Magnesium Sulfate Versus Lidocaine as an Adjunct for Renal Colic in the Emergency Department: A Randomized, Double-Blind Controlled Trial.

STUDY OBJECTIVE: We wished to determine whether the addition of magnesium sulfate (MgSO4) or lidocaine to diclofenac could improve the analgesic efficacy in emergency department (ED) patients with acute renal colic. METHODS: In this prospective, double-blinded, randomized controlled trial of patients aged 18 to 65 years with suspected acute renal colic, we randomized them to receive 75 mg intramuscular (IM) diclofenac and then intravenous (IV) MgSO4, lidocaine, or saline solution control. Subjects reported their pain using a numerical rating scale (NRS) before drug administration and then 5, 10, 20, 30, 60, and 90 minutes afterwards. Our primary outcome was the proportion of participants achieving at least a 50% reduction in the NRS score 30 minutes after drug administration. RESULTS: We enrolled 280 patients in each group. A 50% or greater reduction in the NRS score at 30 minutes occurred in 227 (81.7%) patients in the MgSO4 group, 204 (72.9%) in the lidocaine group, and 201 (71.8%) in the control group, with significant differences between MgSO4 and lidocaine (8.8%, 95% confidence interval [CI] [1.89 to 15.7], P=.013) and between MgSO4 and control (9.9%, 95% CI [2.95 to 16.84], P=.004). Despite this, differences between all groups at every time point were below the accepted 1.3 threshold for clinical importance. There were no observed differences between groups in the frequency of rescue analgesics and return visits to the ED for renal colic. There were more adverse events, although minor, in the MgSO4 group. CONCLUSION: Adding intravenous MgSO4, but not lidocaine, to IM diclofenac offered superior pain relief but at levels below accepted thresholds for clinical importance.

Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Zinc supplementation has been considered a potential therapy for coronavirus disease 2019 (COVID-19). We aimed to examine zinc efficacy in adult patients with COVID-19 infection. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled multicenter trial. Patients who were tested positive for COVID-19 without end-organ failure were randomized to oral zinc (n = 231) or matching placebo (n = 239) for 15 days. The primary combined outcome was death due to COVID-19 or intensive care unit (ICU) admission ≤30 days after randomization. Secondary outcomes included length of hospital stay for inpatients and duration of COVID-19 symptoms with COVID-19-related hospitalization for outpatients. RESULTS: 190 patients (40.4%) were ambulatory and 280 patients (59.6%) were hospitalized. Mortality at 30 days was 6.5% in the zinc group and 9.2% in the placebo group (OR: .68; 95% CI .34-1.35); ICU admission rates were, respectively, 5.2% and 11.3% (OR: .43; 95% CI .21-.87). Combined outcome was lower in the zinc group versus the placebo group (OR: .58; 95% CI .33-.99). Consistent results were observed in prespecified subgroups of patients aged <65 years, those with comorbidity, and those who needed oxygen therapy at baseline. Length of hospital stay was shorter in the zinc group versus the placebo group (difference: 3.5 days; 95% CI 2.76-4.23) in the inpatient group; duration of COVID-19 symptoms decreased with zinc treatment versus placebo in outpatients (difference: 1.9 days; 95% CI .62-2.6). No severe adverse events were observed during the study. CONCLUSIONS: Our results showed that, in COVID-19 patients, oral zinc can decrease 30-day death, ICU admission rate and can shorten symptom duration. Clinical Trials Registration. ClinicalTrials.gov, NCT05212480.

Pulse amplitude ratio under noninvasive ventilation as a new method in the diagnosis of left heart failure in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Left heart failure (LHF) is commonly associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) but its role is often underestimated. AIM OF STUDY: To evaluate the performance of a new diagnostic technique based on the measurement of the pulse amplitude ratio (PAR) using non-invasive ventilation (NIV) for the early identification LHF in patients admitted to the emergency department (ED) for AECOPD. RESULTS: 73 patients were included in this study: 32 in LHF group and 41 in non LHF- group. The two groups had comparable demographic and clinical characteristics at admission. The mean values of PARNIV was significantly higher among LHF patients (0.86 vs. 0.71; p < 0.01). The area under the receiver operating characteristic curve of PARNIV was 0.75. Using the best cut-off (0.6), the sensitivity of PARNIV was 93% with a specificity 21%, a positive predictive value of 48%, and a negative predictive value of 81%. Correlation between PARNIV and BNP was significant (r = 0.52; p = 0.002). CONCLUSION: Measurement of PARNIV in patients presenting to the ED with AECOPD had a good diagnostic performance for the detection of LHF and could represent an interesting alternative for the currently available methods. Trial registration The study was registered in the Clinical Trial Registration System (clinicaltrials.gov) under the study number NCT05189119, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000BOO4&selectaction=Edit&uid=U0000QAM&ts=2&cx=qrmluh .

