Recombinant human insulin-like growth factor I (rhIGF-I) for the treatment of amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Recombinant human insulin-like growth factor I (rhIGF-I) is a possible disease modifying therapy for amyotrophic lateral sclerosis (ALS, which is also known as motor neuron disease (MND)). OBJECTIVES: To examine the efficacy of rhIGF-I in affecting disease progression, impact on measures of functional health status, prolonging survival and delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival in ALS. Occurrence of adverse events was also reviewed. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (21 November 2011), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to November 2011) and EMBASE (January 1980 to November 2011) and sought information from the authors of randomised clinical trials and manufacturers of rhIGF-I. SELECTION CRITERIA: We considered all randomised controlled clinical trials involving rhIGF-I treatment of adults with definite or probable ALS according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months of treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: Each author independently graded the risk of bias in the included studies. The lead author extracted data and the other authors checked them. We generated some missing data by making ruler measurements of data in published graphs. We collected data about adverse events from the included trials. MAIN RESULTS: We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. AUTHORS' CONCLUSIONS: Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

A Randomized Trial for the Treatment of Refractory Status Epilepticus.

BACKGROUND: Refractory status epilepticus (RSE) has a mortality of 16-39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to assess the effectiveness (RSE control, adverse events) of the first course of propofol versus barbiturates in the treatment of RSE. METHODS: In this randomized, single blind, multi-center trial studying adults with RSE not due to cerebral anoxia, medications were titrated toward EEG burst-suppression for 36-48 h and then progressively weaned. The primary endpoint was the proportion of patients with RSE controlled after a first course of study medication; secondary endpoints included tolerability measures. RESULTS: The trial was terminated after 3 years, with only 24 patients recruited of the 150 needed; 14 subjects received propofol, 9 barbiturates. The primary endpoint was reached in 43% in the propofol versus 22% in the barbiturates arm (P = 0.40). Mortality (43 vs. 34%; P = 1.00) and return to baseline clinical conditions at 3 months (36 vs. 44%; P = 1.00) were similar. While infections and arterial hypotension did not differ between groups, barbiturate use was associated with a significantly longer mechanical ventilation (P = 0.03). A non-fatal propofol infusion syndrome was detected in one patient, while one subject died of bowel ischemia after barbiturates. DISCUSSION: Although undersampled, this trial shows significantly longer mechanical ventilation with barbiturates and the occurrence of severe treatment-related complications in both arms. We describe practical issues necessary for the success of future studies needed to improve the current unsatisfactory state of evidence.

Anaesthesia for electroconvulsive therapy: time for a change?

Introduction: Electroconvulsive therapy (ECT) may be used to treat severe depression and needs a specific general anaesthesia. Important cardiovascular changes occur during the ECT with a parasympathetic induced bradycardia followed by a sympathetic response. A dedicated protocol was designed 6 years ago. The goal of this study was to analyse the management of anaesthesia for ECT in our institution, the adherence to the protocol and the occurrence of adverse events during anaesthesia. Methods: After Institutional Ethics Committee approval, we conducted a retrospective analysis of our anaesthesia protocol for patients scheduled for electroshock therapy during a five years period (2004- 2008). The protocol includes administration of atropine subcutaneously 30 minutes before the procedure, followed by general anaesthesia induced with etomidate (0.2 mg/kg). Suxamethonium (1 mg/kg) is administered after the inflation of a pneumatic tourniquet on the opposite arm, in order to observe the electroshocks convulsive effects. The psychiatrist initiates the convulsive crisis once curarisation is achieved. Face mask ventilation is then applied during the post-ictal phase with closed blood pressure monitoring. : 228 ECT were performed in 25 patients. The median dosage of etomidate was 0.37 mg/kg and suxamethonium 1.20 mg/kg. Hypertension during the ECT procedure was present in 62.7% of cases, tachycardia 23.2% and bradycardia 10.5%. Esmolol was administered in 73.4% of hypertensive patients in a range of 0 to 30 mg. The protocol was followed in half of the cases in regards to atropine administration (50.4%). We observed a significant increase of hypertension (73.9%, p = 0.001) after atropine administration, without effect on heart rate. Conclusions: The management of anaesthesia for ECT is specific and follows a predefined protocol in our institution. Adherence to our protocol was poor. Adverse events are frequent and significant association between the administration of atropine and the incidence of hypertension as well as poor protocol adherence implies reconsideration of our anaesthesia protocol for electroconvulsive therapy and better quality control of the clinical practice.

Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse

Rrésumé: La première description dans une publication médicale des douleurs neuropathiques remonte à 1872, le Dr S.W. Mitchell les résumant ainsi [...]" la causalgie est la plus terrible des tortures qu'une lésion nerveuse puisse entraîner "[...]. Par définition, la douleur neuropathique est une douleur chronique faisant suite à une lésion ou dysfonction du système nerveux. Malgré les progrès faits dans la compréhension de ce syndrome, le détail des mécanismes impliqués nous échappe encore et son traitement reste insuffisant car moins de 50% des patients sont soulagés par les thérapies actuelles. Différents modèles expérimentaux ont été élaborés chez l'animal de laboratoire, en particulier des modèles de lésion de nerfs périphériques chez le rat, permettant des investigations tant moléculaires que fonctionnelles des mécanismes impliqués dans le développement de ces douleurs. En revanche, peu de modèles existent chez la souris, alors que cet animal, grâce à la transgénèse, est très fréquemment utilisé pour l'approche fonctionnelle ciblée sur un gène. Dans l'étude présentée ici, nous avons évalué chez la souris C57BL/6 l'adaptation d'un modèle neuropathique, proposé une nouvelle modalité de mesure de la sensibilité douloureuse adaptée à la souris et défini une méthode d'analyse performante des résultats. Ce modèle, dit de lésion avec épargne nerveuse (spared Werve injury, SNI), consiste en la lésion de deux des trois branches du nerf sciatique, soit les nerfs peronier commun et tibial. La troisième branche, le nerf sural est laissé intact et c'est dans le territoire cutané de ce dernier que la sensibilité douloureuse à des stimulations mécaniques est enregistrée. Des filaments calibrés de force croissante sont appliqués sur la surface de la patte impliquée et la fréquence relative de retrait de la patte a été modélisée mathématiquement et analysée par un modèle statistique intégrant tous les paramètres de l'expérience (mixed-effects model). Des variantes chirurgicales lésant séquentiellement les trois branches du nerf sciatique ainsi que la réponse en fonction du sexe de l'animal ont également été évaluées. La lésion SNI entraîne une hypersensibilité mécanique marquée comparativement aux souris avec chirurgie contrôle; cet effet est constant entre les animaux et persiste durant les quatre semaines de l'étude. De subtiles différences entre les variables, y compris une divergence de sensibilité mécanique entre les sexes, ont été démontrées. La nécessité de léser le nerf tibial pour le développement des symptômes a également été documentée par notre méthode d'évaluation et d'analyse. En conclusion, nous avons validé le modèle SNI chez la souris par l'apparition d'un symptôme reproductible et apparenté à l'allodynie mécanique décrite par les patients souffrant de douleurs neuropathiques. Nous avons développé des méthodes d'enregistrement et d'analyse de la sensibilité douloureuse sensibles qui permettent la mise en évidence de facteurs intrinsèques et extrinsèques de variation de la réponse. Le modèle SNI utilisé chez des souris génétiquement modifiées, de par sa précision et reproductibilité, pourra permettre la discrimination de facteurs génétiques et épigénétiques contribuant au développement et à la persistance de douleurs neuropathiques.

Asthme aigu sévère [Severe acute asthma]

Acute severe asthma is defined by the occurrence of an acute exacerbation resistant to the initial medical treatment, complicated by life-threatening respiratory distress due to severe lung hyperinflation. The conventional therapeutic approach is based on oxygen therapy and on the combined treatment of inhaled beta2-agonists at repeated doses and systemic corticosteroids. Inhaled or systemic magnesium sulfate is also recommended. The unresponsiveness to the initial bronchodilating therapy and the development of respiratory distress requiring intubation significantly increases mortality, due to the complications induced by mechanical ventilation. In these situations, a ventilatory strategy, including controlled hypoventilation with permissive hypercapnia, aiming at preventing lung hyperinflation, is indicated. Non-invasive ventilation may be successful in certain patients and represents an effective alternative to intubation. In ventilated patients, helium-oxygen mixtures can be considered as adjunctive therapies. After having reviewed the basic pathophysiological principles, this article will focus on the current medical treatment and of the modalities of mechanical ventilation in acute severe asthma.

Influence des conditions de travail sur la santé des employés de production

Une intervention ergonomique a été réalisée dans la maison-mère d'un grand groupe suisse constructeur d'équipements. Les situations de travail qui ont été étudiées sont des ateliers de tôleries, de mécanique et de soudure. La demande d'intervention à l'IST (Institut universitaire romand de santé au travail) est partie du constat par la hiérarchie et par l'infirmière du travail qu'un nombre croissant d'employés de production souffraient de maux de dos et de stress et qu'il était nécessaire d'entreprendre des améliorations du travail afin de réduire ces symptômes. [Auteurs]

Occupational exposure of truck drivers to dust and polynuclear aromatic hydrocarbons: a pilot study in Geneva, Switzerland.

The exposure to dust and polynuclear aromatic hydrocarbons (PAH) of 15 truck drivers from Geneva, Switzerland, was measured. The drivers were divided between "long-distance" drivers and "local" drivers and between smokers and nonsmokers and were compared with a control group of 6 office workers who were also divided into smokers and nonsmokers. Dust was measured on 1 workday both by a direct-reading instrument and by sampling. The local drivers showed higher exposure to dust (0.3 mg/m3) and PAH than the long-distance drivers (0.1 mg/m3), who showed no difference with the control group. This observation may be due to the fact that the local drivers spend more time in more polluted areas, such as streets with heavy traffic and construction sites, than do the long-distance drivers. Smoking does not influence exposure to dust and PAH of professional truck drivers, as measured in this study, probably because the ventilation rate of the truck cabins is relatively high even during cold days (11-15 r/h). The distribution of dust concentrations was shown in some cases to be quite different from the expected log-normal distribution. The contribution of diesel exhaust to these exposures could not be estimated since no specific tracer was used. However, the relatively low level of dust exposure dose not support the hypothesis that present day levels of diesel exhaust particulates play a significant role in the excess occurrence of lung cancer observed in professional truck drivers.

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective: To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with ALI or ARDS receiving mechanical ventilation. P–V curves were fitted to a sigmoidal equation with a mean R2 of 0.994 ± 0.003. Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with high intraclass correlation coefficients. Bias and limits of agreement for LIP, UIP and PMC obtained with the two methods in the same patient were clinically acceptable.

Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.

INTRODUCTION: Mutations in the TMEM70 are the most common cause of nuclear ATP synthase deficiency resulting in a distinctive phenotype characterized by severe neonatal hypotonia, hypertrophic cardiomyopathy (HCMP), facial dysmorphism, severe lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria (3-MGA). METHODS AND RESULTS: We collected 9 patients with genetically confirmed TMEM70 defect from 8 different families. Six were homozygous for the c.317-2A>G mutation, 2 were compound heterozygous for mutations c.317-2A>G and c.628A>C and 1 was homozygous for the novel c.701A>C mutation. Generalized hypotonia, lactic acidosis, hyperammonemia and 3-MGA were present in all since birth. Five patients presented acute respiratory distress at birth requiring intubation and ventilatory support. HCMP was detected in 5 newborns and appeared a few months later in 3 additional children. Five patients showed a severe and persistent neonatal pulmonary hypertension (PPHN) requiring Nitric Oxide (NO) and/or sildenafil administration combined in 2 cases with high-frequency oscillatory (HFO) ventilation. In 3 of these patients, echocardiography detected signs of HCMP at birth. CONCLUSIONS: PPHN is a life-threatening poorly understood condition with bad prognosis if untreated. Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient. This report further expands the clinical and genetic spectrum of the syndrome indicating PPHN as a frequent and life-threatening complication regardless of the type of mutation. Moreover, in these children PPHN appears even in the absence of an overt cardiomyopathy, thus representing an early sign and a clue for diagnosis.

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients.

BACKGROUND AND AIMS: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. METHODS: Prospective observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+/-SD, linear regressions between energy balance and outcome variables. RESULTS: Forty eight patients aged 57+/-16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11+/-8 days, ICU stay 15+/-9 was days, and 30-days mortality was 38%. Time to feeding was 3.1+/-2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090+/-930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+/-10,520 kcal, and correlated with complications (P < 0.001), already after 1 week. CONCLUSION: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.

Responses to exercise in normobaric hypoxia: comparison of elite and recreational ski mountaineers.

PURPOSE: Hypoxia is known to reduce maximal oxygen uptake (VO(2max)) more in trained than in untrained subjects in several lowland sports. Ski mountaineering is practiced mainly at altitude, so elite ski mountaineers spend significantly longer training duration at altitude than their lower-level counterparts. Since acclimatization in hypobaric hypoxia is effective, the authors hypothesized that elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to that of recreational ski mountaineers. METHODS: Eleven elite (E, Swiss national team) and 12 recreational (R) ski mountaineers completed an incremental treadmill test to exhaustion in normobaric hypoxia (H, 3000 m, F(1)O(2) 14.6% ± 0.1%) and in normoxia (N, 485 m, F(1)O(2) 20.9% ± 0.0%). Pulse oxygen saturation in blood (SpO(2)), VO(2max), minute ventilation, and heart rate were recorded. RESULTS: At rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 ± 1.9 vs 0.3 ± 0.6 L · min⁻¹ · kg⁻¹). At maximal intensity, SpO(2) was significantly lower (P < .01) in E than in R, both in N (91.1% ± 3.3% vs 94.3% ± 2.3%) and in H (76.4% ± 5.4% vs 82.3% ± 3.5%). In both groups, SpO(2) was lower (P < .01) in H. Between N and H, VO(2max) decreased to a greater extent (P < .05) in E than in R (-18% and -12%, P < .01). In E only, the VO(2max) decrement was significantly correlated with the SpO(2) decrement (r = .74, P < .01) but also with VO(2max) measured in N (r = .64, P < .05). CONCLUSION: Despite a probable better acclimatization to altitude, VO(2max) was more reduced in E than in R ski mountaineers, confirming previous results observed in lowlander E athletes.

Nava enhances ventilatory variability and diaphragmatic activity/tidal volume coupling

INTRODUCTION. Neurally Adjusted Ventilatory Assist (NAVA) is a new ventilatory mode in which ventilator settings are adjusted based on the electrical activity detected in the diaphragm (Eadi). This mode offers significant advantages in mechanical ventilation over standard pressure support (PS) modes, since ventilator input is determined directly from patient ventilatory demand. Therefore, it is expected that tidal volume (Vt) under NAVA would show better correlation with Eadi compared with PS, and exhibit greater variability due to the variability in the Eadi input to the ventilator. OBJECTIVES. To compare tidal volume variability in PS and NAVA ventilation modes, and its correlation with patient ventilatory demand (as characterized by maximum Eadi). METHODS. Acomparative study of patient-ventilator interaction was performed for 22 patients during standard PS with clinician determined ventilator settings; and NAVA, with NAVA gain set to ensure the same peak airway pressure as the total pressure obtained in PS. A 20 min continuous recording was performed in each ventilator mode. Respiratory rate, Vt, and Eadi were recorded. Tidal volume variance and Pearson correlation coefficient between Vt and Eadi were calculated for each patient. A periodogram was plotted for each ventilator mode and each patient, showing spectral power as a function of frequency to assess variability. RESULTS. Median, lower quartile and upper quartile values for Vt variance and Vt/Eadi correlation are shown in Table 1. The NAVA cohort exhibits substantially greater correlation and variance than the PS cohort. Power spectrums for Vt and Eadi are shown in Fig. 1 (PS and NAVA) for a typical patient. The enlarged section highlights how changes in Eadi are highly synchronized with NAVA ventilation, but less so for PS. CONCLUSIONS. There is greater variability in tidal volume and correlation between tidal volume and diaphragmatic electrical activity with NAVA compared to PS. These results are consistent with the improved patient-ventilator synchrony reported in the literature.

Volemic status influences the response of plasma atrial natriuretic factor to positive airway pressure.

STUDY OBJECTIVE; To evaluate interactive effects of volemic status and positive end-expiratory pressure (PEEP) on the plasma levels of atrial natriuretic factor (ANF) in assist-controlled mechanical ventilation (MV). DESIGN: Three successive protocols applied in randomized order to each participant. SETTING: Clinical investigation laboratory. PARTICIPANTS: Twenty-one young, healthy adults. INTERVENTIONS: The three protocols were as follows: (1) MV+PEEP, normovolemia; (2) MV+PEEP, hypervolemia; and (3) spontaneous breathing (SB), hypervolemia. In protocols 1 and 2, a preliminary period of SB lasting 2 h was followed by MV alone (0.5 h), MV+20 cm H2O PEEP (1 h), and a recovery period of SB (1.5 h). Hypervolemia was induced by the continuous i.v. infusion of 3 L of 0.9% NaCl in 5 h (protocols 2 and 3). MEASUREMENTS AND RESULTS: Heart rate, BP, and the plasma levels of immunoreactive ANF and catecholamines were measured serially. During hypervolemia, ANF significantly decreased when PEEP was added to MV (protocol 2: from 31.1 +/- 2.7 to 20.7 +/- 1.5 fmol/mL; p < 0.01). This did not occur in normovolemia (protocol 1: from 20.0 +/- to 16.7 +/- 1.2 fmol/mL; p = NS). The different effects of MV+PEEP in normovolemia and hypervolemia were not related to differences in circulating catecholamine levels. CONCLUSIONS: These results demonstrate for the first time (to our knowledge) that volemic status modulates the response of plasma ANF to PEEP in humans. The role of ANF in the water and salt retention induced by MV with PEEP might be limited to hypervolemic conditions.

