Role of Smoking in Allergy and Asthma: Lessons from the ECRHS

The European Community Respiratory Health Survey is an international multicenter cohort study of asthma, allergy, and lung function that began in the early-1990s with recruitment of population-based samples of 20- to 44-year-old adults, mainly in Europe. The aims of the study are broad ranging but include assessment of the role of in utero exposure to tobacco smoke, exposure to environmental tobacco smoke, and active smoking on the incidence, prevalence, and prognosis of allergy and asthma. Cross-sectional and longitudinal analyses looking at these associations have been conducted, sometimes only using information collected in one country, and on other occasions using information collected in all the participating centers. This article summarizes the results from these various publications from this large epidemiologic study.

Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: An international multicenter cohort study

Long-term viral suppression is a major goal to prevent disease progression in patients with HBV. Aim of this study was to investigate the efficacy and safety of entecavir plus tenofovir combination in 57 CHB partial responders or multidrug resistant patients. Investigator-initiated open-label cohort study. Quantitative HBV-DNA measurement and resistance testing (line-probe-assays and direct-sequencing) at baseline and every 3 months. Fifty seven patients (37 HBeAg+), median age 45 years, previously treated with a median of three lines of antiviral therapy (range 1-6), 24/57 with advanced liver disease, were included. Median ALT at baseline was 1.0 ULN (range 0.3-22) and HBV-DNA 1.5 × 10(4)IU/ml (range 500-1 × 10(11)IU/ml). Median treatment duration of combination therapy was 21 months. HBV-DNA level dropped 3 logs (median, range 0-8 log; p<0.0001), 51/57 patients became HBV-DNA undetectable, median after 6 months (95% CI, 4.6-7). The probability for HBV DNA suppression was not reduced in patients with adefovir or entecavir resistance or in patients with advanced liver disease. Viral suppression led to decline in ALT (median 0.7 ULN; range 0.2-2.4; p=0.001). Five patients lost HBeAg (after 15, 18, 20, 21, and 27 months, respectively), one patient showed HBs-seroconversion. Patients with advanced disease did not show clinical decompensation, two patients with cirrhosis and undetectable HBV DNA developed HCCs. No death, newly induced renal impairment or lactic acidosis were reported. Rescue therapy with entecavir and tenofovir in CHB patients harboring viral resistance patterns or showing only partial antiviral responses to preceding therapies was efficient, safe, and well tolerated in patients with and without advanced liver disease (249).

P1-229 Diet quality of male adult participants him study- Brazil (natural history of hpv infection in men): multicentric study

IntroductionThe study “Natural History of HPV Infection in Men” (HIM study) is an international multicenter prospective cohort study that seeks to determine the incidence, persistence and remission of human papillomavirus...

Influence of the factor II G20210A variant or the factor V G1691A mutation on symptomatic recurrent venous thromboembolism in children: an international multicenter cohort study.

To determine the relative importance of the factor (F) II G20210A or FV G1691A mutations as risk factors or predictors for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. In the present cohort, the rate of VTE recurrence and the time to recurrence in relation to FII, FV, age, and sex was determined in consecutively enrolled patients with VTE aged newborn to <or=18 years carrying the FII (n = 64) or FV (n = 194) mutation. 158 children with VTE without thrombophilia served as controls. Patients were followed for a median of 58 months. Data were pooled across participating sites to increase power and to enhance the generalizability of the data. Incidence rates were given as events per 1000 person-years. Of the 416 children enrolled, 44 had recurrent VTE at a median of 12 months following VTE onset. The overall incidence rate of recurrence was 19.8, 57.9 in patients with the FII variant, 17.9 for FV carriers, and 11.8 in the control cohort. When comparing FII patients, FV children and the control cohort multivariate analysis (Cox regression) adjusted for age and sex showed that the FII variant (hazard ratio 2.6; 95% confidence interval 1.1-5.9) influenced the hazard for recurrent VTE. Based on multivariate analysis, the presence of the FII variant was associated with an increased risk of VTE recurrence.