Value of inferior vena cava collapsibility index as marker of heart failure in chronic obstructive pulmonary disease exacerbation.

INTRODUCTION: Inferior vena cava (IVC) diameter variability with respiration measured by ultrasound was found to be useful for the diagnosis of heart failure (HF) in ED patients with acute dyspnea. Its value in identifying HF in acute exacerbation of chronic obstructive pulmonary disease exacerbation (AECOPD) was not specifically demonstrated. OBJECTIVE: To determine the value of ΔIVC in the diagnosis of HF patients with AECOPD. METHODS: This is a prospective study conducted in the ED of three Tunisian university hospitals including patients with AECOPD. During this period, 401 patients met the inclusion criteria. The final diagnosis of HF is based on the opinion of two emergency experts after consulting the data from clinical examination, cardiac echocardiography, and BNP level. The ΔIVC was calculated by two experienced emergency physicians who were blinded from the patient's clinical and laboratory data. A cut off of 15% was used to define the presence (< 15%) or absence of HF (≥ 15%). Left ventricular ejection fraction (LVEF) was also measured. The area under the ROC curve, sensitivity, specificity, and positive and negative predictive values were calculated to determine the diagnostic and predictive accuracy of the ΔIVC in predicting HF. RESULTS: The study population included 401 patients with AECOPD, mean age 67.2 years with male (68.9%) predominance. HF was diagnosed in 165 (41.1%) patients (HF group) and in 236 patients (58.9%) HF was excluded (non HF group). The assessment of the performance of the ΔIVC in the diagnosis of HF showed a sensitivity of 37.4% and a specificity of 89.7% using the threshold of 15%. The positive predictive value was 70.9% and the negative predictive value was 66.7%. The area under the ROC curve was 0.71(95%, CI 0.65-0.76). ΔIVC values were not different between HF patients with reduced LVEF and those with preserved LVEF. CONCLUSION: Our results showed that ΔIVC has a good value for ruling out HF in ED patients consulting for AECOPD.

Analgesic Effect of Topical Piroxicam vs Phytotherapy Gel in the Treatment of Acute Soft Tissue Injuries: A Randomized Controlled Noninferiority Study.

OBJECTIVE: The study compared the efficacy and tolerability of piroxicam gel and a new topical combination of medicinal plant products (Soulagel®; Belpharma Tunisia) to treat pain caused by soft tissue injuries. METHODS: Patients (n = 1,525) were assigned to receive piroxicam gel or Soulagel. Efficacy assessments included a change of at least 50% in the pain-on-movement visual numeric scale rating from emergency department discharge (baseline) to day 7 final assessment, as well as the time required to reach pain resolution criteria, the need for rescue analgesia, patients' satisfaction, and the rate of adverse effects. RESULTS: At day 7, 1,216 patients (79.7%) achieved at least 50% reduction in visual numeric scale rating from baseline: 623 patients (82.4%) in the Soulagel group vs 593 patients (77.1%) in the piroxicam group (P = 0.01). Time to decrease pain on movement by 50% was significantly higher with piroxicam gel than with Soulagel (34 ± 1 vs 33 ± 1 days, respectively; P = 0.54). At day 7, 96.4% of patients in the Soulagel group declared being "very satisfied" to "satisfied," vs 68% in the piroxicam group (P < 0.001). There were no major adverse events in either group. CONCLUSIONS: Soulagel is not inferior to piroxicam gel for managing pain related to a soft tissue injuries. Further studies will help ascertain whether this new gel offers an alternative treatment option for this common emergency department condition.

External validations of the ABCD2 score in prediction of stroke risk after transient ischemic attack. A Tunisian hospital-based cohort study.

