Cause Of Withdrawal Research Articles

A phase II multicenter study of aflibercept (AFL) in combination with cisplatin (C) and pemetrexed (P) in patients with previously untreated advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC).

7541 Background: AFL is a recombinant human fusion protein that acts as a decoy receptor and prevents the interaction of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor with their receptors. This study evaluated the efficacy and safety of AFL in combination with first-line chemotherapy of C and P in NSCLC. Methods: This phase II, single arm, open label, multicenter trial in patients with previously untreated, locally advanced, or metastatic NSCLC excluded patients with squamous histology, cavitating lesions, ECOG > 1, uncontrolled hypertension, or brain/CNS metastases. All patients received IV AFL 6 mg/kg, P 500 mg/m2, and C 75mg/m2, every 3 weeks for up to 6 cycles. For those who completed the combined chemotherapy, Q3W administration of AFL was to continue until disease progression, intolerable toxicity, or any other cause for withdrawal. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). Planned sample size was 72 patients. Results: The study was closed prematurely due to 3 confirmed cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 54.8% were male, 85.7% white and 50% ECOG 0. A median of 4 cycles of AFL was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. The 3 patients with RPLS were Caucasian women. Two had a history of hypertension and both experienced elevated BP and reduced CrCl. Of the 38 patients evaluable for response, ORR was 26.3% (95% CI, 12.3-40.3%) and median PFS was 5 months (95% CI, 4.3-7.1). Conclusions: The rate of RPLS observed in this study with AFL + C + P was higher than anticipated. A meta-analysis of safety from three large placebo-controlled studies reported no RPLS among 1333 patient treated with AFL + chemotherapy, and none was reported in prior combination studies of AFL + P or AFL + C + docetaxel. Though the study was stopped early, ORR and PFS were in accordance with most historical first-line NSCLC studies.

Establishment of T cell stimulation by flucloxacillin in HLA-B*5701+ flucloxacillin-naïve individuals (52.21)

Abstract Rational: Drug induced liver injury (DILI) is a main cause of drug withdrawal. A particularly interesting example is flucloxacillin (FLUX)-DILI, which is associated with the HLA-B*5701 allele. To better understand this side effect, we established an in vitro model for FLUX induced T cell activation. Methods: Peripheral blood mononuclear cells from FLUX-naïve, HLA-B*5701+ healthy donors were induced by iterative in vitro restimulations with FLUX. FLUX-specific T cells (FLUX-Tc) were enriched by positive selection of CD107a expressing cells and characterized by flow cytometry and 51Cr-release assay. Results: FLUX-Tc are mainly CD8+. They react by IFNγ secretion and CD107a upregulation upon drug stimulation and are cytotoxic against autologous antigen presenting cells (APC). Cytotoxicity and reactivity was observed only if free FLUX was added to the system. FLUX-pulsed APC were not able to elicit a FLUX specific T cell response if FLUX was not additionally added. The direct addition of FLUX to FLUX-Tc resulted in their activation even in the absence of APC. This self-presentation and reactivation was still observed in the presence of the proteasome inhibitors lactacystin and bortezomib. Conclusion: The APC independent T cell reactivity and the non-involvement of the proteasome is best explained by a direct interaction of FLUX with the restricting HLA-B*5701 molecule. How and why this activation leads to a preferential damage of liver cells needs further investigation.

Duration and reasons for changing the first antiretroviral therapy: an 8-year follow-up

BackgroundFailure of first highly active antiretroviral therapy (HAART) reduces both the duration and the chances of viral control in subsequent regimens, due to cross-resistance and common toxicity between and within...

Editorial: New drugs for Alzheimer's disease in Japan

Editorial: New drugs for Alzheimer's disease in Japan

Adalimumab is effective in long-term real life clinical practice in both luminal and perianal Crohn's disease. The Madrid experience

Objective To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response. Methods Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed. Results 174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to everyweek. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them. Conclusions Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.

