DRESS characteristics according to the causative medication.

BACKGROUND: To date, no study has identified a clear relationship between drug and a specific clinical presentation of DRESS. OBJECTIVES: To investigate the particularities of DRESS and analyze the variation of DRESS pattern according to culprit drugs. METHODS: We analyzed cases of DRESS notified to the Department of Clinical Pharmacology at the University Hospital of Monastir over a 15-year period. The statistical study was performed using the comparative and multivariate analysis. RESULTS: DRESS was mostly induced by anticonvulsive agents (27%) followed by allopurinol (26.3%) and antibiotics (24%): For anticonvulsive agents, the occurrence of lymphadenopathy was higher, renal involvement was rare and mild, and positive skin tests were more frequent. The allopurinol group was associated with the patient's older age and a lower incidence of lymphadenopathy and kidney injury. For antibiotics, eosinophilia rate was lower, time to recovery was shorter, and RegiSCAR score was low. The multivariate analysis showed a link of allopurinol with severe renal impairment, antibiotics with short latency period and low RegiSCAR score, and anticonvulsants with high propensity of positive skin test. CONCLUSION: We report the largest African and south Mediterranean cohort of DRESS and evaluated the usefulness of skin tests in identifying the culprit drug. The prominent finding was that latency period and renal involvement may independently differ according to culprit drugs.

[Myocardial infarction in the young : clinical characteristics, therapeutic aspects and in-hospital complications.] / Infarctus du myocarde chez le sujet jeune en Tunisie : caractéristiques cliniques, aspects thérapeutiques et complications intra-hospitalières.

AIM OF THE STUDY: The aim of our study was to assess the clinical, electrical, angiographic and therapeutic characteristics of young patients with acute myocardial infarction and to describe the prevalence of in-hospital complications. PATIENTS AND METHODS: FromJanuary 2014 to May 2017, we retrospectively studied data of patients with acute myocardial infarction younger than 45 years old in the department of cardiology of Charles Nicolle hospital of Tunis. RESULTS: We enrolled 108 patients in the study. The prevalence of myocardial infarction in young patients was 8.5%. The mean age was 39.5 ± 5.5 years with a sex-ratio of 11. The most frequent cardiovascular risk factors were smoking (88%) and dyslipidaemia (51.9%). We reported 75 cases of ST segment elevation myocardial infarction. Primary angioplasty was performed in 41.3% of cases while lytic therapy was administered for the rest of the patients. It was successful in 75% of cases. Among 33 patients who presented with non-ST segment elevation myocardial infarction, percutaneous coronary angioplasty was performed in 60.6% of patients while 15.2% have undergone coronary artery bypass surgery and 24.2% received medical treatment only. In-hospital complications occurred in 39.8% of cases. In-hospital mortality was 1.9 %. CONCLUSIONS: Acute myocardial infarction in the young represents a serious health problem. Primary preventive measures aimed at preventing our youth from adopting tobacco use and developing dyslipidemia should be implemented to delay and even to avoid the onset of coronary artery disease.

Population pharmacokinetic model of isoniazid in patients with tuberculosis in Tunisia.

AIMS: To develop a pharmacokinetic model of isoniazid (INH) concentration taking into account demographic factors and genetic variables [N-acetyltransferase 2 (NAT2) genotype], and to propose an initial INH dosage that could maximize the probability of achieving the desired INH concentration. METHODS: A retrospective analysis was undertaken of INH concentration data collected from patients with tuberculosis in Tunisia. RESULTS: In total, 118 patients were included in this study. The one-compartment model [volume of distribution (V), elimination rate (Ke)] was found to have good predictive performance. Multi-variate analysis showed that NAT2 affected both V and Ke significantly, but age, gender and weight did not. Internal validation of the final model showed correlation of 0.95 between individual predicted INH concentration 3 h after drug intake (C3) and observed C3. External validation showed that percentage mean absolute prediction error and percentage root mean squared error were 9.11% (range 0.62-35.8%) and 11.6%, respectively. Monte-Carlo simulation showed that doses of at least 225 mg/24 h and at least 450 mg/24 h attained a therapeutic concentration in >80% of patients in the NAT2 slow acetylator group and the NAT2 rapid/intermediate acetylator group, respectively. CONCLUSION: The pharmacokinetic model allowed optimization of individual dosing regimens of INH in patients with tuberculosis in Tunisia. This tool may facilitate improved efficacy of INH and prevent its toxicity in this population.