BACKGROUND AND PURPOSE: Identification of patients with high risk of stroke after transient ischemic attack (TIA) could be helpful to optimize stroke prevention. We aimed to externally validate the ABCD2 score for the prediction of stroke after TIA in a Tunisian population. METHODS: We conducted a retrospective observational study of consecutive patients admitted for TIA in four university hospitals in Tunisia. Patients were screened for onset of stroke. Sensitivity, specificity, positive and negative predictive values with areas under the receiver operating characteristic (ROC) curves were calculated for risk of stroke at 2, 7, 30 and 90 days after the index event. RESULTS: Of 415 patients screened in this study, the total cumulative subsequent stroke rates after TIA at 2, 7, 30 and 90 days were respectively, 4.8%, 10.6%, 13.5% and 20.2%. Using a cut-off value of 4, the ABCD2 showed an overall good sensitivity (95%, 97.7%, 96.4% and 97.6% respectively at 2, 7, 30 and 90 days). Areas under ROC cure of the ABCD2 score in patients with TIA for stroke onset at 2, 7, 30 and 90 days were respectively 0.67 (95% CI, 0.55-0.79), 0.79 (95% CI, 0.71-0.85), 0.79 (95% CI, 0.72-0.85), and 0.76 (95% CI, 0.70-0.81). CONCLUSION: Our findings suggest that the ABCD2 score could be used in our population to discriminate patient with TIA at low and high risk of developing recurrent stroke.

Comparison of simulation and video-based training for acute asthma.

BACKGROUND: Emergency medicine is particularly well suited to simulation training. However, evidence for the efficacy of simulation-based medical training remains limited especially to manage high-risk cases such as acute asthma. OBJECTIVE: The objective of our study was to compare the performance of high-fidelity simulation (HFS) and interactive video-case challenge-based training (IVC) for final-year medical students in the management of acute asthma. METHODS: This was a prospective randomized controlled study conducted at the emergency department (ED) of Monastir University hospital ( Tunisia). 69 final-year medical students were randomized to HFS (n = 34) and IVC (n = 35) training on acute asthma topic. The study was conducted over a 1-week period. Efficacy of each teaching method was compared through the use of multiple-choice questionnaires (MCQ) before (pre-test), after (post-test) training and a simulation scenario test conducted 1 week later. The scenario was based on acute asthma management graded on predefined critical actions using two scores: the checklist clinical score (range 0 to 30), and the team skills score (range 0 to 16). Student satisfaction was also evaluated with the Likert 5 points scale. Two years after the post-test, both groups underwent a third MCQ testing to assess sustainability of knowledge. RESULTS: There were no differences in age between groups. There was no statistically significant difference between the HFS and IVC groups pre-test scores (p = 0.07). Both groups demonstrated improvement in MCQ post-test from baseline after training session; the HFS MCQ post-test score increased significantly more than the IVC score (p < 0.001). The HFS group performed better than the IVC group on the acute asthma simulation scenario (p < 0.001). Mean checklist clinical score and mean team skills score were significantly higher in HFS group compared to IVC group (respectively 22.9 ± 4.8 and 11.5 ± 2.5 in HFS group vs 19.1 ± 3 and 8.4 ± 3.1 in IVC group) (p < 0.001). After 2 years, MCQ post-test scores decreased in both groups but the decrease was lower in HFS group compared to the IVC group. CONCLUSION: High-fidelity simulation-based training was superior to interactive video-case challenge for teaching final year medical students,and led to more long-term knowledge retention in the management of simulated acute asthma patients. TRIAL REGISTRATION: The study was registered at www. CLINICALTRIALS: gov NCT02776358 on 18/05/2016.

30 day predicted outcome in undifferentiated chest pain: multicenter validation of the HEART score in Tunisian population.

BACKGROUND: Chest pain remains one of the most challenging serious complaints in the emergency department (ED). A prompt and accurate risk stratification tool for chest pain patients is paramount to help physcian effectively progrnosticate outcomes. HEART score is considered one of the best scores for chest pain risk stratification. However, most validation studies of HEART score were not performed in populations different from those included in the original one. OBJECTIVE: To validate HEART score as a prognostication tool, among Tunisian ED patients with undifferentiated chest pain. METHODS: Our prospective, multicenter study enrolled adult patients presenting with chest pain at chest pain units. Patients over 30 years of age with a primary complaint of chest pain were enrolled. HEART score was calculated for every patient. The primary outcome was major cardiovascular events (MACE) occurrence, including all-cause mortality, non-fatal myocardial infarction (MI), and coronary revascularisation over 30 days following the ED visit. The discriminative power of HEART score was evaluated by the area under the ROC curve. A calibration analysis of the HEART score in this population was performed using Hosmer-Lemeshow goodness of test. RESULTS: We enrolled 3880 patients (age 56.3; 59.5% males). The application of HEART score showed that most patients were in intermediate risk category (55.3%). Within 30 days of ED visit, MACE were reported in 628 (16.2%) patients, with an incidence of 1.2% in the low risk group, 10.8% in the intermediate risk group and 62.4% in the high risk group. The area under receiver operating characteristic curve was 0.87 (95% CI 0.85-0.88). HEART score was not well calibrated (χ2 statistic = 12.34; p = 0.03). CONCLUSION: HEART score showed a good discrimination performance in predicting MACE occurrence at 30 days for Tunisian patients with undifferentiated acute chest pain. Heart score was not well calibrated in our population.

