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

Evaluation of medication adherence among Lebanese diabetic patients

Background: Diabetes type 2 is considered one of the main public health concerns. Lack of adherence to treatment leads to poor therapeutic outcome, poor glycemic control, and high risk for developing diabetes complications. Objectives: The aim of this study is to evaluate adherence to oral antidiabetic medication in Diabetes type 2 Lebanese patients, and to evaluate factors leading to low adherence. Methods: A cross-sectional study was conducted in outpatients endocrinology clinics of two hospitals and four private clinics located in Beirut-Lebanon. Data was collected using a well-structured questionnaire by trained pharmacists. Adherence level was measured by the Lebanese Medication Adherence Scale (LMAS-14). Bivariate and multivariate analyses were conducted using SPSS version 20. Results: Overall, 245 patients were included in the study with the majority being females (54.3%) and obese (47.8%). Only 29% of the participants had controlled glycemia (HbA1c <7%) with 31.8% of subjects had high adherence to their medication compared to 68.2% with low adherence. Increased working hours/day was associated with a decrease in adherence to oral antidiabetic medication (OR=0.31; 95% CI 0.11:0.88; p=0.029). Other factors significantly associated with decreased adherence to treatment were forgetfulness, high drug costs, complex treatment regimens, experiencing side effects, and perception of treatment inefficacy. Postponing physician office visits also decreased the probability of being adherent to oral antidiabetic medication (OR=0.36; 95% CI 0.15:0.86; p=0.022). Skipping or doubling the dose in case of hypo/hyperglycemia and the sensation of treatment burden also decreased medication adherence (OR=0.09; 95% CI 0.02:0.34; p=0.001, and OR=0.04; 95% CI 0.01:0.13; p<0.001 respectively). Conclusions: Adherence to oral antidiabetic medication is low for Lebanese patients, which leads to a poor glycemic control and increases the diabetes complications. Intervention programs including patient education strategies are essential to improve medication adherence

Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009

In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs).From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation.In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation

The Role of Bulk and Interface Recombination in High‐Efficiency Low‐Dimensional Perovskite Solar Cells

2D Ruddlesden–Popper perovskite (RPP) solar cells have excellent environmental stability. However, the power conversion efficiency (PCE) of RPP cells remains inferior to 3D perovskite-based cells. Herein, 2D (CH(CH)NH)(CHNH)PbI perovskite cells with different numbers of [PbI] sheets (n = 2–4) are analyzed. Photoluminescence quantum yield (PLQY) measurements show that nonradiative open-circuit voltage (V) losses outweigh radiative losses in materials with n > 2. The n = 3 and n = 4 films exhibit a higher PLQY than the standard 3D methylammonium lead iodide perovskite although this is accompanied by increased interfacial recombination at the top perovskite/C interface. This tradeoff results in a similar PLQY in all devices, including the n = 2 system where the perovskite bulk dominates the recombination properties of the cell. In most cases the quasi-Fermi level splitting matches the device V within 20 meV, which indicates minimal recombination losses at the metal contacts. The results show that poor charge transport rather than exciton dissociation is the primary reason for the reduction in fill factor of the RPP devices. Optimized n = 4 RPP solar cells had PCEs of 13% with significant potential for further improvements

Visualization and suppression of interfacial recombination for high-efficiency large-area pin perovskite solar cells

The performance of perovskite solar cells is predominantly limited by non-radiative recombination, either through trap-assisted recombination in the absorber layer or via minority carrier recombination at the perovskite/transport layer interfaces. Here, we use transient and absolute photoluminescence imaging to visualize all non-radiative recombination pathways in planar pin-type perovskite solar cells with undoped organic charge transport layers. We find significant quasi-Fermi-level splitting losses (135 meV) in the perovskite bulk, whereas interfacial recombination results in an additional free energy loss of 80 meV at each individual interface, which limits the open-circuit voltage (V) of the complete cell to ~1.12 V. Inserting ultrathin interlayers between the perovskite and transport layers leads to a substantial reduction of these interfacial losses at both the p and n contacts. Using this knowledge and approach, we demonstrate reproducible dopant-free 1 cm perovskite solar cells surpassing 20% efficiency (19.83% certified) with stabilized power output, a high V (1.17 V) and record fill factor (>81%)

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

Factors affecting medication adherence in Lebanese patients with chronic diseases

Background: Non-adherence to prescribed medications represents an obstacle toward achieving treatment goals. This problem is more pronounced in patients with chronic illness. Objective: To identify the extent of adherence in Lebanese outpatients with chronic diseases, and to suggest possible predictors of non-adherence in this population. The secondary objective was to assess if medication adherence affects patients' quality of life. Methods: A questionnaire was administered face-to-face to a sample of Lebanese adults visiting the external clinics at two Tertiary Care Hospitals in Beirut. The level of adherence was assessed using the 8-item Morisky Medication Adherence Scale which was first validated. The health-related quality of life (HRQoL) of patients was measured using the EQ-5D. Linear regression and logistic regression analyses examined possible predictors of adherence. Results: Out of the 148 patients included in this study, 42.6% were classified as adherent. In the univariate analyses, statistically significant predictors of high adherence included good physician-patient relationship (p=0.029) and counseling (p=0.037), a high level of HRQoL (p<0.001), and a high level of perceived health (p<0.001). Predictors of low adherence included a declining memory (p<0.001), anxiety/depression (p=0.002), little drug knowledge (p<0.001), and postponing physician appointments (p<0.001). The multivariate analyses revealed similar results. In the linear regression, the most powerful predictor of non-adherence was the disbelief that the drug is ameliorating the disease (beta=0.279), however, in logistic regression, patient who were willing to skip or double doses in case of amelioration/deterioration were found to be 7.35 times more likely to be non-adherent than those who were not (aOR=0.136, 95%CI: 0.037-0.503). Conclusion: The findings of this study reassure the view that patients should be regarded as active decision makers. Patient education should be regarded as a cornerstone for treatment success. Additional studies as well are needed to test the practicability and effectiveness of interventions suggested to enhance adherence

Unexpected substitution of dominant rotavirus G genotypes in French hospitalized children over five consecutive seasons

International audienceThe study was designed to evaluate the circulation of group A rotaviruses in French hospitalized children, and to detect unusual strains. This prospective study was conducted from 2001 to 2006 in children consulting for acute diarrhea at the pediatric emergency department in three French University Hospitals. The rotaviruses were detected by rapid test and genotyped by RT-PCR on the basis of their outer capsid proteins VP4 (P-type) and VP7 (G-type). The stools from 757 children were analyzed. G1P[8] strains were predominant (44.0%), followed by G9P[8] (17.7%), G3P[8] 13.1%, G4P[8] (9.5%), and G2P[4] (1.8%); mixed rotavirus infections occurred in 2.3%. G9 rotaviruses emerged during the 2004-2005 season (73.4%) and remained the second most prevalent strains. Few unusual strains, G6, G8, G12 and P[6]-types, were detected. The monitoring of rotavirus infections should be maintained to document strain distribution and to assess the emergence of new reassortants that may not respond to current rotavirus vaccines