DRESS syndrome following furosemide administration: An unusual association.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and rare adverse drug reaction. Several drugs are known to induce DRESS. Furosemide, a sulfonamide loop diuretic drug, is known to induce hypersensitive reactions such as bullous eruptions, acute generalized exanthematous pustulosis and lichenoid eruptions, but rarely DRESS. We describe herein a case of furosemide-induced DRESS that recurred after bumetanide administration. CASE REPORT: A 67-year-old man was admitted to the nephrology department for hypertension, gout and chronic renal failure. He received a multidrug therapy including captopril, nifedipine, allopurinol and furosemide. Six weeks after starting this treatment, he developed a maculopapular itchy and edematous skin reaction, facial edemaand fever. The laboratory findings showed 2200/mm3 of eosinophils (20%). Creatinine clearance decreased from 18.9 to 14.4 mL/min. Lactate dehydrogenase was at 600 IU/L (normal range 190-390 IU/L). Chest X-ray showed an interstitial lung injury. Skin biopsy findings were in accordance with a hypersensitive reaction. Furosemide was withdrawn and symptoms resolved completely three weeks later. A patch test with furosemide performed six weeks later was negative. The patient was given bumetanide, another sulfonamide loop diuretic, with recurrence of symptoms two months later. Bumetanide was withdrawn with a complete resolution of both clinical and biological symptoms within three weeks. CONCLUSION: We add to the literature another case of furosemide-induced DRESS with the particularity of cross reactivity with bumetanide.

[Social determinants of contraceptive use in Tunisia]. / Les déterminants sociaux de l'utilisation des méthodes contraceptives en Tunisie.

BACKGROUND: In Tunisia, the "Revolution" of January 2011 highlighted significant regional disparities and social inequalities in access to health care, including reproductive health services. The purpose of this study was to analyze the social determinants of the use of contraception in Tunisia. METHODS: A cross-sectional national study conducted in 2012; on a sample of 15 to 49-year married women (n=4374) drawn by a two levels random sampling. Prevalence of contraception and its association factors were assessed. Logistic regression was used to evaluate the variation of contraception prevalence with area of residence, age, level of education, number of children and household income. RESULTS: The prevalence of contraception was 66.4 %. Eighty-two percent of women used a modern contraceptive method. The use of contraceptive methods was significantly dependent on the age (P<0.001), area of residence (P=0.008), education (P<0.001). The prevalence of contraception was higher in North West (OR=1.1 [0.81-1.5]; P<0.001), among multiparous women (OR=4.49 [3.57-5.66]; P<0.001), among the youngest women (OR=1.4 [0.9-2,19]; P<0.001) and among those with higher levels of education (OR=1.62 [1.19-2.21]; P=0.008). CONCLUSION: Tunisia, precursor Arab country in family planning, is recording a slowdown in the use of contraception in comparison with other countries of North Africa. Social determinants, such as, age, living conditions, area of residence and level of education are indicators to consider when targeting interventions.

Assessment of cardiovascular risk in Tunisia: applying the Framingham risk score to national survey data.

OBJECTIVE: This paper aims to assess the socioeconomic determinants of a high 10 year cardiovascular risk in Tunisia. SETTING: We used a national population based cross sectional survey conducted in 2005 in Tunisia comprising 7780 subjects. We applied the non-laboratory version of the Framingham equation to estimate the 10 year cardiovascular risk. PARTICIPANTS: 8007 participants, aged 35-74 years, were included in the sample but effective exclusion of individuals with cardiovascular diseases and cancer resulted in 7780 subjects (3326 men and 4454 women) included in the analysis. RESULTS: Mean age was 48.7 years. Women accounted for 50.5% of participants. According to the Framingham equation, 18.1% (17.25-18.9%) of the study population had a high risk (≥20% within 10 years). The gender difference was striking and statistically significant: 27.2% (25.7-28.7%) of men had a high risk, threefold higher than women (9.7%; 8.8-10.5%). A higher 10 year global cardiovascular risk was associated with social disadvantage in men and women; thus illiterate and divorced individuals, and adults without a professional activity had a significantly higher risk of developing a cardiovascular event in 10 years. Illiterate men were at higher risk than those with secondary and higher education (OR=7.01; 5.49 to 9.14). The risk in illiterate women was more elevated (OR=13.57; 7.58 to 24.31). Those living in an urban area had a higher risk (OR=1.45 (1.19 to 1.76) in men and OR=1.71 (1.35 to 2.18) in women). CONCLUSIONS: The 10 year global cardiovascular risk in the Tunisian population is already substantially high, affecting almost a third of men and 1 in 10 women, and concentrated in those more socially disadvantaged.