Value of Dynamic Variation of Impedance Cardiac output in the diagnosis of Heart Failure in emergency department patients with undifferentiated dyspnea.

AIM OF STUDY: Cardiac output (CO) responses to acute changes in body position and Valsalva maneuver (VM) were proposed to assess cardiac contractile reserve. We investigated the value of sitting position (SP), leg raising (LR), and VM for identifying heart failure (HF) in patients with undifferentiated dyspnea. MATERIALS AND METHODS: It is a prospective study including patients over 18 years old admitted to the emergency department (ED) for dyspnea. Bioimpedance CO was measured at baseline, under SP, LR, and VM. HF diagnosis was based on clinical assessment, serum levels of brain natriuretic peptide (BNP) and echocardiography findings. Study population was divided into patients with heart failure (HF group) and patients without HF (HF- group). Diagnostic performance of CO change under the three maneuvers was calculated by sensitivity, specificity, likelihood ratio and receiver operating characteristic (ROC) curve. RESULTS: 290 patients were enrolled in the study. The final diagnosis was dyspnea due to congestive heart failure in 147 patients (50.7%). CO change with VM was the most accurate exam in identifying congestive heart failure as the cause of dyspnea with a sensitivity, specificity, positive and negative likelihood ratios of 79%, 60%, 1.97, and 0.36 respectively. Area under ROC curve was 0.62(95% CI, 0.55-0.69), 0.63(95% CI, 0.56-0.69), and 0.70(95% CI, 0.64-0.76) respectively for SP, LR, and VM. In a multivariate analysis, CO change with VM, but not with SP or LR, carried independent diagnostic value (p < 0.001). CONCLUSION: the diagnosis of HF can be aided with use of analyzing the effect of VM on non-invasively measured CO among patients admitted to the ED with undifferentiated dyspnea. Diagnostic yield of SP and LR was poor.

Bacterial and Viral Infection in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Implication for Antimicrobial Management and Clinical Outcome.

Patients with chronic obstructive pulmonary disease (COPD) exhibit frequent acute exacerbations (AE). The objectives of this study were first to evaluate the prevalence of pathogens associated to these episodes by combining conventional bacteriology and multiplex viral and bacterial PCR assays in sputum specimens, and second to determine whether C-reactive protein (CRP) value and clinical outcome could be influenced by the type of microbial agent(s) recovered from these samples. A cohort of 84 Tunisian patients hospitalized at the emergency room for AECOPD was investigated prospectively for the semi-quantitative detection of bacteria by conventional culture (the threshold of positivity was of 107 CFU/ml) and for the detection of viral genome and DNA of atypical bacteria by quantitative PCR using two commercial multiplex respiratory kits (Seegene and Fast-track). The two kits exhibited very similar performances although the Seegene assay was a bit more sensitive. A large number and variety of pathogens were recovered from the sputum samples of these 84 patients, including 15 conventional bacteria, one Chlamydia pneumoniae and 63 respiratory viruses, the most prevalent being rhinoviruses (n = 33) and influenza viruses (n = 13). From complete results available for 74 patients, the presence of bacteria was significantly associated with risk of recurrence at 6 and 12 months post-infection. The combination of these different markers appears useful for delineating correctly the antimicrobial treatment and for initiating a long-term surveillance in those patients with high risk of recurrent exacerbation episodes. A prospective study is required for confirming the benefits of this strategy aimed at improving the stewardship of antibiotics.

Value of systolic time intervals in the diagnosis of heart failure in emergency department patients with undifferentiated dyspnea.

AIM OF THE STUDY: The diagnosis of heart failure in the emergency department (ED) is challenging. The aim of this study was to evaluate systolic time intervals (STIs) using phonoelectrocardiography for the diagnosis of heart failure (HF) in ED patients with undifferentiated dyspnea. METHODS: A total of 855 patients with dyspnea and suspected HF were prospectively enrolled. They underwent echocardiographic measurements of left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP) testing and computerised phonoelectrocardiography to assess STIs including electromechanical activation time (EMAT), left ventricular ejection time (LVET) and EMAT/LVET ratio. Diagnosis accuracy of STIs was calculated including sensitivity, specificity, likelihood ratio and receiver operating characteristic (ROC) curve. RESULTS: Patients with HF (n = 530) had significantly higher EMAT and lower LVET compared with non-HF patients. ROC curve c-statistic was 0.74, 0.72 and 0.78 for EMAT, LVET and EMAT/LVET respectively. Sensitivity and specificity of EMAT/LVET at a cut-off = 40% were 72% and 88% respectively. EMAT/LVET had the highest correlation with LVEF (r = 0.48). In patients with intermediate BNP (n = 107), positive likelihood ratio increased from 1.8 with BNP alone to 3.6 with BNP combined to EMAT/LVET. Patients without HF had STIs values not significantly different from those with preserved LVEF (≥45%). CONCLUSIONS: Given their immediate availability, phonoelectrocardiography STIs' parameters and particularly EMAT/LVET ratio could have an important role in the diagnosis approach of HF in patients with undifferentiated dyspnea in the ED.