Prediction of hepatotoxicity in zebrafish

Expression patterns of adult liver markers. Detection of GSH depletion Conclusions Olaia Holgado, Maria Diez, Carles Callol-Massot, M. Luz Martinez-Chantar, Ainhoa Letamendia BIOBIDE S.L Donostia-San Sebastian, Spain PREDICTION OF HEPATOTOXICITY IN ZEBRAFISH Drug induced hepatotoxicity is one of the most important causes of drug withdrawal in the Drug Discovery process. The low correlation of the in vitro cytotoxicity studies, with human hepatotoxicity, especially in the early stages of Drug Discovery, make human hepatotoxicity difficult to be predicted. Therefore the finding of new methods and models to predict hepatotoxicity is a growing area of research. The zebrafish model has been extensively studied in the last decades for its ability to regenerate. Specifically, the liver is one of the organs with the highest regenerative capacity. Researchers over the past 10 years have characterized many of the mechanisms that occur during this process leading to an important knowledge of the signaling pathways that govern zebrafish liver function and development. Therefore, because of the functional as well as developmental similarities between the liver of zebrafish and mammals, we propose to analyze the potential of zebrafish for prediction of hepatotoxic agents. For this purpose, the following aspects have been studied: i) The stage at which adult liver markers are expressed has been identified. ii) Several techniques have been developed for assessing the hepatotoxicity of a compound in zebrafish. iii) These techniques will be validated by testing different drugs. iv) The results will be compared with those obtained in mammals. Our results indicate that zebrafish embryos could be used as an alternative model in the Drug Discovery process complementing the information of in vitro models and mammals and providing pharmaceutical industry of new assays which might decrease the current huge gap between in vitro and in vivo assays. Necrosis Glutathion (GSH) depletion Steatosis Q-PCR analysis Detection of steatosis In order to study the expression pattern of adult liver markers, we performed Q-PCR analysis of MAT1A, MAT2A, GNMT in zebrafish. Total RNA was isolated at 0, 5, 10, 15 and 25 dpf (days post-fertilization) using TRIZOL method. Approximately 20-100 embryos were pooled for each stage. cDNA was synthesized from total RNA using a high efficiency reverse transcriptase with oligo dT. Q-PCR analysis of MAT1A, MAT2A and GNMT was performed. Due to the differences in stages between the samples, no housekeeping gene was used for normalization. Then, three independent experiments were conducted to confirm the results. To evaluate the potential of zebrafish for the detection of liver necrosis, six compounds were selected (five positives and one negative) and tested at different concentrations for 24 or 48 hours. 10 embryos per compound and concentration were used. After treatment the embryos were anesthesized and the color intensity of the liver was quantified by using a specific software. Under conditions of oxidative stress, cells may transiently incorporate glutathione into proteins. Stressed cells incubated with BioGEE will also incorporate this biotinylated glutathione derivative into proteins, facilitating the identification of oxidation-sensitive proteins. Once embryos are fixed and permeabilized, glutathiolation levels are detected with a fluorescent streptavidin conjugate. Embryos were fixed with 4% paraformaldehyde, washed with PBS, incubated with a graded series of propylene glycol, and stained with Oil Red in 100% propylene glycol. Stained larvae were washed with decreasing concentrations of propylene glycol followed by several rinses with PBS and transferred to glycerol.

CLINICAL OUTCOME OF DIABETIC PERITONEAL DIALYSIS PATIENTS AND EVALUATION OF FACTORS AFFECTING MORTALITY: A SINGLE CENTRE’S EXPERIENCE FROM TURKEY