Focal liver hyperplasia in a patient with Alagille syndrome: Diagnostic difficulties. A case report.

INTRODUCTION: Alagille syndrome is a multisystem autosomal disorder. The main clinical features are chronic cholestasis due to paucity of intrahepatic bile ducts, which can progress to cirrhosis and liver failure. PRESENTATION OF CASE: A 15 year-old girl with Alagille syndrome was referred for liver transplantation. She developed severe cirrhosis with refractory ascites. In the pre-transplant evaluation, imaging studies disclosed liver atrophy with a high density pseudotumor in the segment 4, raising the possibility of a hepatocellular carcinoma. However, behavior of the lesion was highly suggestive of focal compensatory hyperplasia surrounded by an atrophic liver. The patient was registered on the waiting list. DISCUSSION: Hepatic lesions have been described in Alagille syndrome in isolated case reports, and most of these have been reported to be hepatocellular carcinoma. However, they can be related to an area of focal compensatory hyperplasia in severe cirrhosis. These findings may also explain why progression of liver disease occurs only in 15% of patients. CONCLUSION: The presence of a large hepatic nodule Alagille syndrome can be benign in these patients also predisposed to hepatocellular carcinoma. Therefore, cautious evaluation with magnetic resonance imaging study before liver transplantation is mandatory.

The Duffy blood group system in the Tunisian population.

BACKGROUND: Tunisia was described to as genetically heterogenous. Besides the 1% native Berber, the genetically influence of the Europeans seems much larger than that of sub-Saharan populations. Due to their ethnic variability, blood group variants have the potential to support population analyses. The aim of this study was to estimate the Duffy blood group system in this mixed population with enhanced characterization of samples with aberrant expression. MATERIALS AND METHODS: Standard serological testing for the Duffy antigen was done for 105 Tunisian blood donors. Samples with altered Fy expression underwent DNA sequencing of the DARC, RHD and RHCE genes. RESULTS: The Fy(a-b+) was the most common phenotype identified in the Tunisian population (38.1%). Five samples with Fy(a-b-) phenotype were determined as FY*02N.01/FY*02N.01 by a homozygous occurrence of the FY*B-67C>T alteration. Another three individuals exhibited a Fy(b+(w))Fy(x) expression, confirmed by a FY*A/FY*02M.01 (n = 1) and a FY*02M.01/FY*02M.01 (n = 2) genotype. RHD and RHCE sequencing (n= 8) revealed altered alleles observed in black populations in 5 samples. One individual with FY*02M.01/FY*02M.01 have the silent 165C>T nucleotide substitution each in the RHD and RHCE gene. DISCUSSION: The composition of blood group variants determined in this study confirms the genetically proximity of Tunisia to Europe. The small sub-Saharan genetic influence was approved by a limited number of variant samples associated with the black population.

Nodular hyperplasia of the gastrointestinal tract after liver transplantation: role of immunosuppressive therapy? A case report.

Nodular lymphoid hyperplasia (NLH) of the gastrointestinal tract is a rare disease usually reported in patients with congenital or acquired immunodeficiency and chronic gastrointestinal infections. However, no case of NLH in a patient receiving immunosuppressive therapy has been reported to date. We describe the case of a woman who developed chronic diarrhea related to NLH 9 years after liver transplantation. Other causes of diarrhea and NLH were excluded. Her immunosuppressive regimen consisted on mycophenolate mofetil (MMF) and tacrolimus. Reduction of MMF dose improved symptoms but led to a rising aminotransferase level. Given the risk of graft rejection, MMF at full dose was resumed and she was started on symptomatic treatment for diarrhea. The role of immunosuppressive drugs in the pathogenesis of NLH may be related to the reduction of T- and B-lymphocyte proliferation and decreasing antibody production. NLH will further develop to compensate functionally inadequate lymphoid tissue, as reported in congenital immunodeficiency states.