Effect on Morphine Requirement of Early Administration of Oral Acetaminophen vs. Acetaminophen/Tramadol Combination in Acute Pain.

OBJECTIVES: To evaluate the effect on opioid requirement of pain treatment starting at triage, and to evaluate satisfaction in emergency department (ED) patients with acute pain. METHODS: This is a single-blind, randomized, prospective study conducted in the ED. The included patients were randomly assigned to single oral doses of placebo, acetaminophen, or a tramadol/acetaminophen combination. Protocol treatment was given at triage. The primary outcome was the need for rescue morphine during ED stay. The secondary outcome included patient satisfaction, ED length of stay, and percentage of patients discharged from the ED with a VAS score of <30. RESULTS: We included 1,485 patients: 496 patients in the placebo group, 497 in the acetaminophen group, and 492 in the tramadol/acetaminophen combination group. The groups were similar regarding demographic and clinical characteristics and baseline VAS pain scores. Rescue morphine was significantly decreased in the tramadol/acetaminophen combination group compared to that in the placebo and acetaminophen groups (11.5%, 23.2%, and 18.9%, respectively; P = 0.03). Patient satisfaction was higher in the tramadol/acetaminophen combination group (77% vs. 69% in the acetaminophen group and 68% in the placebo group). A VAS score of <30 was observed in 84% of patients in the placebo group, 83% in the acetaminophen group, and 87% in the tramadol/acetaminophen combination group (P = 0.01 between the acetaminophen group and tramadol/acetaminophen combination group). The ED length of stay was 60 minutes for the acetaminophen group and tramadol/acetaminophen combination group and 71 minutes for the placebo group (P = 0.04). CONCLUSION: Oral tramadol/acetaminophen combination administered early in triage was associated with a decrease in intravenous morphine requirement and increase in satisfaction among ED patients with acute pain when compared with patients taking acetaminophen. No significant increase in side effects was found. This intervention may be considered in EDs with an aim of similar benefits.

Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype?

PURPOSE: Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). METHODS: We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. RESULTS: We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759). CONCLUSIONS: Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. TRIAL REGISTRATION: Clinical Trials.gov NCT03373552 (Registered 13 December 2017).

Value of early change of serum C reactive protein combined to modified Alvarado score in the diagnosis of acute appendicitis.

BACKGROUND: The aim of this study is to test the diagnostic value of baseline and early change of C-reactive protein (CRP) concentrations, evaluated separately or in combination with the modified Alvarado score (MAS), in patients with clinically suspected acute appendicitis. METHODS: This is a prospective observational study including all patients presenting to the emergency department with an equivocal diagnosis of acute appendicitis. After inclusion, clinical and demographic data are recorded and blood samples were taken at baseline and 3 h after for serum CRP measurements (3 h CRP). The MAS is also calculated for all patients. The ultimate diagnosis of appendicitis was based on the histologic findings of the excised appendix in operated patients and clinical follow-up in emergency department discharged patients. Diagnostic accuracy of admission CRP, early change of CRP 3 h CRP minus admission CRP, MAS and the combination of these parameters was expressed by sensitivity, specificity, positive predictive value, negative predictive value and area under receiver operating characteristics curve. RESULTS: Five hundred patients were included from January 2010 to December 2013. Overall, 387 patients were operated the negative appendectomy rate was 8,3%. CRP concentrations were higher in patients with acute appendicitis. However, the diagnostic value of admission CRP, delta CRP and MAS was moderate with area under ROC curve respectively equal to 0.63, 0.53 and 0.6. Combining admission CRP and delta CRP values to MAS did not result in a better performance. The area under ROC curve did not exceed 0.7 with the different combinations. CONCLUSION: Early change of CRP has a moderate diagnostic value in patients with clinically suspected acute appendicitis. Combining CRP values to MAS did not improve diagnostic accuracy.

ABCB1 and SLCO1B3 Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population.

BACKGROUND: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. METHODS: ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose. RESULTS: SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs. CONCLUSION: Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.