The purpose of this study is to analyse the outcome of the diabetic peritoneal dialysis (PD) patients and compare the findings of those remaining on treatment with those who withdrew from treatment. Participants were 61 patients starting PD between 2001 and 2009, data were evaluated retrospectively. PD treatment was withdrawn in 48 patients forming Group 1 = drop-out; 26 F, mean age 59 ± 13 years; 13 patients in Group 2 = treatment; 4 F, mean age 50 ± 10 years, still receiving PD therapy. Demographics, laboratory and blood pressure data were compared in both groups. The causes for withdrawal were: death (54%), transfer to HD (33%), other causes (13%). Most frequent cause of death: cardiac events (57.7%), peritonitis and/or sepsis (38,4%). Transfer to HD - peritonitis (50%), insufficient PD (50%). Most frequent cause of peritonitis was Staph. Aureus in 42 instances in Group 1. We found positive correlation between mortality and age (p:0.008, r:0,345) and negative correlation between mortality and follow-up time, pretreatment albumin, calcium and PTH, systolic and diastolic BP in the last follow-up appointment. Cardiovascular events and peritonitis were the most important causes of withdrawal of patients. The presence of hypo-parathyroidaemia, hypocalcaemia and hypo-albuminaemia were associated with mortality.

Incidence of Cancer in Kidney Transplantation Waiting List Patients: A Single Center Experience

Introduction It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. Materials and Methods We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). Results Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. Conclusion The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Causes of camptocormia

Purpose. To identify and highlight the variable causes of camptocormia.Method. Literature review.Results. Camptocormia (bent spine syndrome) is an acquired postural disease characterised by forward flexion of the thoraco-lumbar spine. Camptocormia leads to lumbar kyphosis and increases during walking or standing and completely disappears in supine position. Camptocormia is multicausal due to central or peripheral nervous system disease, idiopathic or due to some rare conditions. Camptocormia is most frequently associated with Parkinson's disease. Other causes include dystonia, multisystem atrophy, Alzheimer's disease, myopathy, motor neuron disease, myasthenia or chronic inflammatory demyelinating polyneuropathy. Rare causes include adverse reactions of drugs, disc herniation, arthritis, spinal trauma, paraneoplastic disorder, or psychiatric disease (more rarely than previously thought). Camptocormia is diagnosed upon clinical investigations, imaging of the cerebrum or spine, electromyography or muscle biopsy. Treatment is limited on supportive conservative measures, to withdrawal of causative drugs, electroconvulsive therapy, surgical correction or deep brain stimulation and effective only in single patients.Conclusions. Camptocormia is organic in the vast majority of the cases due to neurological disease, or rarely drugs, trauma, orthopedic abnormalities or idiopathic.

In-hospital prescription of QT-prolonging drugs in a cohort of more than 100,000 patients

In-hospital prescription of QT-prolonging drugs in a cohort of more than 100,000 patients

Drug‐Induced QT‐Interval Prolongation: Considerations for Clinicians

Drug-induced proarrhythmia is a frequently encountered clinical problem and a leading cause for withdrawal or relabeling of prescription drugs. Suppression of the rapid component of the delayed rectifier potassium current, I(Kr), represents the principal pharmacodynamic mechanism leading to heterogeneous prolongation of the ventricular action potential and prolongation of the QT interval clinically. However, the risk of proarrhythmia by QT-interval-prolonging drugs is variable and critically dependent on several factors leading to multiple reductions in the cardiac repolarization reserve. As antiarrhythmic drugs that prolong the QT interval are usually aggressively managed with continuous electrocardiogram monitoring and screening for drug interactions when administered to patients who have a high risk of sudden cardiac death, their risk of mortality is not increased. However, noncardiovascular QT-interval-prolonging drugs, which often produce less QT-interval prolongation compared with antiarrhythmic drugs, are found to be associated with increased rates of death in patients who have a markedly lower de novo risk of sudden cardiac death. Thus, it is important for clinicians, particularly pharmacists, to be cognizant of the levels of risk associated with varying degrees of QT-interval prolongation caused by drugs so that they can develop strategies to either prevent or reduce the risk of proarrhythmias.