[Accuracy of ultrasound estimated fetal weight performed by residents at delivery day]. / Performance de l'estimation échographique du poids fœtal réalisée par les internes de spécialité le jour de l'accouchement.

UNLABELLED: Ultrasound fetal weight estimation (EFW) has become a routine practice in obstetrics with a major impact on obstetrical management. OBJECTIVES: To evaluate the accuracy of sonographic fetal weight estimations performed by residents in obstetrics at the delivery day and to search parameters influencing this exam. METHODS: A prospective study performed in 299 patients at 37 weeks of gestation or more, during their delivery day. Ultrasound fetal weight estimations were performed by residents and compared to birth weights (BW). The estimated fetal weight (EFW) was calculated using the formula of Hadlock: Log10 EPF=1,335+0.0316 BIP+0,0457 PA+0,1623 LF-0,0034 PA LF. RESULTS: Mean absolute difference between EFW and BW was 200g [100-450]. Mean absolute percentage error was 5.71 % [2.7-11.37]. The proportion of the EFW within 10 % of BW was 69.6 %. There was a good correlation between EFW and BW (R=0.79). Obesity and fetal macrosomia had negatively influenced ultrasound performance. For the diagnosis of macrosomia, ultrasound has a sensibility of 38 % and a specificity of 99.59 %. CONCLUSION: Ultrasound fetal weight estimations performed by residents in the delivery room were as accurate as those performed by experimented sonographers. Thus, the predictive performance remains limited with a low sensitivity in the diagnosis of macrosomia.

[Clinico-biological and immunohaematological profile of patients with ß-thalassemia in Tunisia: about 26 cases]. / Profil clinico-biologique et immunohématologique des patients atteints de ß-thalassémie en Tunisie : à propos de 26 cas.

AIM OF THE STUDY: To study the clinical and biological profile of ß-thalassemic patients in our region, reflecting the quality of their care. PATIENTS AND METHODS: A retrospective study (2010-2011) on 26 ß-thalassemic patients followed in the pediatrics service at CHU Farhat Hached Sousse, Tunisia. Epidemiological, clinical and biological data were collected from medical records and transfusion files of patients. The transfusion protocol adopted was to maintain a hemoglobin level>10g/dL by regular transfusions every 3-4 weeks. Iron chelation therapy, in order to maintain serum ferritin<1500ng/mL, was introduced when serum ferritin exceeded 800-1000ng/mL. RESULTS: The mean age of patients at diagnosis was 15 months. The clinical impact of anemia had resulted in failure to thrive in 54% of patients and facial dysmorphism in 23%. The average transfusion requirement was estimated at 311.02mL/kg/year with 6 cases of hyperconsumption. The immunohaematological monitoring showed the appearance of anti-RBC alloimmunization in one patient and 4 cases of autoimmunization. Poor adherence of chelation therapy was 62% and causing 5 cases of cardiac complications, 4 cases of liver injury and 14 cases of endocrine complications. CONCLUSION: Improving the therapeutic care of ß-thalassemic children requires better monitoring of transfusion recovery and improved adherence to chelation therapy.

[National survey of maternal mortality of 2010 : data of Tunisia]. / L'enquête Nationale Tunisienne sur la mortalité maternelle de 2010 : A propos des données de Tunis.

BACKGROUND: Tunisia has investigated maternal mortality in 2010 to determine maternal mortality ratio (MMR) nationally and regionally, in addition to the indentifying main causes of this mortality. OBJECTIVES: Describe methodology of this study and its principal findings in the region of Tunis and discuss the national maternal mortality strategy. METHODOLOGY: This is a Ramos study (Reproductive Ag Mortality Studies) that consists on identifying maternal deaths from reproductive age group (RAG) women deaths. We started by the a rehearsal and targeting of (RAG) women deaths , then we investigated a next of kin person of the decedent women by verbal autopsy, thereafter we identified maternal deaths to be confidentially investigated to judge the potential avoidability of the death. The study took place in 2010, it was carried out by 5 couples of investigators supervised by a coordinator doctor. RESULTS: A total of 200 deaths of (RAG) women were found in Tunis, 7 deaths among them were maternal deaths, that corresponds to an MMR of 41/100000 live births. The mean age of the deceased women was 35 years. The main causes of maternal deaths were hemorrhage (3/7), thrombo-embolic diseases (2 times for7) and HELLP syndrome (1/7). Four of a total of 4 deaths (3 deaths were not marked), were avoidable. The majority of late women had a satisfying educational level, 4 of 7 had financial autonomy. All of them had pregnancy monitoring, 5 times of 7 in university hospital. All the childbirth were medically assisted, Caesarean section was carried in 6 of 7 cases. Nationally, the MMR was estimated to 44.8/100 000 LB, that to say a decrease of 35% compared to 1993. The decrease was significant for all the regions of the country, except the great Tunis where opposite trend was recorded. This could be more likely related to quality of care rather than socio-economic conditions seeing that social determinants in Tunis are favorable. In fact, the Tunisian maternal mortality strategy had essentially focused on the monitoring system of maternal deaths rather than the quality of care improvement interventions, results were disappointing due to the lack of institutional engagement. The achievement of the OMD5 objectives is compromised, due to socio-economic constraint especially in certain regions, poor governance and lack of engagement of ministry of health in reducing maternal mortality. CONCLUSION: Tunisian maternal mortality strategy should be revised and adapted to regional context, also should includ multisectoral interventions. Priority would be given to quality of care improvement, by launching the experience of care setting accreditation in one hand, and in the other improving partnership between different levels of care.

Anti-D auto-immunization in a patient with weak D type 4.0.

We report the case of a 56-year-old patient with blood group O+C-c+E-e+K-, followed for a myelodysplasic syndrome and treated by regular pheno-identical and compatible (RBCs) transfusion since December 2007. In June 2009, a positive crossmatch was found with 2 RBCs O+C-c+E-e+K-. A positive anti-body screening with a positive autocontrol was detected and anti-D was unidentified in the patient's serum. The DAT was positive (IgG) and elution identified an anti-D. The following assumptions were then made: it could be a partial D phenotype with anti-D alloantibodies or RH: 1 phenotype with an anti-D auto-antibodies. Molecular analysis by multiplex PCR and sequencing have depisted a weak D type 4.0 phenotype. In October 2009, over three months of RH:-1 RBC transfusion, the antibody screening and DAT (IgG) remained positive, and an eluate made from the patient's erythrocytes contained an anti-D. All these funding confirmed the autoimmune nature of the anti-D. This case report illustrates the importance of a well-conducted and immunohematological laboratories test in order to distinguish between auto- or allo-immune of anti-D in a RH: 1 poly-transfused patients. This distinction is of great importance for transfusion support.

RHD*weak partial 4.0 is associated with an altered RHCE*ce(48C, 105T, 733G, 744C, 1025T) allele in the Tunisian population.

BACKGROUND AND OBJECTIVES: D is the most immunogenic blood group antigen. About 1% of whites carry an altered RHD allele leading to quantitative or qualitative changes in the antigen D expression. T201R and F223V encoded by 602C>G and 667T>G are specific amino acid substitutions of the weak D type 4 cluster of African origin, comprising the alleles RHD*09.01, RHD*09.02, RHD*09.03, RHD*09.04 and RHD*09.05. The purpose of this study was to estimate the presence of these RHD genotypes in the Tunisian population. MATERIALS AND METHODS: Ethylenediaminetetraacetate blood samples from 907 D+ and 93 D- blood donors were tested for markers 602G and 667G by allele-specific primer-polymerase chain reaction (PCR-ASP). Samples with positive reactions were re-evaluated by DNA sequencing for RHD and RHCE exons 1-10 and adjacent intronic sequences. RESULTS: Among 907 D+ samples, 19 individuals were identified to harbour the RHD*weak partial 4.0 allele. RHCE sequencing post-haplotype-specific extraction (HSE) revealed an altered RHCE*ce(48C, 105T, 733G, 744C, 1025T) in those samples. The linkage of the RHCE polymorphisms to one haplotype was proven by DNA sequencing post-HSE. CONCLUSION: The RHD*weak partial 4.0 allele syn. RHD*09.03 was estimated to occur 1 in 47 among D+ Tunisians. There was no evidence for other RHD alleles included in the weak D type 4 cluster.

