Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study

Abstract Background The aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity. Methods A cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods. Results Our results showed that the frequencies of GSTM1 (−) null allele and GSTT1 null (−) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (−) allele than in GSTM1 (+) (p = 10−3.and 0.004, respectively). The level of ALT was significantly higher in combination of GSTM1 (−)/T1(−) than in combined GSTM1(−)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(−)/T1(−) and in combination of GSTM1(+)/T1(−) than in combination of GSTM1(+)/T1(+) (p = 10−3 and 10−3, respectively). Conclusions Our findings suggest that the GSTM1 (−) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (−) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions

Burden and predictions of hospitalized injuries in a low-middle income country: results from a Tunisian university hospital

ABSTRACTInjuries are responsible for a high premature mortality and disability. They are poorly explored in low and middle income-countries. We aimed to estimate the burden of hospitalized injuries in the Monastir governorate (Tunisia) according to the nature of the injury, trends and projections of hospitalizations for injuries up until 2024, and to identify the distribution of this disease burden based on age and sex. We performed a descriptive study from 2002 to 2012 including all hospitalizations for injuries. Data were collected from morbidity and mortality register of the University Hospital of Monastir (Tunisia). We estimated the burden of injuries using the Disability Adjusted Life Years (DALYs). We described injuries (crude prevalence rate (CPR) and age standardized prevalence rate (ASR)), related mortality (lethality and standardized mortality ratio (SMR)), trends and prediction for 2024. A total of 18,632 hospitalizations for injuries representing 10% of all hospitalizations during study period were recorded. Per 1000 inhabitants per year, CPR was 3.36 and the ASR was 3.44. The lethality was of 17.5 deaths per 1000 injured inpatients per year and the SMR was of 2.95 (Confidence Interval of 95%: 2.64–3.29). Burden related to injuries was 2.36 DALYs per 1000 population per year, caused mainly by Years of Life Lost (83.4%), most frequent among men aged under 40 years. The predicted ASR for 2024 was 4.46 (3.81–5.23) per 1000 person-years. Injuries to the head was the most prevalent (20.7%) causing 67.7% of DALYs; and increasing by 226% through 2024. Injuries had a high prevalence and an important burden in a Tunisian university hospital. Prediction showed increased prevalence for 2024. Preventive measures and a trauma surveillance register should be implemented soon

Management of acute coronary syndrome in emergency departments: a cross sectional multicenter study (Tunisia)

Abstract Background We aimed to describe diagnosed acute coronary syndrome (ACS) and its care management and outcomes in emergency departments (EDs) and to determine related cardiovascular risk factors (CVRFs). Methods We conducted a cross sectional multicenter study that included 1173 adults admitted to EDs for acute chest pain (ACP) in 2015 at 14 sites in Tunisia. Data included patients’ baseline characteristics, diagnosis, treatment and output. Results ACS represented 49.7% of non-traumatic chest pain [95% CI: 46.7–52.6]; 74.2% of ACS cases were unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI). Males represented 67.4% of patients with ACS (p < 0.001). The median age was 60 years (IQR 52–70). Emergency medical service transportation was used in 11.9% of cases. The median duration between chest pain onset and ED arrival was two hours (Inter quartile ranges (IQR) 2–4 h). The age-standardized prevalence rate was 69.9/100,000 PY; the rate was 96.24 in men and 43.7 in women. In the multivariable analysis, CVRFs related to ST segment elevation myocardial infarction were age correlated to sex and active smoking. CVRFs related to UA/NSTEMI were age correlated to sex, familial and personal vascular history and type 2 diabetes. We reported 27 cases of major adverse cardiovascular events (20.0%) in patients with STEMI and 36 in patients with UA/NSTEMI (9.1%). Conclusion Half of the patients consulting EDs with ACP had ACS. Emergency medical service transportation calls were rare. Management delays were acceptable. The risk of developing an UA/NSTEMI was equal to the number of CVRFs + 1. To improve patient outcomes, it is necessary to increase adherence to international management guidelines

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs