Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study.

OBJECTIVE: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. PATIENTS AND METHODS: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. RESULTS: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). CONCLUSION: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

High-dose etanercept in ankylosing spondylitis: results of a 12-week randomized, double blind, controlled multicentre study (LOADET study).

OBJECTIVES: Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS. METHODS: Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit. RESULTS: A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate. CONCLUSIONS: High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.

Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism.

RATIONALE: Concomitant deep vein thrombosis (DVT) in patients with acute pulmonary embolism (PE) has an uncertain prognostic significance. OBJECTIVES: In a cohort of patients with PE, this study compared the risk of death in those with and those without concomitant DVT. METHODS: We conducted a prospective cohort study of outpatients diagnosed with a first episode of acute symptomatic PE. Patients underwent bilateral lower extremity venous compression ultrasonography to assess for concomitant DVT. MEASUREMENTS AND MAIN RESULTS: The primary study outcome, all-cause mortality, and the secondary outcome of PE-specific mortality were assessed during the 3 months of follow-up after PE diagnosis. Multivariate Cox proportional hazards regression was done to adjust for significant covariates. Of 707 patients diagnosed with PE, 51.2% (362 of 707) had concomitant DVT and 10.9% (77 of 707) died during follow-up. Patients with concomitant DVT had an increased all-cause mortality (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.24 to 3.38; P = 0.005) and PE-specific mortality (adjusted HR, 4.25; 95% CI, 1.61 to 11.25; P = 0.04) compared with those without concomitant DVT. In an external validation cohort of 4,476 patients with acute PE enrolled in the international multicenter RIETE Registry, concomitant DVT remained a significant predictor of all-cause (adjusted HR, 1.66; 95% CI, 1.28 to 2.15; P < 0.001) and PE-specific mortality (adjusted HR, 2.01; 95% CI, 1.18 to 3.44; P = 0.01). CONCLUSIONS: In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

Association of anaemia and mortality in patients with acute pulmonary embolism.

This study aimed to evaluate the relationship between anaemia and pulmonary embolism (PE) prognosis. We analysed a cohort of 764 patients with acute PE referred to a single center for diagnosis and management. Patients were divided into groups by quartiles of haemoglobin (Hb): Hb < 11.7 g/dl; Hb 11.7 to 12.9 g/dl; Hb 13.0 to 14.1 g/dl; Hb > 14.1 g/dl. Patients had a mean Hb of 12.9 g/dl, and values ranged from to 4.3 to 19.5 g/dl. Lower Hb was associated with recent bleeding, an impaired haemodynamic profile and higher creatinine. Patients in the lower Hb quartiles more commonly had female gender (p < 0.001), a diagnosis of cancer (p < 0.001), and an indication for an inferior vena cava (IVC) filter (p < 0.002), compared to patients in the higher Hb quartiles. Patients in higher Hb quartiles had higher survival at three months (75%, 86%, 90% and 91% for lowest to highest quartiles, respectively). On multivariate analysis, adjusting for known PE prognostic factors, low Hb proved to be an independent predictor of mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05 to 1.28 for each decrease of 1 g/dl). Hb level remained an independent predictor of all-cause mortality when cancer patients were excluded from the analysis (adjusted HR 0.81; 95% CI, 0.66 to 0.99; p = 0.04). Moreover, patients with anaemia showed a higher risk of fatal PE (unadjusted HR 1.19, 95% CI 1.04 to 1.37). In conclusion, in patients with acute symptomatic PE, anaemia severity is associated with worsened survival.

[Anti-factor Xa activity of enoxaparin for thromboprophylaxis in nonsurgical patients is dependent on body mass]. / La actividad anti-Xa depende del peso en pacientes médicos que reciben tromboprofilaxis con enoxaparina.

OBJECTIVE: Thromboprophylaxis with a fixed dose of low-molecular-weight heparin is recommended for hospitalized acutely ill medical patients. The purpose of this study was to assess whether the anti-factor Xa (anti-Xa) activity of enoxaparin prescribed for venous thromboembolism prophylaxis depends on body mass index (BMI) in patients hospitalized for an acute respiratory disease. PATIENTS AND METHODS: All patients admitted to the respiratory medicine department (January-December 2006) for an acute respiratory disease, and for whom pharmacologic thromboprophylaxis was indicated, were included in the study. Anti-Xa activity was measured 4 hours after administration of enoxaparin on the third day of hospitalization. The primary outcome was anti-Xa activity in relation to BMI. RESULTS: One hundred twelve patients were enrolled. Mean anti-Xa activity decreased with each BMI quartile (0.28, 0.23, 0.15, and 0.13 U/mL for quartiles 1, 2, 3, and 4, respectively). In the multivariate analysis, BMI was the only predictor of inadequate anti-Xa activity (odds ratio, 1.14; 95% confidence interval, 10.5-1.24; P< .002) after adjustment for age, sex, and serum creatinine levels. Two episodes of symptomatic proximal deep vein thrombosis were diagnosed in the month after hospitalization; both occurred in patients who had inadequate anti-Xa activity. CONCLUSIONS: Anti-Xa activity is dependent on BMI in hospitalized acute medical patients receiving enoxaparin for thromboprophylaxis.

Incobotulinumtoxin A for Sialorrhea in Neurological Disorders: A Real-Life Experience.

Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the Drooling Severity Scale (DSS), and the Drooling Frequency Scale (DFS). Patients' perceptions of clinical benefit were recorded via the Patient Global Impression of Improvement (PGI-I) scale. Following treatment, there was a significant difference in both the DFS and the DSS (p < 0.001). Clinical benefits on the basis of the PGI-I were present in up to 90% of patients.

Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy.

OBJECTIVE: To assess the performance of two prognostic models in predicting short-term mortality in patients with pulmonary embolism (PE). SUBJECTS AND METHODS: We compared the test characteristics of two prognostic models for predicting 30-day outcomes (mortality, thromboembolic recurrences, and major bleeding) in a cohort of 599 patients with objectively confirmed PE. Patients were stratified into the PE severity index (PESI) risk classes I-V and the Geneva low-risk and high-risk strata. We compared the discriminatory power of both prognostic models. RESULTS: The PESI classified fewer patients as low risk (strata I and II) [36%; 216 of 599 patients; 95% confidence interval (CI), 32 to 40%] compared to the Geneva prediction rule (84%; 502 of 599 patients; 95% CI, 81 to 87%) [p < 0.0001]. Using either prediction rule, the low-risk groups showed statistically relevant 30-day mortality difference (PESI, 0.9%; 95% CI, 0.3 to 2.2; vs Geneva, 5.6%; 95% CI, 3.6 to 7.6) [p < 0.0001], although nonfatal recurrent venous thromboembolism or major bleeding rates were statistically similar (PESI, 2.8%; 95% CI, 0.6 to 5.0%; vs Geneva, 4.2%; 95% CI, 2.4 to 5.9%). The area under the receiver operating characteristic curve was higher for the PESI (0.76; 95% CI, 0.69 to 0.83) than for the Geneva score (0.61; 95% CI, 0.51 to 0.71) [p = 0.002]. CONCLUSIONS: The PESI quantified the prognosis of patients with PE better than the Geneva score. This study demonstrated that PESI can select patients with very low adverse event rates during the initial days of acute PE therapy and assist in selecting patients for treatment in the outpatient setting.

Prognostic significance of delays in diagnosis of pulmonary embolism.

STUDY OBJECTIVE: To investigate the prognostic significance of a diagnostic delay of greater than 1 week after symptom onset in patients with pulmonary embolism (PE). DESIGN: Prospective cohort study. LOCATION: Emergency Department of Ramón y Cajal Hospital, a 1500-bed tertiary-care center in Madrid, Spain. PATIENTS: Diagnosed with PE by objective testing between January 1, 2003, and June 30, 2005. INTERVENTIONS: All patients received standard anticoagulation therapy during follow-up. ENDPOINTS: Death from any cause or symptomatic recurrent venous thromboembolism (VTE), confirmed by standard objective testing, within 3 months after PE diagnosis. RESULTS: Of the 397 patients with acute PE, 72 (18%) had a diagnostic delay while 325 (82%) did not. The all-cause mortality rate was 13.1% at 3 months (95% CI=9.8-16.4%); due to 9 (12.5%) deaths in the diagnostic delay group and 43 (13.2%) deaths in the group without diagnostic delay (OR 0.9; 95% CI=0.4-2.0). Though multivariate analysis of clinical variables at the time of PE diagnosis identified active cancer, heart failure and immobility for more than 4 days as independent risk factors for death, diagnostic delay was not predictive. Recurrent VTE was observed in 3 (4.2%) of 72 patients with diagnostic delay and in 15 (4.6%) of 325 patients without diagnostic delay (odds ratio: 0.9; 95% CI=0.2-3.2). None of the variables analysed, including diagnostic delay, was associated with an increased risk of recurrent VTE during follow-up. CONCLUSIONS: Among survivors diagnosed with acute PE in the Emergency Department, we did not detect an association between a delay in diagnosis and an increased risk of death or VTE recurrence during the ensuing 3 months of treatment.