Circulating antimyenteric autoantibodies in Tunisian patients with idiopathic achalasia.

The physiopathology of idiopathic achalasia is still unknown. The description of circulating antimyenteric autoantibodies (CAA), directed against enteric neurons in sera of patients, suggests an autoimmune process. Recent data showed controversies according to the existence and the significance of CAA. The aims of this study were to investigate whether CAA are detected in Tunisian patients with idiopathic achalasia and to look for associated clinical or manometrical factors with CAA positivity. Twenty-seven patients with idiopathic achalasia and 57 healthy controls were prospectively studied. CAA were assessed by indirect immunofluorescence on intestinal monkey tissue sections. Western blot on primate cerebellum protein extract and dot technique with highly purified recombinant neuronal antigens (Hu, Ri, and Yo) were further used to analyze target antigens of CAA. CAA were significantly increased in achalasia patients compared with controls when considering nuclear or cytoplasmic fluorescence patterns. (33% vs. 12%, P = 0.03 and 48% vs. 23%, P = 0.001 respectively). By immunoblot analysis, CAA did not target neuronal antigens, however 52/53 and 49 kDa bands were consistently detected. CAA positivity was not correlated to specific clinical features. The results are along with previous studies demonstrating high CAA prevalence in achalasia patients. When reviewing technical protocols and interpretation criteria, several discrepancies which could explain controversies between studies were noted.

Trends in secondary prevention of coronary heart disease in Tunisia: prevention of recurrences of MI and stroke.

OBJECTIVES: The survival benefits achieved by prescription of antiplatelet agents, B-adrenoreceptor antagonists (beta-blockers), angiotensin II receptor blockers (ARB), and lipid lowering agents in patients surviving the myocardial infarction (MI) have been well documented in large clinical trial. Despite well-established benefits, these pharmacological agents continue to be underutilized. The main objective of this study was to evaluate the progress of cardiovascular secondary prevention practices in Tunisia. METHODS: The PREMISE (Prevention of Recurrence of Myocardial Infarction and Stroke) is a descriptive, cross-sectional study conducted in Tunisia in two phases (2002 and 2009). Seven hundred eighty two patients were recruited. The recruitment criteria were: previous MI, stable angina, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA) or carotid endarterectomy. This analysis is limited to coronary heart disease (CHD) patients. Five hundred hospital patients were interviewed and their medical records were reviewed: 250 in 2002 and 250 in 2009. Patients were included if they had confirmed diagnosis of MI, angina, CABG or PTCA, and if their first cardiovascular event had occurred more than one month but not later than 3 years ago. We compared the total of both patient groups, using the prevalence of Cardio-Vascular Risk Factors (CVRF) and the treatment prescribed at hospital discharge. RESULTS: The proportion of patients with reported hypertension, diabetes, hypercholesterolemia and current smoker patients had decreased. Concerning pharmacological prescriptions, a significant increase was observed in prescribing statins (38.9% vs. 70.3%) and ACE inhibitors (49.3% vs. 69.9%), non pharmacological prescriptions as healthy diet or tobacco cessation had opposite trends. Adherence to treatment did not change substantially. CONCLUSION: Although the use of cardioprotective drugs had increased in CHD patients, there are still gaps in secondary prevention in Tunisia. The recommended strategies of secondary prevention need to be applied more intensively in clinical practice.

Health and behaviours of Tunisian school youth in an era of rapid epidemiological transition.

To assess youth health behaviours and related quality of life in urban Tunisia, we conducted a cross-sectional survey of a representative sample of 699 secondary-school students. The overweight rate was 20.7%. Most of the sample had an insufficient level of physical activity and were unfamiliar with the recommended frequency of moderate physical activity. Norm-based scores of psychological state were about average, slightly better for boys than girls. Girls perceived themselves to be more stressed than boys. Of all students, 35% declared having smoked a cigarette and 14% having drunk alcohol at least once in their lives. The main sources of health education were mass media (59%) and medical staff (36%).