Clinical outcome and risk factors related to extended-spectrum beta-lactamase-producing Klebsiella spp. infection among hospitalized patients

Over the past two decades, nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. have become a major problem all around the world. This situation is of concern because there are limited antimicrobial options to treat patients infected with these pathogens, and also because this kind of resistance can spread to a wide variety of Gram-negative bacilli. Our objectives wereto evaluate among in-patients at a publicuniversity tertiary-care hospital with documented infection due to Klebsiella spp., which were the risk factors (cross-sectional analysis) and the clinical impact (prospective cohort) associated with an ESBL-producing strain. Study subjects were all patients admitted at the study hospital between April 2002 and October 2003, with a clinically and microbiologically confirmed infection caused by Klebsiella spp. at any body site, except infections restricted to the urinary tract. Of the 104 patients studied, 47 were infected with an ESBL-producing strain and 57 with a non-ESBL-producing strain. Independent risk factors associated with infection with an ESBL-producing strain were young age, exposure to mechanical ventilation, central venous catheter, use of any antimicrobial agent, and particularly use of a 4th generation cephalosporin or a quinolone. Length of stay was significant longer for patients infected with ESBL-producing strains than for those infected with non-ESBL-producing strains, although fatality rate was not significantly affected by ESBL-production in this cohort. In fact, mechanical ventilation and bacteremia were the only variables withindependent association withdeath detected in this investigation.

Indoor air quality in a public building following smoking bans

Introduction: Exposure to environmental tobacco smoke (ETS) is a major environmental risk factor. Indoor contaminants come from a variety of sources, which can include inadequate ventilation, volatile organic compounds (VOCs), biological agents, combustion products, and ETS. Because ETS is one of the most frequent causes of IAQ complaints as well as the high mortality of passive smoking, in June 2004 the University of Geneva made the decision to ban smoking inside the so called "Uni-Mail" building, the biggest Swiss University human science building of recent construction, and the ordinance was applied beginning in October 2004. This report presents the finding related to the IAQ of the "Uni-Mail" building before and after smoking bans using nicotine, suspended dust, condensate and PAHs level in air as tracers to perform an assessment of passive tobacco exposure for non-smokers inside the building. Methods: Respirable particles (RSP) A real time aerosol monitor (model DataRAM)was place at sampling post 1, level ground floor. Condensate It consists in extracting any organic matter taken on the glass fibre filters by MeOH, and then measuring the total absorbent of the MeOH extract to the UV wavelength of 447 nm. Nicotine Nicotine was taken by means of cartridges containing of XAD-4 to the fixed flow of 0.5 L/min. The analytical method used for the determination of nicotine is based on gas chromatography with Nitrogen selective detector GC-NPD. Results: Figure 1 shows the box plot density display of 3 parameters before and after smoking bans for all 7 sampling posts: dust, condensate and nicotine in air in μg/m3. Conclusion: Before the smoking ban, the level of the concentrations of respirable particles (RSP) is raised more, average of the day 320 μg/m3, with peaks of more than 1000 μg/m3, compared with the values of the surrounding air between 22 and 30 μg/m3. The nicotine level is definitely more important (average 5.53 μg/m3, field 1.5 to 17.9 μg/m3). Once the smoking bans inside the building were applied, one notes a clear improvement in terms of concentrations of pollutants. For dust, the concentration fell by 3 times (average: 130 μg/m3, range: 40 to 160 μg/m3) and that of nicotine by 10 times (average: 0.53 μg/m3, range: 0 to 1.69 μg/m3) compared to that found before smoking bans. The outdoor air RSP concentration was 22 μg/m3 or 10 times lower. Nicotine seems to be the best tracer for ETS free of interference, independent of location or season.