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.

[Prognostic value of transthoracic echocardiography in hemodynamically stable patients with acute symptomatic pulmonary embolism]. / Valor pronóstico de la ecocardiografía transtorácica en pacientes estables hemodinámicamente con tromboembolia de pulmón aguda sintomática.

OBJECTIVE: To determine the prognostic value of transthoracic echocardiography in hemodynamically stable patients diagnosed with acute symptomatic pulmonary embolism. PATIENTS AND METHODS: Hemodynamically stable outpatients diagnosed with acute symptomatic pulmonary embolism at a tertiary university hospital were prospectively included in the study. All patients underwent transthoracic echocardiography within 48 hours of diagnosis. The primary endpoint was all-cause mortality at 1 month. RESULTS: Right ventricular dysfunction was documented by echocardiography in 86 of the 214 patients (40%) in our series. In the first month of follow-up, 7 patients died--4 with positive echocardiographic findings and 3 with negative findings (odds ratio, 2.0; 95% confidence interval, 0.4-9.3; P=.41). For the primary endpoint, the negative predictive value of transthoracic echocardiography was 98%, the positive predictive value was 5%, and the negative likelihood ratio was 0.7. The negative predictive value was 100% and the positive predictive value was 3% when we analyzed death due to pulmonary embolism only. CONCLUSIONS: In our setting, transthoracic echocardiography is not useful for prognostic stratification of hemodynamically stable patients with pulmonary embolism.

The risk of recurrent venous thromboembolism in patients with unprovoked symptomatic deep vein thrombosis and asymptomatic pulmonary embolism.

Patients with a first episode of symptomatic pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than patients with a first episode of proximal lower extremity deep vein thrombosis (DVT). Patients with symptomatic DVT and silent PE may have a different risk of VTE recurrence than patients that have symptomatic DVT without PE. Therefore, it was the aim of this prospective cohort study to compare the risk of recurrent symptomatic VTE in patients with proximal lower extremity DVT and silent PE to the risk in patients that only have proximal lower extremity DVT. Ninety-one consecutive outpatients presenting to the emergency department of a university hospital subsequently hospitalised with a first episode of unprovoked symptomatic proximal lower extremity DVT, and without new pulmonary symptoms were included. Standard initial treatment consisted of intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin for 5-7 days, overlapped with oral vitamin-K antagonist therapy, with long-term oral vitamin-K antagonist therapy (goal INR 2.5 [2.0-3.0]). Study endpoints were: symptomatic recurrent DVT, new PE, and recurrent PE, evaluated by standard objective testing. At enrollment, 28 of 91 (31%) patients with DVT had silent PE. In the patients with DVT and silent PE, there were 3 VTE recurrences during 20 person-years of follow-up, while there were no VTE recurrences during 61 person-years of follow- up in the patients with isolated DVT. The Kaplan-Meier estimated VTE recurrence rate at 1 year after the diagnosis of DVT was 11% (95% CI: 2-28%) for patients with symptomatic DVT and silent PE, compared to 0% in patients with isolated symptomatic DVT (p=0.0045). In patients with a first episode of unprovoked symptomatic acute proximal lower extremity DVT, the risk of recurrent VTE was significantly higher in those with silent PE compared to those without PE.

[Thromboembolic events in patients after a negative computed tomography pulmonary angiogram: A retrospective study of 165 patients]. / Aparición de episodios tromboembólicos en pacientes con angiotomografía axial computarizada simple negativa. Estudio retrospectivo de 165 pacientes.

OBJECTIVE: To determine the value of computed tomography (CT) angiography of the chest as a diagnostic test to exclude pulmonary embolism and to assess compliance with diagnostic protocols for thromboembolic disease. PATIENTS AND METHODS: We retrospectively studied patients who underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. All the patients were followed for 3 months. The percentage of patients diagnosed with a thromboembolic event based on an objective test during the follow-up period was determined. We analyzed the percentage of patients with a negative CT angiogram on whom additional diagnostic tests (ultrasound of the lower limbs and/or ventilation-perfusion lung scintigraphy) were performed. RESULTS: One hundred sixty-five patients underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. Four of the patients were excluded from the study because they were on chronic anticoagulation therapy and a further 2 were excluded because they had a life expectancy of under 3 months. Of the remaining 159 patients, 60 had CT angiograms that were interpreted as high probability for pulmonary embolism (prevalence of 38%). Thirty-nine of the 99 patients with a negative CT angiogram experienced an objectively confirmed thromboembolic event (63% sensitivity; 95% confidence interval, 53%-73%). Other diagnostic tests were not performed in 46% of the cases. CONCLUSIONS: In our setting, a negative single-detector helical CT angiogram was not sensitive enough to exclude the diagnosis of pulmonary embolism. Furthermore, compliance with internationally accepted diagnostic protocols was far from optimal.

Etiology and prognostic significance of massive pleural effusions.

It has been stated that malignancy is the most common aetiology of massive pleural effusions. To determine the most frequent causes of massive pleural effusions and to assess the diagnostic yield of different diagnostic procedures and survival, we prospectively studied 1084 patients with pleural effusion. Massive pleural effusions were identified in 121 of 1084 patients (11.2%). Compared with non-massive pleural effusions, massive pleural effusions were significantly more likely to be malignant (53.7% vs. 38.3%, P=0.03) or secondary to cirrhosis (9.9% vs. 2.6%, P=0.0000). On the other hand, massive pleural effusions were significantly less likely to be secondary to infection (10.7% vs. 19.2%, P=0.003) or congestive heart failure (0.8% vs. 6.7%, P=0.03). There was a significant increase in the yield of diagnostic studies in patients with massive malignant pleural effusions (56.9% for cytological studies and 36.9% for biopsies). On the other hand, there was no difference in the diagnostic yield of microbiological and histological studies in the group of tuberculous pleural effusions. In our study population, patients with non-massive malignant pleural effusions had a significantly better survival than those with massive malignant pleural effusions, with a median survival of 8 months (95% confidence interval, 7-9) compared with 5 months (95% confidence interval, 4-6) (P=0.0009). We conclude that malignancy is the most common cause of a massive exudative effusion. Massive malignant pleural effusions are associated with worse survival, independent of age and histologic subgroup, than are non-massive malignant pleural effusions.

Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport.

BACKGROUND: Prolonged air travel and the associated immobilization are risk factors for venous thromboembolism. The occurrence of pulmonary thromboembolism (PTE) under these circumstances is referred to as economy class syndrome. We assessed the incidence of symptomatic PTE in passengers on long-haul flights arriving at Madrid-Barajas Airport, Madrid, Spain, and the association with the number of flight hours. METHODS: We retrospectively reviewed cases of PTE among international travelers arriving at Madrid-Barajas Airport between January 1995 and December 2000. Patients presenting with symptoms of deep venous thrombosis but without symptoms of PTE were excluded. Pulmonary thromboembolism was identified using an algorithm of diagnostic tests. The incidence of PTE and the association with flight duration was assessed. RESULTS: The average number of passengers per year who arrived at the airport on flights originating abroad in the period analyzed was 6 839 222. Sixteen cases of PTE were detected over the 6-year period. All patients with travel-associated PTE had flight durations of greater than 6 hours. The overall incidence of PTE was 0.39 per 1 million passengers (95% confidence interval [CI], 0.20-0.58). On flights that lasted between 6 and 8 hours, the incidence was 0.25 per 1 million passengers (95% CI, 0-0.75), while on flights longer than 8 hours, the incidence was 1.65 per 1 million passengers (95% CI, 0.81-2.49) (P<.001). CONCLUSIONS: Air travel is a risk factor for PTE, and the incidence of PTE increases with the duration of the air travel. However, the low incidence of PTE among long-distance passengers, similar to that observed in other international airports, does not justify social alarm.

Mercury, lead and cadmium levels in the urine of 170 Spanish adults: a pilot human biomonitoring study.

Human biomonitoring is a well-recognized tool for estimating the exposure of human populations to environmental pollutants. However, information regarding biomarker concentrations of many environmental chemicals in the general population is limited for many countries. The Spanish Environment Ministry has recently funded a human biomonitoring study on the Spanish general population. This study aims to determine reference levels for several biomarkers, especially heavy metals, persistent organic pollutants (POPs) and cotinine, in urine, whole blood, serum and hair, and will involve 2000 volunteers throughout Spain. Samples were taken during 2009-2010 and analyses are currently underway. The results presented herein were obtained in a pilot study carried out in the Madrid region. The study group comprised 170 volunteers, of which 79% were female and 21% male (age: 23-66 years). All participants were asked to complete a questionnaire regarding diet and living habits and provides a morning urine sample. The geometric means for total mercury (Hg), lead (Pb) and cadmium (Cd) were 1.23, 1.11 and 0.25 µg/g creatinine, respectively. Levels of Pb and Hg were higher than those reported for the general population in the USA and Germany, whereas Cd was in the same range (CDC, 2009; Becker et al., 2003). The values reported here are similar to those reported in other Spanish studies.