Role of c-Jun N-terminal kinase (JNK) in regulating tumor necrosis factor-alpha (TNF-.ALPHA.) mediated increase of acetaminophen (APAP) and chlorpromazine (CPZ) toxicity in murine hepatocytes

Drug induced liver injury (DILI) accounts for more than 50% of the cases of acute liver failure in this country, and is the major cause of drug withdrawal from the market. DILI has been associated with the induction of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). Pro-inflammatory cytokines activate the mitogen activated protein kinase, c-Jun-N-terminal kinase (JNK) in the liver. Recent studies have shown that JNK can regulate the hepatotoxicity of the analgesic, acetaminophen (APAP). Several reports have shown that inflammation induced by the endotoxin, lipopolysaccharide (LPS) augments the toxic response to hepatotoxicants in vivo. However, the mechanism by which inflammation alters drug-induced hepatotoxicity is not known. This study investigated the role of inflammatory mediators in regulating the toxicity of the hepatotoxic drugs, APAP or chlorpromazine (CPZ) in primary mouse hepatocytes. We found that, pre-treatment with TNF-alpha resulted in approximately 50 to 60% increase in alanine aminotransferase (ALT) levels by APAP or CPZ, while interleukin-1beta (IL-1beta) or IL6 treatments showed only 15-20% increase in ALT release. The bacterial components, LPS or lipoteichoic acid (LTA) increased ALT release by approximately 35 to 38% upon drug treatment of the hepatocytes. The JNK inhibitor, SP600125 significantly diminished APAP and CPZ toxicity with or without TNF-alpha. Pre-treatment with TNF-alpha resulted in prolonged activation of JNK (upto 2 hr) in the presence of APAP or CPZ. These results show that TNF-alpha is the major cytokine involved in sensitizing hepatocytes to APAP- or CPZ-induced hepatotoxicity, likely by a mechanism involving sustained activation of JNK.

A suspected case of carbimazole-associated torsades de pointes

Torsades de pointes (TdP) or polymorphic ventricular tachycardia owing to drug-induced QT prolongation is a common cause of withdrawal of marketed drugs and has caused increasing concern in the recent past. Carbimazole, the common antithyroid drug, is not a very well-known offender to cause QT prolongation and TdP. Only a few cases of carbimazole-induced TdP have been reported so far. We report a 53-year-old woman who was on tab. carbimazole (10 mg) twice daily for one month and who presented with respiratory distress, palpitation and syncope attack. Her surface electrocardiogram (ECG) was showing the evidence of TdP and subsequently hypokalemia was also detected. She received conservative management including potassium supplementation. However, QT prolongation persisted even after normalization of serum potassium level. Carbimazole was withdrawn and the patient was discharged as she remained stable and symptom free. This study highlights a possible association between carbimazole and TdP.

Antimicrobial Agents-Associated with QT Interval Prolongation

QT interval prolongation is one of the most important causes of withdrawal of drugs from the market, due to its association with Torsades de Pointes (TdP), a potentially fatal arrhythmia. Although many antimicrobial drugs are capable of inducing this type of arrhythmia, the importance of this effect is usually underestimated. Macrolides, quinolones, azoles, pentamidine, protease inhibitors, antimalarial drugs and cotrimoxazole are the anti-infective agents more frequently associated with this adverse effect. Despite the fact that the risk of QT prolongation and TdP under single antimicrobial therapy is low, these drugs are so extensively used that sporadic cases of this arrhythmia are reported. Moreover, antimicrobial drugs are susceptible to pharmacokinetic and pharmacodynamic interactions with other drugs, which may increase the risk of this arrhythmia. Therefore, physicians must be familiar with not only the antimicrobial drugs capable of producing QT interval prolongation, but also their potential interactions. In addition, patient's specific risk factors of prolonging QT interval or producing TdP must be taken into account. This article reviews the role of anti-infective drugs in QT prolongation, focusing on QT prolongation mechanisms, potential drug interactions, and patients' predisposing factors to this arrhythmia.

Seguridad y tolerancia del tratamiento con bloqueadores beta en el paciente anciano con insuficiencia cardíaca. Estudio BETANIC

Background and objetive Prescription of beta-blockers (BB) in elderly patients with heart failure (HF) is very low, and it probably owes to an excessive concern about the risk of adverse reactions. The objective of our study was to determine the safety and tolerance of BB in elderly patients with HF in an Internal Medicine clinical practice. Material and methods This observational prospective study of clinical practice included 119 patients older than 70 years with HF evaluated in 10 Internal Medicine services. Patients must have started treatment with BB (carvedilol or bisoprolol) within the last month. After 6 months of follow-up, the percentage of patients on BB, the dose achieved and the causes of withdrawal were analyzed. Results At the end of the study, 100 patients (84%) were on BB treatment. There were 3 deaths (2.5%), none related to BB use, and 6 losses to follow-up (5%). The treatment was stopped in 10 patients (8.4%). Maximum dose was achieved in 38.7% of the patients. Adverse reactions responsible for treatment withdrawal were: symptomatic hypotension (3 cases; 2.5%); asymptomatic hypotension (1 case; 0.8%); heart failure (2 cases; 1.7%); bradycardia (2 cases; 1.7%); bronchospasm (1 case; 0.8%); and unknown cause (1 case; 0.8%). Conclusions BB are excellently tolerated in elderly patients with HF treated in an Internal Medicine setting.

The role of Emotional Intelligence in the decision to persist with academic studies in HE

Failure to adapt to the demands of higher education (HE) is often cited as a cause of withdrawal from the course. Parker and others (Parker, J.D.A., L.J. Summerfeldt, M.J. Hogan, and S.A. Majeski. 2004. Emotional intelligence and academic success: Examining the transition from high school to university. Personality and Individual Differences 36: 163–72) considered the role of individual differences in Emotional Intelligence (EI) and demonstrated a link between EI, withdrawal/retention and measures of academic achievement. In this study we ask whether EI mediates withdrawal in a UK HE institution and whether an EI‐based intervention might improve retention rates. Study 1 considers the effects of EI upon retention, revealing that students with higher levels of EI are more likely to progress to Year 2 of study. Study 2 evaluates an EI‐based intervention programme, demonstrating that students who show an increase in EI are more likely to persist with their studies. These findings are discussed in the light of current theoretical work. The prospects for EI‐based intervention programmes are also considered.

Who withdraws from initial teacher preparation programmes and why?

Background: In recent years, withdrawal from initial teacher preparation (ITP) programmes, in England and elsewhere, has become a cause for concern amongst both ITP providers and policy-makers. Purpose: This paper seeks to enhance the presently underdeveloped evidence base on the causes of withdrawal from ITP and on the characteristics of student teachers who are most likely to withdraw. Sample: All ITP providers in England were stratified by ITP route (including university-administered undergraduate and postgraduate programmes, school-centred and employment-based programmes) and a random sample within each route was selected. Of the 110 providers invited to participate in the research, 74 agreed to take part. All student teachers following the specified ITP routes in these institutions were then invited to participate in a longitudinal survey about their experiences of ITP and early professional development. Design and methods: Student teachers (n = 4790) completed an initial questionnaire about their reasons for undertaking ITP and their preconceptions about ITP and teaching. Of these, 3162 took part in a follow-up telephone interview about their experiences of ITP and, for 135 of these participants, about their experiences of withdrawing from ITP. Descriptive and inferential statistics were employed: (a) to explore the experiences of those who withdrew from ITP; (b) to examine the extent to which withdrawal might be predicted by their reasons for undertaking ITP or their preconceptions of ITP and teaching; (c) to compare the responses to a number of key questions of those who withdrew from ITP and those who did not. Results: The findings show that withdrawal from ITP is differentiated by a number of variables including the ITP route being followed, whether student teachers are seeking to teach in primary or secondary schools, their age, gender and prior commitment to the profession. Data suggest that the main causes of withdrawal relate to workload and an apparent lack of support from ITP providers. Conclusions: The findings support some those of earlier studies but contradict others, for example by showing that those who report more prior experience of working in schools are not less likely to withdraw from ITP. A number of implications are presented for teacher educators and policy-makers.

Physical activity readiness in patient withdrawals from cardiac rehabilitation

Adherence to cardiac rehabilitation (CR) programmes may be an important element for improving and maintaining physical activity (PA) behaviour in secondary prevention. Little is known about the PA behaviour in patients who have withdrawn from CR programmes. Therefore, a study was carried out to identify the reasons for withdrawal and the stage of PA readiness in those patients previously engaged in a Leeds-based community CR programme. A cross-sectional study was conducted using a telephone questionnaire to determine causes of withdrawal. A questionnaire based on the transtheoretical model of change was used to assess changes in PA readiness in these patients. 101 withdrawn patients (mean age = 61 years; 72% male) were identified. It was found that 20 patients had relapsed beyond baseline (preparation phase) into pre-contemplation and contemplation phases and 15 reported they were in the preparation phase. However, the majority of patients remained in the action (18) and maintenance (48) phases of the transtheoretical model. Patients reported the following reasons for withdrawal: joined other facilities (16%); injury or illness (3%); family demands (7%); work demands (14%); lack of motivation (4%); lack of enjoyment (11%); lack of transport (10%); lack of time (10%); too expensive (6%); too crowded (4%). 66% of patients who had withdrawn from a phase IV CR programme remained in an advanced stage of PA readiness. Drop-out was due to a combination of financial, physical and lifestyle factors.

Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the science

Drug-induced liver injury (DILI) represents a major impediment to the development of new drugs and is a leading cause of drug withdrawal. The occurrence of hepatotoxicity has been closely associated with the formation of chemically reactive metabolites. Huge investment has focused on the screening of chemically reactive metabolites to offer a pragmatic approach to produce safer drugs and also reduce drug attrition and prevent market place withdrawal. However, questions surrounding the importance of chemically reactive metabolites still remain. Increasing evidence now exists for the multi-factorial nature of DILI, in particular the role played by the host immune system or disease state in the pathogenesis of DILI. This review aims to evaluate the current measures for the prediction and diagnosis of DILI and to highlight investigations being made to understand the multidimensional nature. Some of the steps being made to generate improved physiological systems to identify more sensitive, reflective mechanism-based biomarkers to aid the earlier identification of DILI and develop safer medicines are also discussed.

The T 380A intrauterine device: a retrospective 5-year evaluation

Background The undue resistance to intrauterine device (IUD) use seen in several settings does not seem to occur in the Family Planning Unit of UNIFESP-EPM (São Paulo Federal University, Brazil). In fact, the Copper T 380A IUD in this clinic has reached an outstanding importance and this motivated us to present our differing experience. The prevalence of this method in this clinic is as high as 40%. This contrasts to the low use in the rest of the country, where tubal ligation is by far the most used contraceptive method (40%) and where IUD is inexpressive (1.1%). Study Design This is a retrospective study of the records of 118 users of Copper T 380A IUD inserted at the clinic and who were followed during 5 years. Results The cumulative pregnancy rate was 0.8%. The main cause for discontinuation of the study was loss to follow-up (21.3%). Other reasons for the withdrawal of the device were personal option (13.6%), dislocation (11.7%) and pregnancy wish (3.4%). There was no withdrawal by pelvic inflammatory disease. Bleeding (0.8%) was not an important cause for withdrawal, and there were no withdrawals due to pain. The continuation rate at 5 years was 46.7%. The structured service and an adequate educative program perhaps could explain at least partially the good performance of IUD use in this clinic. There was an amazing prevalence of the components of the metabolic syndrome. This could represent contraindications for hormonal contraception, and, in consequence, it could influence the increased option for and continuation of the IUD. Conclusion These data show a good performance of the IUD for long duration, in relation to other studies, and this should be considered as a reliable alternative to the high prevalence of female sterilization in this country.