Adverse drug events associated with vitamin K antagonists: factors of therapeutic imbalance

Nancy El-Helou, Amal Al-Hajje, Rola Ajrouche, Sanaa Awada, Samar Rachidi, Salam Zein, Pascale SalamehClinical and Epidemiological Research Laboratory, Faculty of Pharmacy, Lebanese University, Beirut, LebanonBackground: Adverse drug events (ADE) occur frequently during treatment with vitamin K antagonists (AVK) and contribute to increase hemorrhagic risks.Methods: A retrospective study was conducted over a period of 2 years. Patients treated with AVK and admitted to the emergency room of a tertiary care hospital in Beirut were included. The aim of the study was to identify ADE characterized by a high international normalized ratio (INR) and to determine the predictive factors responsible for these events. Statistical analysis was performed with the SPSS statistical package.Results: We included 148 patients. Sixty-seven patients (47.3%) with an INR above the therapeutic range were identified as cases. The control group consisted of 81 patients (54.7%) with an INR within the therapeutic range. Hemorrhagic complications were observed in 53.7% of cases versus 6.2% of controls (P < 0.0001). No significant difference was noticed between cases and controls regarding the indication and the dose of AVK. Patients aged over 75 years were more likely to present an INR above the therapeutic range (58.2%, P = 0.049). Recent infection was present in 40.3% of cases versus 6.2% of controls (P < 0.0001) and hypoalbuminemia in 37.3% of cases versus 6.1% of controls (P < 0.0001). Treatment with antibiotics, amiodarone, and anti-inflammatory drugs were also factors of imbalance (P < 0.0001).Conclusion: Many factors may be associated with ADE related to AVK. Monitoring of INR and its stabilization in the therapeutic range are important for preventing these events.Keywords: adverse drug events, vitamin K antagonists, bleeding risks, therapeutic imbalanc

Environmental, maternal, and reproductive risk factors for childhood acute lymphoblastic leukemia in Egypt : a case-control study

BACKGROUND\ud Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. The exact cause is not known in most cases, but past epidemiological research has suggested a number of potential risk factors. This study evaluated associations between environmental and parental factors and the risk for ALL in Egyptian children to gain insight into risk factors in this developing country.\ud METHODS\ud We conducted a case-control design from May 2009 to February 2012. Cases were recruited from Children's Cancer Hospital, Egypt (CCHE). Healthy controls were randomly selected from the general population to frequency-match the cumulative group of cases by sex, age groups (<1; 1 - 5; >5 - 10; >10 years) and region of residence (Cairo metropolitan region, Nile Delta region (North), and Upper Egypt (South)). Mothers provided answers to an administered questionnaire about their environmental exposures and health history including those of the father. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated using logistic regression with adjustment for covariates.\ud RESULTS\ud Two hundred ninety-nine ALL cases and 351 population-based controls frequency-matched for age group, gender and location were recruited. The risk of ALL was increased with the mother's use of medications for ovulation induction (ORadj = 2.5, 95 % CI =1.2 -5.1) and to a lesser extend with her age (ORadj = 1.8, 95 % CI = 1.1 - 2.8, for mothers ≥ 30 years old). Delivering the child by Cesarean section, was also associated with increased risk (ORadj = 2.01, 95 % CI =1.24-2.81).\ud CONCLUSIONS\ud In Egypt, the risk for childhood ALL appears to be associated with older maternal age, and certain maternal reproductive factors

Quantitative health impact of indoor radon in France

International audienceRadon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m3) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m3. Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk. © The Author(s) 201

Statins decrease mortality in Lebanese patients with sepsis: A multicenter study

Background: Sepsis is a significant public health concern. The clinical response to statins is variable among sepsis patients. Objective: The aim of the study was to determinate the effect of statin-treatment on mortality in Lebanese patients with sepsis.Methods: A retrospective multicenter study on Lebanese patients with sepsis between January 2008 and March 2012 was conducted. Patients with a primary diagnosis of sepsis admitted to the intensive care unit of two tertiary care hospitals in Beirut were included. Patients who continued to receive statin therapy for dyslipidemia during the hospital course were included in the statin treatment group. The control group consisted of patients not taking statin. Demographic characteristics, clinical signs, standard laboratory test and treatment received were compared between these two groups using univariate analysis. Logistic regression and survival analysis were performed by SPSS. Results: Three hundred fifty one Lebanese patients were included (age: 71.33 SD=14.97 years; Male: 56%). Among them, 30% took a statin at the doses recommended for dyslipidemia. The comparison of the two groups showed that in the statin treatment group: The mean serum level of C-reactive protein at the time of sepsis was significantly decreased (P=0.050), the length-stay at ICU significantly increased (P=0.047) and mortality significantly reduced (P<0.001). Results were confirmed by logistic regression, particularly for mortality. In the Cox regression analysis, hypothermia and shock were significantly associated with high mortality while statin treatment decreased mortality (hazard ratio = 0.540; 95% CI: 0.302-0.964; P=0.037). Conclusion: At usual doses for dyslipidemia, statin treatment decreased incidence of mortality related to sepsis and improved the survival in this Lebanese septic population. Large randomized controlled clinical trials must be realized to give conclusive results about the potential beneficial effect of statins in sepsis

Quantitative Health Risk Assessment of Indoor Radon A Systematic Review

International audienceExposure to radon is a well-established cause of lung cancer in the general population. The aim of the present work is to identify and summarize the results of studies that have assessed the risk of lung cancer due to indoor radon, based on a systematic review of relevant published studies. Sixteen studies from 12 different countries met eligibility criteria. Large differences in radon concentrations were noted between and within individual countries, and variety of risk models used to estimate the attributable fraction. Calculating again the attributable fraction in each of these studies using the same model (coefficient of 16% per 100 becquerels per cubic meter (Bq/m3) derived from the European residential radon study), the new attributable fraction of these selected studies ranged from 3% to 17%. Radon remains a public health concern. Information about radon health risks is important and efforts are needed to decrease the associated health problems. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email [email protected]

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study

International audiencePurpose To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). Methods The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010–2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. Results AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8–2.0)] with a significant positive dose–response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1–1.5)] and AML [OR = 1.5 (1.0–2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8–1.2)], or maternal coffee [OR = 0.9 (0.8–1.1)] or tea drinking [OR = 0.9 (0.8–1.1)] during pregnancy. However, a high consumption of coffee (\textgreater2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0–1.8)]. Conclusions The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the diseas

Caesarean delivery and risk of childhood leukaemia: A pooled analysis from the Childhood Leukemia International Consortium (CLIC)

Background: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child&apos;s birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (&gt;99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). Interpretation: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. Funding: National Cancer Institute. © 2016 Elsevier Ltd

Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE)

International audienceBackground: Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). Methods: The national registry-based case-control study, ESTELLE, was carried out in France in 2010-2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders. Results: In all, 617 ALL and 1225 controls aged >= 1 year were included. Inverse associations between ALL and early common infections (OR = 0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (>= 3 vs 1; OR = 0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR = 0.7, 95% CI: 0.5, 1.0), breastfeeding (OR = 0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR = 0.8, 95% CI: 0.7, 1.0) in infancy were observed. Conclusions: The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL